Absorption Spectra of Isomeric OH Adducts of 1,3,7-Trimethylxanthine 1 M. S. Vinchurkar and B. S. M. Rao* Department of Chemistry, UniVersity of Pune, Pune 411 007, India H. Mohan and J. P. Mittal* Chemistry DiVision, Bhabha Atomic Research Centre, Mumbai 400 085, India K. H. Schmidt and C. D. Jonah* Chemistry DiVision, Argonne National Laboratory, Argonne, Illinois 60439 ReceiVed: October 21, 1996; In Final Form: January 3, 1997 X The reactions of OH • ,O •- , and SO 4 •- with 1,3,7-trimethylxanthine (caffeine) were studied by pulse radiolysis with optical and conductance detection techniques. The absorption spectra of transients formed in OH • reaction in neutral solutions exhibited peaks at 310 and 335 nm, as well as a broad absorption maximum at 500 nm, which decayed by first-order kinetics. The rate (k ) (4.0 ( 0.5) × 10 4 s -1 ) of this decay is independent of pH in the range 4-9 and is in agreement with that determined from the conductance detection (k ) 4 × 10 4 s -1 ). The spectrum in acidic solutions has only a broad peak around 330 nm with no absorption in the higher wavelength region. The intermediates formed in reaction of O •- absorb around 310 and at 500 nm, and the first-order decay at the latter wavelength was not seen. The OH radical adds to C-4 (X-4OH • ) and C-8 (X-8OH • ) positions of caffeine in the ratio 1:2 as determined from the redox titration and conductivity measurements. H abstraction from the methyl group is an additional reaction channel in O •- reaction. Dehydroxylation of the X-4OH • adduct occurs, whereas the X-8OH • adduct does not undergo ring opening. The rate constant for addition of O 2 to X-4OH • is estimated to be ∼1 × 10 9 M -1 s -1 , whereas it is unreactive toward X-8OH • . The spectrum obtained for OH • reaction in oxygenated solutions is similar to that observed in SO 4 •- reaction in basic solutions. The radical cation of caffeine formed from its reaction with SO 4 •- (λ max ) 320-340 nm) is hydrolyzed in basic solutions to yield the X-8OH • adduct. The molar absorptivities of the X-8OH • and the X-4OH • adducts at 300 and 335 nm are 6500 and 5300 M -1 cm -1 , respectively. The yield of 1,3,7-trimethyluric acid in OH • reaction in the absence of O 2 (28%) is reduced by more than 50% in its presence. The differences in the mechanism of OH • reaction with caffeine and its isomer 1,3,9-trimethylxanthine (isocaffeine) are discussed. Introduction Radiation chemical studies on the reactions of primary radicals of water (e - aq , OH • , and H • ) and secondary radicals (e.g., SO 4 •- ,Br 2 •- , and O •- ) derived from them with pyrimidines and purines are of current interest due to their importance in the understanding of DNA radiation chemistry (see refs 2-4 for recent reviews). Both e - aq and OH • show high reactivity (k ) 10 9 - 10 10 M -1 s -1 ) toward these compounds. 4,5 Of particular importance are the studies carried out on the reactions of oxidizing radicals with the derivatives of guanine 6-8 and adenine. 9-11 It has been reported 10 that at least two different isomeric OH adducts are formed in the reaction of OH • with adenine derivatives. The additives have been identified as the radicals formed by OH • addition to C-4 (A-4OH • ) and C-8 (A-8OH • ) positions of these compounds. In contrast to pyrimidines, 12-14 the A-4OH • and A-8OH • radical adducts of purines are shown 9-11 to undergo unimo- lecular transformation reactions involving dehydration of the former and ring opening of the latter. The opening of the imidazole ring of the A-8OH • adduct of purines was manifested in the first order increase of absorption around 350 nm, while the decrease in the higher wavelength region was attributed to the elimination of OH - from the A-4OH • adduct. In the case of fully alkylated adenines such as N 6 ,N 6 ,9-trimethyladenine, 10 the rate constant values for the OH - elimination and the ring opening reactions are 2.2 × 10 6 and 2.3 × 10 5 s -1 . Furthermore, the rate of the dehydration process as compared to the ring opening reaction has been found to be strongly influenced by the substituent at C-6. Xanthine and its methyl derivatives are structurally similar to purines, but the six-membered ring closely resembles that of uracil. Thus, the methylated xanthines form an interesting class of compounds for examining the effect of the nature and position of the substituents on the rates of transformation processes of the adducts formed in the reaction with primary radicals of water radiolysis. We have undertaken a comprehensive study of reac- tions of these radicals with xanthine derivatives and have pre- viously reported 15 the reactions of e - aq with di- and trimeth- ylxanthines. This paper deals with the study of reactions of OH • ,O •- , and SO 4 •- with caffeine (structure 1, Scheme 1). The double bond in the imidazole ring of this compound is between C-8 and N-9, unlike other purine derivatives. This structural difference, combined with the possibility to employ conductance detection in addition to optical absorption techniques to investigate the nature of the transformation reactions as in the case of other fully substituted adenines, 9,10 makes the study interesting. While our study has been in progress, results from the oxidation of methyl derivatives of xanthine were re- ported. 16,17 In their work on isocaffeine, an isomer of caffeine X Abstract published in AdVance ACS Abstracts, March 1, 1997. 2953 J. Phys. Chem. A 1997, 101, 2953-2959 S1089-5639(96)03272-0 CCC: $14.00 © 1997 American Chemical Society