[Au(dien)(N-heterocycle)]³⁺: Reactivity with Biomolecules and Zinc Finger Peptides

Abstract

The reaction of [Au­(dien)­(N-heterocycle)]³⁺ (AuN₄) coordination compounds with simple amino acids and zinc finger proteins is reported. Compared to [AuCl­(dien)]²⁺, NMR studies show that the presence of a more substitution-inert N-donor as the putative leaving group slows the reaction with the sulfur-containing amino acids <i>N</i>-acetylmethionine (NAcMet) and <i>N</i>-acetylcysteine (NAcCys). Lack of ligand dissociation upon reaction with NAcCys indicates, to our knowledge, the first long-lived N-heterocycle–Au–S species in solution. Reactions with zinc finger proteins show a higher reactivity with the Cys₃His zinc finger than with Cys₂His₂, likely due to the presence of fewer aurophilic cysteines in the latter. Of the Au­(III) compounds studied, [Au­(dien)­(DMAP)]³⁺ (DMAP = 4-dimethylaminopyridine) appears to be the least reactive, with ESI-MS studies showing the presence of intact zinc fingers at initial reaction times. These results, in combination with previously reported characterization and pH dependency studies, will further aid in optimizing the structure of these AuN₄ species to obtain a substitution-reactive yet selective compound for targeting zinc finger proteins