title: Water solubility, antioxidant activity and cytochrome C binding of four families of exohedral adducts of C60 and C70.
abstract: Over the past decade, surface-modified, water soluble fullerenes have been shown by many different investigators to exhibit strong antioxidant activity against reactive oxygen species (ROS) in vitro and to protect cells and tissues from oxidative injury and cell death in vivo. Nevertheless, progress in developing fullerenes as bona fide drug candidates has been hampered by three development issues: 1) lack of methods for scalable synthesis; 2) inability to produce highly purified, single-species regioisomers compatible with pharmaceutical applications; and 3) inadequate understanding of structure-function relationships with respect to various surface modifications (e.g., anionic versus cationic versus charge-neutral polarity). To address these challenges, we have designed and synthesized more than a dozen novel water soluble fullerenes that can be purified as single isomers and which we believe can be manufactured to scale at reasonable cost. These compounds differ in addition pattern, lipophilicity and number and type of charge and were examined for their water solubility, antioxidant activity against superoxide anions and binding of cytochrome C. Our results indicate that dendritic water soluble fullerene[60] monoadducts exhibit the highest degree of antioxidant activity against superoxide anions in vitro as compared with trismalonate-derived anionic fullerenes as well as cationic fullerenes of similar overall structure. Among the higher adducts, anionic derivatives have a higher antioxidant activity than comparable cationic compounds. To achieve sufficient water solubility without the aid of a surfactant or co-solvent at least three charges on the addends are required. Significantly, anionic in contrast to cationic fullerene adducts bind with high affinity to cytochrome C.
authors.affiliation: The Institut für Organische Chemie, Universität Erlangen-Nürnberg, Henkestrasse 42, Erlangen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Witte
authors.forename: Florian
authors.initials: F
authors.lastname: Beuerle
authors.forename: Uwe
authors.initials: U
authors.lastname: Hartnagel
authors.forename: Russell
authors.initials: R
authors.lastname: Lebovitz
authors.forename: Anastasia
authors.initials: A
authors.lastname: Savouchkina
authors.forename: Sevda
authors.initials: S
authors.lastname: Sali
authors.forename: Dirk
authors.initials: D
authors.lastname: Guldi
authors.forename: Nikos
authors.initials: N
authors.lastname: Chronakis
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirsch
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D037741:Fullerenes / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008314:Malonates / Q000737:chemistry; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013481:Superoxides / Q000737:chemistry; D013696:Temperature; D014867:Water
chemical_list: D000975:Antioxidants; D037741:Fullerenes; D008314:Malonates; D014867:Water; D013481:Superoxides; D045304:Cytochromes c; C069837:fullerene C60