Effect of molecular structure on membrane diffusion: Triphenylmethanes across Escherichia coli studied by second harmonic light scattering.

This article focuses on comparing the passive membrane transport rates and antimicrobial efficacies of two structurally similar triphenylmethane dyes, malachite green (MG) and brilliant green (BG), in Escherichia coli (E. coli) cells and biomimetic liposomes. Using time-resolved second harmonic light scattering (SHS), BG was found to diffuse across the E. coli cytoplasmic membrane approximately 3.8 times faster than MG, a difference attributed primarily to BG’s significantly higher lipophilicity (log D7.4 of 2.6 versus 1.2 for MG). Similar transport rate ratios observed in protein-free liposomes suggest that passive diffusion through the lipid bilayer governs this process. Additionally, BG exhibited about 2.4 times greater antimicrobial efficacy against E. coli than MG, correlating with its enhanced membrane permeability. These findings align with Lipinski’s propensity rules relating molecular lipophilicity, hydrogen bonding capacity, and polar surface area to membrane permeability, offering insights relevant to drug design aimed at improving cellular uptake of hydrophobic ion-like molecules.