Original Contribution REACTIONS OF e - aq , CO 2 - , HO ,O 2 - AND O 2 ( 1 g ) WITH A DENDRO[60]FULLERENE AND C 60 [C(COOH) 2 ] n (n = 2– 6) R. V. BENSASSON,* M. BRETTREICH, J. FREDERIKSEN, H. G¨ OTTINGER,* A. HIRSCH, E. J. LAND, §,1 S. LEACH, D. J. MCGARVEY, and H. SCH ¨ ONBERGER *Laboratoires de Biophysique et de Photobiologie, Muse ´um National d’Histoire Naturelle, CNRS UMR 8646, INSERM U201, Paris Cedex, France; Institut fu ¨r Organische Chemie der Universita ¨t Erlangen-Nurnberg, Erlangen, Germany; School of Chemistry and Physics, Lennard-Jones Laboratories, Keele University, Keele, Staffordshire, UK; § CRC Drug Development Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK; and DAMAP, Observatoire de Paris-Meudon, CNRS UMR 8588, Meudon, France (Received 28 February 2000; Revised 30 March 2000; Accepted 13 April 2000) Abstract—Using pulse radiolysis and laser flash photolysis, we have investigated the reactions of the deleterious species, e - aq , HO ,O 2 - and O 2 ( 1 g ) with 10 water-soluble cyclopropyl-fused C 60 derivatives including a mono-adduct dendro[60]fullerene (d) and C 60 derivatives based on C 60 [C(COOH) 2 ] n=2–6 , some of which are known to be neuro- protective in vivo. The rate constants for reactions of e - aq and HO lie in the range 0.5–3.3 10 10 M -1 s -1 . The d and bis-adduct monoanion radicals display sharp absorption peaks around 1000 nm (= 7 000–11 500 M -1 cm -1 ); the anions of the tris-, tetra-, and penta-adduct derivatives have broader, weaker absorptions. The monohydroxylated radicals have their most intense absorption maxima around 390 – 440 nm (= 1000 –3000 M -1 cm -1 ). The anion and hydroxylated radical absorption spectra display a blue-shift as the number of addends increases. The radical anions react with oxygen (k 10 7 –10 9 M -1 s -1 ). The reaction of O 2 - with the C 60 derivatives does not occur via an electron transfer. The rate constants for singlet oxygen reaction with the dendrofullerene and eee-derivative in D 2 O at pH 7.4 are k 7 10 7 and 2 10 7 M -1 s -1 respectively, in contrast to 1.2 10 5 M -1 s -1 for the reaction with C 60 in C 6 D 6 . The large acceleration of the rates for electron reduction and singlet oxygen reactions in water is due to a solvophobic process. © 2000 Elsevier Science Inc. Keywords—Pulse radiolysis, Laser flash photolysis, Water-soluble fullerenes, dendro[60]fullerene, C 60 malonic acid derivatives, Hydrated electron, Oxyradicals, Singlet oxygen, Free radicals INTRODUCTION C 60 fullerenes, with their 30 carbon-carbon double bonds, are able to scavenge a large number of radicals per molecule [1,2]. For the addition of radicals such as the benzyl radical, the rate constants are larger, by three to four orders of magnitude [3], for C 60 than those observed for simple alkenes. Such properties have in- spired an interest in potential biological applications of fullerenes [4], including the inhibition of radical-initiated lipid peroxidation [5] and the interception of deleterious reactive oxygen species [6]. Dugan et al. have observed the efficiency of water-soluble malonic acid derivatives, C 60 [C(COOH) 2 ] 3 , as neuroprotective agents in living systems and assessed their ability to scavenge O 2 - and HO oxyradicals in solution by EPR analysis [6]. Using pulse radiolysis, we have now measured in aqueous solution the rate constants for the reactions of hydrated electrons (e - aq ), CO 2 - ,O 2 - , and HO radicals with a dendritic monoadduct (d) of C 60 with 18 carbox- ylic groups and a series of nine malonic acid C 60 deriv- atives based on C 60 [C(COOH) 2 ] n (n = 2– 6). The bis- adducts studied were trans-2-, trans-3-, trans-4-, and e-C 60 [C(COOH) 2 ] 2 . The tris-adducts were e,e,e- and t333-C 60 [C(COOH) 2 ] 3 , the tetra-, penta-, and hexa-ad- ducts being the all-e-regioisomers. The structures, sym- metries and abbreviated names of the fullerene deriva- tives under study are shown in Fig. 1. We have determined in water at pH 7.4 (i) the spectra Address correspondence to: R. V. Bensasson, Laboratoires de Bio- physique et de Photobiologie, Muse ´um National d’Histoire Naturelle, CNRS UMR 8646, INSERM U201, 43 rue Cuvier, 75231 Paris Cedex 05, France; Fax: +33 (1) 40 79 37 05; E-Mail: rvb@mnhn.fr. 1 Senior Research Fellow in Chemistry, Keele University. Free Radical Biology & Medicine, Vol. 29, No. 1, pp. 26 –33, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0891-5849/00/$–see front matter PII S0891-5849(00)00287-2 26