STEREOSELECTIVE COVALENT BINDING OF AQUARUTHENIUM(II) COMPLEXES TO DNA

A group of seven mono- and diaquapolypyridyl complexes of Ru(II) have been shown to bind covalently to DNA by ultrafiltration, extensive dialysis, and ethanol precipitation. Incubation of the metal complex with calf thymus DNA in 50 mM phosphate buffer produces solutions of DNA exhibiting visible absorptions clearly due to the metal complex. These absorptions remain unchanged upon prolonged ultrafiltration or dialysis, demonstrating covalent binding of the metal complex to the DNA. Determination of the amount of bound metal complex either from the spectrum of the labeled DNA or from quantitation of the free metal complex in the filtrate obtained following ultrafiltration gives r(b) = [Ru]b/[DNA-nucleotide phosphate] = 0.01-0.02 for all of the complexes. Circular dichroism (CD) spectroscopy of the filtrate obtained following the reaction of DNA with racemic Ru(phen)2(py)OH22+ shows an enrichment of the solution in the DELTA-isomer by comparison with the known CD spectrum of the complex. Careful quantitation of the degree of enrichment in the filtrate shows that 90 +/- 2% of the complexes bound to DNA are the LAMBDA-isomer, giving an enantiomeric excess for binding of the LAMBDA-isomer of 80 +/-4%. Other chiral complexes give lower selectivities, although the LAMBDA-isomer is preferred in all of the tested cases.