Abstract
The rates of detritiation of benzimidazole -2-T, 1-alkylbenzimidazole-2-T, 1,3-dimethylbenzimidazolium-2-T bromide, imidazo [4,5-b] pyridine-2-T, purine-8-T, 9-alkylpurine-8-T, adenine-8-T, adenosine-8-T, guanine-8-T, guanosine-8-T, hypoxanthine-8-T, inosine-8-T and 9-inethyl-hypoxanthine-8-T have been measured as a function of pH at 85. The pH- rate profiles obtained showed that the reactive species for exchange are the protonated and neutral forms of the substrate. The exchange was specifically catalysed by hydroxide ion. The mechanism proposed involves parallel rate determining deprotonation of the conjugate acid by hydroxide ion, giving a ylide intermediate, and deprotonation of the neutral compound producing a carbonion intermediate. The latter pathway was not observed for benzimidazoles, purine, adenine and imidazo [4,5-b]pyridine and reasons for this behaviour are given. Evidence in support of the proposed mechanism includes pH-rate profiles, primary kinetic isotope effects, substituent effects, exchange from model compounds and the realisation of similar base-catalysed hydrogen exchange mechanisms in other heterocyclic systems. The variation of rate with pH for guanosine is in close agreement with the very recent findings of Tomasz et al. [42]. Triton magnetic resonance spectroscopy is being developed as a non-destructive method for elucidating the position and exact distribution of the label in tritiated organic compounds, A series of tritiated heterocyclic compounds were prepared by base catalysed exchange using tritiated water as the source of label, and their triton magnetic resonance spectra were obtained, A direct correlation between triton and proton chemical shifts was obtained thus enabling the prediction and assignment of triton magnetic resonance spectra by using the wealth of published proton chemical shift data.