Membrane Insertion of a Dinuclear Polypyridylruthenium(II) Complex Revealed by Solid-State NMR and Molecular Dynamics Simulation: Implications for Selective Antibacterial Activity

Abstract

Dinuclear polypyridylruthenium(II) complexes bridged by a flexible methylene linker have received considerable interest as potential antibacterial agents. Their potency and uptake into bacterial cells is directly modulated by the length of the bridging linker, which has implicated membrane interactions as an essential feature of their mechanism of action. In this work, a combination of molecular dynamics (MD) simulations and solid-state NMR was used to present an atomistic model of a polypyridylruthenium(II) complex bound and incorporated into a bacterial membrane model. The results of 31P, 2H, 1H, and 13C NMR studies revealed that the antibacterial [{Ru(phen)2}2(μ-bb12)]4+ complex (Rubb12),..