Aryl-Substituted Ruthenium(II) Complexes: A Strategy for Enhanced Photocleavage and Efficient DNA Binding

Inorg Chem. 2017 Aug 7;56(15):9084-9096. doi: 10.1021/acs.inorgchem.7b01108. Epub 2017 Jul 20.

Abstract

Ruthenium polypyridine complexes have shown promise as agents for photodynamic therapy (PDT) and tools for molecular biology (chromophore-assisted light inactivation). To accomplish these tasks, it is important to have at least target selectivity and great reactive oxygen species (ROS) photogeneration: two properties that are not easily found in the same molecule. To prepare such new agents, we synthesized two new ruthenium complexes that combine an efficient DNA binding moiety (dppz ligand) together with naphthyl-modified (1) and anthracenyl-modified (2) bipyridine as a strong ROS generator bound to a ruthenium complex. The compounds were fully characterized and their photophysical and photochemical properties investigated. Compound 2 showed one of the highest quantum yields for singlet oxygen production ever reported (ΦΔ= 0.96), along with very high DNA binding (log Kb = 6.78). Such photochemical behavior could be ascribed to the lower triplet state involving the anthracenyl-modified bipyridine, which is associated with easier oxygen quenching. In addition, the compounds exhibited moderate selectivity toward G-quadruplex DNA and binding to the minor groove of DNA, most likely driven by the pendant ligands. Interestingly, they also showed DNA photocleavage activity even upon exposure to a yellow light-emitting diode (LED). Regarding their biological activity, the compounds exhibited an exciting antibacterial action, particularly against Gram-positive bacteria, which was enhanced upon blue LED irradiation. Altogether, these results showed that our strategy succeeded in producing light-triggered DNA binding agents with pharmacological and biotechnological potential.

MeSH terms

  • 2,2'-Dipyridyl / chemical synthesis
  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / pharmacology
  • 2,2'-Dipyridyl / radiation effects
  • Anthracenes / chemical synthesis
  • Anthracenes / chemistry
  • Anthracenes / pharmacology
  • Anthracenes / radiation effects
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / radiation effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Coordination Complexes / radiation effects
  • DNA / chemistry*
  • DNA Damage
  • Ethidium / pharmacology
  • Gram-Positive Bacteria / drug effects
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology*
  • Intercalating Agents / radiation effects
  • Ligands
  • Light
  • Oxygen / chemistry
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / radiation effects
  • Reactive Oxygen Species / chemical synthesis
  • Ruthenium / chemistry*

Substances

  • Anthracenes
  • Anti-Bacterial Agents
  • Coordination Complexes
  • Intercalating Agents
  • Ligands
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • 2,2'-Dipyridyl
  • Ruthenium
  • DNA
  • Ethidium
  • Oxygen