Ian H. Hillier

A theoretical interpretation of the bonding, and the photoelectron and ultra-violet spectra of sulphur dioxide

Ab initio SCFMO calculations are described for SO2, using Slater-type orbitals expanded in gaussian-type functions. The electronic structures of SO, O3 and O2 are investigated, to facilitate analysis of the nature of sulphur 3d orbital participation in SO2. The theoretical interpretation of the photoelectron and ultra-violet spectra of SO2 is considered.

Ab initio molecular orbital calculations of transition metal complexes: I. The electronic structure of nickel tetracarbonyl and chromium hexacarbonyl

All electron ab initio SCF-MO calculations in a better-than-minimal basis of the electronic structure of Ni(CO)4 and Cr(CO)6 are reported. The results are compared with the measured ionization potentials, force constants and dissociation energies of these molecules, and with the electronic structures calculated by a number of semi-empirical schemes.

On the bonding of the ions PO4 3-, SO4 2-, ClO4 -, ClO3 - and CO3 2- as studied by X-ray spectroscopy and ab initio SCF-MO calculations

The ionization energies of the valence electrons of the ions PO4 3-, SO4 2-, ClO4 -, ClO3 - and CO3 2- are measured by X-ray photoelectron spectroscopy. An assignment of the spectra is made using the results of all electron ab initio SCF-MO calculations, reported here, together with X-ray emission spectra from the literature. The calculated atomic orbital composition of the molecular orbitals allows the intensities of the X-ray spectra to be understood, and provides further evidence for d-orbital participation in the bonding of the second row atoms.

X-Ray and molecular dynamics studies of concanavalin-A glucoside and mannoside complexes Relating structure to thermodynamics of binding

Crystallographic and computational methods have been used to study the binding of two monosaccharides (glucoside and mannoside) to concanavalin-A. The 2 A structure of glucoside bound concanavalin-A is reported and compared with the 2 A structure of the mannoside complex. The interaction energies of the substrate in each crystallographic subunit were calculated by molecular mechanics and found to be essentially the same for both sugars. Further energy minimisation of the active site region of the subunits did not alter this conclusion. Information from crystallographic B-factors was interpreted in terms of mobility of the sugars in the combining site. Molecular dynamics (MD) was employed to investigate mobility of the ligands at the binding sites. Switching between different binding states was observed for mannoside over the ensemble in line with the crystallographic B-factors. A calculated average interaction energy was found to be more favourable for mannoside than glucoside, by 4.9±3.6 kcal mol-1 (comparable with the experimentally determined binding energy difference of 1.6±0.3 kcal mol-1). However, on consideration of all terms contributing to the binding enthalpy a difference is not found. This work demonstrates the difficulty in relating structure to thermodynamic properties, but suggests that dynamic models are needed to provide a more complete picture of ligand–receptor interactions.

Tautomerism in uracil, cytosine and guanine: a comparison of electron correlation predicted by ab initio and density functional theory methods

Abstract The structures and relative energies of the tautomers of uracil, cytosine and guanine are predicted using high level ab initio methods and a Kohn-Sham density functional method employing a B-LYP functional. The structures calculated at the MP2 level are in better accord with available microwave data than are those at either the SCF or the B-LYP level. For both uracil and guanine highly correlated ab initio wavefunctions (MP4) and the density functional treatment (B-LYP) give relative energies of the tautomers to within 4 kJ mol−1, whilst for cytosine the corresponding value is somewhat larger. In the case of uracil and guanine, this difference is not sufficient to alter the ordering of the tautomers. For cytosine, where three tautomers are within about 5 kJ mol−1, the ordering given by the two approaches is different, with that from the ab initio method being in agreement with experiment. These results indicate that density functional theory methods, as presently used, may not be as accurate as traditional ab initio methods in describing tautomeric equilibria.

Computer simulation of zeolite structure and reactivity using embedded cluster methods

The use of bare cluster models to understand the nature of zeolite–substrate interactions may be improved to take account of the environment of the Bronsted acid site. We consider two models for introducing the electrostatic effects of the zeolite lattice. The first involves generating a specialised correction potential by fitting a non-periodic array of ca. 60 point charges to the difference between the bare cluster and periodic potentials. The second starts by fitting a periodic array of atomic charges to the potential of the infinite lattice and then builds up a classical cluster of ca. 2000 atoms into which the QM cluster is embedded. Such embedded cluster calculations, employing a T3 cluster, with electron correlation at the density functional theory level, are described, to model the interaction of water at a Bronsted acid site. Structures of the water–zeolite complex, and associated vibrational frequencies and 1H NMR shifts are calculated and compared with calculations of bare clusters of varying size and with experimental data. We then describe a mixed quantum mechanical–molecular mechanical (QM–MM) model derived by combining charges from the second model with a standard aluminosilicate force field. We report preliminary results on the effect of embedding on the energetics of a prototypical hydrocarbon cracking reaction; the methyl-shift reaction of a propenium ion coordinated to the acid site.

Carbohydrate-Protein Recognition: Molecular Dynamics Simulations and Free Energy Analysis of Oligosaccharide Binding to Concanavalin A

Carbohydrate ligands are important mediators of biomolecular recognition. Microcalorimetry has found the complex-type N-linked glycan core pentasaccharide beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man-(1-->6)]-Man to bind to the lectin, Concanavalin A, with almost the same affinity as the trimannoside, Man-alpha-(1-->6)-[Man-alpha-(1-->3)]-Man. Recent determination of the structure of the pentasaccharide complex found a glycosidic linkage psi torsion angle to be distorted by 50 degrees from the NMR solution value and perturbation of some key mannose-protein interactions observed in the structures of the mono- and trimannoside complexes. To unravel the free energy contributions to binding and to determine the structural basis for this degeneracy, we present the results of a series of nanosecond molecular dynamics simulations, coupled to analysis via the recently developed MM-GB/SA approach (Srinivasan et al., J. Am. Chem. Soc. 1998, 120:9401-9409). These calculations indicate that the strength of key mannose-protein interactions at the monosaccharide site is preserved in both the oligosaccharides. Although distortion of the pentasaccharide is significant, the principal factor in reduced binding is incomplete offset of ligand and protein desolvation due to poorly matched polar interactions. This analysis implies that, although Concanavalin A tolerates the additional 6 arm GlcNAc present in the pentasaccharide, it does not serve as a key recognition determinant.

Aspects of hybrid QM/MM calculations: The treatment of the QM/MM interface region and geometry optimization with an application to chorismate mutase

The location of stationary points on potential energy surfaces calculated by hybrid quantum mechanical (QM)/molecular mechanical (MM) methods, allowing for relaxation of both the QM and MM regions, is discussed and illustrated with results from a study of the enzyme chorismate mutase. Enhanced interactions between carboxylate groups and neighboring arginine residues are shown to be important in the catalysis of chorismate to prephenate by this enzyme. The treatment of the interface between the QM and MM regions is studied by calculations on a series of models of amino acids.

Cooperative effects in the structuring of fluoride water clusters: Ab initio hybrid quantum mechanical/molecular mechanical model incorporating polarizable fluctuating charge solvent

A new hybrid quantum mechanical/molecular mechanical model of solvation is developed and used to describe the structure and dynamics of small fluoride/water clusters, using an ab initio wave function to model the ion and a fluctuating charge potential to model the waters. Appropriate parameters for the water–water and fluoride–water interactions are derived, with the fluoride anion being described by density functional theory and a large Gaussian basis. The role of solvent polarization in determining the structure and energetics of F(H2O)4− clusters is investigated, predicting a slightly greater stability of the interior compared to the surface structure, in agreement with ab initio studies. An extended Lagrangian treatment of the polarizable water, in which the water atomic charges fluctuate dynamically, is used to study the dynamics of F(H2O)4− cluster. A simulation using a fixed solvent charge distribution indicates principally interior, solvated states for the cluster. However, a preponderance of tris...

What is the initiation step of the Grubbs-Hoveyda olefin metathesis catalyst?

Density function theory calculations reveal that the Grubbs-Hoveyda olefin metathesis pre-catalyst is activated by the formation of a complex in which the incoming alkene substrate and outgoing alkoxy ligand are both clearly associated with the ruthenium centre. The computed energies for reaction are in good agreement with the experimental values, reported here.