First ruthenium organometallic complex of antibacterial agent ofloxacin. Crystal structure and interactions with DNA.
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.
Turel
Iztok
I
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia. iztok.turel@fkkt.uni-lj.si
Kljun
Jakob
J
Perdih
Franc
F
Morozova
Elena
E
Bakulev
Vladimir
V
Kasyanenko
Nina
N
Byl
Jo Ann W
JA
Osheroff
Neil
N
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015242:Ofloxacin / Q000737:chemistry* / Q000494:pharmacology*; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D017975:Ruthenium Compounds; D004247:DNA; D015242:Ofloxacin