Two rhenium compounds with benzimidazole ligands: synthesis and DNA interactions.

ABSTRACT

Two rhenium compounds cis-tetrachlorotetrabenzimidazoldirhenium(iii) chloride - I and tetrabenzimidazoldioxorhenium(v) - II have been synthesized and characterized. X-ray data are presented for the new complex II. I and II show strong emission that has been used to investigate their interaction with several non-canonical DNA structures. Both compounds have a quenching effect on the fluorescence intensity upon addition of the investigated oligonucleotides; I was more selective for binding G4-than II. Association constant values obtained for I and II with G-quadruplexes reached 106 M-1, which suggests a strong interaction between both complexes and these sequences. FRET-melting assays show that I and II have a rather high level of stabilization of ckit1 and ckit2 quadruplexes. I is toxic against macrophages RAW267.7 only in high concentrations, while complex II shows no toxicity against these cells. I and II accumulate inside cells in different degrees. Molecular dynamic simulation studies have provided insights into the binding modes of II with ckit1 and ckit2 G-quadruplexes. The results obtained show the DNA binding activity of the rhenium complexes and their ability to be players in the anti-cancer fight since they can bind to non-canonical DNA forms in oncogene promoters, accumulate in some cancer cells, and influence the cancer cells microenvironment.