Au(iii) compounds as HIV nucleocapsid protein (NCp7)-nucleic acid antagonists.

The HIV nucleocapsid NCp7-SL2 RNA interaction is interrupted in the presence of a formally substitution-inert gold(dien)-nucleobase/N-heterocycle AuN compound where the N-heterocycle serves the dual purposes of a template for "non-covalent" molecular recognition of the essential tryptophan of the protein, mimicking the natural reaction and subsequent "fixation" by Au-Cys bond formation providing a chemotype for a new distinct class of nucleocapsid-nucleic acid antagonist.

[Au(dien)(N-heterocycle)](3+): reactivity with biomolecules and zinc finger peptides.

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 N-acetylmethionine (NAcMet) and N-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.

Synthesis and properties of the first [Au(dien)(N-heterocycle)]3+ compounds.

Novel Au(III)(dien)(N-heterocycle) compounds, including the first Au(III)N3(N-purine) examples, are reported. The acidity of the dien ligand is affected by the nature of the fourth ligand as a leaving group. The metal center of [Au(dien)(N-heterocycle)](3+) compounds was shown to be more stable to reduction than when Cl(-) is present, with consequences for reactivity with biomolecules: specifically, significant enhancement of π-π-stacking interactions with tryptophan relative to isostructural and isoelectronic platinum(II) and palladium(II) compounds.

Modulation of the stacking interaction of MN4 (M=Pt, Pd, Au) complexes with tryptophan through N-heterocyclic ligands.

A survey of selected N-heterocycle ligands showed that platination of 4-N-dimethylaminopyridine (DMAP) in [Pt(dien)L](2+) (dien=diethylenetriamine) gave especially strong π-π stacking interactions with tryptophan and the tryptophan-containing C-terminal zinc finger (ZF) of the HIV (human immunodeficiency virus) nucleocapsid protein NCp7. The association constants (all at 10(3)M(-1)) were significantly stronger (25.0 and 28.