Mechanism of hydrogen-deuterium exchange in hypoxanthines

The first aromatic proton in hypoxanthines to undergo exchange for deuterium is that at position 8, with the exception of 3-methyl derivatives, which undergo deuteriation first at C-2. Thus rapid deuteriation takes place always in that ring to which a proton is attached to form the monocation. The anions react faster than the neutral molecules; only 1-methylhypoxanthine shows the reverse behaviour. The exchange can be conveniently described by a protonation-deprotonation mechanism, which for anions involves formation of a zwitterion as reactive species. If zwitterion formation is impossible, as in the dianion of hypoxanthine or in the monoanion of its 1-methyl derivative, the exchange is very slow.