Use of chelating ligands to tune the reactive site of half-sandwich ruthenium(II)-arene anticancer complexes.
We show that the chelating ligand XY in Ru(II) anticancer complexes of the type [Ru(eta6-arene)(XY)Cl]n+ has a major influence on the rate and extent of aquation, the pKa of the aqua adduct, and the rate and selectivity of binding to nucleobases. Replacement of neutral ethylenediamine (en) by anionic acetylacetonate (acac) as the chelating ligand increases the rate and extent of hydrolysis, the pKa of the aqua complex (from 8.25 to 9.41 for arene=p-cymene), and changes the nucleobase specificity. For the complexes containing the hydrogen-bond donor en, there is exclusive binding to N7 of guanine in competitive nucleobase reactions, and in the absence of guanine, binding to cytosine or thymine but not to adenine. In contrast, when XY is the hydrogen-bond acceptor acac, the overall affinity for adenosine (N7 and N1 binding) is comparable to that for guanosine, but there is little binding to cytidine or thymidine.
Fernández
Rafael
R
School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3 JJ, UK.
Melchart
Michael
M
Habtemariam
Abraha
A
Parsons
Simon
S
Sadler
Peter J
PJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D002614:Chelating Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012428:Ruthenium / Q000737:chemistry*; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D000970:Antineoplastic Agents; D002614:Chelating Agents; D008024:Ligands; D017975:Ruthenium Compounds; D012428:Ruthenium