Diastereomeric bactericidal effect of Ru(phenanthroline)2 dipyridophenazine

Chirality. 2016 Nov;28(11):713-720. doi: 10.1002/chir.22656.

Abstract

Metal susceptibility assays and spot plating were used to investigate the antimicrobial activity of enantiopure [Ru(phen)2 dppz]2+ (phen =1,10-phenanthroline and dppz = dipyrido[3,2-a:2´,3´-c]phenazine) and [μ-bidppz(phen)4 Ru2 ]4+ (bidppz =11,11´-bis(dipyrido[3,2-a:2´,3´-c]phenazinyl)), on Gram-negative Escherichia coli and Gram-positive Bacillus subtilis as bacterial models. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined for both complexes: while [μ-bidppz(phen)4 Ru2 ]4+ only showed a bactericidal effect at the highest concentrations tested, the antimicrobial activity of [Ru(phen)2 dppz]2+ against B. subtilis was comparable to that of tetracyline. In addition, the Δ-enantiomer of [Ru(phen)2 dppz]2+ showed a 2-fold higher bacteriostatic and bactericidal effect compared to the Λ-enantiomer. This was in accordance with the enantiomers relative binding affinity for DNA, thus strongly indicating DNA binding as the mode of action.

Keywords: antimicrobial activity; chirality; confocal microscopy; emission; metal susceptibility assay; minimum bactericidal concentration; minimum inhibitory concentration; ruthenium complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Escherichia coli / drug effects
  • Microbial Sensitivity Tests
  • Organometallic Compounds / chemistry
  • Phenanthrolines / chemistry
  • Ruthenium / chemistry*
  • Ruthenium / pharmacology
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Organometallic Compounds
  • Phenanthrolines
  • Ruthenium