CA2339054C - E-isomeric fullerene derivatives - Google Patents

Abstract

An E-isomeric fulleropyrrolidine compound of formula (I): (see formula I) is disclosed. Also disclosed is a method for preparing and polymers prepared from such a compound.

Description

E-ISOMERIC FULLERENE DERIVATIVES
BACKGROUND OF THE INVENTION

Cancer remains a formidable disease with a high mortality rate in today's society. Indeed, cancer is second only to cardiovascular disease as a cause of death, killing one out of four people in developed countries.
Cancerous tumors commonly originate from normal cells which transform into malignant cells or tumors. The initial tumor growth may be slow and thus may be difficult to detect. The growth often becomes more aggressive and invasive with time, eventually spreading throughout the whole body and resulting in death.
Photodynamic therapy (PDT) is one of the methods for treating tumors. For review, see Dougherty, T. J. Photochem. Photobiol. 1993, 58, 895. At present, the most commonly used sensitizers for clinical PDT practices are Photofrin IITM, an enriched active fraction of hematoporphyrin derivatives, and disulfonated aluminum phthalocyanine. These compounds, once photoactivated, induce severe oxidative damage to the structure of lipids, proteins, and nucleic acids. Since many biologically active molecules, e.g., DNA, demonstrate higher affinity toward stereospecific ligands, it is therefore desirable to develop stereospecific PDT sensitizers to enhance cytotoxicity of such antitumor agents.

SUMMARY
An aspect of this invention relates to a compound of formula (I):

Docket No.: 06897-002006 Y OH

Ff NH (I) { OH

R2 R~ s x F f is F(-K),,,(-Y-Z)q. F is a fullerene core. Each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -COZH, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)Z, -O-PO(O-)-O-CH2CHZ-NH 3+, -O-PO(07-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCHZ(CHOH)4-CHZOH, -OCHZ(CHOH)Z-CHZOH, -NH-CH2-CO2H, -[CH(C02H)-CH2]1_,oo-OH, -[CH(COZRa)-CHZ]j_ioo-OH, -[C(CH3)(CO2H)-CH2],_ioo-OH, -[C(CH3)(C02 R')-CH2]1_1oo-OH, -N(OH)2, -NH3+, -N+HZR', -N+HR'Rb, or -N+RaRbR`. Each Y is -A-B-, in which A is -0-, -NH-, -S-, -CO-O-, -0-CO-, -0-CO-O-, -0-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -Ra-O-[Si(CH3)Z-O-]i_100, CI.Zooo allcyl, C6-40 aryl, C7_2000 alkylaryl, C7-2ooo arylalkyl, (Ci_30 alkyl ether),-ioo, (C6-4o aryl ether)1.100, (C7-2ooo alkylaryl ether),.Ioo, (C7-Zooo arylalkyl ether),-ioo, (CI_30 alkyl thioether)1_100, (C6_40 aryl thioether)1-100, (C7-20oo alkylaryl thioether),-ioo, (C7.2000 arylalkyl thioether)l.Ioo, (CZ-so alkyl ester),_ioo, (C7.2000 aryl ester)i-ioo, (C8.2ooo alkylaryl ester),-ioo, (C8.2000 arylalkyl ester)1_100, -R'-CO-O-(CI_30 alkyl ether)I_ioo, -R'-CO-O-(C6-40 aryl ether)i_loo, -R'-CO-O-(C7.2000 alkylaryl ether)1.100, -R'-CO-O-(C7_Z000 arylalkyl ether)t_ioo, (C4.50 alkyl urethane)i-ioo, (C14-6o aryl urethane),.1oo, (C10-2000 alkylaryl urethane)i_100, (Cio.2ooo arylallcyl urethane),_too, (Cs-so alkyl urea)l_ioo, (C14-60 aryl urea)i_ioo, (Cio-2ooo alkylaryl urea)i.loo, (Cio-2ooo arylalkyl urea)t.Ioo, (Cz-so alkyl amide),.ioo, (C7_6o aryl amide)i_Ioo, (Ca-2ooo alkylaryl amide),_Ioo, (Ca-2ooo arylalkyl amide)1.100, (C3-3o alkyl anhydride), .loo, (Cs-so aryl anhydride)i.ioo, (C9-2ooo alkylaryl anhydride),.ioo, (C9-ZOOO arylalkyl anhydride),.loo, (C2-30 alkyl carbonate),., 00, (C7-so aryl carbonate)i-ioo, (Cs.ZOOO alkylaryl carbonate)i-, 00, (Cg-2ooo arylalkyl carbonate),.ioo, Docket No.: 06897-002006 -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(Ci.30 alkyl ether, C6.oo aryl ether, C7_2000 alkylaryl ether, or C7.2ooo arylalkyl ether), -loo, -R'-O-CO-NH-(Rb or Ar-R-Ar)-NH-CO-O-(CZ-5o allcyl ester, C7.60 aryl ester, C8-ZOOO alkylaryl ester, or Cg-2ooo arylallcyl ester)i-100, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1.30 alkyl ether, C6.40 aryl ether, C7_2000 alkylaryl ether, or C7.2000 arylalkyl ether), .i00-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2-50 allcyl ester, C7.6o aryl ester, CB.2000 alkylaryl ester, or Cg.2ooo arylalkyl ester), -ioo-R`-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C6-40 aryl ether, C7-alkylaryl ether, or C7-2000 arylalkyl ether)i.Ioo, -R'NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CZ-5o alkyl ester, C7.6o aryl ester, Cg-ZOOO alkylaryl ester, or C8-2ooo arylalkyl ester)i.,()O, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1.3o alkyl ether, C6.40 aryl ether, C7.2000 alkylaryl ether, or C7_2000 arylalkyl ether), -1oo-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2.5o alkyl ester, C7.6o aryl ester, C8.2000 alkylaryl ester, or Cg-2ooo arylalkyl ester)I_, 00-R`-O-CO-NH-(Rb or Ar-R-Ar)-NH-CO-O-, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(CZ-5o alkyl amide, C7.60 aryl amide, C8-Zooo alkylaryl amide, or C8-2000 arylalkyl amide)i-Ioo, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(CZ.5o alkyl amide, C7.6o aryl amide, C8.2000 alkylaryl amide, or C8-2000 arylalkyl amide)1.100, or a bond;
each Z, independently, is -G-D, wherein G is -R'-, -R'-Ar-, -Ar-R'-, or -Ar-;
and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NHZ)-COZH, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CHZCH2NH3+, -O-PO(O")-O-CHZCH2-N`(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CHZOH, -CO-OCHZ(CHOH)4-CHZOH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CHZCH2OH)3, -[CH2-CH(CO2R')]I_ioo-H, -NH3+, -N+H2R', -N+HR'Rb, or -N+R'RbR`. Each of R', Rb, and R`, independently, is Ci_ZO alkyl and Ar is aryl. q is 0-30, and m is 0-30. Note that the sum of q and m is 0-30. Each of R' and R4, independently, is =0 or Ci_ZO hydrocarbon. A
hydrocarbon is a moiety containing carbon and hydrogen, e.g., alkyl, alkenyl, or alkynyl.
Each of R2 and R5, independently, is CI_20 hydrocarbon; wherein R' and R2, or R4 and RS can join together to form C&4o aryl which is optionally substituted with halide, -OH, -NHNH2, -NHZOH, -NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CHZ-D, -CO-B-Z, -0-B-Z, or Docket No.: 06897-0uz006 -NH-B-Z. Each of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid. E is Ei, E2, or E3, in which Ei is Yi,Y2-amino, (YI,YZ-alkyl)-amino, Yi,Y2-ethylenediamino, (dihydroxymethyl)alkylamino, (Xt,X3-aryl)amino, or X1,X3-aryloxy; E2 is Yi,Y2-alkoxy, (Yi,Y2-amino)alkoxy, (Yi,YZ,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (YI,YZ,Y3-alkyl)amino, (Yi,Y2,Y3-aryl)amino, dihydroxyalkylamino, YI,YZ,Y3-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyallcyl)amino, (Y1,Y2,Y3-alkyl)thio, (Xl,X3-aryl)thio, (Yt,YZ-alkyl)thio, (dihydroxyalkyl)thio, Yi,YZ-dioxoalkyl, or tri-(Yl,Y2iY3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (XI,XZ,X3-heteroaryl)amino, (Xi-diarylketone)amino, (X,Xi-oxoaryl)amino, (X,XI-dioxoaryl)amino, (Yi-alkyl,Y2-alkyldioxoheteroaryl)amino, (Yi-alkyl,YZ-alkyldioxoaryl)amino, (di(Y,,YZ-methyl)dioxoheteroaryl)amino, (di(Yl,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (XbXZ,X3-alkylaryl)amino, (XI,XZ,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (Xi,XZ,X3-oxoheteroaryl)oxy, (Xi,X2,X3-oxoaryl)oxy, (Xi,YI-oxoheteroaryl)oxy, (Xi-diarylketone)oxy, (X,XI-oxoaryl)oxy, (Xi,XZ-dioxoaryl)oxy, (YI,YZ,di-aminodihydroxy)alkyl, (Xi,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (Xi,X2-oxoaryl)thio, (Xi,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Yi-alkyl(thiocarbonyl)thio, YI,YZ,-alkyl(thiocarbonyl)thio, Yt,Y2,Y3-alkyl(thiocarbonyl)thio, (YI,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl),-iooamino, (pyranosyl)amino, (Yi-aminoaryl)i_tooamino, (amino(sulfoaryl))i_Iooamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy. X is halide. Each of Xi, X2, and X3, independently, is -Yl, -O-YI, -S-Y1, -NH-Yi, -CO-O-Yi, -O-CO-YI, -CO-NH-Yi, -CO-NYiYZ, -NH-CO-Yi, -S02-Yi, -CHYiY2, or -NYIY2. Each of Yi, Y2, and Y3, independently, is -Z or -B-Z. Each of x and y, independently, is 0 or 1; and s is 1-6. Note that when x is 0, R' is =0; that when y is 0, R4 is =0; that when x is 1, R' and R2join together to form C6-ao aryl; and that when y is 1, R4 and R5 join together to form C&40 aryl.
Another aspect of this invention relates to a method for preparing a compound of formula (I). The method includes reacting a compound of formula (II):

. =

y N -. -Aii (II) R2 X R' wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion, with a fullerene compound Ff of the formula F(-K)m(-Y-Z)q wherein the sum of q and m is 0 to form a compound of formula (III):

y Ff N........ M (III) O

s 2 x Rt M is then removed from a compound of formula (III), e.g., by using an ion exchange resin such as Dowex,to form a compound of formula (1) wherein the sum of q and m is 0.
The compound of formula (I) wherein the sum of q and m is 0 can be further treated with a nitrating or sulfating agent to form a nitrofullerene or cyclosulfated fullerene, and contacting the nitrofullerene or cyclosulfated fullerene with a nucleophilic agent to form a compound of formula (I) wherein the sum of q and m is greater than 0, i.e., a derivatized fulleropyrrolidine compound of this invention. .
The compound of formula (II) can be prepared by reacting a compound of formula (IV):

-S-Docket No.: 06897-002006 y Rs OH

N (IV) 2 x R' with a metal salt MX, wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion, and X is an anion such as sulfate, halide, acetate, and nitrate. As to the compound of formula (IV), it is prepared by reacting a compound of formula (V):

R Rs (V) R5 y with a compound of formula (VI):
O OH

R' (vI) R
x RZ

Yet another aspect of this invention relates to a compound of formula (VII).
R s R4 R' RZ Rio y R9'~
X (VII) =1 N R8 Ff =, ,Rs p . ~t z Docket No.: 06897-002006 Ff is F(-K)m(-Y-Z)y. F is a fullerene core. Each K, independently, is -OH, -SH, -NHZ, -NHOH, -SO3H, -OSO3H, -COZH, -CONH2, -CONHNHZ, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)Z, -O-PO(O-)-O-CHZCHZ-NH 3 -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCHZ(CHOH)4-CHZOH, -OCHZ(CHOH)2-CHZOH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]t_,oo-OH, -[CH(CO2R')-CH2]i_ioo-OH, -[C(CH3)(CO2H)-CH2]t_ioo-OH, -[C(CH3)(CO2 Ra)-CHZ]1_loo-OH, -N(OH)2, -NH3+, -N+HZR', -N+HR'Rb, or -N+R'RbR`. Each Y is -A-B-, in which A is -0-, -NH-, -S-, -CO-O-, -0-CO-, -O-CO-O-, -0-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -R'-O-[Si(CH3)2-0-]1-too, Ci-2ooo alkyl, C6-4o aryl, C7-2000 alkylaryl, C7.2ooo arylalkyl, (C1-30 alkyl ether)t-ioo, (C6-ao aryl ether),.Ioo, (C7-ZOOO alkylaryl ether),.ioo, (C7_2000 arylalkyl ether),.Ioo, (Ci-3o alkyl thioether)i-loo, (C6-40 aryl thioether),-Ioo, (C7-zo0o alkylaryl thioether)1-100, (C7-2o0o arylalkyl thioether)1.100, (C2-so alkyl ester),-ioo, (C7-2000 aryl ester),-Ioo, (C8-20oo alkylaryl ester)i_ioo, (C8-ZOOO arylalkyl ester),_ioo, -R'-CO-O4Ci-30 alkyl ether)1-1oo, -R'-CO-O-(C6.4o aryl ether)l.loo, -R'-CO-O-(C7-2oo0 alkylaryl ether)i-100, -R'-CO-O-(C7.ZOOO arylalkyl ether),-ioo, (C4.50 alkyl urethane)i-ioo, (Ci4-6o aryl urethane)i-ioo, (Cio-zooo alkylaryl urethane),.too, (Clo-2ooo arylalkyl urethane),_ioo, (Cs-so alkyl urea)l.ioo, (C14-6o aryl urea)i-ioo, (Cio-2ooo alkylaryl urea)1_100, (CIo-zooo arylalkyl urea)l.ioo, (CZ-so alkyl amide),.ioo, (C7-60 aryl amide)i.Ioo, (C8.2ooo alkylaryl amide)i-ioo, (Cs-zooo arylalkyl amide),-Ioo, (C3_30 alkyl anhydride), -1 oo, (Ca-so aryl anhydride)i-loo, (C9-i0oo alkylaryl anhydride)i-ioo, (C9-20o0 arylalkyl anhydride)i.ioo, (C2-30 alkyl carbonate)i-ioo, (C7-so aryl carbonate), -too, (C8_2ooo alkylaryl carbonate) 1 -ioo, (Ce.zooo arylalkyl carbonate)l.ioo, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C6-4o aryl ether, C7-2ooo alkylaryl ether, or C7.2000 arylalkyl ether)i.ioo, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CZ-so alkyl ester, C7_6o aryl ester, C8-2000 alkylaryl ester, or C8-ZOOO
arylalkyl ester)i-100, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C6_40 aryl ether, C7-2oo0 alkylaryl ether, or C7-20oo arylalkyl ether),.ioo-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2-so alkyl ester, C7-60 aryl ester, Cs_iooo alkylaryl ester, or C8-2ooo arylalkyl ester)i.joo-R`-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1.3o alkyl ether, C6.do aryl ether, C7-2oo0 alkylaryl ether, or C7-ZOOO arylalkyl ether)i-ioo, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CZ-so alkyl ester, C7_6o aryl ester, C8.zooo alkylaryl ester, or Cg-2ooo arylalkyl ester)i-ioo, Docket No.: 06897=0u2006 -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CI _30 alkyl ether, C6.40 aryl ether, C7_2000 alkylaryl ether, or C7-2ooo arylalkyl ether)1.100-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2.50 alkyl ester, C7-60 aryl ester, C8_2ooo alkylaryl ester, or C8-Zooo arylalkyl ester), _i00-R`-O-CO-NH-(Rb or Ar-R'-Ar)-NH-CO-O-, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2.50 alkyl amide, C7-60 aryl amide, C8_2000 alkylaryl amide, or C8-Z000 arylalkyl amide)1_100, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2_So alkyl amide, C7-60 aryl amide, C8_2ooo alkylaryl amide, or C8.2000 arylalkyl amide)1.100, or a bond; each Z, independently, is -G-D, wherein G is -R'-, -R'-Ar-, -Ar-R'-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNHZ, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)Z, -O-PO(O-)-O-CH2CHZNH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCHZ(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CHZOH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CHZOH)3, -[CH2-CH(C02R')]i_Ioo-H, -NH3+, -N+HZR', -N+HR'Rb, or -N~R'RbR`. Each of R', Rb, and R`, independently, is C1_20 alkyl and Ar is aryl. q is 0-30, and m is 0-30. Note that the sum of q and m is 0-30. Each of R' and R4, independently, is =0 or C1_20 hydrocarbon.
Each of R2 and R5, independently, is C1_20 hydrocarbon. R' and R2, or R4 and R5 can join together to form C640 aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, -NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z.
Each of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E or a side chain of an amino acid. Each of B, D, and Z having been defined above. E is EI, E2, or E3, in which Ei is Y1,YZ-amino, (YI,YZ-alkyl)-amino, YI,Y2-ethylenediamino, (dihydroxymethyl)-alkylamino, (X1,X3-aryl)amino, or Xi,X3-aryloxy; E2 is Yi,Y2-alkoxy, (Yi,YZ-amino)alkoxy, (YI,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Yi,YZ,Y3-alkyl)amino, (Yi,Yz,Y3-aryl)amino, dihydroxyallcylamino, YI,YZ,Y3-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)-alkylamino, (dicarboxyalkyl)amino, (Yi,YZ,Y3-alkyl)thio, (Xi,X3-aryl)thio, (Yi,Y2-alkyl)thio, (dihydroxyalkyl)thio, YbYZ-dioxoalkyl, or tri-(Yi,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (Xi,XZ,X3-heteroaryl)amino, (Xi-diarylketone)amino, J

Docket No.: 06897-002006 (X,Xi-oxoaryl)amino, (X,Xi-dioxoaryl)amino, (Yi-alkyl,YZ-alkyldioxoheteroaryl)amino, (Yi-allcyl,Y2-allcyldioxoaryl)amino, (di(Yi,YZ-methyl)dioxoheteroaryl)amino, (di(Yl,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (XhX2,X3-alkylaryl)amino, (X,,XZ,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (Xi,X2,X3-oxoheteroaryl)oxy, (X1,XZ,X3-oxoaryl)oxy, (X,,Yi-oxoheteroaryl)oxy, (XI-diarylketone)oxy, (X,Xi-oxoaryl)oxy, (XI,Xz-dioxoaryl)oxy, (Y1iYZ,di-aminodihydroxy)allcyl, (Xt,XZ-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (Xl,X2-oxoaryl)thio, (X1,XZ-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Yi-alkyl(thiocarbonyl)thio, Y1,Y2,-alkyl(thiocarbonyl)thio, Yl,Y2,Y3-alkyl(thiocarbonyl)thio, (Y1iYZ-aminothio-carbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)I.iooamino, (pyranosyl)amino, (Yi-aminoaryl)1_100amino, (amino(sulfoaryl))1_iooamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy. X is halide. Each of Xi, X2, and X3, independently, is -Y1, -O-YI, -S-Y1, -NH-YI, -CO-O-Y1, -O-CO-Y1, -CO-NH-Y1, -CO-NY1Y2, -NH-CO-Y1, -SOZ-Yi, -CHYiYZ, or -NYlY2. Each of YI, Y2, and Y3, independently, is -Z or -B-Z. R7 is -R or -0-R`. Rd is -OH, -0M, -NHNH2, -NHOH, -NH-CH2-CO2H, -O-B-Z, -NH-B-Z, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E. M is Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion. R` is -H, -CH2-CH2-D, -CH2-B-Z, -CH2-G-E, -CH2-G-CO-E, -CO-CH2-D, -CO-B-Z, -CO-G-E, or -CO-G-CO-E. RS is W. R9 is -0- or a bond. R10 is -Rd or -R . Each of x and y, independently, is 0 or 1; and p is 1-30. Note that when x is 0, R, is =0, and R7 is -Rd; that when y is 0, R4 is =0, and R9 is a bond, and R10 is -Rd; that when x is 1, Rl and RZ join together to form C6.4 aiyl, and R' is -O-R`; and that when y is 1, R4 and R5join together to form C6_4 aryl, R9 is -0-, and R'0 is -R`. In addition, when p is greater than 1,xis0.
Still another aspect of this invention relates to a compound of formula (VIII):

Docket No.: 06897-002006 R' R5 R4 R' R2 Rio y \R
f " (VIII) F N R$
f Ff is F(-K)n,(-Y-Z)y. F is a fullerene core. Each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CHZCHZ-NH 3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3i -glycoside, -OCH3, -OCHZ(CHOH)4-CH2OH, -OCHZ(CHOH)Z-CHZOH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1_ioo-OH, -[CH(C02R')-CH2]i_ioo-OH, -[C(CH3)(CO2H)-CH2]1_joo-OH, -[C(CH3)(CO2 R')-CHZ]t_ioo-OH, -N(OH)2, -NH3+, -N+H2Ra, -N+HR'Rb, or -N+R'RbR`; each Y is -A-B-, in which A is -0-, -NH-, -S-, -CO-O-, -0-CO-, -0-CO-O-, -0-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-. B is -Ra-O-[Si(CH3)2-0-]1.ioo, CI.zooo alkyl, C6.40 aryl, C7-Zooo alkylaryl, C7-2000 arylalkyl, (Ci-3o alkyl ether),-1oo, (C6.4o aryl ether),-ioo, (C7-ZOOO alkylaryl ether);.100, (C7-2ooo arylalkyl ether),-ioo, (CI.30 alkyl thioether)i.Ioo, (C6_40 aryl thioether)1-100, (C7_2000 alkylaryl thioether),-ioo, (C7_2000 arylalkyl thioether)1.ION (C2.5o alkyl ester)i.ioo, (C7.2000 aryl ester)1.100, (C8.2000 alkylaryl ester)t-100, (C8-2ooo arylalkyl ester)l-ioo, -R'-CO-O-(C1-30 alkyl ether),-ioo, -Ra-CO-O-(C6.40 aryl ether)t.100, -R'-CO-O-(C7-2ooo allcylaryl ether)l.ioo, -R'-CO-O-(C7-2000 arylalkyl ether)1.100, (C4-5o alkyl urethane)1.100, (Ci4.6o aryl urethane)i-ioo, (Clo-ZOOO alkylaryl urethane)t-too, (Cio.iooo arylalkyl urethane)l.loo, (C5-5o alkyl urea)1.100, (C14-60 aryl urea)1-ioo, (Clo-2o0o alkylaryl urea)1_100, (Cio-iooo arylalkyl urea)i-ioo, (Cz-5o alkyl amide)i.ioo, (C7.60 aryl amide)i-Ioo, (C8.2ooo alkylaryl amide)i_100, (Cg.ZOOO arylalkyl amide)1.100, (C3.30 alkyl anhydride)t.ioo, (Cs-5o aryl anhydride)i-ioo, (C9-2000 alkylaryl anhydride), -loo, (C9.2000 arylalkyl anhydride),.ioo, (C2.30 alkyl carbonate)l.ioo, (C7.50 aryl carbonate)1-ioo, (C8.2ooo alkylaryl carbonate),.ioo, (C8.2000 arylalkyl carbonate)i_ioo, -R'-O-CO-NH-(Rb or Ar-R-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-4o aryl ether, C7-ZOOO alkylaryl ether, or C7-2ooo arylalkyl ether),-too, -R'-O-- to -~

Docket No.: 06897-002006 CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2.So alkyl ester, C7.6o aryl ester, Cg.2ooo alkylaryl ester, or C8.2000 arylalkyl ester)i.ioo, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1.30 alkyl ether, C6-40 aryl ether, C7.20()O alkylaryl ether, or C7.2ooo arylalkyl ether), .too-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2.50 alkyl ester, C7-60 aryl ester, C8.2ooo alkylaryl ester, or C8.200o arylalkyl ester) I .ioo-R`-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(Cl.30 alkyl ether, C6-4o aryl ether, C7.2000 alkylaryl ether, or C7.2000 arylalkyl ether),.100, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2.50 alkyl ester, C7.60 aryl ester, C8.2000 alkylaryl ester, or C8.2ooo arylalkyl ester),.Ioo, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(Ci.3o alkyl ether, C6.40 aryl ether, C7.2000 alkylaryl ether, or C7.2000 arylalkyl ether)1.100-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CZ.5o alkyl ester, C7.60 aryl ester, C8.2ooo alkylaryl ester, or C8.2ooo arylallcyl ester)i.ioo-R`-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -R'-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(CZ.5o alkyl amide, C7.60 aryl amide, C8.2000 alkylaryl amide, or C8.
20()o arylalkyl amide),.1oo, -R'-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2.50 allcyl amide, C7-60 aryl amide, C8.2()Oo alkylaryl amide, or C8.2000 arylalkyl amide)1.i00, or a bond. Each Z, independently, is -G-D, wherein G is -R'-, -R'-Ar-, -Ar-Ra-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)Z, -0-PO(O-)-O-CH2CHZNH3+, -O-PO(O-)-O-CH2CHZ-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CHZOH, -OCHZ(CHOH)Z-CH2OH, -CO-OCH2(CHOH)4-CHZOH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CHZOH)3, -[CH2-CH(C02R')]I_ioo-H, -NH3+, -N+iZR',-N'+HR'Rb, or -N+R'RbR`. Each of R', Rb, and R`, independently, is C1_20 alkyl and Ar is aryl. q is 0-30, and m is 0-30. Note that the sum of q and m is 0-30.
Each of R' and R4, independently, is =0 or CI_20 hydrocarbon; and each of R2 and R5, independently, is Ci_ZO hydrocarbon. R' and R2, or R4 and R5 can join together to form C6.40 aryl which is optionally substituted with halide, -OH, -NHNHZ, -NHZOH, -NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z. Each of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E or a side chain of an amino acid. E is Ei, E2, or E3, in which Ei is YI,Y2-amino, (Yi,Y2-alkyl)-amino, Yi,Y2-ethylenediamino, . = { ,L.

Docket No.: 06897-002006 (dihydroxymethyl)alkylamino, (Xi,X3-aryl)amino, or Xi,X3-aryloxy; E2 is YI,YZ-alkoxy, (Yi,Y2-amino)alkoxy, (Yi,YZ,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Yi,YZ,Y3-alkyl)amino, (Yi,Y2,Y3-aryl)amino, dihydroxyalkylamino, Yi,Y2,Y3-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Yi,YZ,Y3-alkyl)thio, (Xi,X3-aryl)thio, (Yi,Y2-alkyl)thio, (dihydroxyallcyl)thio, YI,Y2-dioxoalkyl, or tri-(Yl,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (Xi,X2,X3-heteroaryl)amino, (XI-diarylketone)amino, (X,Xi-oxoaryl)amino, (X,Xi-dioxoaryl)amino, (YI-alkyl,Y2-alkyldioxoheteroaryl)amino, (Yi-alkyl,Y2-alkyldioxoaryl)amino, (di(Yi,Y2-methyl)dioxoheteroaryl)amino, (di(Yt,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X,,Xz,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (XI,Xi,X3-oxoheteroaryl)oxy, (Xi,X2,X3-oxoaryl)oxy, (Xj,YI-oxoheteroaryl)oxy, (Xi-diarylketone)oxy, (X,X1-oxoaryl)oxy, (Xi,X2-dioxoaryl)oxy, (YI,Y2,di-aminodihydroxy)alkyl, (XI,XZ-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (Xl,X2-oxoaryl)thio, (Xi,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y,-alkyl(thiocarbonyl)thio, Yi,Y2,-alkyl(thiocarbonyl)thio, Yl,Y2,Y3-alkyl(thiocarbonyl)thio, (Yi,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-iooamino, (pyranosyl)amino, (Yi-aminoaryl)1_i00amino, (amino(sulfoaryl))j_iooamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy. X is halide. Each of Xi, X2, and X3, independently, is -YI, -O-Yi, -S-YI, -NH-Y1, -CO-O-Y1, -O-CO-Y1, -CO-NH-Yi, -CO-NYiY2, -NH-CO-Y1, -SOZ-YI, -CHYIYZ, or -NYIYZ. Each of Yi, Y2, and Y3, independently, is -Z or -B-Z. R7 is -Rd or -0-R`. Rd is -OH, -OM, -NHNH2, -NHOH, -NH-CH2-CO2H, -O-B-Z, -NH-B-Z, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E. M is Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion. R` is -H, -CH2-CH2-D, -CH2-B-Z, -CH2-G-E, -CH2-G-CO-E, -CO-CH2-D, -CO-B-Z, -CO-G-E, or -CO-G-CO-E. R8 is R. R9 is -O-Rf or -Rg-. Rf is -CO-B-G-O-, -CO-B-G-NH-, -CO-B-G-CO-O-, or -CO-B-G-CO-NH-. Rg is -NH-, -0-, -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-. R10 is -H. Each of x and y, independently, is 0 or 1; and r is 1-100.
Note that when x is 0, R' is =0, and R7 is -Rd; that when y is 0, R4 is =0, and R9 is -Rg, and R10 is -H; that when x is 1, R' and R2 join together to form C6-40 aryl, and R7 is -O-Re and that when y is 1, R4 and R5 join together to form C6-4 aryl, R9 is -O-Rf, and R10 is -H. Further, when r is greater than 1, x is 0.
Still another aspect of this invention relates to a compound of formula (I):

y OH

Ff NH (I) OH
R3 s `

wherein Ff is F(-K)m(-Y-Z)y in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2-NH 3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1-ioo-OH, -[CH(CO2Ra)-CH2]i-ioo-OH, -[C(CH3)(CO2H)-CH2]1-ioo-OH, -[C(CH3)(CO2 Ra)-CH2]i-ioo-OH, -N(OH)2, -NH3+, -N+H2Ra, -N+HRaRb, or -N+RaRbR ; each Y is -A-B-, in which A is -0-, -NH-, -S-, -CO-O-, -0-CO-, -O-CO-O-, -0-CO-NH-, -NH-CO-NH-, -CO-NH-, or-NH-CO-; and B is -Ra-0-[Si(CH3)2-0-]1 -100, Ci-2ooo alkyl, C6_40 aryl, C7-2ooo alkylaryl, C7-2oo0 arylalkyl, (C1_30 alkyl ether)1-loo, (C6-40 aryl ether)1-loo, (C7-2oo0 alkylaryl ether)1-1o0, (C7-2o0o arylalkyl ether)1_100, (Ci-3o alkyl thioether)1_100, (C6-40 aryl thioether)1_100, (C7-2ooo alkylaryl thioether)1_loo, (C7-2ooo arylalkyl thioether)1_100, (C2-50 alkyl ester)1-100, (C7-2oo0 aryl ester)1_loo, (Cs-20o0 alkylaryl ester)1_loo, (Cs-2ooo arylalkyl ester)1-loo, -Ra-CO-O-(C1_30 alkyl ether)1_100, -Ra-CO-O-(C6-4o aryl ether)1-100, -Ra-CO-O-(C7-2ooo alkylaryl ether)1-100, -Ra-CO-O-(C7-20o0 arylalkyl ether)1-1o0, (Ca-5o alkyl urethane)1-loo, (Ci4-6o aryl urethane)1-loo, (Cio-2ooo alkylaryl urethane),_loo, (Cio-2oo0 arylalkyl urethane)1_loo, (C5-5o alkyl urea),-Ioo, (Ci4-6o aryl urea),-Ioo, (Cio-2ooo alkylaryl urea),-Ioo, (Cio-2ooo arylalkyl urea),-Ioo, (C2-so alkyl amide)1-loo, (C7-60 aryl amide)1-loo, (Cs-2ooo alkylaryl amide)1-loo, (Cs-2ooo arylalkyl amide)1_1o0, (C3-30 alkyl anhydride)1-lo0, (C8_50 aryl anhydride)1-loo, (C9-2ooo alkylaryl anhydride)1_1oo, (C9-2ooo arylalkyl anhydride)1_too, (C2-3o alkyl carbonate)1-loo, (C7-50 aryl carbonate)t_loo, (Ca-2ooo alkylaryl carbonate)1-lo0, (Cs-2ooo arylalkyl carbonate)1_loo, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-ao aryl ether, C7-2ooo alkylaryl ether, or C7-2oo0 arylalkyl ether)1_loo, -Ra-O-CO-NH-(RborAr-Rb-Ar)-NH-CO-O-(C2-5o alkyl ester, 60 aryl ester, C8-2ooo alkylaryl ester, or C8-zooo arylalkyl ester)1_100, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C640 aryl ether, C7-zooo alkylaryl ether, or C7-2ooo arylalkyl ether)1-loo-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CZ-5o alkyl ester, C7-60 aryl ester, C8_2ooo alkylaryl ester, or C8_ 2ooo arylalkyl ester)1_loo-R -O-CO-NH-(Rb orAr-R-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C640 aryl ether, C7-2ooo alkylaryl ether, or C7_2000 arylalkyl ether)1-loo, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(CZ-5o alkyl ester, C7-60 aryl ester, Cg-Zooo alkylaryl ester, or C8_2000 arylalkyl ester)1_100, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C640 aryl ether, C7-2ooo alkylaryl ether, or C7_2000 arylalkyl ether)1-loo-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-R-Ar)-NH-CO-O-(C2_50 alkyl ester, C7-60 aryl ester, C8_2ooo alkylaryl ester, or Cg-Zooo arylalkyl ester)t_loo-R -O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2-5o alkyl amide, C7_60 aryl amide, C8-2ooo alkylaryl amide, or C8-2ooo arylalkyl amide)1_100, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-NH-(C2-5o alkyl amide, C7_60 aryl amide, C8_2000 alkylaryl amide, or C8-2ooo arylalkyl amide)1-1o0, or a bond; each Z, independently, is -G-D, wherein G is -Ra-, -Ra-Ar-, -Ar-Ra-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CHZ-COZH, -P(OH)3, -PO(OH)2, -0-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CH2OH, -OCHZ(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CHZOH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CH2OH)3, -[CHz-CH(CO2Ra)]1-1oo-H, -NH3+, -N+H2Ra ,-N+HRaRb, or -N+RaRbR , each of Ra, Rb, and Rc, independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30; each of Rl and R4, independently, is =0 or C1_20 alkyl;
and each -13a-of R2 and R5, independently, is C1-20 alkyl; wherein R' and R2, or R4 and R5 can join together to form C6-4o aryl which is optionally substituted with halide, -OH, -NHNHz, -NH2OH,-NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -0-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

one of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, and the other, independently, is -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being EI, E2, or E3, in which El is (Y1,YZ)-amino, (YI,Y2-alkyl)-amino, (Y1,Yz)-ethylenediamino, (dihydroxymethyl)alkylamino, (Xl,X3-aryl)amino, or (XI,X3)-aryloxy; EZ is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,YZ,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,YZ,Y3-alkyl)amino, (Y1,YZ,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Yz,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,YZ-alkyl)thio, (dihydroxyalkyl)thio, (Yl,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (X,X1-oxoaryl)amino, (X,X1-dioxoaryl)amino, (Yl-alkyl,Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Yz-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,XZ,X3-oxoheteroaryl)oxy, (XI,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (Xl-diarylketone)oxy, (X,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,YZ,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Yl-alkyl(thiocarbonyl)thio, (Y1,Y2),-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1_100amino, (pyranosyl)amino, (Yl-aminoaryl)1_looamino, (amino(sulfoaryl))1_looamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein -13b-X is halide; each of Xt, X2, and X3, independently, is -Y1, -O-YI, -S-YI, -NH-YI, -CO-O-YI, -O-CO-YI, -CO-NH-YI, -CO-NYlY2, -NH-CO-YI, -S02-Yl, -CHYlY2i or -NYlY2; and each of Yl, Y2, and Y3, independently, is -Z
or -B-Z;
each of x and y, independently, is 0 or 1; and s is 1-6;
provided that when x is 0, Rl is =0; that when y is 0, R4 is =0; that when x is 1, Rl and R2join together to form C6.40 aryl; and that when y is 1, R4 and R5 join together to form C6-40 aryl; or a salt thereof.
In a further embodiment, at least one of x and y may be 1.
In a further embodiment, R' and RZ, or R4 and R5 may join together to form a benzene ring.
In a further embodiment, the sum of q and m may be 0-20.
In a further embodiment, only one of x and y is 1.
In a further embodiment, x is 1, y is 0, and Rl and R2 join together to form a benzene ring.
In a further embodiment, R3 is H, B-Z, -G-E, or -G-CO-E.
In a further embodiment, R6 is -G-E, -G-CO-E, or a side chain of an amino acid.

In a further embodiment, R6 is a side chain of alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine.
In a further embodiment, R3 is H, -B-Z, -G-E, or -G-CO-E.
In a further embodiment, F is C60, and the sum of q and m is 0-20.
In a further embodiment, both x and y may be 0.

In a further embodiment, F is C60, C61, C62, C63, C64, C65, C70, C76, C78, C82, C84, or C92, or La@Cn, Ho@Cn, Gd@Cn, or Er@Cn, in which n is 60, 74, or 82.
In a further embodiment, the sum of q and m is 0-20.
In a further embodiment, each K, independently, is -SH, -NHOH, -SO3H, -OSO3H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -0-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O")-O-CH2CH2NH3+, -glycoside, -0-CH2-(CHOH)4--13c-CHZOH,-O-CH2-(CHOH)2-CH2OH, -N+HRaRb, or N+RaRbR.
In a further embodiment, D is -SH, -NHOH, -SO3H, -OSO3H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O')-O-CH2CH2NH3+, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -O-CH2-(CHOH)4-CH2OH, -O-CHZ-(CHOH)2-CH2OH, -N+HRaRb, or N+RaRbRc.
In a further embodiment, each of R3 and R6, independently, is -B-Z, -G-E, -G-CO-E, or a side chain of alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine.
In a further aspect of said embodiment, F is C60, and the sum of q and m is 0-20.
Still another aspect of this invention relates to a method for preparing a compound of formula (I):

Rs s y OH

Ff NH (I) OH
R3`~ s wherein Ff is F(-K)m(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2i -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)Z, -O-PO(O-)-O-CH2CH2-NH 3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CHZOH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1_loo-OH, -[CH(CO2Ra)-CH2]1_loo-OH, -[C(CH3)(CO2H)--13d-CH2]1-too-OH, -[C(CH3)(CO2 Ra)-CH2]1-ioo-OH, -N(OH)2, -NH3+, -N+H2Ra, -N+HRaRb, or -N+RaRbR ; each Y is -A-B-, in which A is -0-, -NH-, -S-, -CO-O-, -0-CO-, -O-CO-O-, -0-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -Ra-O-[Si(CH3)2-0-]1_i00, C1_2000 alkyl, C640 aryl, C7_2ooo alkylaryl, C7_2000 arylalkyl, (C1_30 alkyl ether)1_loo, (C6-4o aryl ether)1_loo, (C7-2000 alkylaryl ether)1_l()o, (C7-20oo arylalkyl ether)i-loo, (C1_3o alkyl thioether)1_100, (C640 aryl thioether)1_loo, (C7-2ooo alkylaryl thioether)1_100, (C7_2000 arylalkyl thioether)1_loo, (C2-50 alkyl ester)1_loo, (C7-2ooo aryl ester)t_loo, (Cs-2ooo alkylaryl ester)1_1o0, (Cs-2ooo arylalkyl ester)1_loo, -Ra-CO-O-(C1_30 alkyl ether)1_loo, -Ra-CO-O-(C6-4o aryl ether)1_loo, -Ra-CO-O-(C7_20oo alkylaryl ether)1_loo, -Ra-CO-O-(C7_2000 arylalkyl ether)1_loo, (C4-50 alkyl urethane)1-1oo, (C14-6o aryl urethane)1_loo, (Clo_2000 alkylaryl urethane)1_loo, (Cio-2ooo arylalkyl urethane)1_100, (C5-50 alkyl urea)1_loo, (Ci4-6o Uyl urea)1_1o0, (Clo-2ooo alkylaryl urea)1_loo, (Cio-2ooo arylalkyl urea)1_loo, (C2-50 alkyl amide)1_loo, (C7-6o aryl amide)1_loo, (C8_20oo alkylaryl amide)1_100, (C8_2000 arylalkyl amide)1_loo, (C3_30 alkyl anhydride)I_loo, (Cs-5o aryl anhydride)1_1oo, (C9_20oo alkylaryl anhydride)1_loo, (C9_20oo arylalkyl anhydride)1_loo, (C2-30 alkyl carbonate)1_l00, (C7_50 aryl carbonate)1_loo, (Ca-20o0 alkylaryl carbonate)1_lo0, (C8_2000 arylalkyl carbonate)1_loo, -Ra-O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C64o aryl ether, C7_2000 alkylaryl ether, or C7_2000 arylalkyl ether)1_loo, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7_ 6o aryl ester, C8_2ooo alkylaryl ester, or C8_2000 arylalkyl ester)1-loo, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C640 aryl ether, C7_2ooo alkylaryl ether, or C7_ 2000 arylalkyl ether)1_1oo-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7_60 aryl ester, C8_2ooo alkylaryl ester, or C8_ 2ooo arylalkyl ester)1_loo-W-O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C6_4o aryl ether, C7_2ooo alkylaryl ether, or C7_20oo arylalkyl ether)1_loo, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2_so alkyl ester, C7_60 aryl ester, C8_20oo alkylaryl ester, or C8_2000 arylalkyl ester)1_100, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1-3o alkyl ether, C640 aryl ether, C7_2000 alkylaryl ether, or C7_2000 arylalkyl ether)1_loo-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7_60 aryl ester, C8_2000 alkylaryl ester, or Cs-2ooo arylalkyl ester)1_loo-R -O-CO-NH-(Rb or Ar-Rb--13e-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(Cz-5o alkyl amide, C7-60 aryl amide, C8.2000 alkylaryl amide, or C8_20oo arylalkyl amide)1_1()O, Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2_5o alkyl amide, C7_60 aryl amide, C8_2ooo alkylaryl amide, or C8.2000 arylalkyl amide)I_loo, or a bond; each Z, independently, is -G-D, wherein G is -Ra-, -Ra-Ar-, -Ar-Ra-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -0-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CHZCH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCHZ(CHOH)4-CH2OH, -OCH2(CHOH)2-CHZOH, -CO-OCH2(CHOH)4-CH2OH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CHZCHZOH)3, -[CH2-CH(CO2R$)]1-loo-H, -NH3+, -N+H2Ra,-N+HRaRb, or -N+RaRbR , each of Ra, Rb, and R , independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;

each of R' and R4, independently, is =0 or C1_20 alkyl; and each of R2 and R5, independently, is Cl_Zo alkyl; wherein R' and R2, or R4 and R5 can join together to form C6-4o aryl which is optionally substituted with halide, -0H, -NHNH2, -NH2OH, -NH- CH2-COzH, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -0-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above; each of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being El, E2, or E3, in which E1 is (Y1,Y2)-amino, (Y1,Y2-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (XI,X3-aryl)amino, or (Xi,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2iY3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,YZ,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Yz,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1iY2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,XZ,X3-heteroaryl)amino, (Xl-diarylketone)amino, (X,XI-oxoaryl)amino, (X,XI--13f-dioxoaryl)amino, (Yl-alkyl,Y2-alkyldioxoheteroaryl)amino, (Yl-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Yz-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (Xi,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (Xt,XZ,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (Xl-diarylketone)oxy, (X,XI-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,XZ-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Yi-alkyl(thiocarbonyl)thio, (Y1,Y2),-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1_10oamino, (pyranosyl)amino, (Yt-aminoaryl)1_looamino, (amino(sulfoaryl))1-looamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of Xl, X2, and X3, independently, is -Yl, -O-YI, -S-Yr, -NH-YI, -CO-O-YI, -O-CO-Yt, -CO-NH-YI, -CO-NYtY2, -NH-CO-YI, -S02-Yl, -CHYlY2, or -NYlY2; and each of Yl, Y2, and Y3, independently, is -Z
or -B-Z;
each of x and y, independently, is 0 or 1; and s is 1-6;
provided that when x is 0, R' is =0; that when y is 0, R4 is =0; that when x is 1, R' and R2 join together to form C640 aryl; and that when y is 1, R4 and R5join together to form C6-40 aryl;
or a salt thereof;
the method comprising:
reacting a compound of formula (II) -13g-C
6 y R O

N-------M (II) wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion;

with a fullerene compound Ff of the formula F(-K)n,(-Y-Z)y wherein the sum of q and m is 0 to form a compound of formula (III) , y O
Ff N M
(III) O

R3 s R2X R~
, removing M from the compound of formula (III) to form a compound of formula (I) wherein the sum of q and m is 0; and optionally treating the compound of formula (I) wherein the sum of q and m is 0 with a nitrating or sulfating agent to form a nitrofullerene or cyclosulfated fullerene, and contacting the nitrofullerene or cyclosulfated fullerene with a nucleophilic agent to form a compound of formula (I) wherein the sum of q and m is greater than 0.
In one embodiment, only one of x and y may be 0.
In a further embodiment, x is 1, y is 0, and Rl and R2join together to form a benzene ring.
In a further embodiment, both x and y are 0.
-13h-In a further embodiment, M is a Cu ion.
In a further embodiment, each of R3 and R6, independently, is H, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, wherein B, E, GS and Z, and Rl, R2, R3, R4, R5 and R6 are as defined above.
Still another aspect of this invention relates to a compound of formula (VII):

R' R2 R1o Y R~
" (VII) F
f s P

wherein Ff is F(-K),,,(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-0-CH2CH2-NH 3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, NH-CH2-CO2H, -[CH(CO2H)-CH2]1_l00-OH, -[CH(CO2Ra)-CH2]1_loo-OH, -[C(CH3)(CO2H)-CH2]1-loo-OH, -[C(CH3)(CO2 Ra)-CH2]1-1oo-OH, -N(OH)2, -NH3+, -N}H2Ra, -N+HRaRb, or -N'RaRbRc; each Y is -A-B-, in which A is -0-, -NH-, -S-, -CO-O-, -0-CO-, -0-CO-O-, -0-CO-NH-, NH-CO-NH-, -CO-NH-, or -NH-CO-;
and B is -Ra-O-[Si(CH3)2-0-]1-100, C1-2ooo alkyl, C6-40 aryl, C7_2000 alkylaryl, C7_2oo0 arylalkyl, (C1-30 alkyl ether)1-100> (C6-ao aryl ether)1-100, (C7-zooo alkylaryl ether)1-100, (C7_2000 arylalkyl ether)1_100, (C1-30 alkyl thioether)1-1oo, (C6-40 aryl thioether)1_loo, (C7_2000 alkylaryl thioether)1_100, (C7_2000 arylalkyl thioether)1-1o0, (C2-50 alkyl ester),-Ioo, (C7_2000 aryl ester),-Ioo, (C8_2ooo alkylaryl ester),-Ioo, (C8_2ooo arylalkyl ester),-Ioo, -Ra-CO-O-(C1_30 alkyl ether)1_loo, -Ra-CO-O-(C6.40 aryl ether)1_loo, -Ra-CO-O-(C7_2000 alkylaryl ether)1_100, -Ra-CO-O-(C7_200o arylalkyl ether)1_loo, (C4-50 alkyl urethane)1_loo, (C14-60 aryl urethane)1-100, (C1o-2o0o alkylaryl urethane)1-100, (C1o-zooo arylalkyl -13i-urethane)1_loo, (C5-5o alkyl urea)1_loo, (Ci4-6o aryl urea)1_loo, (Cio-2oo0 alkylaryl urea)1_loo, (Cio-2oo0 arylalkyl urea)1-loo, (C2-50 alkyl amide)1_loo, (C7_60 aryl amide)1_loo, (Cs-2000 alkylaryl amide)1_loo, (Cs-zooo uylalkyl amide)1_loo, (C3-30 alkyl anhydride)1_1oo, (C8-50 aryl anhydride)i_ioo, (C9-2ooo alkylaryl anhydride)1_loo, (C9-2oo0 arylalkyl anhydride)i-loo, (C2-3o alkyl carbonate)1_l00, (C7_50 aryl carbonate)1_loo, (C8-2ooo alkylaryl carbonate)1-loo, (C8_20oo arylalkyl carbonate)1_loo, -Ra-O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C6.40 aryl ether, C7_2000 alkylaryl ether, or C7_2000 arylalkyl ether)1_loo, -Ra O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7_60 aryl ester, C8-200o alkylaryl ester, or C8_2ooo arylalkyl ester)1_100, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C6_40 aryl ether, C7_2000 alkylaryl ether, or C7_2000 arylalkyl ether)1_loo-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7-60 aryl ester, C8-2ooo alkylaryl ester, or C8-2ooo arylalkyl ester)1_loo-R -O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C6-40 aryl ether, C7_2000 alkylaryl ether, or C7_2000 arylalkyl ether)1_loo, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7_60 aryl ester, C8-2ooo alkylaryl ester, or C8_2000 arylalkyl ester)1-loo, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C640 aryl ether, C7-2o0o alkylaryl ether, or C7-2000 arylalkyl ether)1_l00-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2_50 alkyl ester, C7_60 aryl ester, C8-2ooo alkylaryl ester, or C8-2ooo arylalkyl ester)1_loo-R -O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2_50 alkyl amide, C7_60 aryl amide, C8_2000 alkylaryl amide, or C8-2000 arylalkyl amide)1_1o0, Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2-5o alkyl amide, C7_60 aryl amide, C8_2oo0 alkylaryl amide, or C8-20W arylalkyl amide)1_1oo, or a bond; each Z, independently, is -G-D, wherein G is -Ra-, -Ra-Ar-, -Ar-Ra-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-COZH, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)Z, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CHZCH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCHZ(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CH2OH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CH2OH)3, -[CHZ-CH(CO2Ra)]1-loo-H, -NH3+, -N+H2Ra, -13j--1V+HRaRb, or -1V+RaRbR~, each of Ra, Rb, and R , independently, being C1_20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;

each of RI and R4, independently, is =0 or C1_20 alkyl; and each of RZ and R5, independently, is C1_20 alkyl; wherein R' and R2, or R4 and RS can join together to form C6-40 aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, NH-CH2-COZH, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

one of R3 and R6, independently, is H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, and the other, independently, is -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being El, E2, or E3, in which El is (Y1,Y2)-amino, (Y1,YZ-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or (X1,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Yi,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (Xl-diarylketone)amino, (X,Xi-oxoaryl)amino, (X,XI-dioxoaryl)amino, (Yl-a1ky1,Y2-alkyldioxoheteroaryl)amino, (Yl-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,YZ-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (Xl-diarylketone)oxy, (X,XI-oxoaryl)oxy, (XI,X2-dioxoaryl)oxy, (Y1,YZ,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Yl-alkyl(thiocarbonyl)thio, (Y1,Y2)-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)--13k-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1_looamino, (pyranosyl)amino, (Yl-aminoaryl)1_l00amino, amino(sulfoaryl))1_looamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of Xl, X2, and X3, independently, is -Yl, -O-YI, -S-YI, -NH-YI, -CO-O-YI, -O-CO-YI, -CO-NH-YI, -CO-NYlY2, -NH-CO-YI, -SOZ-Yt, -CHYlY2, or -NYlY2; and each of Yl, Y2, and Y3, independently, is -Z
or -B-Z; B and Z having been defined above;
R7 is -Ra or -O-Re; wherein Rd is -OH, -OM, -NHNH2, -NHOH, -NH-CHZ-CO2H, -O-B-Z, -NH-B-Z, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E;
M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and Re is -H, -CH2-D, -CH2-B-Z, -CH2-G-E, -CH2-G-CO-E, -CO-CH2-D, -CO-B-Z, -CO-G-E, or -CO-G-CO-E; each of B, D, E, Q and Z having been defined above;

R8 is Re;
R9 is -0- or a bond;
R10 is -Rd or -Re; each of which having been defmed above;
each of x and y, independently, is 0 or 1; and p is 1-30;
provided that when x is 0, R' is =0, and R7 is -Rd; that when y is 0, R4 is =0, and R9 is a bond, and R10 is -R ; that when x is 1, R1 and R2 join together to form C6_40 aryl, and R7 is -O-Re; and that when y is 1, R4 and R5join together to form C640 aryl, R9 is -0-, and R10 is -Re; and further provided that when p is greater than 1, x is 0; or a salt thereof.

In a further embodiment, F is C60, C61, C62, C63, C64, C65, C70, C76, C78, C82, C84, or C92, or La@C,,, Ho@C,,, Gd@Cn, or Er@C,,, in which n is 60, 74, or 82.
In a further embodiment, the sum of q and m is 0-20.
In a further embodiment, p is 2-10.

In a further embodiment, one of R3 and R6, independently, is -H, -B-Z, -G-E, -G-CO-E or a side chain of an amino acid.

In a further embodiment, Rd is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -0-G-CO-E, or -NH-G-CO-E.

In a further embodiment, Re is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.
In a further embodiment, both x and y are 0.
In a further aspect of said embodiment, Rd is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.
In a further aspect thereof, Re is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.
In a further aspect thereof, p is 2-10.
In a further aspect thereof, said compound is oligo(1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic N-amide).
Still another aspect of this invention relates to a compound of formula (VIII):

R R2 I Rio y \R
r " (VIII) F N R$
f 6 wherein Ff is F(-K),õ(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2-NH 3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1-1oo-OH, -[CH(CO2Ra)-CH2]1-1oo-OH, -[C(CH3)(CO2H)-CH2]1-1oo-OH, -[C(CH3)(CO2 Ra)-CH2]1-1oo-OH, -N(OH)2, -NH3+, -N+H2Ra, -N+HRaRb, or -N+RaRbR; each Y is -A-B-, in which A is -0-, NH-, -S-, -CO-O-, -0-CO-, -O-CO-O-, -0-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -Ra-O-[Si(CH3)2-0-]1-100, C1-2ooo alkyl, C6-40 aryl, -13m-C7_2ooo alkylaryl, C7_2000 arylalkyl, (Cl-3o alkyl ether)1_1o0, (C6-4o aryl ether)1_1o0, (C7-2oo0 alkylaryl ether)1-loo, (C7-2ooo arylalkyl ether)1_loo, (C1_3o alkyl thioether)1_1oo, (C6-40 aryl thioether)1_loo, (C7_2000 alkylaryl thioether)1_loo, (C7-2ooo arylalkyl thioether)1_100, (C2-50 alkyl ester)1_1o0, (C7-aooo aryl ester)1-loo, (Cs-2ooo alkylaryl ester)1_100, (Ca-2o0o arylalkyl ester)1-100, -Ra-CO-O-(Cl-3o alkyl ether)1_loo, -Ra-CO-O-(C6_4o aryl ether)1_Ioo, -Ra-CO-O-(C7.2ooo alkylaryl ether)t.loo, -Ra-CO-O-(C7.2ooo arylalkyl ether)1-1o0, (C4-50 alkyl urethane)1-loo, (C14-6o aryl urethane)1-loo, (Cio-2ooo alkylaryl urethane)1-loo, (Cio-2oo0 arylalkyl urethane)1_100, (C5-50 alkyl urea)1_1o0, (Ci4-6o aryl urea)1_1o0, (Cio-2ooo alkylaryl urea)1-loo, (Cio-Zooo arylalkyl urea)l.loo, (C2-50 Ayl amide)l.loo, (C7-6o aryl amide)1_loo, (Cs-sooo alkylaryl amide)i_ioo, (Cs-2ooo arylalkyl amide)t_ioo, (C3_30 alkyl anhydride)1_loo, (Ca-5o aryl anhydride)1_loo, (C9-2ooo alkylaryl anhydride)i.loo, (C9-2ooo arylalkyl anhydride)1_loo, (C2-3o alkyl carbonate)1_loo, (C7-50 aryl carbonate)1_loo, (Cs-2ooo alkylaryl carbonate)1_loo, (C8_2000 arylalkyl carbonate)1_loo, -Ra-O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C6-40 aryl ether, C7-2ooo alkylaryl ether, or C7_2oo0 arylalkyl ether)1-loo, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2-5o alkyl ester, C7-6o aryl ester, C8-2ooo alkylaryl ester, or C8_2ooo arylalkyl ester)1_loo, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(Cl_30 alkyl ether, C6-4o aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1_loo-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(C2-5o alkyl ester, C7-6o aryl ester, C8-2ooo alkylaryl ester, or C8_ 200o arylalkyl ester)1_loo-W-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-O-(CI-30 alkyl ether, C6_40 aryl ether, C7-ZOOO
alkylaryl ether, or C7-2000 arylalkyl ether)1-lo0, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C2-5o alkyl ester, C7-60 aryl ester, C8_2ooo alkylaryl ester, or C8_2ooo arylalkyl ester)1_loo, -Ra-NH-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-(C1_30 alkyl ether, C6_4o aryl ether, C7_2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-1oo-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-NH-CO-NH-(Rb or Ar-Rb-.Ar)-NH-CO-O-(C2_50 alkyl ester, C7_60 aryl ester, C8_2ooo alkylaryl ester, or C8-2ooo arylalkyl ester)1-loo-R`-O-CO-NH-(Rb orAr-Rb-Ar)-NH-CO-O-, -Ra-O-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7_60 aryl amide, C8_2000 alkylaryl amide, or C8_2ooo arylalkyl amide)1-loo, Ra-NH-CO-NH-(Rb or Ar-Rb-Ar)-NH-CO-NH-(C2-so alkyl amide, C7-60 aryl amide, C8_2000 alkylaryl amide, or C8_2000 arylalkyl amide)1_1o0, or a bond; each Z, independently, is -G-D, wherein G is -Ra-, -Ra-Ar-, -Ar-Ra-, or -Ar-; and D is -H, -OH, -SH5 -13n--NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NHZ)-COZH, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -0-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CHZOH, -OCH2(CHOH)2-CHZOH, -CO-OCHZ(CHOH)4-CH2OH, -C6H3(OH)2, N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CHZOH)3, -[CHZ-CH(COZRa)]1-1oo-H, -NH3+, -N+H2Ra, -WHRaRb, or N+RaRbR , each of Ra, Rb, and R`, independently, being Cl_ZO alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;

each of R' and R4, independently, is =0 or C1-20 alkyl; and each of R2 and R5, independently, is C1_20 alkyl; wherein R' and R2, or R4 and RS can join together to form C6-4o aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, -NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -0-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

one of R3 and R6, independently, is H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, and the other, independently, is -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being El, E2, or E3, in which El is (Y1,Y2)-amino, (Y1,Y2-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or (X1,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Yz)-dioxoalkyl, or tri-(YI,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (Xl,X2,X3-eteroaryl)amino, (Xl-diarylketone)amino, (X,XI-oxoaryl)amino, (X,XI-dioxoaryl)amino, (Yl-alkyl,Y2-alkyldioxoheteroaryl)amino, (Yl-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, -13o-((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (Xl,X2,X3-oxoaryl)oxy, (X1,Yt-oxoheteroaryl)oxy, (Xl-diarylketone)oxy, (X,XI-oxoaryl)oxy, (XI,XZ-dioxoaryl)oxy, (Y1,YZ,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (XI,Xz-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Yl-alkyl(thiocarbonyl)thio, (Y1,Y2)-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1_looamino, (pyranosyl)amino, (Yl-aminoaryl)1-looamino, (amino(sulfoaryl))1-looamino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of Xl, X2, and X3, independently, is -Yl, -O-YI, -S-YI, -NH-YI, -CO-O-YI, -O-CO-YI, -CO-NH-YI, -CO-NYlY2, -NH-CO-YI, -SOZ-Yl, -CHYlY2, or -NYlY2; and each of Yl, Y2, and Y3, independently, is -Z
or -B-Z; B and Z having been defined above; R7 is Ra or -O-Re; wherein Rd is -OH, -OM, -NHNH2, -NHOH, -NH-CH2-CO2H, -O-B-Z, -NH-B-Z, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E; M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and Re is -H, -CH2-CH2-D, -CH2-B-Z, -CH2-G-E, -CH2-G-CO-E, -CO-CH2-D, -CO-B-Z, -CO-G-E, or -CO-G-CO-E; each of B, D, E, Q and Z having been defined above;
R8 is Re, which has the same meaning as set forth above;
R9 is -O-Rt- or -Rg-; wherein Rf is -CO-B-G-O-, -CO-B-G-NH-, -CO-B-G-CO-O-, or -CO-B-G-CO-NH-; and Rg is -NH-, -0-, -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-; B and G having been defined above;
R10 is -H;
each of x and y, independently, is 0 or 1; and r is 1-100;
provided that when x is 0, Rl is =0, and R7 is -Rd; that when y is 0, R4 is =O, and R9 is -Rg, and R10 is -H; that when x is 1, Rl and R2join together to form aryl, and R7 is -13p--0-Re; and that when y is 1, R4 and R5join together to form C640 aryl, R9 is -0-R ;
and R10 is -H; and further provided that when r is greater than 1, x is 0;
or a salt thereof.

In a further embodiment, F is C60, C61, C62, C63, C64, C659 C70, C769 C78, C82, C&a, or C92, or La@C,,, Ho@C,,, Gd@Cn, or Er@Cn, in which n is 60, 74, or 82.
In a further embodiment, the sum of q and m is 0-20.
In a further embodiment, r is 2-30.

In a further embodiment, one of R3 and R6, independently, is -H, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid.

In a further embodiment, Rd is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.

In a further embodiment, Re is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.

In a further embodiment, Rf is -CO-B-G-NH- or -CO-B-G-CO-NH-.
In a further embodiment, Rg is -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-.
In a further embodiment, both x and y are 0.
In a further aspect of said embodiment, one of R3 and R6, independently, may be -H, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid.

In a further embodiment thereof, Rd is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.

In a further embodiment thereof, Re is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.

In a further embodiment thereof, Rf is -CO-B-G-NH- or -CO-B-G-CO-NH-.
In a further embodiment thereof, Rg is -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-.
In a further embodiment thereof, r is 2-30.

A salt of a compound of the present invention is also within the scope of this invention. For example, a salt can form between an amino moiety and an anion such as -13q-sulfate, pyrosulfate bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, or maleate.

As used herein, a fullerene core is C60, C61, C62, C63 C64, C65, C70, C7(1 C84, or C92, or La@C,,, Ho@Cn, Gd@Cn, or Er@C,,, in which n is 60, 74, or 82.
An amino acid is a molecule containing both an amino group and a carboxylic acid, e.g., alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine. Side chain of an amino acid is the substituent that is bonded to the carbon atom adjacent to the carbonyl carbon, i.e., the -carbon atom. For example, the side chain of each of alanine and ornithine is -CH3 and (CH2)3 NH2, respectively. A peptidyl is a peptide moiety containing 2-100 amino acid residues.
By the term "alkyl" is meant a straight chain that contains 1-30 carbon atoms, or a branched alkyl chain of 3-30 carbon atoms, or cyclic alkyl groups containing 3-30 carbon atoms, or otherwise indicated. These alkyl groups may also contain one or more double bond or triple bond and the cyclic alkyl groups may contain one or more heteroatoms, which are, typically, nitrogen, oxygen, or sulfur. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, amyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, pentadecyl, icosyl, allyl, 2-butenyl, 2-pentenyl, 3-hexenyl, 4-decenyl, 5-nonadecenyl, 2-butnyl, 3-octnyl, 5-octadecnyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, norbornyl, isobornyl, cyclopentyl-methyl, cyclohexylmethyl, 1- or 2-cyclohexylethyl, cyclo-pentenyl, cyclohexenyl, cycloheptenyl, -13r-Docket No.: 06897-0v1006 cyclo-octenyl; tetra-hydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl groups.
As used herein, the term "aryl" refers to C6_40 aromatic rings. These moieties may also be fused rings and can be fused with aryl or heteroaryl which is as defined below. Fused rings are rings that share a common carbon-carbon bond. Typically aryl groups include phenyl, naphthyl, biphenyl, indazolyl, phenanthryl, and anthracyl.
By the term "heteroaryl" in this disclosure is meant C640 aromatic rings that contain one or more heteroatoms as defined above. These moieties may also be fused rings.
Examples of heteroaryl groups include pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, coumarinyl, indolyl, benzofuranyl, benzthiazolyl, benzothienyl, and benzothiadiazolyl.
As used herein, the term "halide" is defined as fluoro, chloro, bromo, or iodo. The term "nucleophilic agent" is defined as an electron-rich species that donates electrons in a reaction. Examples of nucleophilic agents that can be employed in the preparation of derivatized fulleropyrrolidines include amine, phenol, alkoxide, organothiolate, carbanion, organoamide anion, thiol, amino acid, and thiol carbamate anion. Note that the just-mentioned nucleophilic agents can be unsubstituted or substituted with other functional groups. Examples of substituted nucleophilic agents include 1,4-naphthoquinonyl-amine, tyrosine, dihydroxypropylthiol, and the like.
The structures of many of the moieties mentioned above are shown below within the pair of parentheses following each of the moieties: alkyl ether (-R-O-), aryl ether (-Ar-O-), alkylaryl ether (-R-Ar-O-), arylalkyl ether (-Ar-R-O-), alkyl thioether (-R-S-), aryl thioether (-Ar-S-), alkylaryl thioether (-R-Ar-S-), arylalkyl thioether (-Ar-R-S-), alkyl ester (-R-O-CO-, -R-CO-O-, -Rj-CO-O-RZ-O-CO-, or -Rj-O-CO-RZ-CO-O-), aryl ester (-Ar-O-CO-, -Ar-CO-O, -Ar1-CO-0-Ar2-0-CO-, or -ArI-O-CO-Ar2-CO-O-), alkylaryl ester (-R-Ar-O-CO- or -R-Ar-CO-O-), arylalkyl ester (-Ar-R-O-CO- or -Ar-R-CO-O-), alkyl urethane (-Ri-O-CO-NH-RZ-NH-CO-O-), aryl urethane (-Ari-O-CO-NH-Ar2-NH-CO-O-), alkylaryl urethane (-Ri-Ar-O-CO-NH-RZ-NH-CO-O-, -R-Arj-O-CO-NH-Ar2-NH-CO-O-, or -Ri-O-CO-NH-Ar-R2-Ar-NH-CO-O-), arylalkyl urethane (-Ar-Ri-O-CO-NH-RZ-NH-CO-O-, -Ar1 -R-O-CO-NH-Ar2-NH-CO-O-, or -Ari-O-CO-NH-Ar2-R-Ar2-NH-CO-O-), alkyl urea (-Ri-NH-CO-NH-R2-NH-CO-NH-), aryl urea (-Arj-NH-CO-NH-ArZ-NH-CO-NH-), alkylaryl Docket No.: 06897-002006 urea (-R, -Ar-NH-CO-NH-R2-NH-CO-NH-, -R-Art-NH-CO-NH-ArZ-NH-CO-NH-, or -RI -NH-CO-NH-Ar-RZ-Ar-NH-CO-NH-), arylalkyl urea (-Ar-Ri-NH-CO-NH-R2-NH-CO-NH-, -Ari-R-NH-CO-NH-Ar2-NH-CO-NH-, or -Arl-NH-CO-NH-Ar2-R-Ar2-NH-CO-NH-), alkyl amide (-R-NH-CO-, -R-CO-NH-, -Rj-CO-NH-RZ-NH-CO-, or -Ri-NH-CO-RZ-CO-NH-), aryl amide (-Ar-NH-CO-, -Ar-CO-NH-, -Ari-CO-NH-ArZ-NH-CO-, or -Ari-NH-CO-ArZ-CO-NH-), alkylaryl amide (-R-Ar-NH-CO-, -R-CO-NH-Ar-NH-CO-, or -R-NH-CO-Ar-CO-NH-), arylalkyl amide (-Ar-R-NH-CO-, -Ar-CO-NH-R-NH-CO-, or -Ar-NH-CO-R-CO-NH-), alkyl anhydride (-R-CO-O-CO-), aryl anhydride (-Ar-CO-O-CO-), alkylaryl anhydride (-R-Ar-CO-O-CO- or -R-CO-O-CO-Ar-CO-O-CO-), arylalkyl anhydride (-Ar-R-CO-O-CO- or -Ar-CO-O-CO-R-CO-O-CO-), alkyl carbonate (-R-O-CO-O-), aryl carbonate (-Ar-O-CO-O-), alkylaryl carbonate (-R-Ar-O-CO-O- or -R-O-CO-O-Ar-O-CO-O-), and arylalkyl carbonate (-Ar-R-O-CO-O- or -Ar-O-CO-O-R-O-CO-O-). Note that the di-substitution pattern on Ar can be para, meta, or ortho.
As will be discussed below, one can employ stereospecific compounds of this invention to treat patients suffering from cancer via photodynamic therapy.
The stereospecific nature of these compounds allow specific interactions with many biologically active compounds, e.g., protein receptors. The compounds of this invention can also be used to develop chromatographic materials for purifying chiral molecules.
Other features and advantages of the present invention will be apparent from the following description of the preferred embodiments, and also from the appending claims.
DETAILED DESCRIPTION
The invention relates to sterospecific fullerene compounds, i.e., E-isomeric fulleropyrrolidine compounds, as well as polymers made of such E-isomeric compounds.
Also disclosed are methods for preparing these E-isomeric compounds and E-isomeric fulleropyrrolidine polymers.
Methods of this invention allow an E-isomeric fulleropyrrolidine compound to be prepared directly, thereby obviating the need to purifying a racemic mixture of both E- and Z-isomers. Separation of optical isomers is generally very difficult due to the close physical properties of optical isomers. Specifically, the methods described herein utilize a key l Docket No.: 06897-002006 starting material, i.e., a bicyclic imine-containing organometallic compound such as 1V-pyruvylidenealaninatoaquocopper (II). This bicyclic imine-containing compound, which is formed of two difunctional compounds, effects a stereospecific cycloaddition reaction when reacts with a fullerene core, e.g., C60, C76, or Gd@CRZ, thus forming only one fullerene isomer, i.e., the E-isomer.
Scheme I below illustrates a method for preparing an E-isomeric fulleropyrrolidine compound of this invention wherein its two carboxylic acid moieties are substituted at the same side of the pyrrolidine moiety. In the first step, an amino acid (H2N-CH(Rb)-COOH) and a pyruvic acid derivative (Rb-C(=0)-COOH) are used as exemplary difunctional compounds which react with each other to form a bicyclic imine-containing copper (II) complex in the presence of copper (II) acetate. See step (i). Note that the coordination of the two carboxylic acid moieties with the copper (II) ion restricts rotations of the N-C bond with respect to the N=C bond, thus forcing the two carboxylic acid to be at the same side of the pyrrolidine that is formed between the imine moiety, i.e., -C=N-C-, of the copper complex and a double bond of a fullerene core, e.g., C60, via a cycloaddition reaction. See step (ii).
Not only does the copper (II) ion enables only one stereospecific isomer, i.e., the E-isomer, to be formed, it also prevents thermal decarboxylation after dicarboxylic acid substituted fulleropyrrolidines are formed. By exchanging the copper (II) ion with the proton on a Dowex resin (H+ form), the corresponding E-isomeric dicarboxylic acid substituted fulleropyrrolidine product was isolated in a high yield (>85%). See Example I
below.
Scheme I

r.t.
RYCO H O (i) Cu(OAc)2 O.Cu.O (ii) C60, NH2 Z + RSIX- COZH OO
R3 Re (V) (VI) (11) CN OH (iii) Dowex resin 0 N Cu-OH2 R' 0 R' 0 (I) (III) Docket No.: 06897-002006 Scheme II below illustrates a method for preparing an E-isomeric fulleropyrrolidine compound of this invention wherein it is substituted with a carboxylic acid and an aromatic ring at the same side of the pyrrolidine moiety. The only difference between the methods shown in Scheme I and Scheme II lies in that the former method employs a difunctional carboxylic acid, e.g., 2-ketoglutaric acid, whereas the latter method employs a difunctional phenol, e.g., salicylaldehyde. The difunctional phenol, e.g., a carbonyl-containing phenol, can then react with a difunctional carboxylic acid, e.g., an amino acid, in the presence of a metal salt, e.g., Cu(OAc)2 or CoC12, to form a bicyclic imine-containing metal complex. See step (i). The next two steps of the method, i.e., cycloaddition (step (ii)) and removal of metal ions (step (iii)), are identical to those described above. See Example 7 below.

Scheme II
s O H20 R~ Co2H + ~ oH (i) Cu(oac)z o_ cU = o (ii) C~, r.t.
NH2 O~N, (V) (VI) (11) O R
O
OH (iii) D

owex resin KFW~

KRR~' (~) (III) Alternatively, the bicyclic imine-containing organometallic compound can also be formed between an amine-containing phenol, e.g., 2'-aminoacetophenone, and a carbonyl-containing carboxylic acid, e.g., pyruvic acid, or a carbonyl-containing phenol, e.g., salicylaldehyde.
The resulting E-isomeric fulleropyrrolidine compound of formula (I) can be further derivatized, e.g., by attaching thereto a methylglucoside, by various known methods. See, e.g., U.S. Patent No. 6,020,523. For example, the fulleropyrrolidine compound can be treated with a nitrating agent or a sulfating agent to form a nitrofulleropyrrolidine or a Docket No.: 06897-ov1006 cyclosulfated fulleropyrrolidine intermediate, which can then be converted into a derivatized E-isomeric fulleropyrrolidine by reacting with a nucleophilic agent. Examples of a nitrating agent include sodium nitrite and concentrated HNO3, dinitrogen tetraoxide, nitrogen dioxide, and fuming nitric acid. Cyclosulfated fullerene intermediates, on the other hand, can be formed by treating the fullerene with neat fuming sulfuric acid in the presence of an oxidant (e.g., P205, V205, or Se02). Examples of a nucleophilic agent include primary and secondary organoamino compound, alkoxide, organothiolate, organophenol compound, carbanion, organoamide anion, thiocarbamate ion, and the like.
The E-isomeric fulleropyrrolidine compound of formula (I) can further react with each other to form a polymer (or an oligomer). The polymer formed can be a homopolymer or a copolymer, e.g., a random, a block, or a branched copolymer. Since a compound of formula (I) contains three tenmini, i.e., a pyrrolidine nitrogen ring atom and two carboxylic acid moieties (or a carboxylic moiety and a phenol hydroxy group, or two phenol hydroxyl groups), a number of polymers can be prepared via different linkages. Take a fullero-pyrrolidine compound containing two carboxylic acid moieties as an example, a polymer can be formed by linking the N-terminus (i.e., the pyrrolidine nitrogen ring atom) of a first compound of formula (I) to the C-terminus (i.e., one of the two carboxylic acid moieties) of a second compound of formula (I), and the N-terminus of this second compound of formula (I) can in turn be linked to the C-terminus of a third compound of formula (I), and so on. This polymer design is similar to that of a peptide. The just-described polymer, i.e., a polymer of formula (VII), supra, can be prepared by fonming an internal anhydride between the two carboxylic acid moieties, which is then treated with a base such as 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) to effect the polymerization reaction. Due to the highly reactive nature of the anhydride moiety, derivatization of the fullerene should be done after the polymerization step. See Scheme III and Example 11 below.

. =1 z Docket No.: 06897-002006 Scheme III

R~ O R3 O O
C DBU H
` OH P205 50 NH NH O - H
, OH DMSO-ODCB/1:6 `100 C ~ O R O OH
4R~
O P

A polymer of formula (VII) can also be prepared using a fulleropyrrolidine compound having a phenol and a carboxylic acid moiety. Since this compound (or monomer) contains one carboxylic acid and one amino group, polymerization can be effected by using common peptide coupling reagents, e.g., dicyclohexylcarbodiimide (DCC), benzotriazol-l-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (BOP), or O-benzo-triazol-l-yl-N,N,N;N'-tetramethyluronium hexafluorophosphate (HBTU). Note that the hydroxy group of the phenol moiety may need to be protected, e.g., by silyl ethers, during polymerization.
Alternatively, a polymer of an E-isomeric fulleropyrrolidine compound of formula (I) can also be formed by linking the carboxylic acid moiety (or the hydroxy group of the phenol moiety) of one fulleropyrrolidine monomer to the carboxylic acid moiety of another fulleropyrrolidine monomer via a divalent linker, thus resulting in a polymer of formula (VIII). For example, a polyamide and a polyester can be formed by reacting a fulleropyrrolidine compound with two carboxylic acid moieties with a diamine (e.g., ethylenediamine) and a diol (e.g., 1,3-propanediol), respectively.
An E-isomeric fulleropyrrolidine compound of formula (I) can be used in photodynamic therapy (PDT) to treat patients suffering from cancer. See Example 16 below.
The photo-induced cytotoxicity of a fullerene compound is connected with its ability to cleave DNA. Specifically, photogenerated triplet fullerene intermediate is involved in the energy transfer process which converts the ground-state triplet oxygen molecules into the excited molecular singlet oxygen 1OZ. Singlet oxygen is capable of inducing DNA damage and degeneration of other tissues that lead to mutagenic effects on biological cells. The Docket No.: 06897-0ut006 stereospecific nature of an E-isomeric fulleropyrrolidine compound of formula (I) can enhance its affinity to DNA which is in the form of a double helix. Polymers of fonnulas (VII) and (VIII), which contain a plurality of fulleropyrrolidine compounds of formula (I), can further enhance its biological activities by allowing delivery of multiple fullero-pyrrolidine compounds in a single molecule.
A pharmaceutical composition containing an effective amount of a fulleropyrrolidine compound of formula (I) (or a polymer formed therefrom) is also within the scope of this invention. The use of such a fulleropyrrolidine compound for the manufacture of a medicament for treating tumors is also within the scope of this invention.
Still another aspect of this invention is a method for treating tumor by administering to a patient a pharmaceutical composition containing an effective amount of a fulleropyrrolidine compound of this invention. An effective amount is defined as the amount which is required to confer a therapeutic effect on the treated patient, and is typically determined based on age, surface area, weight, and condition of the patient. The interrelationship of dosages for animals and humans (based on milligrams per meter squared of body surface) is described by Freireich et al., Cancer Chemother. Rep. 1966, 50, 219. Body surface area may be approximately determined from height and weight of the patient. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardley, New York, 1970, 537. An effective amount of a pyridyl cyanoguanidine compound of this invention can range from about 1 mg/kg to about 150 mglkg (e.g., about 1 mg/kg to about 100 mg/kg) . Effective doses will also vary, as recognized by those skilled in the art, dependant on route of administration, excipient usage, and the possibility of co-usage with other therapeutic treatments including use of other antitumor agents and radiation therapy.
The pharmaceutical composition may be administered via the parenteral route, including orally, topically, subcutaneously, intraperitoneally, intramuscularly, and intravenously. Examples of parenteral dosage forms include aqueous solutions of the active agent, in a isotonic saline, 5% glucose or other well-known pharmaceutically acceptable excipient. Solubilizing agents such as cyclodextrins, or other solubilizing agents well-known to those familiar with the art, can be utilized as pharmaceutical excipients for delivery of the therapeutic compounds.

~
1ir /f I

A fulleropyrrolidine compound of this invention can be formulated into dosage forms for other routes of administration utilizing conventional methods. For example, it can be formulated in a capsule, a gel seal, or a tablet for oral administration. Capsules may contain any standard pharmaceutically acceptable materials such as gelatin or cellulose. Tablets may be formulated in accordance with conventional procedures by compressing mixtures of a pyridyl cyanoguanidine compound with a solid carrier and a lubricant. Examples of solid carriers include starch and sugar bentonite. The fulleropyrrolidine compound can also be administered in a form of a hard shell tablet or a capsule containing a binder, e.g., lactose or mannitol, a conventional filler, and a tableting agent.
Without further elaboration, it is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent.
The following specific examples are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

Example 1 Synthesis of E-isomer of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid. In a conical flask charged with DL-alanine (2.25 g, 25 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added pyruvic acid (2.2 g, 25 mmol). The reaction mixture was stirred at ambient temperature for 1.0 h. To the resulting yellowish solution was then added copper (II) acetate (4.99 g, 25 mmol) in water-ethanol (20 ml) and stirred for an additional 24 h, causing precipitation of pale blue solids. The solids were filtered, washed with ethanol, and dried to yield 1V-pyruvylidenealaninatoaquocopper (II) complex.
To a solution of C60 (350 mg, 0.49 mmol) in o-dichlorobenzene (140 ml),1V-pyruvylidenealaninatoaquocopper (II) complex (0.34 g, 1.96 mmol, 4.0 equiv.) in pyridine (25 ml) was added via syringe under N2. The solution mixture was stirred for a period of 15 h at ambient temperature. It was added hexane (100 ml) to effect precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo. It was further washed twice by water, brine, and CH3CN (20 ml each) Docket No.: 06897-0u2006 and dried in vaccuo to afford brown solids of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylatoaquocopper (II) complex (0.53 g). IR ,n,, (KBr) 3424 (br, s), 1749 (w), 1716 (w), 1622 (s), 1385 (s), 1218 (w), 1182 (w), 1154 (w), 1070 (w), 751, 696, and 525.
Brown solids of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylatoaquocopper (II) complex (0.5 g) were dissolved in a mixture of pyridine (25 ml) and water (25 ml). It was stirred in the presence of Dowex acid resin (50WX8, 2.0 g) for a period of 2.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.5 g) for an additiona130 min. At the end of the ion exchanging reaction, Dowex resin was filtered. After solvent evaporation of the filtrate, the resulting dark solids were washed with ethanol and dried in vaccuo to give the product of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid (0.4 g). IR ,. (KBr) 3422 (br, s), 3 101 (w), 1779 (w), 1717, 1635 (s), 1488, 1388, 1242, 1162, 1036, 751, 681, and 526.
Treatment of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid with dil. HCI (2.0 N) gave the corresponding N-protonated 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid containing free carboxylic acids. IR ,tõx (KBr) 3421 (br, s), 3245, 2930, 2859, 2575 (COZH), 1723 (s, COZH), 1641, 1453, 1414, 1169, 1111 (s), 955 (w), 801, 665 (w), 599 (w), and 470.
Example 2 Synthesis of E-isomer of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylic acid. In a conical flask charged with DL-tyrosine (4.52 g, 25 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added pyruvic acid (2.2 g, 25 mmol). The reaction mixture was stirred at 50 C for 2.0 h under basic condition at pH 8 10 using NaOH as a titration agent. The resultirtg yellowish solution was then added copper (II) chloride (3.4 g, 25 mmol) in water-ethanol (20 ml) and stirred for an additional 2 4 h, causing precipitation of pale blue solids. The solids were filtered, washed wittLwater, ethano6diethylether, and dried to yield N-pyruvylidenetyrosinatoaquocopper (II) complex. IR ,,,,,, (KBr) 3490, 3371, 3290, 3151, 3052, 2971, 2932, 1613 (s), 1580, 1520, 1448, 1408, 1335, 1242, 1123, 1070, 891, 848, 810, 744, 705, 600, and 539.
Alternatively, in a conical flask charged with DL-alanine (2.27 g, 25 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added p-" -22-Docket No.: 06897-0u1006 hydroxyphenylpyruvic acid (4.5 g, 25 mmol). The reaction mixture was stirred at ambient temperature for 2.0 h. The resulting yellowish solution was then addedcopper (II) acetate (5.0 g, 25 mmol) in water-ethanol (20 ml) and stirred for an additional 2 4 h, causing precipitation of greenish blue solids. The solids were filtered, washed with ethanol, diethylether, and dried to yield blue solids of N-hydroxyphenylpyruvylidene-alaninatoaquocopper (II) complex. IR ,. (KBr) 3423, 3255, 2975, 2941, 1621 (s), 1518, 1457, 1396, 1363, 1250, 1154, 1122, 859, 848, 792, 778, 715, 678, and 576.
To a solution of C60 (500 mg, 0.69 mmol) in o-dichlorobenzene (150 ml), IV-pyruvylidenetyrosinatoaquocopper (II) complex (1.04 g, 3.44 mmol, 5.0 equiv.) or 1V-hydroxyphenylpyruvylidene-alaninatoaquocopper (II) complex (1.35 g, 4.2 mmol, 6.0 equiv.) in pyridine (40 ml) and triethylamine was added via syringe in sequence under N2. The solution mixture was stirred for a period of 24 h at ambient temperature.
Unreacted copper complex partially suspended in the solution was removed. It was added hexane (100 ml) to effect precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo. It was further washed twice by water, brine, and CH3CN (20 ml each) and dried in vaccuo to afford brown solids of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylatoaquocopper (II) complex (665 mg).
Brown solids of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylato-aquocopper (II) complex (0.5 g) were dissolved in a mixture of pyridine (25 ml) and water (25 ml) or o-dichlorobenzene EtOH. It was stirred in the presence of Dowex acid resin (50WX8, 2.0 g) for a period of 4.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.5 g) for an additional 30 min. At the end of the ion exchanging reaction, Dowex resin was filtered.
After solvent evaporation of the filtrate, the resulting dark solids were washed with ethanol and dried in vaccuo to give the product of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylic acid. IR ,ax (KBr) 3430 (br, s), 2933 (w), 2866, 1659 (s), 1620, 1517, 1442, 1364, 1321, 1237, 1175, 1112, 821, and 528. Treatment of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylic acid with dil. HCI
(2.0 N) gave the corresponding N-protonated 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid Docket No.: 06897-0U2006 containing free carboxylic acids. IR .,, (KBr) 3401 (br, s), 3230, 2933, 2851, (br, COZH), 1758, 1718, 1646 (s), 1516, 1442, 1363, 1320, 1174, 1036, 991, 822, and 504.
Example 3 Synthesis of E-isomer of 1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxylic acid. In a conical flask charged with 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA, 1.0 g, 5.1 mmol) and a mixture of water and ethanol (10 mi, 2:1) and stirred for a period of 20 min was added pyruvic acid (446 mg, 5.1 mmol). The reaction mixture was stirred at 40 C for 2.0 h. The resulting yellowish solution was then added copper (II) acetate (1.0 g, 5.1 mmol) in water-ethanol (10 ml) and stirred for an additional 2 4 h, causing precipitation of pale blue solids. The solids were filtered, washed with water, ethanol, and dried to yield N-pyruvylidene-3-(3,4-dihydroxyphenyl)alaninatoaquocopper (II) complex (1.02 g). IR ,,,a,, (KBr) 3412 (br, s), 3251 (br, s), 1615 (s), 1500, 1382, 1282, 1251, 1157, 869, 721, and 645.
To a solution of C6o (100 mg, 0.14 mmol) in o-dichlorobenzene (40 ml), IV-pyruvylidene-3-(3,4-dihydroxyphenyl)alaninatoaquocopper (II) complex (288 mg, 0.84 mmol, 6.0 equiv.) in pyridine (35 ml) was added via syringe under N2. The solution mixture was stirred for a period of 15 h at 50-60 C. It was added hexane (100 ml) to effect precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo. It was further washed twice by water, brine, and CH3CN (20 ml each) and dried in vaccuo to afford dark brown solids of 1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-l,3-dicarboxylato-aquocopper (II) complex (150 mg).
Brown solids of 1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxyl-atoaquocopper (II) complex (150 mg) were dissolved in a mixture of pyridine (20 ml) and water (20 ml). It was stirred in the presence of Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g) for an additiona130 min. At the end of the ion exchanging reaction, Dowex resin was filtered. After solvent evaporation of the filtrate, the resulting dark solids were washed with ethanol and dried in vaccuo to give the product of 1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-l,3-dicarboxylic Docket No.: 06897-002006 acid (200 mg). IR (KBr) 3395 (br, s), 2950 (w), 2922 (w), 2800-2500 (br), 1613, 1545, 1470, 1427, 1302, 1187, 1162, 1067 (w), 862, 701 (w), 625 (w), and 525.

Example 4 Synthesis of E-isomer of fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acid. In a conical flask charged with L-glutamic acid (1.47 g, 10.0 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added 2-ketoglutaric acid (1.46 g, 10.0 mmol). The reaction mixture was stirred at ambient temperature for a period of 2.0 h at pH 6.0 7.0 using NaOH as a titrating agent. The resulting colorless solution was then added copper (II) acetate (1.99 g, 10.0 mmol) in water-ethanol (10 ml) and stirred for an additional 2 h, causing precipitation of pale blue solids. The solids were filtered, washed with ethanol and ether, and dried in vaccuo to yield N-(2-ketoglutarylidene)- [.-glutamitoaquocopper (II) complex (2.6 g). IR T. (KBr) 3439 (br, s), 3282 (br, s), 2949, 2581, 1623 (s), 1392, 1343, 1231, 1147, 1095, 939, 676, and 641.
To a solution of C6o (400 mg, 0.64 mmol) in o-dichlorobenzene (100 ml), N-(2-ketoglutarylidene)- L-glutamitoaquocopper (II) complex (1.3 g, 6.0 equiv.) in pyridine (50 ml) was added via syringe under N2. The solution mixture was stirred in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 300 mg) for a period of 5 h at ambient temperature.
At the end of reaction, hexane (100 ml) was added to the reaction mixture causing precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo. It was further washed twice by water, brine, and CH3CN (20 ml each) and dried in vaccuo to afford dark brown solids of fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylato-aquocopper (II) complex. It was then dissolved in DMSO (30 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h.
The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g) for an additiona130 min. At the end of the ion exchanging reaction, Dowex resin was filtered. Solid products were precipitated from the filtrate by addition of a mixture of ether and acetone. The precipitates were washed with ether and acetone and dried in vaccuo to give brown solids of fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acid (550 mg). IR (KBr) 3422 (br, s), 2928 (w), 2857 (w), 1716, t . ti ,~

Docket No.: 06897-002046 1635 (s), 1435, 1371, 1200 (w), 1018, 952, and 527. Treatment of fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acid with dil. HCl (2.0 N) gave the corresponding N-protonated fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acid containing free carboxylic acids. IR T,,, (KBr) 3433 (br, s), 2928, 2853, 2800 2500 (br, COzH), 1792 (w), 1721 (s), 1630 (s), 1440, 1411, 1328, 1184, 1004, 949, 764, and 526.

Example 5 Synthesis of E-isomer of 1-methyl-3-thiomethyl-fulleropyrrolidine-1,3-dicarboxylic acid. In a conical flask charged with L-cysteine (1.21 g, 10.0 nunol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added pyruvic acid (880 mg, 10.0 mmol). "I'he reaction mixture was stirred at ambient temperature for a period of 1.0 h.
The resulting colorless solution was then added copper (II) acetate (1.99 g, 10.0 mmol) in water-ethanol (10 ml) and stirred for an additional 2 h, causing precipitation of dark gray solids. The solids were filtered, washed with ethanol and ether, and dried in vaccuo to yield N-pyruvylidene-L-cysteinatoaquocopper (II) complex (1.6 g). IR ,. (KBr) 3447 (br), 3221 (br), 2994 (w), 2935 (w), 1666, 1625, 1598 (s), 1574 (s), 1423, 1404, 1378, 1315, 1178, 1016, 970, 937, 884, 759, 713, and 642.
To a solution of C60 (400 mg, 0.64 mmol) in o-dichlorobenzene (100 ml),1V
pyruvylidene-t,-cysteinatoaquocopper (II) complex (600 mg, 6.0 equiv.) in pyridine (30 ml) was added via syringe under N2. The mixture was stirred for a short period of 10 min at ambient temperature to give a solution containing suspended brown solids. At the end of reaction, hexane (100 ml) was added to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo. It was then dissolved in a mixture of o-dichlorobenzene and ethanol (1:1, 40 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g) for an additiona130 min. At the end of the ion exchanging reaction, Dowex resin was filtered. Ethanol was removed from the filtrate and solid products were precipitated by addition of ether to the remaining liquid. The precipitates were washed with ether and dried in vaccuo to give brown solids of 1-methyl-3-thiomethyl-fulleropyrrolidine-Docket No.: 06897-W2006 1,3-dicarboxylic acid (520 mg). IR ,f,aX (KBr) 3429 (br, s), 2979 (w), 2935 (w), 1721, 1631 (s), 1540 (w), 1377, 1232, 1180, 955 (w), 767, and 525.

Example 6 Synthesis of E-isomer of 1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid. In a conical flask charged with L-serine (1.19 g, 10.0 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added pyruvic acid (880 mg, 10.0 mmol). The reaction mixture was stirred at ambient temperature for a period of 2.0 h.
The resulting colorless solution was then added copper (II) acetate (1.99 g, 10.0 mmol) in water-ethanol (10 ml) and stirred for an additional 2 h, causing precipitation of pale blue solids. The solids were filtered, washed with ethanol and ether, and dried in vaccuo to yield N-pyruvylidene-L-serinatoaquocopper (II) complex (1.7 g). IR . (KBr) 3369 (br, s), 2988 (w), 1731, 1625 (s), 1398, 1341, 1222, 1199, 1145 (w), 1106, 1073, 957 (w), 894, 857, 723, 648, and 589.
To a solution of C6o (400 mg, 0.64 mmol) in o-dichlorobenzene (100 ml),1V-pyruvylidene-[.-serinatoaquocopper (II) complex (590 mg, 6.0 equiv.) in pyridine (30 ml) was added via syringe under N2. The mixture was stirred in the presence of triethylamine for a period of 12 h at ambient temperature to give a solution containing suspended brown solids.
At the end of reaction, hexane (100 ml) was added to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo. It was then dissolved in a mixture of o-dichlorobenzene and ethanol (1:1, 40 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g) for an additiona130 min. At the end of the ion exchanging reaction, Dowex resin was filtered. Ethanol was removed from the filtrate and solid products were precipitated by addition of ether to the remaining liquid. The precipitates were washed with ether and dried in vaccuo to give brown solids of 1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid (500 mg). IR ,. (KBr) 3445 (br, s), 2926 (w), 2853 (w), 1786, 1729, 1633 (s), 1454 (w), 1381, 1168, 1107, 1076, 1042, and 533. Treatment of 1-methyl-3-hydroxymethyl-fulleropyrrolidine-l,3-dicarboxylic acid with dil.
HC1(2.0 N) Docket No.: 06897-002006 gave the corresponding N-protonated 1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid containing free carboxylic acids. IR ma,, (KBr) 3421 (br, s), 3211, 2954, 2800 2500 (br, COZH), 1762, 1719 (COZH), 1630 (s), 1428 (w), 1380, 1183, 1112 (w), 1036, 991, 928 (w), 755 (w), 625 (w), and 526.

Example 7 Synthesis of E-isomer of 1-isobutyl-3-(o-hydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid. In a conical flask charged with L-leucine (2.44 g, 20.0 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 20 min was added salicylaldehyde (2.62 g, 20.0 mmol). The reaction mixture was stirred at 50 C for a period of 5.0 h at pH 7.0 using NaOH as a titrating agent. The resulting pale yellow solution was then added copper (II) acetate (4.0 g, 20.0 mmol) in water-ethanol (10 ml) and stirred for an additional 30 min, causing precipitation of pale blue-green solids. The solids were filtered, washed with ethanol and ether, and dried in vaccuo to yield N-(2-hydroxybenzylidene)-L-leucinatoaquocopper (II) complex (4.5 g). IR ,. (KBr) 3383 (br, w), 3322 (br, w), 3252 (br, w), 2961, 2912, 2875, 1649 (s), 1628, 1606, 1528, 1451, 1336, 1198, 1147, 1079 (w), 861 (w), 802, 767, 730, and 564.
To a solution of C6o (1.0 g, 1.3 mmol) in o-dichlorobenzene (300 ml), N-(2-hydroxybenzylidene)-L-leucinatoaquocopper (II) complex (1.64 g, 5.2 mmol, 4.0 equiv.) in pyridine (100 ml) was added via syringe under N2. The mixture was stirred in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.0 g) for a period of 15 h at ambient temperature to give a solution containing suspended brown solids. At the end of reaction, hexane (100 ml) was added to effect complete precipitation of solid products.
The solid precipitates were isolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo, yielding 1.4 g of products. It was then dissolved in a mixture of toluene and ethanol (9:1, 100 ml, brown solution) and treated with Dowex acid resin (50WX8, 2.0 g) for a period of 2.0 4.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.5 g) for an additional 30 min. At the end of the ion exchanging reaction, Dowex resin was filtered. Solvent was removed from the filtrate and resulting solid products were washed with hexane and dried in vaccuo to give brown solids Docket No.: 06897-Ou2006 of 1-isobutyl-3-(o-hydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid (900 mg). Rf 0.35 (thin layer chromatography, Si02, toluene-ethanoU9:1); IR ~õaX (KBr) 3440 (br, s), 2957, 2929, 2866, 1706, 1619, 1575, 1495 (w), 1446, 1387 (w), 1293 (w), 1252, 1228, 1179, 1155, 1043, and 650; m/z 955 (M).

Example 8 Synthesis of E-isomer of 1-methyl-3-ethyl-3'-(o-hydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid. Into a conical flask charged with L-alanine (1.78 g, 20.0 mmol), molecular sieves (4A), and ethanol (20 ml) was added 2-hydroxypropiophenone (3.0 g, 20.0 mmol).
The reaction mixture was stirred at the reflux temperature for a period of 24.0 h at pH 8.0 using NaOH as a titrating agent. The resulting yellow solution was then added copper (II) acetate (4.0 g, 20.0 mmol) in water-ethanol (15 ml, 2:1) and stirred for an additiona12.0 h, causing precipitation of green solids. The solids were filtered, washed with ethanol and ether, and dried in vaccuo to yield N-(2-hydroxypropiophenonylidene)-L-alainatoaquocopper (II) complex (4.0 g). IR ,,,aX (KBr) 3470 (br, w), 3305, 3245, 2981, 2933, 2880, 1622 (s), 1575, 1465, 1401, 1363, 1298, 1142, 1125, 1076, 1028, 928, 857, 788, 709, 672, 618, and 575.
To a solution of C60 (300 mg, 0.4 mmol) in o-dichlorobenzene (100 mi), N-(2-hydroxypropiophenonylidene)-L-alainatoaquocopper (II) complex (590 mg, 1.8 mmol, 4.5 equiv.) in pyridine (30 ml) was added via syringe under N2. The mixture was stirred in the presence of triethylamine (0.5 ml) for a period of 24 h at ambient temperature to give a solution containing suspended brown solids. At the end of reaction, hexane (50 ml) was added to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with hexane (30 ml), and dried in vaccuo. It was then dissolved in a mixture of o-dichlorobenzene and ethanol (1:1, 40 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g) for an additional 30 min. At the end of the ion exchanging reaction, Dowex resin was filtered.
Solvent was removed from the filtrate and resulting solid products were washed with hexane CH3CN and dried in vaccuo to give brown solids of 1-methyl-3-ethyl-3'-(o-hydroxyphenyl)-:' Docket No.: 06897-0u2006 fulleropyrrolidine-l-carboxylic acid (310 mg). IR ,,. (KBr) 3435 (br, s), 3089, 2933, 1722 (w), 1625 (s), 1520 (w), 1413, 1364, 1308, 1168, 1118 (s), 1037 (s), 1010 (s), 677, and 528.
Treatment of 1-methyl-3-ethyl-3'-(o-hydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid with dil. HCI (2.0 N) gave the corresponding N-protonated derivative containing free carboxylic acids. IR õ. (KBr) 3427 (br, s), 2950, 2800-2500 (br, COZH), 1726 (CO2H), 1637 (s), 1514, 1418 (w), 1258 (w), 1205, 1119, 1038, and 612.

Example 9 Synthesis of E-isomer of 1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid. In a conical flask charged with L-alanine (0.98 g, 10.0 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for a period of 10 min was added 2.3.4-trihydroxybenzaldehyde (1.54 g, 10.0 mmol). The reaction mixture was stirred at 40 C for a period of 2.0 h. The resulting yellow solution was then added copper (II) acetate (2.0 g, 10.0 mmol) in water-ethanol (5.0 ml) and stirred for an additional 30 min, causing precipitation of dark green solids. The solids were filtered, washed with ethanol and ether, and dried in vaccuo to yield N-(2.3.4-trihydroxybenzylidene)-[,-alainnatoaquocopper (II) complex (1.95 g). IR ,ax (KBr) 3322 (br), 3248 (br), 2919, 2853, 1574 (s), 1484, 1443, 1399, 1320, 1278, 1187 (w), 1098, 1041 (w), 791, 731, 671, and 519.
To a solution of C6o (300 mg, 0.4 mmol) in o-dichlorobenzene (100 ml), N-(2.3.4-trihydroxybenzylidene)-L-alainnatoaquocopper (II) complex (630 mg, 2.0 mmol, 5.0 equiv.) in pyridine (30 ml) was added via syringe under N2. The mixture was stirred for a period of 15 h at ambient temperature to give a solution containing suspended brown solids. At the end of reaction, hexane (50 ml) was added to effect complete precipitation of solid products.
The solid precipitates were isolated by centrifuge, washed with hexane (30 ml), and dried in vaccuo. It was then dissolved in a mixture of o-dichlorobenzene and ethanol (1:1, 40 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filtered off. The remaining solution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g) for an additional 30 min. At the end of the ion exchanging reaction, Dowex resin was filtered. Solvent was removed from the filtrate and solids were precipitated by addition of diethylether. The solid precipitates were washed with hexane and dried in vaccuo to give Docket No.: 06897-Uu2006 brown solids of 1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid (290 mg). IR . (KBr) 3422 (br, s), 2972, 2927, 2846, 1706 (w), 1635 (s), 1447, 1374, 1314, 1162, 1013, 951, and 526. Treatment of 1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-l-carboxylic acid with dil. HCl (2.0 N) gave the corresponding N-protonated derivative containing free carboxylic acids. IR t. (KBr) 3420 (br, s), 3245 (br), 2978 (w), 2932 (w), 2857 (w), 2800-2500 (br, CO2H), 1709 (C02H), 1636 (s), 1448, 1403, 1178, 1129, 1037, 1011, 952, and 527.

Example 10 Synthesis of 1,3-dimethyl-N-(p-bromobenzyl)fulleropyrrolidine-1,3-dicarboxylic anhydride. To a solution of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid (220 mg, 0.25 mmol) in a mixture of o-dichlorobenzene and DMSO (6:1, 50 ml), phosphorous pentaoxide (250 mg) was added under N2. The mixture was stirred at 50 C for a period of 12.0 h to effect dehydrative anhydride formation. At the end of reaction, the insoluble solids were separated by centrifuge. The remaining solution was transferred via syringe into the second reaction flask containing p-bromobenzyl chloride (66 mg, 0.3 mmol) and triethylamine (0.1 ml). The mixture was stirred at 50 C for an additiona18.0 h under NZ.
Diethyl ether (50 ml) was then added to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, washed with diethyl ether (30 ml), water, ethanol, and diethyl ether in sequence and dried in vacuo to give brown solids of 1,3-dimethyl-N-(p-bromobenzyl)fulleropyrrolidine-l,3-dicarboxylic anhydride (180 mg). 'H
NMR (two amide isomers in an equal amount) 1.14 (s, 6H), 1.24 (s, 6H), 7.75 (dd, 4H), 8.15 (dd, 4H); IR ,,x (KBr) 3402 (br, s), 2984, 2925, 1787 (w), 1737 (s), 1630, 1591, 1513 (w), 1399, 1255, 1173, 1094, 1071, 1008, 751, and 527.

Example 11 Synthesis of oligo[1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic N-amidel.
To a solution of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid (220 mg, 0.25 mmol) in a mixture of o-dichlorobenzene and DMSO (6:1, 50 ml), phosphorous pentaoxide (250 mg) CA 02339054 2001-03-02 T=
Docket No.: 06897-0u2006 was added under N2. The mixture was stirred at 50 C for a period of 12.0 h to effect dehydrative anhydride formation. At the end of reaction, the insoluble solids were separated by centrifuge. The remaining solution was transferred via syringe under N2 into the second reaction flask containing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.0 g). The mixture was stirred at 100 C for an additiona124.0 h under N2 to afford a dark brown-black solution.
Diethyl ether (50 ml) was then added to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, washed twice with diethyl ether (30 ml), ethanol, and diethyl ether in sequence. It was treated with dil HCl (2 N) in THF, washed with THF, and dried in vaccuo. to give dark brown solids of oligo[1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic N-amide] (165 mg). IR ,T,,,, (KBr) 3402 (br, s), 2931, 2861, 1712 (w), 1661 (s), 1613, 1442, 1372, 1324, 1156 (s), 1036 (s), 990, 675, and 611.
Example 12 Synthesis of 1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid, C60[C(CH3)CO2Hj2NCO-CH2CH2CO2H. To a solution of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid (440 mg, 0.5 mmol) in a mixture of o-dichlorobenzene and DMSO
(6:1, 80 ml), succinic anhydride (100 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.0 g ) were added under N2. The mixture was stirred at 30 C for a period of 4.0 h. At the end of reaction, the solution was treated with dil. HCI (2.0 N). Diethyl ether (50 ml) was then added to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, washed twice with diethyl ether (30 ml), water, and diethyl ether in sequence and dried in vaccuo. to give dark brown solids of 1,3-dimethyl-IV-succinamitofulleropyrrolidine-1,3-dicarboxylic acid (480 mg). IR ,t,ax (KBr) 3426 (br, s), 2930, 2595 (br, COZH), 1752 (w), 1718 (s, CO2H), 1626, 1402, 1180, 1086, 1000, 773 (w), 653 (w), and 525 (w).

ti ` ~ Z

Docket No.: 06897-(,v).006 Example 13 Synthesis of tris(hexadecaanilino)-1,3-dimethyl-N-succinamitofulleropyrrolidine-l,3-dicarboxylate, C60 [C(CH3)CO-(NH-C6H4-N=C6H4=N-C6H4-NH-C6Ha-)a-H] ZNCO-CH2CHZCO-(NH-C6H4-N=C6H4=N-C6H4-NH-C6H4-),-H. To a solution of 1,3-dimethyl-N-succinamito-fulleropyrrolidine-1,3-dicarboxylic acid, C60[C(CH3)CO2H]2NCO-CH2CH2CO2H, (498 mg, 0.5 mmol) in a mixture of o-dichlorobenzene and DMSO
(6:1, 100 ml), hexadecaaniline (emeraldine base form, 2.2 g, 1.5 mmol), 1,3-dicyclohexylcarbodiimide (DCC, 340 mg, 1.65 mmol), and 1-hydroxybenzotriazole (BtOH, 223 mg, 1.65 mmol) were added under N2. The mixture was stirred at 40 C for a period of 24.0 h. At the end of reaction, the solution was added diethyl ether (100 ml) to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, treated with aqueous NHaOH, washed twice with water and diethyl ether and dried in vaccuo. to give dark blue solids of tris(hexadecaanilino)-1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylate (2.5 g). IR ,,,X (KBr) 3433 (br, s), 3284, 2932 (w), 2859 (w), 1596, 1506 (s), 1305, 1252, 1150, 822, 749, 696, and 506.

Example 14 Synthesis of tris(glycylglycyl)-1,3-dimethyl-N-succinamitofulleropyrrolidine-l,3-dicarboxylate, C60[C(CH3)CO-(NHCHZCO-NHCH2COZH]2NCO-CHZCHZCO-NHCHZCO-NHCH2COZH. To a solution of 1,3-dimethyl-1V succinamito-fulleropyrrolidine-l,3-dicarboxylic acid, C6o[C(CH3)CO2H]2NCO-CH2CH2CO2H, (498 mg, 0.5 mmol) in a mixture of o-dichlorobenzene and DMSO (6:1, 100 ml), glycylglycine (198 mg, 1.5 mmol), 1,3-dicyclohexylcarbodiimide (DCC, 340 mg, 1.65 mmol), and 1-hydroxybenzotriazole (BtOH, 223 mg, 1.65 mmol) were added under N2. The mixture was stirred at 40 C for a period of 24.0 h. At the end of reaction, the solution was added diethyl ether (100 ml) to effect complete precipitation of solid products. The solid precipitates were isolated by centrifuge, treated with dil. HCl (2.0 N), washed twice with water and diethyl ether and dried in vaccuo. to give dark brown solids of tris(glycylglycyl)-1,3-dimethyl-N-Docket No.: 06897-(,v1006 succinamitofulleropyrrolidine-1,3-dicarboxylate (480 mg). IR rx (KBr) 3431 (br, s), 2929, 2860 (w), 1773, 1701, 1654 (s), 1550, 1391, 1227, 1178, 1056 (w), 999 (w), and 527.
Example 15 Detection of high free radical scavenging potency of hydrophilic fullerene derivatives.
The xanthine/xanthine oxidase enzymatic system is highly effective for the production of superoxide radicals (02 ). Reaction of superoxide radicals with cytochrome (Fe+) C may result in a product of reduced cytochrome (Fe+2) C which shows a respectable optical absorption at 550 nm. Therefore, the detected optical absorption intensity of the reduced cytochrome (Fe+2) C can be correlated to the quantity of superoxide radicals reacted with cytochrome (Fe+3) C. Scavenging of superoxide radicals by hydrophilic fullerene derivatives in the bio-medium inhibits the formation of reduced cytochrome (Fe+2) C and thus reduce the optical absorption at 550 nm.
In one experiment, xanthine (50 M) was added to a physiological medium (3 ml) containing cytochrome C (10 M), ethylenediaminetetraacetic acid (EDTA) (10 mM) and a phosphate buffer (50 mM) at pH 7.8. The mixture was then added xanthine oxidase in quantity enough to induce 0.025 unit of optical absorption at 550 nm per 5 min (Mc Cord, et al. J. Biol. Chem. 1969, 244, 6049.). Subsequently, 1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid, C60[C(CH3)CO2H]2NCO-CH2CH2CO2H, prepared in Example 12, in a concentration of 0, 5.0, 10.0, 25.0, 50, and 100 M was added in separated runs while the absorption intensity of the reduced cytochrome C
was recorded. A rapid decrease of reduced cytochrome C to roughly 50% and 20%
of the control value was obtained with the dose of 1,3-dimethyl-N-succinamitofulleropynrolidine-1,3-dicarboxylic acid as 25 and 100 M, respectively. These results substantiated efficient scavenging of superoxide radicals by 1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid that led to the inhibition of cytochrome C reduction.

Example 16 The growth inhibitory effect of 1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid, C60[C(CH3)CO2H]2NCO-CH2CH2CO2H, which was prepared as described in Example 12, on fibrosarcoma tumor cells upon photo-irradiation was studied in vitro.

Fibrosarcoma tumor cells (0.5 ml, 4 x 104/ml, CCRC 60037) were grown in the MEM
medium in a 24-well plate for a period of 24 h. It was treated by 1,3-dimethyl-N-succinamitofulleropyrrolidine-l,3-dicarboxylic acid in a concentration of 0.0, 2.5, 5.0, 7.5, and 10.0 M for a period of 24 hours. The MEM medium was removed and replaced by the fresh medium (1.0 ml). The cell-containing plates were exposed to a fluorescence light source (27 W) in a distance of 5-6 cm for a period of 10, 20, 40, and 60 min. The plates were then kept in incubator at 37 C a period of 48 h.
Measurement of cell viability in each plate was performed by the MTT assay using optical absorption at 540 nm. The data indicated a rapid decrease in the tumor cell count under application of 1,3-dimethyl-N-succinamitofulleropyrrolidine-l,3-dicarboxylic acid in a concentration of only 2.5 M with a photo-irradiation period of more than 20 min. These results substantiated high efficacy of the growth inhibition on fibrosarcoma tumor cells upon photo-irradiation.

Other Embodiments From the above description, one skilled in the art can easily ascertain the essential characteristics of the present invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, other embodiments are also within the claims.

Claims (60)

1. A compound of formula (I):

wherein F f is F(-K)m(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2-NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1-100-OH, -[CH(CO2R a)-CH2]1-100-OH, -[C(CH3)(CO2H)-CH2]1-100-OH, -[C(CH3)(CO2 R a)-CH2]1-100-OH, -N(OH)2, -NH3+, -N+H2R a, -N+HR a R b, or -N+R a R b R c; each Y is -A-B-, in which A is -O-, -NH-, -S-, -CO-O-, -O-CO-, -O-CO-O-, -O-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -R a-O-[Si(CH3)2-O-]1-100, C1-2000 alkyl, C6-40 aryl, C7-2000 alkylaryl, C7-2000 arylalkyl, (C1-30 alkyl ether)1-100, (C6-40 aryl ether)1-100, (C7-2000 alkylaryl ether)1-100, (C7-2000 arylalkyl ether)1-100, (C1-30 alkyl thioether)1-100, (C6-40 aryl thioether)1-100, (C7-2000 alkylaryl thioether)1-100, (C7-2000 arylalkyl thioether)1-100, (C2-50 alkyl ester)1-100, (C7-2000 aryl ester)1-100, (C8-2000 alkylaryl ester)1-100, (C8-2000 arylalkyl ester)1-100, -R a-CO-O-(C1-30 alkyl ether)1-100, -R a-CO-O-(C6-40 aryl ether)1-100, -R a-CO-O-(C7-2000 alkylaryl ether)1-100, -R a-CO-O-(C7-2000 arylalkyl ether)1-100, (C4-50 alkyl urethane)1-100, (C14-60 aryl urethane)1-100, (C10-2000 alkylaryl urethane)1-100, (C10-2000 arylalkyl urethane)1-100, (C5-50 alkyl urea)1-100, (C14-60 aryl urea)1-100, (C10-2000 alkylaryl urea)1-100, (C10-2000 arylalkyl urea)1-100, (C2-50 alkyl amide)1-100, (C7-60 aryl amide)1-100, (C8-2000 alkylaryl amide)1-100, (C8-2000 arylalkyl amide)1-100, (C3-30 alkyl anhydride)1-100, (C8-50 aryl anhydride)1-100, (C9-2000 alkylaryl anhydride)1-000, (C9-2000 arylalkyl anhydride)1-100, (C2-30 alkyl carbonate)1-100, (C7-50 aryl carbonate)1-100, (C8-2000 alkylaryl carbonate)1-100, (C8-2000 arylalkyl carbonate)1-100, -R a-O-CO-NH-(R
b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R
b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-1000-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, or a bond; each Z, independently, is -G-D, wherein G is -R a-, -R a-Ar-, -Ar-R
a-, or -Ar-; and D is -H, -OH, -SH, NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CH2OH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CH2OH)3, -[CH2-CH(CO2R a)]1-100-H, -NH3+, -N+H2R a,-N+HR a R b, or -N+R a R b R c, each of R a, R b, and R c, independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;
each of R1 and R4, independently, is =O or C1-20 alkyl; and each of R2 and R5, independently, is C1-20 alkyl; wherein R1 and R2, or R4 and R5 can join together to form C6-40 aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, -NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

one of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, and the other, independently, is -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E1, E2, or E3, in which E1 is (Y1,Y2)-amino, (Y1,Y2-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or (X1,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino,(Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (X,X1-oxoaryl)amino, (X,X1-dioxoaryl)amino, (Y1-alkyl,Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (X,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, (Y1,Y2),-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of X1, X2, and X3, independently, is -Y1, -O-Y1, -S-Y1, -NH-Y1, -CO-O-Y1, -O-CO-Y1, -CO-NH-Y1, -CO-NY1Y2, -NH-CO-Y1, -SO2-Y1, -CHY1Y2, or -NY1Y2; and each of Y1, Y2, and Y3, independently, is -Z
or -B-Z;
each of x and y, independently, is 0 or 1; and s is 1-6;
provided that when x is 0, R1 is =O; that when y is 0, R4 is =O; that when x is 1, R1 and R2 join together to form C6-40 aryl; and that when y is 1, R4 and R5 join together to form C6-40 aryl;
or a salt thereof.

2. The compound of claim 1, wherein at least one of x and y is 1.

3. The compound of claim 2, wherein R1 and R2, or R4 and R5 join together to form a benzene ring.

4. The compound of claim 3, wherein F is C60, C61, C62, C63, C64, C65, C70, C76, C78, C82, C84, or C92, or La@C n, Ho@C n, Gd@C n, or Er@C n, in which n is 60, 74, or 82.

5. The compound of claim 3, wherein the sum of q and m is 0-20.

6. The compound of claim 3, wherein each K, independently, is -SH, -NHOH, -SO3H, -OSO3H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -glycoside, -O-CH2-(CHOH)4-CH2OH, -O-CH2-(CHOH)2-CH2OH, -N+HR a R b, or N+R a R b R c.

7. The compound of claim 3, wherein D is -SH, -NHOH, -SO3H, -OSO3H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -0-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -O-CH2-(CHOH)4-CH2OH, -O-CH2-(CHOH)2-CH2OH, -N+HR a R b, or N+R a R b R c.

8. The compound of claim 3, wherein only one of x and y is 1.

9. The compound of claim 8, wherein x is 1, y is 0, and R1 and R2 join together to form a benzene ring.

10. The compound of claim 9, wherein R3 is -H, -B-Z, -G-E, or -G-CO-E.

11. The compound of claim 9, wherein R6 is -G-E, -G-CO-E, or a side chain of an amino acid.

12. The compound of claim 9, wherein R6 is a side chain of alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine.

13. The compound of claim 12, wherein R3 is -H, -B-Z, -G-E, or -G-CO-E.

14. The compound of claim 13, wherein F is C60, and the sum of q and m is 0-20.

15. The compound of claim 14, wherein said compound is the E-isomer of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylic acid, 1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxylic acid, 1-isobutyl-3-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid, 1-methyl-3-ethyl-3'-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid, or 1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid.

16. The compound of claim 1, wherein both x and y are 0.

17. The compound of claim 16, wherein F is C60, C61, C62, C63, C64, C65, C70, C76, C78, C82, C84, or C92, or La@C n, Ho@C n, Gd@C n, or Er@C n, in which n is 60, 74, or 82.

18. The compound of claim 16, wherein the sum of q and m is 0-20.

19. The compound of claim 16, wherein each K, independently, is -SH, -NHOH, -SO3H, -OSO3H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -glycoside, -O-CH2-(CHOH)4-CH2OH, -O-CH2-(CHOH)2-CH2OH, -N+HR a R b, or N+R a R b R c.

20. The compound of claim 16, wherein D is -SH, -NHOH, -SO3H, -OSO3H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -O-CH2-(CHOH)4-CH2OH, -O-CH2-(CHOH)2-CH2OH, -N+HR a R b, or N+R a R b R c.

21. The compound of claim 16, wherein each of R3 and R6, independently, is -B-Z, -G-E, -G-CO-E, or a side chain of alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine.

22. The compound of claim 21, wherein F is C60, and the sum of q and m is 0-20.

23. The compound of claim 22, wherein said compound is the E-isomer of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid, fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acid, 1-methyl-3-thiomethyl-fulleropyrrolidine-1,3-dicarboxylic acid, or 1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid.

24. A method for preparing a compound of formula (I):

wherein F f is F(-K)m(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2-NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1-100-OH, -[CH(CO2R a)-CH2]1-100-OH, -[C(CH3)(CO2H)-CH2]1-100-OH, -[C(CH3)(CO2 R a)-CH2]1-100-OH, -N(OH)2, -NH3+, -N+H2R a, -N+HR a R b, or -N+R a R b R c each Y is -A-B-, in which A is -O-, -NH-, -S-, -CO-O-, -O-CO-, -O-CO-O-, -O-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -R a-O-[Si(CH3)2-0-]1-100, C1-2000 alkyl, C6-40 aryl, C7-2000 alkylaryl, C7-2000 arylalkyl, (C1-30 alkyl ether)1-1000, (C6-40 aryl ether)1-100, (C7-2000 alkylaryl ether)1-100, (C7-2000 arylalkyl ether)1-100, (C1-30 alkyl thioether)1-100, (C6-40 aryl thioether)1-100, (C7-2000 alkylaryl thioether)1-100, (C7-2000 arylalkyl thioether)1-100, (C2-50 alkyl ester)1-100, (C7-2000 aryl ester)1-100, (C8-2000 alkylaryl ester)1-100, (C8-2000 arylalkyl ester)1-100, -R a-CO-O-(C1-30 alkyl ether)1-100, -R a-CO-O-(C6-40 aryl ether)1-100, -R a-CO-O-(C7-2000 alkylaryl ether)1-100, -R a-CO-O-(C7-2000 arylalkyl ether)1-100, (C4-50 alkyl urethane)1-100, (C14-60 aryl urethane)1-100, (C10-2000 alkylaryl urethane)1-100, (C10-2000 arylalkyl urethane)1-100, (C5-50 alkyl urea)1-100, (C14-60 aryl urea)1-100, (C10-2000 alkylaryl urea)1-100, (C10-2000 arylalkyl urea)1-100, (C2-50 alkyl amide)1-100, (C7-60 aryl amide)1-100, (C8-2000 alkylaryl amide)1-100, (C8-2000 arylalkyl amide)1-100, (C3-30 alkyl anhydride)1-100, (C8-50 aryl anhydride)1-100, (C9-2000 alkylaryl anhydride)1-100, (C9-2000 arylalkyl anhydride)1-100, (C2-30 alkyl carbonate)1-100, (C7-50 aryl carbonate)1-100, (C8-2000 alkylaryl carbonate)1-100_loo, (Cs-z000 arylalkyl carbonate)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R
b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, or a bond; each Z, independently, is -G-D, wherein G is -R a-, -R a-Ar-, -Ar-R
a-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CH2OH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CH2OH)3, -[CH2-CH(CO2R a)]1-100-H, -NH3+, -N+H2R a,-N+HR a R b, or -N+R a R b R c, each of R a, R b, and R c, independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;
each of R1 and R4, independently, is =O or C1-20 alkyl; and each of R2 and R5, independently, is C1-20 alkyl; wherein R1 and R2, or R4 and R5 can join together to form C6-40 aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, -NH- CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

each of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E or a side chain of an amino acid; each of B, D, and Z having been defined above, and E
being E1, E2, or E3, in which E1 is (Y1,Y2)-amino, (Y1,Y2-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or (X1,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (X,X1-oxoaryl)amino, (X,X1-dioxoaryl)amino, (Y1-alkyl,Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (X,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, (Y1,Y2),-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of X1, X2, and X3, independently, is -Y1, -O-Y1, -S-Y1, -NH-Y1, -CO-O-Y1, -O-CO-Y1, -CO-NH-Y1, -CO-NY1Y2, -NH-CO-Y1, -SO2-Y1, -CHY1Y2, or -NY1Y2; and each of Y1, Y2, and Y3, independently, is -Z
or -B-Z;

each of x and y, independently, is 0 or 1; and s is 1-6;
provided that when x is 0, R1 is =0; that when y is 0, R4 is =0; that when x is 1, R1 and R2 join together to form C6-40 aryl; and that when y is 1, R4 and R5 join together to form C6-40 aryl;
or a salt thereof;
the method comprising:
reacting a compound of formula (II) wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion;

with a fullerene compound F f of the formula F(-K)m(-Y-Z)g wherein the sum of q and m is 0 to form a compound of formula (III) removing M from the compound of formula (III) to form a compound of formula (I) wherein the sum of q and m is 0; and optionally treating the compound of formula (I) wherein the sum of q and m is 0 with a nitrating or sulfating agent to form a nitrofullerene or cyclosulfated fullerene, and contacting the nitrofullerene or cyclosulfated fullerene with a nucleophilic agent to form a compound of formula (I) wherein the sum of q and m is greater than 0.

25. The method of claim 24, wherein only one of x and y is 0.

26. The method of claim 25, wherein x is 1, y is 0, and R1 and R2 join together to form a benzene ring.

27. The method of claim 24, wherein both x and y are 0.

28. The method of claim 24, wherein M is a Cu ion.

29. The method of claim 24, wherein the compound of formula (II) is prepared by reacting a compound of formula (IV) with a metal salt MX, wherein x, y, R1, R2, R3, R4, R5, R6 and M are as defined in claim 24, and X is an anion.

30. The method of claim 29, wherein X is halide, sulfate, nitrate, or acetate.

31. The method of claim 29, wherein the compound of formula (IV) is prepared by reacting a compound of formula (V) with a compound of formula (VI) wherein x, y, R1, R2, R3, R4, R5 and R6 are as defined in claim 24.

32. The method of claim 31, wherein each of R3 and R6, independently, is -H, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, wherein B, E, Q and Z
are as defined in claim 24 and x, y, R1, R2, R3, R4, R5 and R6 are as defined in claim 24.

33. A compound of formula (VII):

wherein F f is F(-K)m(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2-NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1-100-OH, -[CH(CO2R a)-CH2]1-100-OH, -[C(CH3)(CO2H)-CH2]1-100-OH, -[C(CH3)(CO2 R a)-CH2]1-100-OH, -N(OH)2, -NH3+, -N+H2R a, -N+HR a R b, or -N+R a R b R c; each Y is -A-B-, in which A is -O-, -NH-, -S-, -CO-O-, -O-CO-, -O-CO-O-, -O-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -R a-O-[Si(CH3)2-O-]1-100, C1-2000 alkyl, C6-40 aryl, C7-2000 alkylaryl, C7-2000 arylalkyl, (C1-30 alkyl ether)1-100, (C6-40 aryl ether)1-100, (C7-2000 alkylaryl ether)1-100, (C7-2000 arylalkyl ether)1-100, (C1-30 alkyl thioether)1-100, (C6-40 aryl thioether)1-100, (C7-2000 alkylaryl thioether)1-100, (C7-2000 arylalkyl thioether)1-100, (C2-so alkyl ester)1-100, P-2000 aryl ester)1-100, (C8-2000 alkylaryl ester)1-100, (C8-2000 arylalkyl ester)1-100, -R a-CO-O-(C1-30 alkyl ether)1-100, -R a-CO-O-(C6-40 aryl ether)1-100, -R a-CO-O-P-2000 alkylaryl ether)1-100, -R a-CO-O-(C7-2000 arylalkyl ether)1-100, (C4-50 alkyl urethane),-100, (C14-60 aryl urethane)1-100, (C10-2000 alkylaryl urethane)1-100, (C10-2000 arylalkyl urethane)1-100, (C5-50 alkyl urea)1-100, (C14-60 aryl urea)1-100, (C10-2000 alkylaryl urea)1-100, (C10-2000 arylalkyl urea)1-100, (C2-50 alkyl amide)1-100, (C7-60 aryl amide)1-100, (C8-2000 alkylaryl amide)1-100, (C8-2000 arylalkyl amide)1-100, (C3-30 alkyl anhydride)1-100, (C8-50 aryl anhydride)1-100, (C9-2000 alkylaryl anhydride)1-100, (C9-2000 arylalkyl anhydride)1-100, (C2-30 alkyl carbonate)1-100, (C7-so aryl carbonate)1-100, (C8-2000 alkylaryl carbonate)i-too, (C8-2000 arylalkyl carbonate)1-l00, -R a-O-CO-NH-(R
b orAr-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-20o0 arylalkyl ether)1-100, -R a-O-CO-NH-(R bor Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-50 aryl ester, C$-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-20()o alkylaryl ether, or C7-200o arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R
b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or Cg-zooo arylalkyl ester)1-100-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-20()o alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-W-O-CO-NH-(R
b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, or a bond; each Z, independently, is -G-D, wherein G is -R a-, -R a-Ar-, -Ar-R a-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CH2OH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CH2OH)3, -[CH2-CH(CO2Ra)] 1-100-H, -NH3+, -N+H2R a, -N+HR a R b, or -N+R a R b R c, each of R a, R b, and R c, independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;

each of R1 and R4, independently, is =O or C1-20 alkyl; and each of R2 and R5, independently, is C1-20 alkyl; wherein R1 and R2, or R4 and R5 can join together to form C6-40 aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, -NH-CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

one of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, and the other, independently, is -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E1, E2, or E3, in which E1 is (Y1,Y2)-amino, (Y1,Y2-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or (X1,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (X,X1-oxoaryl)amino, (X,X1-dioxoaryl)amino, (Y1-alkyl,Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (X,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, (Y1,Y2)-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of X1, X2, and X3, independently, is -Y1, -O-Y1, -S-Y1, -NH-Y1, -CO-O-Y1, -O-CO-Y1, -CO-NH-Y1, -CO-NY1Y2, -NH-CO-Y1, -SO2-Y1, -CHY1Y2, or -NY1Y2; and each of Y1, Y2, and Y3, independently, is -Z
or -B-Z; B and Z having been defined above;

R7 is R d or -O-R e; wherein R d is -OH, -OM, -NHNH2, -NHOH, -NH-CH2-CO2H, -O-B-Z, -NH-B-Z, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E;
M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and R e is -H, -CH2-D, -CH2-B-Z, -CH2-G-E, -CH2-G-CO-E, -CO-CH2-D, -CO-B-Z, -CO-G-E, or -CO-G-CO-E; each of B, D, E, G, and Z having been defined above;
R8 is R e;
R9 is -O- or a bond;
R10 is -R d or -R e; each of which having been defined above;
each of x and y, independently, is 0 or 1; and p is 1-30;
provided that when x is 0, R1 is =0, and R7 is -R d; that when y is 0, R4 is =O, and R9 is a bond, and R10 is -R d; that when x is 1, R1 and R2 join together to form C6-40 aryl, and R7 is -O-R e; and that when y is 1, R4 and R5 join together to form C6-40 aryl, R9 is -0-, and R10 is -R e; and further provided that when p is greater than 1, x is 0;
or a salt thereof.

34. The compound of claim 33, wherein F is C60, C61, C62, C631 C64, C655 C70, C76, C78, C82, C84, or C92, or La@C11,, Ho@C n, Gd@C n, or Er@C n, in which n is 60, 74, or 82.

35. The compound of claim 33, wherein the sum of q and m is 0-20.

36. The compound of claim 33, wherein p is 2-10.

37. The compound of claim 33, wherein one of R3 and R6, independently, is -H, -B-Z, -G-E, -G-CO-E or a side chain of an amino acid.

38. The compound of claim 33, wherein R d is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.

39. The compound of claim 33, wherein R e is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.

40. The compound of claim 33, wherein both x and y are 0.

41. The compound of claim 40, wherein R d is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.

42. The compound of claim 41, wherein R e is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.

43. The compound of claim 42, wherein p is 2-10.

44. The compound of claim 43, said compound is oligo(1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic N-amide).

45. A compound of formula (VIII):

wherein F f is F(-K)m(-Y-Z)q in which F is a fullerene core; each K, independently, is -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2-NH 3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -NH-CH2-CO2H, -[CH(CO2H)-CH2]1-100-OH, -[CH(CO2R a)-CH2]1-100-OH, -[C(CH3)(CO2H)-CH2]1-100-OH, -[C(CH3)(CO2 R a)-CH2]1-100-OH, -N(OH)2, -NH3+, -N+H2R a, -N+HR a R b, or -N+R a R b R c; each Y is -A-B-, in which A is -O-, -NH-, -S-, -CO-O-, -O-CO-, -O-CO-O-, -O-CO-NH-, -NH-CO-NH-, -CO-NH-, or -NH-CO-; and B is -R a-O-[Si(CH3)2-O-]1-100, C1-2000 alkyl, C6-40 aryl, C7-2000 alkylaryl, C7-2000 arylalkyl, (C1-30 alkyl ether),-100, (C640 aryl ether),-100, (C7-2000 alkylaryl ether)1-100, (C7-2000 arylalkyl ether),-100, (C1-30 alkyl thioether)1-100, (C640 aryl thioether)1-100, (C7-2000 alkylaryl thioether)1-100, (C7-2000 arylalkyl thioether)1-100, (C2-50 alkyl ester)1-100, (C7-2000 aryl ester)1-100, (C8-2000 alkylaryl ester)1-100, (C8-2000 arylalkyl ester)1-100, -R a-CO-O-(C1-3o alkyl ether)1-100, -R a-CO-O-(C6-40 aryl ether)1-100, -R a-CO-O-(C7-2000 alkylaryl ether)1-100, -R a-CO-O-(C7-2000 arylalkyl ether)1-100, (C4-50 alkyl urethane)1-100, (C14-60 aryl urethane)1-100, (C10-2000 alkylaryl urethane)1-100, (C10-2000 arylalkyl urethane)1-100, (C5-50 alkyl urea)1-100, (C14-60 aryl urea)1-100, (C10-2000 alkylaryl urea)1-100, (C10-2000 arylalkyl urea)1-100, (C2-50 alkyl amide)1-100, (C7-60 aryl amide)1-100, (C8-2000 alkylaryl amide)1-100, (C8-2000 arylalkyl amide)1-100, (C3-30 alkyl anhydride)1-100, (C8-50 aryl anhydride)1-100, (C9-2000 alkylaryl anhydride)1-100, (C9-2000 arylalkyl anhydride)1-100, (C2-30 alkyl carbonate)1-100, (C7-50 aryl carbonate)1-100, (C8-2000 alkylaryl carbonate)1-100, (C8-2000 arylalkyl carbonate)1-100, -R a-O-CO-NH-(R
b or Ar-R b-Ar)-NH-CO-O- (C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b orAr-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-alkyl ester, C7-6o aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-(C2-5o alkyl ester, C7-6o aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-R c-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-O-, -R a-O-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, -R a-NH-CO-NH-(R b or Ar-R b-Ar)-NH-CO-NH-(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, or a bond; each Z, independently, is -G-D, wherein G is -R a-, -R a-Ar-, -Ar-R a-, or -Ar-; and D is -H, -OH, -SH, -NH2, -NHOH, -SO3H, -OSO3H, -CO2H, -CONH2, -CONHNH2, -CH(NH2)-CO2H, -NH-CH2-CO2H, -P(OH)3, -PO(OH)2, -O-PO(OH)2, -O-PO(OH)-O-PO(OH)2, -O-PO(O-)-O-CH2CH2NH3+, -O-PO(O-)-O-CH2CH2-N+(CH3)3, -glycoside, -oligosaccharide, -CO-glycoside, -CO-oligosaccharide, -OCH3, -OCH2(CHOH)4-CH2OH, -OCH2(CHOH)2-CH2OH, -CO-OCH2(CHOH)4-CH2OH, -C6H3(OH)2, -N(CH2CO2H)2, -CO-N(CH2CO2H)2, -CO-NH-C(CH2CH2CO2H)3, -CO-NH-C(CH2CH2OH)3, -[CH2-CH(CO2R a)]1-100-H, -NH3+, -N+H2R a, -N+HR a R b, or -N+R a Rb R c, each of R a, R b, and R c, independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30;

each of R1 and R4, independently, is =O or C1-20 alkyl; and each of R2 and R5, independently, is C1-20 alkyl; wherein R1 and R2, or R4 and R5 can join together to form C6-40 aryl which is optionally substituted with halide, -OH, -NHNH2, -NH2OH, -NH- CH2-CO2H, -CH2-CH2-D, -CH2-B-Z, -CO-CH2-D, -CO-B-Z, -O-B-Z, or -NH-B-Z; each of B, D, and Z having been defined above;

one of R3 and R6, independently, is -H, -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid, and the other, independently, is -CH2-D, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E1, E2, or E3, in which E1 is (Y1,Y2)-amino, (Y1,Y2-alkyl)-amino, (Y1,Y2)-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or (X1,X3)-aryloxy; E2 is (Y1,Y2)-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, (Y1,Y2,Y3)-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, (Y1,Y2)-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (X,X1-oxoaryl)amino, (X,X1-dioxoaryl)amino, (Y1-alkyl,Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (X,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, (Y1,Y2)-alkyl(thiocarbonyl)thio, (Y1,Y2,Y3)-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalanyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
wherein X is halide; each of X1, X2, and X3, independently, is -Y1, -O-Y1, -S-Y1, -NH-Y1, -CO-O-Y1, -O-CO-Y1, -CO-NH-Y1, -CO-NY1Y2, -NH-CO-Y1, -SO2-Y1, -CHY1Y2, or -NY1Y2, and each of Y1, Y2, and Y3, independently, is -Z
or -B-Z; B and Z having been defined above;

R7 is -R d or -O-R e; wherein R d is -OH, -OM, -NHNH2, -NHOH, -NH-CH2-CO2H, -O-B-Z, -NH-B-Z, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E;
M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and R e is -H, -CH2-D, -CH2-B-Z, -CH2-G-E, -CH2-G-CO-E, -CO-CH2-D, -CO-B-Z, -CO-G-E, or -CO-G-CO-E; each of B, D, E, Q and Z having been defined above;
R8 is R e, which has the same meaning as set forth above;
R9 is -O-R f- or -R g-; wherein R f is -CO-B-G-O-, -CO-B-G-NH-, -CO-B-G-CO-O-, or -CO-B-G-CO-NH-; and R g is -NH-, -O-, -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-; B and G having been defined above;
R10 is -H;
each of x and y, independently, is 0 or 1; and r is 1-100;
provided that when x is 0, R1 is =O, and R7 is -R d; that when y is 0, R4 is =O, and R9 is -R g, and R10 is -H; that when x is 1, R1 and R2 join together to form C6-40 aryl, and R7 is -O-R e; and that when y is 1, R4 and R5 join together to form C6-40 aryl, R9 is -O-R f, and R10 is -H; and further provided that when r is greater than 1, x is 0;
or a salt thereof.

46. The compound of claim 45, wherein F is C60, C61, C62, C63, C64, C65, C70, C76, C78, C82, C84, or C92, or La@C n, Ho@C n, Gd@C n, or Er@C n, in which n is 60, 74, or 82.

47. The compound of claim 45, wherein the sum of q and m is 0-20.

48. The compound of claim 45, wherein r is 2-30.

49. The compound of claim 45, wherein one of R3 and R6, independently, is -H, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid.

50. The compound of claim 45, wherein R d is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.

51. The compound of claim 45, wherein R e is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.

52. The compound of claim 45, wherein R f is -CO-B-G-NH- or -CO-B-G-CO-NH-.

53. The compound of claim 45, wherein R g is -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-.

54. The compound of claim 45, wherein both x and y are 0.

55. The compound of claim 54, wherein one of R3 and R6, independently, is -H, -B-Z, -G-E, -G-CO-E, or a side chain of an amino acid.

56. The compound of claim 55, wherein R d is -OH, -NHNH2, -E, -O-G-E, -NH-G-E, -O-G-CO-E, or -NH-G-CO-E.

57. The compound of claim 56, wherein R e is -H, -CH2-G-E, -CH2-G-CO-E, -CO-G-E, or -CO-G-CO-E.

58. The compound of claim 57, wherein R f is -CO-B-G-NH- or -CO-B-G-CO-NH-.

59. The compound of claim 58, wherein R g is -O-B-G-O-, -NH-B-G-O-, -NH-B-G-NH-, -O-CO-B-G-CO-O-, or -NH-CO-B-G-CO-NH-.

60. The compound of claim 59, wherein r is 2-30.