Substituted fullerene compositions and their use as antioxidants

1. A substituted fullerene, comprising a fullerene core (Cn), wherein n is an even integer greater than or equal to 60, and at least one of i–iv:

(i) m (>CX 1 X 2 ) groups bonded to the fullerene core, wherein:

(i-a) m is an integer from 1 to 6, inclusive,

(i-b) each X 1 and X 2 is independently selected from —H; —COOH; —CONH 2 ; —CONHR′; —CONR′ 2 ; —COOR′; —CHO; —(CH 2 ) d OH; a peptidyl moiety; —R; —RCOOH; —RCONH 2 ; —RCONHR′; —RCONR′ 2 ; —RCOOR′; —RCHO; —R(CH 2 ) d OH; a heterocyclic moiety; a branched moiety comprising one or more terminal —OH, —NH 2 , triazole, tetrazole, or sugar groups; or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20; and

(i-c) when m is 3, at least one X 1 or X 2 is not —COOH;

(ii) p —X 3 groups bonded to the fullerene core, wherein:

(ii-a) p is an integer from 1 to 18, inclusive; and

(ii-b) each —X 3 is independently selected from —N + (R 2 )(R 3 )(R 4 ), wherein R 2 , R 3 , and R 4 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20; —N + (R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —C(R 5 )(R 6 )(R 7 ), wherein R 5 , R 6 , and R 7 are independently —COOH, —H, —CH(═O), —CH 2 OH, or a peptidyl moiety; —C(R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —(CH 2 ) e —COOH, —(CH 2 ) e —CONH 2 , —(CH 2 ) e —COOR′, wherein e is an integer from 1 to about 6 and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol; a peptidyl moiety; or an aromatic heterocyclic moiety containing a cationic nitrogen;

(iii) q —X 4 — groups bonded to the fullerene core, wherein

(iii-a) q is an integer from 1 to 6, inclusive; and

(iii-b) each —X 4 — group is independently

 wherein R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , and f is an integer from 1 to about 20;

 wherein each R 2 and R 3 is independently —H or —(CH 2 ) d —CH 3 and d is an integer from 0 to about 20; or

wherein each R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and each R 9 is independently —H, —OH, —OR′, —NH 2 , —NHR′, —NHR′ 2 , or —(CH 2 ) d OH, wherein each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol.

(iv) r dendrons bonded to the fullerene core and s nondendrons bonded to the fullerene core, wherein:

(iv-a) r is an integer from 1 to 6, inclusive;

(iv-b) s is an integer from 0 to 18, inclusive;

(iv-b) each dendron has at least one protic group which imparts water solubility,

(iv-d) each nondendron independently comprises at least one drug, amino acid, peptide, nucleotide, vitamin, or organic moiety, and

(iv-e) when r is 1 and the dendron comprises 18 —COOH groups, s is an integer from 1 to 18, inclusive.

2. The substituted fullerene of claim 1 , wherein the substituted fullerene comprises a fullerene core (Cn) having 60 carbon atoms or 70 carbon atoms.

3. The substituted fullerene of claim 1 , wherein the substituted fullerene comprises C 60 and 3 (>CX 1 X 2 ) groups in the C3 orientation or the D3 orientation.

4. The substituted fullerene of claim 1 , wherein the substituted fullerene comprises C 60 and 2 (>CX 1 X 2 ) groups in the trans-2 orientation, the trans-3 orientation, the e orientation, or the cis-2 orientation.

5. The substituted fullerene of claim 1 , wherein the substituted fullerene comprises C 70 and 2 (>CX 1 X 2 ) groups in the bis orientation.

6. The substituted fullerene of claim 1 , wherein n is 60, m is 3, p is 0, q is 0, r is 0, s is 0, from 1 to 3 X 1 , inclusive, are —H, and all X 2 are —COOH.

7. The substituted fullerene of claim 1 , wherein the substituted fullerene has the structure shown in FIG. 7B .

8. The substituted fullerene of claim 1 , wherein the substituted fullerene has a structure selected from FIGS. 8A–8G .

9. The substituted fullerene of claim 1 , wherein m is 3, p is 0, q is 0, r is 0, s is 0, and at least one X 1 is a peptidyl moiety selected from —C(═O)O—(CH 2 ) 3 —C(═O)-alanine, —C(═O)O—(CH 2 ) 3 —C(═O)-alanine-phenylalanine, or —C(═O)O—(CH 2 ) 3 —C(═O)-alanine-alanine.

10. The substituted fullerene of claim 1 , wherein m is 3, p is 0, q is 0, r is 0, s is 0, and at least one X 1 is a peptidyl moiety selected from Z- D -Phe- L -Phe-Gly, Z- L -Phe, Z-Gly- L -Phe- L -Phe, Z-Gly- L -Phe, Z- L -Phe- L -Phe, Z- L -Phe- L -Tyr, Z- L -Phe-Gly, Z- L -Phe- L -Met, Z- L -Phe- L -Ser, Z-Gly- L -Phe- L -Phe-Gly, wherein Z is a carbobenzoxy group.

11. The substituted fullerene of claim 1 , wherein the substituted fullerene comprises an endohedral metal.

12. A composition, comprising:

a carrier, and,

a substituted fullerene, comprising a fullerene core (Cn), wherein n is an even integer greater than or equal to 60, and at least one of i-iv:

(i) m (>CX 1 X 2 ) groups bonded to the fullerene core, wherein:

(i-a) m is an integer from 1 to 6, inclusive,

(i-b) each X 1 and X 2 is independently selected from —H; —COOH; —CONH 2 ; —CONHR′; —CONR′ 2 ; —COOR′; —CHO; —(CH 2 ) d OH; a peptidyl moiety; —R; —RCOOH; —RCONH 2 ; —RCONHR′; —RCONR′ 2 ; —RCOOR′; —RCHO; —R(CH 2 ) d OH; a heterocyclic moiety; a branched moiety comprising one or more terminal —OH, —NH 2 , triazole, tetrazole, or sugar groups; or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20; and

(i-c) when m is 3, at least one X 1 or X 2 is not —COOH;

(ii) p —X 3 groups bonded to the fullerene core, wherein:

(ii-a) p is an integer from 1 to 18, inclusive; and

(ii-b) each —X 3 is independently selected from —N + (R 2 )(R 3 )(R 4 ), wherein R 2 , R 3 , and R 4 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20; —N + (R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —C(R 5 )(R 6 )(R 7 ), wherein R 5 , R 6 , and R 7 are independently —COOH, —H, —CH(═O), —CH 2 OH, or a peptidyl moiety; —C(R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —(CH 2 ) e —COOH, —(CH 2 ) e —CONH 2 , —(CH 2 ) e —COOR′, wherein e is an integer from 1 to about 6 and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol; a peptidyl moiety; or an aromatic heterocyclic moiety containing a cationic nitrogen;

(iii) q —X 4 — groups bonded to the fullerene core, wherein

(iii-a) q is an integer from 1 to 6, inclusive; and

(iii-b) each —X 4 — group is independently

 wherein R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , and f is an integer from 1 to about 20;

 wherein each R 2 and R 3 is independently —H or —(CH 2 ) d —CH 3 and d is an integer from 0 to about 20; or

wherein each R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and each R 9 is independently —H, —OH, —OR′, —NH 2 , —NHR′, —NHR′ 2 , or —(CH 2 ) d OH, wherein each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol.

(iv) r dendrons bonded to the fullerene core and s nondendrons bonded to the fullerene core, wherein:

(iv-a) r is an integer from 1 to 6, inclusive;

(iv-b) s is an integer from 0 to 18, inclusive;

(iv-b) each dendron has at least one protic group which imparts water solubility,

(iv-d) each nondendron independently comprises at least one drug, amino acid, peptide, nucleotide, vitamin, or organic moiety, and

(iv-e) when r is 1 and the dendron comprises 18 —COOH groups, s is an integer from 1 to 18, inclusive.

13. The composition of claim 12 , wherein the carrier is a pharmaceutically-acceptable carrier or a comestibly-acceptible carrier.

14. The composition of claim 12 , wherein the substituted fullerene comprises a fullerene core (Cn) having 60 carbon atoms or 70 carbon atoms.

15. The composition of claim 12 , wherein the substituted fullerene comprises C 60 and 3 (>CX 1 X 2 ) groups in the C3 orientation or the D3 orientation.

16. The composition of claim 12 , wherein the substituted fullerene comprises C 60 and 2 (>CX 1 X 2 ) groups in the trans-2 orientation, the trans-3 orientation, the e orientation, or the cis-2 orientation.

17. The composition of claim 12 , wherein the substituted fullerene comprises C 70 and 2 (>CX 1 X 2 ) groups in the bis orientation.

18. The composition of claim 12 , wherein n is 60, m is 3, p is 0, q is 0, r is 0, s is 0, from 1 to 3 X 1 , inclusive, are —H, and all X 2 are —COOH.

19. The composition of claim 12 , wherein the substituted fullerene has the structure shown in FIG. 7B .

20. The composition of claim 12 , wherein the substituted fullerene has a structure selected from FIGS. 8A–8G .

21. The composition of claim 12 , wherein m is 3, p is 0, q is 0, r is 0, s is 0, and at least one X 1 is a peptidyl moiety selected from —C(═O)O—(CH 2 ) 3 —C(═O)-alanine, —C(═O)O—(CH 2 ) 3 —C(═O)-alanine-phenylalanine, or —C(═O)O—(CH 2 ) 3 —C(═O)-alanine-alanine.

22. The composition of claim 12 , wherein m is 3, p is 0, q is 0, r is 0, s is 0, and at least one X 1 is a peptidyl moiety selected from Z- D -Phe- L -Phe-Gly, Z- L -Phe, Z-Gly- L -Phe- L -Phe, Z-Gly- L -Phe, Z- L -Phe- L -Phe, Z- L -Phe- L -Tyr, Z- L -Phe-Gly, Z- L -Phe- L -Met, Z- L -Phe- L -Ser, Z-Gly- L -Phe- L -Phe-Gly, wherein Z is a carbobenzoxy group.

23. The composition of claim 12 , wherein the substituted fullerene comprises an endohedral metal.

24. A method of ameliorating an oxidative stress disease, comprising:

administering to a mammal an effective amount of a composition comprising a substituted fullerene, wherein the substituted fullerene comprises a fullerene core (Cn), wherein n is an even integer greater than or equal to 60, and at least one of i-iv:

(i) m (>CX 1 X 2 ) groups bonded to the fullerene core, wherein:

(i-a) m is an integer from 1 to 6, inclusive,

(i-b) each X 1 and X 2 is independently selected from —H; —COOH;

—CONH 2 ; —CONHR′; —CONR′ 2 ; —COOR′; —CHO; —(CH 2 ) d OH; a peptidyl moiety; —R; —RCOOH; —RCONH 2 ; —RCONHR′; —RCONR′ 2 ; —RCOOR′; —RCHO; —R(CH 2 ) d OH; a heterocyclic moiety; a branched moiety comprising one or more terminal —OH, —NH 2 , triazole, tetrazole, or sugar groups; or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20; and

(i-c) when m is 3, at least one X 1 or X 2 is not —COOH;

(ii) p —X 3 groups bonded to the fullerene core, wherein:

(ii-a) p is an integer from 1 to 18, inclusive; and

(ii-b) each —X 3 is independently selected from —N + (R 2 )(R 3 )(R 4 ), wherein R 2 , R 3 , and R 4 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20; —N + (R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —C(R 5 )(R 6 )(R 7 ), wherein R 5 , R 6 , and R 7 are independently —COOH, —H, —CH(═O), —CH 2 OH, or a peptidyl moiety; —C(R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —(CH 2 ) e —COOH, —(CH 2 ) e —CONH 2 , —(CH 2 ) e —COOR′, wherein e is an integer from 1 to about 6 and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol; a peptidyl moiety; or an aromatic heterocyclic moiety containing a cationic nitrogen;

(iii) q —X 4 — groups bonded to the fullerene core, wherein

(iii-a) q is an integer from 1 to 6, inclusive; and

(iii-b) each —X 4 — group is independently

 wherein R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , and f is an integer from 1 to about 20;

 wherein each R 2 and R 3 is independently —H or —(CH 2 ) d —CH 3 and d is an integer from 0 to about 20; or

wherein each R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and each R 9 is independently —H, —OH, —OR′, —NH 2 , —NHR′, —NHR′ 2 , or —(CH 2 ) d OH, wherein each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol,

(iv) r dendrons bonded to the fullerene core and s nondendrons bonded to the fullerene core, wherein:

(iv-a) r is an integer from 1 to 6, inclusive;

(iv-b) s is an integer from 0 to 18, inclusive;

(iv-b) each dendron has at least one protic group which imparts water solubility,

(iv-d) each nondendron independently comprises at least one drug, amino acid, peptide, nucleotide, vitamin, or organic moiety, and

(iv-e) when r is 1 and the dendron comprises 18 —COOH groups, s is an integer from 1 to 18, inclusive.

25. The method of claim 24 , wherein the mammal suffers or is susceptible to an oxidative stress disease selected from central nervous system (CNS) neurodegenerative diseases, stroke, atherosclerosis, myocardial ischemia, myocardial reperfusion, diabetes, complications of diabetes, circulatory impairment, retinopathy, blindness, kidney disease, pancreas disease, neuropathy, gum disease, cataracts, skin disease, skin damage, radiation damage, damage caused by tobacco use, excessive angiogenesis, insufficient angiogenesis, hearing loss, collateral damage of chemotherapy; mucositis, or senescence.

26. The method of claim 25 , wherein the CNS neurodegenerative disease is Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, or Huntington's disease.

27. The method of claim 25 , further comprising a pharmaceutically-acceptable carrier or a comestibly-acceptible carrier.

28. The method of claim 25 , wherein the substituted fullerene comprises a fullerene core (Cn) having 60 carbon atoms or 70 carbon atoms.

29. The method of claim 25 , wherein the substituted fullerene comprises C 60 and 3 (>CX 1 X 2 ) groups in the C3 orientation or the D3 orientation.

30. The method of claim 25 , wherein the substituted fullerene comprises C 60 and 2 (>CX 1 X 2 ) groups in the trans-2 orientation, the trans-3 orientation, the e orientation, or the cis-2 orientation.

31. The method of claim 25 , wherein the substituted fullerene comprises C 70 and 2 (>CX 1 X 2 ) groups in the bis orientation.

32. The method of claim 25 , wherein n is 60, m is 3, p is 0, q is 0, r is 0, s is 0, from 1 to 3 X 1 , inclusive, are —H, and all X 2 are —COOH.

33. The method of claim 25 , wherein the substituted fullerene has the structure shown in FIG. 7B .

34. The method of claim 25 , wherein the substituted fullerene has a structure selected from FIGS. 8A–8G .

35. The method of claim 25 , wherein m is 3, p is 0, q is 0, r is 0, s is 0, and at least one X 1 is a peptidyl moiety selected from —C(═O)O—(CH 2 ) 3 —C(═O)-alanine, —C(═O)O—(CH 2 ) 3 —C(═O)-alanine-phenylalanine, or —C(═O)O—(CH 2 ) 3 —C(═O)-alanine-alanine.

36. The method of claim 25 , wherein m is 3, p is 0, q is 0, r is 0, s is 0, and at least one X 1 is a peptidyl moiety selected from Z- D -Phe- L -Phe-Gly, Z- L -Phe, Z-Gly- L -Phe- L -Phe, Z-Gly- L -Phe, Z- L -Phe- L -Phe, Z- L -Phe- L -Tyr, Z- L -Phe-Gly, Z- L -Phe- L -Met, Z- L -Phe- L -Ser, Z-Gly- L -Phe- L -Phe-Gly, wherein Z is a carbobenzoxy group.

37. The method of claim 25 , wherein the substituted fullerene comprises an endohedral metal.

38. A method of ameliorating damage to tissues for transplantation, ameliorating spoilage of food, inhibiting microbes, or reducing free radical levels in tobacco, comprising:

contacting the tissues for transplantation, the food, the microbes, or the tobacco with an effective amount of a composition comprising a substituted fullerene and a carrier, wherein the substituted fullerene comprises a fullerene core (Cn), wherein n is an even integer greater than or equal to 60, and at least one of i-iv:

(i) m (>CX 1 X 2 ) groups bonded to the fullerene core, wherein:

(i-a) m is an integer from 1 to 6, inclusive,

(i-b) each X 1 and X 2 is independently selected from —H; —COOH; —CONH 2 ; —CONHR′; —CONR′ 2 ; —COOR′; —CHO; —(CH 2 ) d OH; a peptidyl moiety; —R; —RCOOH; —RCONH 2 ; —RCONHR′; —RCONR′ 2 ; —RCOOR′; —RCHO; —R(CH 2 ) d OH; a heterocyclic moiety; a branched moiety comprising one or more terminal —OH, —NH 2 , triazole, tetrazole, or sugar groups; or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20; and

(i-c) when m is 3, at least one X 1 or X 2 is not —COOH;

(ii) p —X 3 groups bonded to the fullerene core, wherein:

(ii-a) p is an integer from 1 to 18, inclusive; and

(ii-b) each —X 3 is independently selected from —N + (R 2 )(R 3 )(R 4 ), wherein R 2 , R 3 , and R 4 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20; —N + (R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —C(R 5 )(R 6 )(R 7 ), wherein R 5 , R 6 , and R 7 are independently —COOH, —H, —CH(═O), —CH 2 OH, or a peptidyl moiety; —C(R 2 )(R 3 )(R 8 ), wherein R 2 and R 3 are independently —H or —(CH 2 ) d —CH 3 , wherein d is an integer from 0 to about 20, and each R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , wherein f is an integer from 1 to about 20; —(CH 2 ) e —COOH, —(CH 2 ) e —CONH 2 , —(CH 2 ) e —COOR′, wherein e is an integer from 1 to about 6 and each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol; a peptidyl moiety; or an aromatic heterocyclic moiety containing a cationic nitrogen;

(iii) q —X 4 — groups bonded to the fullerene core, wherein

(iii-a) q is an integer from 1 to 6, inclusive; and

(iii-b) each —X 4 — group is independently

 wherein R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and R 8 is independently —(CH 2 ) f —SO 3 − , —(CH 2 ) f —PO 4 − , or —(CH 2 ) f —COO − , and f is an integer from 1 to about 20;

 wherein each R 2 and R 3 is independently —H or —(CH 2 ) d —CH 3 and d is an integer from 0 to about 20; or

wherein each R 2 is independently —H or —(CH 2 ) d —CH 3 , d is an integer from 0 to about 20, and each R 9 is independently —H, —OH, —OR′, —NH 2 , —NHR′, —NHR′ 2 , or —(CH 2 ) d OH, wherein each R′ is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol.

(iv) r dendrons bonded to the fullerene core and s nondendrons bonded to the fullerene core, wherein:

(iv-a) r is an integer from 1 to 6, inclusive;

(iv-b) s is an integer from 0 to 18, inclusive;

(iv-b) each dendron has at least one protic group which imparts water solubility,

(iv-d) each nondendron independently comprises at least one drug, amino acid, peptide, nucleotide, vitamin, or organic moiety, and

(iv-e) when r is 1 and the dendron comprises 18 —COOH groups, s is an integer from 1 to 18, inclusive.