DNA binding, prominent photonuclease activity and antibacterial PDT of cobalt(II) complexes of phenanthroline based photosensitizers

Nucleosides Nucleotides Nucleic Acids. 2018;37(10):546-562. doi: 10.1080/15257770.2018.1508691. Epub 2018 Nov 26.

Abstract

The chemistry of Co(II) complexes showing efficient light induced DNA cleavage activity, binding propensity to calf thymus DNA and antibacterial PDT is summarized in this article. Complexes of formulation [Co(mqt)(B)2]ClO4 1-3 where mqt is 4-methylquinoline-2-thiol and B is N,N-donor heterocyclic base, viz. 1,10-phenanthroline (phen 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq 2) and dipyrido[3,2-a:2',3'-c]phenazine (dppz 3) have been prepared and characterized. The DNA-binding behaviors of these three complexes were explored by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes 1, 2 and 3 were determined to be 1.6 × 103 M-1, 1.1 × 104 M-1 and 6.4 × 104 M-1 respectively. The experimental results suggest that these complexes interact with DNA through groove binding mode. The complexes show significant photocleavage of supercoiled (SC) DNA proceeds via a type-II process forming singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against E. coli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.

Keywords: Groove binding; photocleavage; photoirradiation; singlet oxygen.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Binding Sites
  • Cobalt / chemistry*
  • Cobalt / pharmacology
  • DNA / chemistry
  • DNA / metabolism
  • Drug Evaluation, Preclinical / methods
  • Escherichia coli / drug effects
  • Magnetic Resonance Spectroscopy
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Phenanthrolines / chemistry
  • Photochemotherapy / methods
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacology*
  • Quinolines / chemistry
  • Quinoxalines / chemistry
  • Triazenes / chemistry
  • Viscosity

Substances

  • Anti-Bacterial Agents
  • Organometallic Compounds
  • Phenanthrolines
  • Photosensitizing Agents
  • Quinolines
  • Quinoxalines
  • Triazenes
  • 4-methylquinoline
  • Cobalt
  • 1-phenyl-3,3-dimethyltriazene
  • DNA
  • calf thymus DNA