Stereoselective covalent binding of aquaruthenium(II) complexes to DNA

Abstract

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 rb = [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 A 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 A isomer, giving an enantiomeric excess for binding of the A isomer of 80 ± 4%. Other chiral complexes give lower selectivities, although the A isomer is preferred in all of the tested cases.Registry No. Ru(tpy)(bpy)OH22+, 20154-63-6; Ru(tpy)(phen)OH22+, 101241-02-5; Ru(tpy)(tmen)OH22+, 127714-17-4; Ru(bpy)2(OH2)22+, 72174-09-5; Ru(bpy)2(py)OH22+, 67202-42-0; Ru(phen)2(OH2)22+, Ru(phen)2(py)OH22+, 47768-50-3. Formation and Reactions of Monoand Bis(peralkylcyclopentadienyl) Complexes of Calcium and Barium. The X-ray Crystal Structure of [ (Me4EtC5)Ca()U-ttSiMe2CH2CH2&iMe2) ]2

Electrochemical Studies of the Intercalation of Ethidium Bromide to DNA

“…According to the strength of interaction, the binding of small molecules with DNA can be differentiated to several interaction modes which ranged from strong covalent attachment [7,8] to weak electrostatic attraction [9,10]. The interactions resulted from the intercalation of aromatic moieties into the DNA strand, hydrogen bonding, and mutual association of hydrophobic regions between the ligands and the DNA strand are typical examples of strong binding interaction.…”

DNA Interaction and Cytotoxicity of Cyclometalated Ruthenium(II) Complexes as Potential Anticancer Drugs

“…There is evidence that DNA is the target for these complexes, which is similar to that of the well-established platinum drugs. [23][24][25][26] Many studies on their mode of action and on structure-activity relationship have been performed. However, many aspects of the tumorinhibiting action displayed by ruthenium complexes are still unknown.…”

Photoadducts of Metallic Compounds with Nucleic Acids − Role Played by the Photoelectron Transfer Process and by the TAP and HAT Ligands in the RuII Complexes

“…The covalent binding of such aqua Ru complexes to DNA has been demonstrated by ultrafiltration, extensive dialysis and ethanol precipitation. [23,24] However, the reaction between [Ru(tpy)(X)(H 2 O)] 2ϩ and double-stranded DNA proceeds with a rather poor yield ([Ru] bound /[DNA-nucleotide] is approximately 0.02) because of the important steric hindrance due to the presence of the polypyridyl (X) ligands and the incoming reactive DNA base. [22] …”