First ruthenium organometallic complex of antibacterial agent ofloxacin. Crystal structure and interactions with DNA

Inorg Chem. 2010 Dec 6;49(23):10750-2. doi: 10.1021/ic101355d. Epub 2010 Oct 26.

Abstract

An organometallic ruthenium complex of quinolone antibacterial agent ofloxacin, [(η(6)-p-cymene)RuCl(O,O-oflo)]·2.8H(2)O (1·2.8H(2)O), was isolated, and its crystal structure was determined. In this "piano-stool" complex, quinolone is bidentately coordinated to the metal through the ring carbonyl and one of the carboxylic oxygen atoms. Interactions of the title complex with DNA were studied by spectroscopic methods [electronic, fluorescence, and circular dichroism (CD)] and atomic force microscopy (AFM). It was established that the electrostatic attraction between the ruthenium complex and DNA in a solution is important for binding because interactions were observed only in a solution with low ionic strengths. An induced-CD (ICD) signal was observed in a solution of DNA and the title complex, which proves interaction between ruthenium and macromolecules. Competitive binding between cisplatin and 1 to DNA revealed that cisplatin prevents binding of 1. Our experiments revealed that binding of the title complex to DNA occurs also if guanine N7 is protonated. AFM has shown that the title complex provokes DNA shrinkage. Preliminary biological tests have also been performed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Bacterial Infections / drug therapy
  • Circular Dichroism
  • Crystallography, X-Ray
  • DNA / metabolism*
  • Humans
  • Models, Molecular
  • Ofloxacin / chemistry*
  • Ofloxacin / pharmacology*
  • Ruthenium Compounds / chemistry*
  • Ruthenium Compounds / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Ruthenium Compounds
  • DNA
  • Ofloxacin