Metal ion – biomolecule interactions. Part 16. C(2)-H isotopic exchange in Co(III)-coordinated imidazoles

Abstract

Transition-metal-bound imidazoles are suitable models for evaluating the roles of metal ions in biomolecules having the imidazole moiety and similar heterocyclic residues as part of their structure. Such studies provide useful insights into metal–biomolecule interactions in biological systems, especially when the lability of the metal–ligand bond is substantially reduced, such that the identity of the metal–ligand complex is preserved during the course of the reaction under investigation. The present paper reports on a kinetic study of tritium exchange from the C(2) position of the imidazole moiety in the substitution-inert complex cations [Co(NH3)5[2-3H]-imidazole]3+ (1) and [Co(NH3)5-1-methyl-[2-3H]-imidazole]3+ (2). Rate–pH profiles have been determined in aqueous solution at 60 °C. Both substrates are believed to react through rate-determining attack of hydroxide ion (kM+ pathway) at C(2)-T. Dissection of the kinetic data reveals an additional pathway for 1 consequent upon deprotonation of its pyrrole-like N-H(T) to yield 3, which is then attacked by hydroxide at C(2) (kM pathway). The ratio kM+/kM = 103 that is obtained is in accord with the expected reduced reactivity of 3. Comparison of the present data with those reported for a variety of heterocyclic substrates shows that the order of reactivity, protonated [Formula: see text] metal ion coordinated [Formula: see text] neutral form of substrates, prevails. The superiority of the proton over metal ions in catalyzing isotopic hydrogen exchange is attributed to its larger ground state acidifying effect coupled with the greater transition state stabilization it affords, relative to metal ions. The exchange reaction of 3 via the kM pathway is the first example of a reactive anionic species in which the negative charge is located α to the exchanging C-H. Keywords: tritium exchange, cobalt (III)-coordinated imidazoles.