Showing papers by "Robert J. Deeth published in 2007"

Osmium(II) and Ruthenium(II) Arene Maltolato Complexes: Rapid Hydrolysis and Nucleobase Binding

Abstract: Density functional calculations show that aquation of [Os(eta(6)-arene)(XY)Cl](n+) complexes is more facile for complexes in which XY=an anionic O,O-chelated ligand compared to a neutral N,N-chelated ligand, and the mechanism more dissociative in character The O,O-chelated XY=maltolato (mal) [M(eta(6)-p-cym)(mal)Cl] complexes, in which p-cvm=p-cymene, M=Os-II (1) and Run (2) were synthesised and the X-ray crystal structures of I and 2-2H(2)O determined Their hydrolysis rates were rapid (too fast to follow by NMR spectroscopy) The aqua adduct of the Os-II complex 1 was 16 pK(a) units more acidic than that of the Ru-II complex 2 Dynamic NMR studies suggested that O,O-chelate ring opening occurs on a millisecond timescale in coordinating proton-donor solvents, and loss of chelated mal in aqueous solution led to the formation of the hydroxo-bridged dimers [(eta(6)-p-cyrn)M(mu-OH)(3)M(eta(6)-p-cym)](+) ne proportion of this dimer in solutions of the Os-II complex 1 increased with dilution and it predominated at micromolar concentrations, even in the presence of 01 M NaCl (conditions close to those used for cytotoxicity testing) Although 9-ethylguanine (9-EtG) binds rapidly to Os-II in 1 and more strongly (log K=44) than to Ru-II in 2 (log K=39), the Os-II adduct [Os(eta(6)-p-cym)(mal)-(9EtG)](+) was unstable with respect to formation of the hydroxo-bridged dimer at micromolar concentrations Such insights into the aqueous solution chemistry of metal-arene complexes under biologically relevant conditions will aid the rational design of organometallic anticancer agents

DFT study of the systematic variations in metal-ligand bond lengths of coordination complexes: the crucial role of the condensed phase.

Abstract: The experimental M−A and M−B distances in several series of [MAnBm-n]-type complexes have been studied by DFT. Many of the structural features of the series, such as trans influences and sterically induced bond elongations, are not reproduced correctly in gas-phase DFT calculations. However, the correct trends are recovered by explicitly including environmental effects via the COSMO solvation model. These observations imply that the condensed-phase environment plays a critical role in determining the geometric structure of coordination complexes. Thus, any apparently satisfactory reproduction of the condensed-phase structure by an in vacuo calculation may mask an incorrect treatment of the interplay between different ligands attached to the same metal center.

Comprehensive molecular mechanics model for oxidized type I copper proteins: active site structures, strain energies, and entatic bulging.

Abstract: The ligand field molecular mechanics (LFMM) model has been applied to the oxidized Type 1 copper center. In conjunction with the AMBER94 force field implemented in DommiMOE, the ligand field extension of the molecular operating environment (MOE), LFMM parameters for Cu-N(imidazole), Cu-S(thiolate), Cu-S(thioether), and Cu-O(carbonyl) interactions were developed on the basis of experimental and theoretical data for homoleptic model systems. Subsequent LFMM optimizations of the active site model complex [Cu(imidazole)2(SMe)(SMe2]+ agree with high level quantum results both structurally and energetically. Stable trigonal and tetragonal structures are located with the latter about 1.5 kcal mol-1 lower in energy. Fully optimized unconstrained structures were computed for 24 complete proteins containing T1 centers spanning four-coordinate, plastocyanin-like CuN2SS' and stellacyanin-like CuN2SO sites, plus the five-coordinate CuN2SS'O sites of the azurins. The initial structures were based on PDB coordinates augmented by a 10 A layer of water molecules. Agreement between theory and experiment is well within the experimental uncertainties. Moreover, the LFMM results for plastocyanin (Pc), cucumber basic protein (CBP) and azurin (Az) are at least as good as previously reported QM/MM structures and are achieved several orders of magnitude faster. The LFMM calculations suggest the protein provides an entatic strain of about 10 kcal mol-1. However, when combined with the intrinsic 'plasticity' of d9 Cu(II), different starting protein/solvent configurations can have a significant effect on the final optimized structure. This 'entatic bulging' results in relatively large fluctuations in the calculated metal-ligand bond lengths. For example, simply on the basis of 25 different starting configurations of the solvent molecules, the optimized Cu-S(thiolate) bond lengths in Pc vary by 0.04 A while the Cu-S(thioether) distance spans over 0.3 A. These variations are the same order of magnitude as the differences often quoted to correlate the spectroscopic properties from a set of proteins. Isolated optimizations starting from PDB coordinates (or indeed, the PDB structures themselves) may only accidentally correlate with spectroscopic measurements. The present calculations support the work of Warshel who contends that adequate configurational averaging is necessary to make proper contact with experimental properties measured in solution. The LFMM is both sufficiently accurate and fast to make this practical.