Investigating CN- cleavage by three-coordinate M[N(R)Ar]3 complexes

Three-coordinate Mo[N((t)Bu)Ar]3 binds cyanide to form the intermediate [Ar((t)Bu)N]3Mo-CN-Mo[N((t)Bu)Ar]3 but, unlike its N2 analogue which spontaneously cleaves dinitrogen, the C-N bond remains intact. DFT calculations on the model [NH2]3Mo/CN- system show that while the overall reaction is significantly exothermic, the final cleavage step is endothermic by at least 90 kJ mol(-1), accounting for why C-N bond cleavage is not observed experimentally. The situation is improved for the [H2N]3W/CN- system where the intermediate and products are closer in energy but not enough for CN- cleavage to be facile at room temperature. Additional calculations were undertaken on the mixed-metal [H2N]3Re+/CN- /W[NH2]3 and [H2N]3Re+/CN-/Ta[NH2]3 systems in which the metals ions were chosen to maximise the stability of the products on the basis of an earlier bond energy study. Although the reaction energetics for the [H2N]3Re+/CN /W[NH2]3 system are more favourable than those for the [H2N]3W/CN- system, the final C-N cleavage step is still endothermic by 32 kJ mol(-1) when symmetry constraints are relaxed. The resistance of these systems to C-N cleavage was examined by a bond decomposition analysis of [H2N]M-L1[triple bond]L2-M[NH2]3 intermediates for L1[triple bond]L2 = N2, CO and CN which showed that backbonding from the metal into the L1[triple bond]L2 pi* orbitals is significantly less for CN than for N2 or CO due to the negative charge on CN- which results in a large energy gap between the metal d(pi), and the pi* orbitals of CN-. This, combined with the very strong M-CN- interaction which stabilises the CN intermediate, makes C-N bond cleavage in these systems unfavourable even though the C[triple bond]N triple bond is not as strong as the bond in N2 or CO.     

Ethylenebis(triphenylphosphine)platinum as a probe for niobium-mediated diphosphorus chemistry

Ethylenebis(triphenylphosphine)platinum is used as a trap for the P2-containing molecule W(CO)5(P2), which is eliminated at room temperature from a niobium-complexed diphosphaazide ligand. The rate of W(CO)5(P2) elimination is unaffected by the presence of the platinum species. Attempts to generate and trap free P2 with the platinum ethylene complex were hindered by the direct reaction between the platinum starting material and the P2 generator, (Mes*NPP)Nb(N[Np]Ar)3. In this case, reductive cleavage of the P-P bond in the diphosphaazide ligand is induced by platinum coordination, resulting in the formation of a trimetallic system with two bridging, three-coordinate phosphorus atoms.     

Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase

Summary R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67•DHF•NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand–ligand and ligand–protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.     

Computational strategies for the optimization of equilibrium geometries and transition-state structures at the semiempirical level

Several improvements have been made to the gradient algorithms commonly used to optimize equilibrium and transition-state geometries at the semiempirical level. A gradient algorithm derived from a combination of a variable metric method (Davidon–Fletcher–Powell/Broyden–Fletcher–Goldfarb–Shanno) and Pulay's direct inversion in the iterative subspace method for geometry optimization (GDIIS) is compared with the variable metric method combined with an accurate linear search algorithm. The latter method is used routinely in the standard semiempirical program packages, MNDO, MOPAC, and AMPAC. The combined variable metric and GDIIS algorithm is also compared with GDIIS which uses a static metric. The performance of these algorithms is examined for a wide range of systems with respect to both choice of coordinate system (for cyclic molecules) and guess for the initial Hessian. The results show that the GDIIS method is up to ca. 40% more efficient than the variable metric combined with accurate line search algorithm: however, the exact savings vary depending on the coordinate system and initial Hessian. For noncyclic systems, variable-metric GDIIS is usually equal or superior to static-metric GDIIS, and consistently performs ca. 30% more efficiently than the variable metric combined with accurate line search algorithm. For the optimization of cyclic molecules, an improved estimate of the initial Hessian has increased the efficiency by at least a factor of two. Greater efficiencies (usually >40%) are also obtained when static-metric GDIIS is used to refine the geometry after the initial application of a transition-state search based on the variable metric combined with line search algorithm. On the basis of these results, we recommend several changes to the algorithms as currently implemented in the standard semiempirical program packages.     

Thermodynamics of Electrolyte Mixtures: HCl + NdCl<Subscript>3</Subscript> + H<Subscript>2</Subscript>O from 5 to 55 <Superscript>∘</Superscript>C

Electromotive-force (emf) measurements of cells containing solutions of hydrochloric acid and neodymium chloride were reported at constant total ionic strengths (I) of 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1.0, and 1.5 mol-kg⁻¹ at 11 temperatures ranging from 5 to 55 ^∘C, and at I = 2.0 mol-kg⁻¹ at 25 ^∘C. Hydrogen and silver–silver chloride electrodes were used in these cells. Results from the emf measurements, the mean molal activity coefficients of HCl in HCl + NdCl₃ + H₂O mixtures, as well as the Harned interaction coefficients using Harned's rule are reported in the preceding article in this issue. The ion-interaction model of Pitzer is applied here for the evaluation of the Pitzer mixing coefficients, ^Sθ_H,Nd and ψ_H,Cl,Nd, as well as the linear representation of the temperature derivatives of ∂^Sθ_H,Nd /∂ T and ∂ψ_H,Nd,Cl/∂T. The activity coefficients at several ionic strength fractions y of NdCl₃ are given at 25 ^∘C. The results are interpreted in terms of ionic interactions.