9-ethylguanine and picolinamide

We show that the binding mode adopted by picolinamide derivatives in organometallic Os(II) and Ru(II) half-sandwich complexes can lead to contrasting cancer cell cytotoxicity. N-Phenyl picolinamide derivatives (XY) in Os(II) (1, 3-5, 7, 9) and Ru(II) (2, 6, 8, 10) complexes [(eta(6)-arene)(Os/Ru)(XY)Cl](n+), where arene = p-cymene (1-8, 10) or biphenyl (9), can act as N,N- or N,O-donors. Electron-withdrawing substituents on the phenyl ring resulted in N,N-coordination and electron-donating substituents in N,O-coordination. Dynamic interconversion between N,O and N,N configurations can occur in solution and is time- and temperature- (irreversible) as well as pH-dependent (reversible). The neutral N,N-coordinated compounds (1-5 and 9) hydrolyzed rapidly (t(1/2) > 4 > 1 > 9). In contrast, N,O-coordinated complexes 7 and 8 hydrolyzed slowly, did not bind to guanine or adenine, and were nontoxic.

Topics: Adenine; Amides; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; DNA; Guanine; Humans; Hydrogen-Ion Concentration; Hydrolysis; Isomerism; Kinetics; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Organometallic Compounds; Osmium; Picolinic Acids; Quantum Theory; Ruthenium; Thermodynamics