Neil A. Burton

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.

Standard Free Energy of Binding from a One-Dimensional Potential of Mean Force

A practical approach that enables one to calculate the standard free energy of binding from a one-dimensional potential of mean force (PMF) is proposed. Umbrella sampling and the weighted histogram analysis method are used to generate a PMF along the reaction coordinate of binding. At each point, a restraint is applied orthogonal to the reaction coordinate to make possible the determination of the volume sampled by the ligand. The free energy of binding from an arbitrary unbound volume to the restrained bound form is calculated from the ratio of the PMF integrated over the bound region to that of the unbound. Adding the free energy changes from the standard-state volume to the unbound volume and from the restrained to the unrestrained bound state gives the standard free energy of binding. Exploration of the best choice of binding paths is also made. This approach is first demonstrated on a model binding system and then tested on the benzamidine-trypsin system for which reasonable agreement with experiment is found. A comparison is made with other methods to obtain the standard free energy of binding from the PMF.

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...

Density functional and semiempirical molecular orbital methods including dispersion corrections for the accurate description of noncovalent interactions involving sulfur-containing molecules

We describe the use of density functional theory (DFT-D) and semiempirical (AM1-D and PM3-D) methods having an added empirical dispersion correction, to treat noncovalent interactions between molecules involving sulfur atoms. The DFT-D method, with the BLYP and B3LYP functionals, was judged against a small-molecule database involving sulfur-π, S-H···S, and C-H···S interactions for which high-level MP2 or CCSD(T) estimates of the structures and binding or interaction energies are available. This database was also used to develop appropriate AM1-D and PM3-D parameters for sulfur. The DFT-D, AM1-D, and PM3-D methods were further assessed by calculating the structures and binding energies for a set of eight sulfur-containing base pairs, for which high-level ab initio data are available. The mean absolute deviations (MAD) for both sets of structures shown by the DFT-D methods are 0.04 Å for the intermolecular distances and less than 0.7 kcal mol(-)(1) for the binding and interaction energies. The corresponding values are 0.3 Å and 1.5 kcal mol(-)(1) for the semiempirical methods. For the complexes studied, the dispersion contributions to the overall binding and interaction energies are shown to be important, particularly for the complexes involving sulfur-π interactions.

Carbohydrate–aromatic π interactions: a test of density functionals and the DFT-D method

The performance of a number of computational approaches based upon density functional theory (DFT) for the accurate description of carbohydrate-pi interactions is described. A database containing interaction energies of a small number of representative complexes, computed at a high ab initio level, is described, and is used to judge 18 different density functionals including the M05 and M06 families as well as the DFT method augmented with empirical dispersive corrections (DFT-D). The DFT-D method and the M06 functionals are found to perform particularly well, whilst traditional functionals such as B3LYP perform poorly. The interaction energies for 23 sugar-aromatic complexes calculated by the DFT-D method are compared with the values from the 18 functionals. Again, the M06 class of functional is found to be superior.

Adsorption of water and methanol on zeolite Bro/nsted acid sites: An ab initio, embedded cluster study including electron correlation

An embedded cluster model, employing a point charge field to correctly account for the electrostatic effect of the surrounding lattice, is used to study the adsorption of water and methanol at zeolite Bro/nsted acid sites. The effects of both the point charge field and electron correlation (studied at the second order Mo/ller–Plesset (MP2) and density functional theory (DFT) levels) are reflected in the predicted substrate structures, binding energies and 1H NMR shifts. Both result in enhanced substrate binding to yield good agreement with experiment, and an increased degree of proton transfer to the substrate, an effect particularly evident in the case of methanol. There is a suggestion from a comparison with measured 1H NMR shifts that this effect is somewhat overestimated by the model used here.

Carbohydrate–protein recognition probed by density functional theory and ab initio calculations including dispersive interactions

Carbohydrate-protein recognition has been studied by electronic structure calculations of complexes of fucose and glucose with toluene, p-hydroxytoluene and 3-methylindole, the latter aromatic molecules being analogues of phenylalanine, tyrosine and tryptophan, respectively. We use mainly a density functional theory model with empirical corrections for the dispersion interactions (DFT-D), this method being validated by comparison with a limited number of high level ab initio calculations. We have calculated both binding energies of the complexes as well as their harmonic vibrational frequencies and proton NMR chemical shifts. We find a range of minimum energy structures in which the aromatic group can bind to either of the two faces of the carbohydrate, the binding being dominated by a combination of OH-pi and CH-pi dispersive interactions. For the fucose-toluene and alpha-methyl glucose-toluene complexes, the most stable structures involve OH-pi interactions, which are reflected in a red shift of the corresponding O-H stretching frequency, in good quantitative agreement with experimental data. For those structures where CH-pi interactions are found we predict a corresponding blue shift in the C-H frequency, which parallels the predicted proton NMR shift. We find that the interactions involving 3-methylindole are somewhat greater than those for toluene and p-hydroxytoluene.

Electron delocalization in the metallabenzenes: a computational analysis of ring currents.

Many metallabenzene complexes appear to exhibit an enhanced thermodynamic stability which has been attributed to the concept of aromaticity. Analysis of the ring currents induced by a magnetic field, either by direct visualization or by considering nuclear or nucleus-independent chemical shielding values (NMR or NICS), have become useful theoretical tools to characterize the aromaticity of many molecules involving the main group elements. We have analyzed 21 metallabenzenes using variations of these techniques, which take account of the large core and metal orbital contributions which often lead to transition-metal-containing systems exhibiting anomalous shielding values. Analysis of individual orbital contributions to both the ring currents and chemical shielding values based upon the ipsocentric and CSGT (continuous set of gauge transformations) methods has shown that complexes such as the 18 electron Ir or Rh(C 5H 5)(PH 3) 2Cl 2 molecules should be classed as aromatic, whereas the 16 electron complexes such as Os or Ru(C 5H 5)(PH 3) 2Cl 2 should not, despite having the same occupancy of pi-MOs. The differences can be directly attributed to the HOMO/LUMO b 2 in-plane (d xy ) molecular orbital, which, when unoccupied, is available to disrupt the delocalized currents typical of aromatic systems. A range of Pd and Pt metallabenzenes with cyclopentadienyl and phosphine ligands is also discussed as having aromatic and nonaromatic character, respectively.