Ian H. Hillier

The accurate prediction of the adsorption energies of unsaturated molecules on graphene in the presence of water is essential for the design of molecules that can modify its properties and that can aid its processability. We here show that a semiempirical MO method corrected for dispersive interactions (PM6-DH2) can predict the adsorption energies of unsaturated hydrocarbons and the effect of substitution on these values to an accuracy comparable to DFT values and in good agreement with the experiment. The adsorption energies of TCNE, TCNQ, and a number of sulfonated pyrenes are also predicted, along with the effect of hydration using the COSMO model.

Forming a ruthenium isomerisation catalyst from Grubbs II: a DFT study

Co-reporter:Allan Young, Mark A. Vincent, Ian H. Hillier, Jonathan M. Percy and Tell Tuttle

Dalton Transactions 2014 vol. 43(Issue 22) pp:8493-8498

Publication Date(Web):14 Apr 2014

DOI:10.1039/C4DT00464G

A DFT investigation into the mechanism for the decomposition of Grubbs 2nd generation pre-catalyst (2) in the presence of methanol, is presented. Gibbs free energy profiles for decomposition of the pre-catalyst (2) via two possible mechanisms were computed. We predict that decomposition following tricyclohexylphosphane dissociation is most favoured compared to direct decomposition of the pre-catalyst (2). However, depending on the reaction conditions, an on-pathway mechanism may be competitive with ruthenium hydride formation.

Olefin Metathesis by Grubbs–Hoveyda Complexes: Computational and Experimental Studies of the Mechanism and Substrate-Dependent Kinetics

Co-reporter:Ian W. Ashworth, Ian H. Hillier, David J. Nelson, Jonathan M. Percy, and Mark A. Vincent

ACS Catalysis 2013 Volume 3(Issue 9) pp:1929

Publication Date(Web):July 12, 2013

DOI:10.1021/cs400164w

The potential energy surfaces for the activation of Grubbs–Hoveyda-type precatalysts with the substrates ethene, propene, 1-hexene, and ethyl vinyl ether (EVE) have been probed at the density functional theory (DFT) (M06-L) level. The energetically favored pathway of the reaction leading to a 14e Fischer carbene and styrene starts with an initiation step in which the incoming substrate and outgoing alkene ligand are both clearly associated with the ruthenium center. For these substrates, with the exception of ethene, the rate determining step is predicted to be the formation of the metallocyclobutane (MCB). We have taken the initial reactant to be a weak van der Waals complex between substrate and precatalyst. This model yields good agreement between the computed activation parameters for both the parent Grubbs–Hoveyda and Grela complex with EVE substrate, and the experimental values, reported here. The alternative model which takes the initial reactant to be two isolated molecules requires an estimate of the entropy loss on formation of the initial complex in solution which is difficult to evaluate. Our estimate of this quantity yields a barrier for the rate determining step for the interchange mechanism which is close to the value we find for the alternative mechanism in which the rate determining step is the initial dissociation of the precatalyst. The relative energetics of these two mechanisms involving different initiation steps but with similar activation barriers, could well be dependent upon the precatalyst and substrate in line with the recent experimental findings of Plenio and co-workers.Keywords: density functional theory; Fischer carbene; Grubbs−Hoveyda type complexes; kinetic studies; olefin metathesis; potential energy surface; reaction mechanism

Searching for the Hidden Hydrides: The Competition between Alkene Isomerization and Metathesis with Grubbs Catalysts

Co-reporter:Ian W. Ashworth;David J. Nelson;Jonathan M. Percy;Mark A. Vincent

European Journal of Organic Chemistry 2012 Volume 2012( Issue 29) pp:5673-5677

Publication Date(Web):

DOI:10.1002/ejoc.201201036

Abstract

Although Grubbs metathesis catalysts have enabled syntheses of a range of molecules, alkene isomerization, a known and problematic side reaction, is poorly understood. Several mechanisms which have been advanced to account for isomerization were studied by using electronic structure calculations. The pathway catalyzed by a ruthenium hydride emerged as the most facile process by a significant margin. For the first time, we have obtained experimental evidence for the presence of this species in a metathesis-active system.

Lithiated Tertiary Carbanions Display Variable Coordination Modes: Evidence from DFT and NMR Studies

Co-reporter:Mark A. Vincent;Dr. Alison CampbellSmith;Dr. Morgan Donnard;Philip J. Harford;Dr. Joanna Haywood; Ian H. Hillier; Jonathan Clayden;Dr. Andrew E. H. Wheatley

Chemistry - A European Journal 2012 Volume 18( Issue 35) pp:11036-11045

Publication Date(Web):

DOI:10.1002/chem.201200734

Abstract

Density functional calculations reveal that, whereas the reaction of 2-propyl-N,N-diisopropylbenzamide (6) with tBuLi in the presence of potentially tridentate donor ligands may result in lateral deprotonation of 6, the behavior of the Lewis base is non-trivial. The ability of N and O donor centers in the co-solvent to resist Li⁺ coordination is found to be synonymous with interaction of lithium with the formally deprotonated carbanion center. Low-energy structures have been identified whose predicted ¹H and ¹³C NMR spectroscopic shifts are in excellent agreement with experiment. Reaction of 2-isopropyl-N,N-diisopropylbenzamide (5) with tBuLi in the presence of bidentate Lewis base N,N,N′,N′-tetramethylethylenediamine (TMEDA) yields material that is suggested by NMR spectroscopy to be laterally deprotonated and to have the formulation 5-Li_l⋅TMEDA. In spite of the tertiary aliphatic group at the 2-position in 5, X-ray crystallography reveals that the crystalline material isolated from the treatment of 5/(−)-sparteine with tBuLi is a lateral lithiate in which amide coordination and solvation by bidentate Lewis base results in the Li⁺ ion interacting with the deprotonated α-C of the 2-iPr group (2.483(8) Å). The tertiary carbanion center remains essentially flat and the adjacent aromatic system is highly distorted. The use of a chiral co-solvent results in two diastereomeric conformers, and their direct observation in solution suggests that interconversion is slow on the NMR timescale.

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

Co-reporter:Ian W. Ashworth, Ian H. Hillier, David J. Nelson, Jonathan M. Percy and Mark A. Vincent

Chemical Communications 2011 vol. 47(Issue 19) pp:5428-5430

Publication Date(Web):11 Apr 2011

DOI:10.1039/C1CC11230A

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.

The structure and interaction energies of the weak complexes of CHClF2 and CHF3 with HCCH: a test of density functional theory methods

Co-reporter:Mark A. Vincent and Ian H. Hillier

Physical Chemistry Chemical Physics 2011 vol. 13(Issue 10) pp:4388-4392

Publication Date(Web):18 Jan 2011

DOI:10.1039/C0CP02626C

The structure and interaction energies of the weak non-covalent complexes of CHClF2 and CHF3 with HCCH have been predicted using a number of density functional based approaches, and compared with both high resolution spectroscopic data recently reported by Sexton et al. [Phys. Chem. Chem. Phys., 2010, 12, 14263–14270], and with high level benchmark calculations reported herein. We find that this is another case where the M05 and M06 families of functionals, as well as the DFT-D approach, are competitive with the more costly wavefunction based methods. We highlight the problem of deriving unique intermolecular structural parameters from the experimental microwave data.

The mechanism of the reduction of [AnO2]2+ (An = U, Np, Pu) in aqueous solution, and by Fe(II) containing proteins and mineral surfaces, probed by DFT calculations

Co-reporter:Mahesh Sundararajan, Rajeev S. Assary, Ian H. Hillier and David J. Vaughan

Dalton Transactions 2011 vol. 40(Issue 42) pp:11156-11163

Publication Date(Web):11 Aug 2011

DOI:10.1039/C1DT10700C

The fate of actinyl species in the environment is closely linked to oxidation state, since the reduction of An(VI) to An(IV) greatly decreases their mobility due to the precipitation of the relatively insoluble An(IV) species. Here we study the mechanism of the reduction of [AnO2]2+ (An = U, Np, Pu) both in aqueous solution and by Fe(II) containing proteins and mineral surfaces, using density functional theory calculations. We find a disproportionation mechanism involving a An(V)–An(V) cation–cation complex, and we have investigated how these complexes are formed in the different environments. We find that the behaviour of U and Pu complexes are similar, but the reduction of Np(V) to Np(IV) would seems to be more difficult, in line with the experimental finding that Np(V) is generally more stable than U(V) or Pu(V). Although the models we have used are somewhat idealised, our calculations suggest that there are strong similarities between the biotic and abiotic reduction pathways.

Mapping the potential energy surfaces for ring-closing metathesis reactions of prototypical dienes by electronic structure calculations

Co-reporter:Ian H. Hillier, Shanthi Pandian, Jonathan M. Percy and Mark A. Vincent

Dalton Transactions 2011 vol. 40(Issue 5) pp:1061-1072

Publication Date(Web):15 Dec 2010

DOI:10.1039/C0DT01314E

The potential energy surfaces for ring-closing metathesis reactions of a series of simple α,ω-dienes which lead to 5–10 membered ring products, have been explored using density functional theory methods. We have investigated both the conformational aspects of the hydrocarbon chain during the course of the reactions, as well as the stationary structures on the corresponding potential energy surfaces. Extensive conformational searches reveal that the reaction proceeds via the conformation that would be expected for the cycloalkene product, though most unexpectedly, cyclohexene forms via complexes in boat-like conformations. The M06-L density functional has been used to map out the potential energy surfaces, and has identified metallocyclobutane fragmentation as being generally the highest barrier along the pathway. The structural variations along the pathway have been discussed for the reactant hydrocarbons of differing chain length to identify points at which cyclisation events may begin to affect reaction rates. Our study provides an excellent starting point from which to begin to learn about the way RCM reaction outcomes are controlled by diene structure.

Understanding the Decomposition Pathways of Mixed Sulfur/Selenium Lead Phosphinato Complexes Explaining the Formation of Lead Selenide

Co-reporter:Javeed Akhtar ; Mohammad Afzaal ; Mark A. Vincent ; Neil A. Burton ; James Raftery ; Ian H. Hillier ;Paul O’Brien

The Journal of Physical Chemistry C 2011 Volume 115(Issue 34) pp:16904-16909

Publication Date(Web):August 4, 2011

DOI:10.1021/jp2053579

Lead selenide (PbSe), as micro- and nanocrystals, has been produced from a mixed lead thioseleno-phosphinato compound, [Pb{(C6H5)2PSSe}2] by chemical vapor deposition. The formation of PbSe nanocrystals in the solution has also been demonstrated at room temperatrure in a mixture of oleylamine and dodecanethiol. Density functional theory calculations of the decomposition of the complex are consistent with a dominant role for thermodynamic factors rather than kinetic ones in controlling the material formed.

Why is RCM Favoured Over Dimerisation? Predicting and Estimating Thermodynamic Effective Molarities by Solution Experiments and Electronic Structure Calculations

Co-reporter:David J. Nelson;Dr. Ian W. Ashworth;Dr. Ian H. Hillier;Dr. Sara H. Kyne;Dr. Shanthi Pian;Dr. John A. Parkinson;Dr. Jonathan M. Percy;Dr. Giuseppe Rinaudo;Dr. Mark A. Vincent

Chemistry - A European Journal 2011 Volume 17( Issue 46) pp:13087-13094

Publication Date(Web):

DOI:10.1002/chem.201101662

Abstract

The thermodynamic effective molarities of a series of simple cycloalkenes, synthesised from α,ω-dienes by reaction with Grubbs’ second generation precatalyst, have been evaluated. Effective molarities were measured from a series of small scale metathesis reactions and agreed well with empirical predictions derived from the number of rotors and the product ring strain. The use of electronic structure calculations (at the M06-L/6-311G** level of theory) was explored for predicting thermodynamic effective molarities in ring-closing metathesis. However, it was found that it was necessary to apply a correction to DFT-derived free energies to account for the entropic effects of solvation.

Modelling the binding of HIV-reverse transcriptase and nevirapine: an assessment of quantum mechanical and force field approaches and predictions of the effect of mutations on binding

Co-reporter:Rajesh K. Raju, Neil A. Burton and Ian H. Hillier

Physical Chemistry Chemical Physics 2010 vol. 12(Issue 26) pp:7117-7125

Publication Date(Web):17 May 2010

DOI:10.1039/C001384F

The importance of the intermolecular interactions which contribute to the binding of HIV-1 RT with the NNRTI inhibitor, nevirapine (NVP), has been studied using quantum mechanical and molecular simulation methods. A range of computational methods, including density functional theory with empirical dispersion corrections, have been employed and show that although π–π stacking interactions are important, the combined effect of a number of C–H/π interactions provides a significant contribution to the binding. The AMBER empirical force-field has been shown to be particularly effective to describe the interactions in this case; MM-GBSA free-energy methods were subsequently used to explore the effects on binding with several known mutations of HIV-1 RT. The relative affinities from the mutation simulations are shown to be in good agreement with experimental data allowing the causes of the binding changes to be discussed.

The effects of perfluorination on carbohydrate–π interactions: computational studies of the interaction of benzene and hexafluorobenzene with fucose and cyclodextrin

Co-reporter:Rajesh K. Raju, Ian H. Hillier, Neil A. Burton, Mark A. Vincent, Slimane Doudou and Richard A. Bryce

Physical Chemistry Chemical Physics 2010 vol. 12(Issue 28) pp:7959-7967

Publication Date(Web):02 Jun 2010

DOI:10.1039/C002058C

The effect of benzene fluorination on C–H⋯π interactions is studied using a number of computational methods applied to a range of intermolecular complexes. High level wavefunction methods (CCSD(T)) predict a slightly greater interaction energy for complexes of benzene with methane or fucose, compared to corresponding complexes involving hexafluorobenzene. A number of more approximate treatments, DFT with the M06-2X functional, PM3-D* and MM methods, give interaction energies within 1 kcal mol−1 of the high level values, and also correctly predict that the interaction energy is slightly greater for benzene compared to hexafluorobenzene. However, the DFT-D model used here predicts that the interaction energy is slightly greater for hexafluorobenzene. Molecular dynamics simulations, employing the GLYCAM-06 force field, validated here, are used to model the complexes of benzene and hexafluorobenzene with β-cyclodextrin in aqueous solution. We predict the binding free energies of the complexes to be within 0.5 kcal mol−1, and suggest that the different chemical shifts of the H5 protons observed in the two complexes arise from their slightly different structures, rather than from different binding energies.

Binding of Pollutant Aromatics on Carbon Nanotubes and Graphite

Co-reporter:Anitha Ramraj and Ian H. Hillier

Journal of Chemical Information and Modeling 2010 Volume 50(Issue 4) pp:585-588

Publication Date(Web):March 31, 2010

DOI:10.1021/ci1000604

The semiempirical PM3 method with dispersive corrections (PM3-D) is used to predict the interaction energy of a number of aromatic pollutants with a graphene surface and with carbon nanotubes. It is found that the dispersive interactions are dominant in determining the magnitude of the interaction and that electron transfer between the adsorbate and the surface is small. Good agreement is found between the calculated interaction energies and the experimental affinities measured in an aqueous environment.

Which density functional should be used to study actinyl complexes?

Co-reporter:Jonathan P. Austin, Neil A. Burton, Ian H. Hillier, Mahesh Sundararajan and Mark A. Vincent

Physical Chemistry Chemical Physics 2009 vol. 11(Issue 8) pp:1143-1145

Publication Date(Web):09 Jan 2009

DOI:10.1039/B821577D

The new M06 functional of Truhlar and co-workers is found to be competitive with high level ab initio methods in the study of the water exchange mechanism of the [UO2(OH2)5]2+ ion, and of the redox potentials of the aqua complexes of [AnO2]2+ (An = U, Np and Pu).

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

Co-reporter:Rajesh K. Raju, Anitha Ramraj, Ian H. Hillier, Mark A. Vincent and Neil A. Burton

Physical Chemistry Chemical Physics 2009 vol. 11(Issue 18) pp:3411-3416

Publication Date(Web):02 Mar 2009

DOI:10.1039/B822877A

The performance of a number of computational approaches based upon density functional theory (DFT) for the accurate description of carbohydrate–π 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.

QM/MM studies of Ni–Fe hydrogenases: the effect of enzyme environment on the structure and energies of the inactive and active states

Co-reporter:Prabha Jayapal, Mahesh Sundararajan, Ian H. Hillier and Neil A. Burton

Physical Chemistry Chemical Physics 2008 vol. 10(Issue 29) pp:4249-4257

Publication Date(Web):11 Jun 2008

DOI:10.1039/B804035D

The catalytically active (Ni–SI and Ni–R) and inactive states (Ni–A and Ni–B) of Ni–Fe hydrogenases have been studied using density functional theory (DFT) methods. Both isolated clusters and clusters embedded in the enzyme have been used to model the Ni–A, Ni–B, Ni–SI and Ni–R states. The BP86 and B3LYP functionals were employed, and hybrid quantum mechanical (QM)/molecular mechanical (MM) methods were used for the embedded calculations. The QM/MM studies, rather than the isolated cluster calculations, were generally found to give structures which correlated better with X-ray data. The structure of the unready state (Ni–A), was correctly predicted by the QM/MM, but not by the isolated cluster calculation. Comparison with the observed crystal structure favoured the catalytically active state, Ni–SI, to be the protonated (Ni–SIII), rather than the unprotonated state (Ni–SII). In the QM/MM studies, the binding of H2 to Ni–SIII is preferred at the Ni (Ni–R(Ni)), rather than at the Fe centre (Ni–R(Fe)), in agreement with xenon binding studies, and in contrast to isolated cluster studies. These calculations cannot say with certainty which functional should be favoured, nor the preferred spin state of the catalytically active species. However, the lack of any predicted structure in which H2 binds to the Fe centre, does favour a low spin state for Ni–SIII, and the use of the BP86 functional. This is in agreement with recent high level ab initio calculations of a model of the Ni–SII state.

High level ab initio and DFT calculations of models of the catalytically active Ni–Fe hydrogenases

Co-reporter:Prabha Jayapal, David Robinson, Mahesh Sundararajan, Ian H. Hillier and Joseph J. W. McDouall

Physical Chemistry Chemical Physics 2008 vol. 10(Issue 13) pp:1734-1738

Publication Date(Web):15 Feb 2008

DOI:10.1039/B719980E

Multi-reference Møller–Plesset calculations of a model of the Ni–SI state of nickel–iron hydrogenase predict a singlet rather than a triplet state for this species, and show that it is better described with a BP86 rather than a B3LYP functional.

The interaction of carbohydrates and amino acids with aromatic systems studied by density functional and semi-empirical molecular orbital calculations with dispersion corrections

Co-reporter:Raman Sharma, Jonathan P. McNamara, Rajesh K. Raju, Mark A. Vincent, Ian H. Hillier and Claudio A. Morgado

Physical Chemistry Chemical Physics 2008 vol. 10(Issue 19) pp:2767-2774

Publication Date(Web):27 Feb 2008

DOI:10.1039/B719764K

Density functional theory (DFT-D) and semi-empirical (PM3-D) methods having an added dispersion correction have been used to study stabilising carbohydrate–aromatic and amino acid–aromatic interactions. The interaction energy for three simple sugars in different conformations with benzene, all give interaction energies close to 5 kcal mol−1. Our original parameterization of PM3 (PM3-D) seriously overestimates this value, and has prompted a reparametrization which includes a modified core–core interaction term. With two additional parameters, the carbohydrate complexes, as well as the S22 data set, are well reproduced. The new PM3 scheme (PM3-D*) is found to describe the peptide bond–aromatic ring interactions accurately and, together with the DFT-D method, it is used to investigate the interaction of six amino acids with pyrene. Whilst the peptide backbone can adopt both stacked and T-shaped structures in the complexes with similar interaction energies, there is a preference for the unsaturated ring to adopt a stacked structure. Thus, peptides in which the latter interactions are maximised are likely to be the most effective for the functionalisation of carbon nanotubes.

The non-covalent functionalisation of carbon nanotubes studied by density functional and semi-empirical molecular orbital methods including dispersion corrections

Co-reporter:Jonathan P. McNamara, Raman Sharma, Mark A. Vincent, Ian H. Hillier and Claudio A. Morgado

Physical Chemistry Chemical Physics 2008 vol. 10(Issue 1) pp:128-135

Publication Date(Web):25 Oct 2007

DOI:10.1039/B711498B

Density functional theory (DFT-D) and semi-empirical (PM3-D) methods having an added empirical dispersion correction have been used to study the binding of a series of small molecules and planar aromatic molecules to single-walled carbon nanotubes (CNTs). For the small molecule set, the PM3-D method gives a mean unsigned error (MUE) in the binding energies of 1.2 kcal mol−1 when judged against experimental reference data for graphitic carbon. This value is close to the MUE for this method compared to high-level ab initio data for biological complexes. The PM3-D and DFT-D calculations describing the adsorption of the planar organic molecules (benzene, bibenzene, naphthalene, anthracene, TCNQ and DDQ) on the outer-walls of both semi-conducting and metallic CNTs give similar binding energies for benzene and DDQ, but do not display a stronger adsorption on [6,6] compared to [10,0] structures shown by another DFT study.

Semi-empirical molecular orbital methods including dispersion corrections for the accurate prediction of the full range of intermolecular interactions in biomolecules

Co-reporter:Jonathan P. McNamara and Ian H. Hillier

Physical Chemistry Chemical Physics 2007 vol. 9(Issue 19) pp:2362-2370

Publication Date(Web):22 Mar 2007

DOI:10.1039/B701890H

Semi-empirical calculations including an empirical dispersive correction are used to calculate intermolecular interaction energies and structures for a large database containing 156 biologically relevant molecules (hydrogen-bonded DNA base pairs, interstrand base pairs, stacked base pairs and amino acid base pairs) for which MP2 and CCSD(T) complete basis set (CBS) limit estimates of the interaction energies are available. The dispersion corrected semi-empirical methods are parameterised against a small training set of 22 complexes having a range of biologically important non-covalent interactions. For the full molecule set (156 complexes), compared to the high-level ab initio database, the mean unsigned errors of the interaction energies at the corrected semi-empirical level are 1.1 (AM1-D) and 1.2 (PM3-D) kcal mol−1, being a significant improvement over existing AM1 and PM3 methods (8.6 and 8.2 kcal mol−1). Importantly, the new semi-empirical methods are capable of describing the diverse range of biological interactions, most notably stacking interactions, which are poorly described by both current AM1 and PM3 methods and by many DFT functionals. The new methods require no more computer time than existing semi-empirical methods and therefore represent an important advance in the study of important biological interactions.

Can the DFT-D method describe the full range of noncovalent interactions found in large biomolecules?

Co-reporter:Claudio Morgado, Mark A. Vincent, Ian H. Hillier and Xiao Shan

Physical Chemistry Chemical Physics 2007 vol. 9(Issue 4) pp:448-451

Publication Date(Web):06 Dec 2006

DOI:10.1039/B615263E

The DFT-D method is shown to yield interaction energies between biologically important groups to an accuracy comparable to that obtained using state-of-the-art ab initio methods.

The binding of nitric oxide at the Cu(I) site of copper nitrite reductase and of inorganic models: DFT calculations of the energetics and EPR parameters of side-on and end-on structures

Co-reporter:Ganga Periyasamy, Mahesh Sundararajan, Ian H. Hillier, Neil A. Burton and Joseph J. W. McDouall

Physical Chemistry Chemical Physics 2007 vol. 9(Issue 20) pp:2498-2506

Publication Date(Web):23 Mar 2007

DOI:10.1039/B701083D

Density functional theory calculations have been used to probe the end-on and side-on bonding motifs of nitric oxide at the Cu(I) centre in the enzyme copper nitrite reductase and in three inorganic model systems. We find that irrespective of a range of functionals used, the end-on structure is preferred by up to 40 kJ mol−1, although this preference is smaller for the enzyme than for the inorganic model systems. We have calculated the g-tensor and atomic hyperfine coupling constants for these structures. When compared to available experimental data, for one model compound the calculated EPR parameters definitely favour an end-on structure, although this preference is somewhat less for the enzyme. Our prediction of NO end-on binding in the enzyme is at variance with structural data.

The role of tetrahydrobiopterin in catalysis by nitric oxide synthase

Co-reporter:Iňaki Morao, Ganga Periyasamy, Ian H. Hillier and John A. Joule

Chemical Communications 2006 (Issue 33) pp:3525-3527

Publication Date(Web):13 Jul 2006

DOI:10.1039/B607426J

Electronic structure calculations show that the cofactor H4B can be a key factor in a proton transfer relay in nitric oxide synthase, and that 4-amino-H4B cannot fulfill this role.

How are the ready and unready states of nickel–iron hydrogenase activated by H2? A density functional theory study

Co-reporter:Prabha Jayapal, Mahesh Sundararajan, Ian H. Hillier and Neil A. Burton

Physical Chemistry Chemical Physics 2006 vol. 8(Issue 35) pp:4086-4094

Publication Date(Web):27 Jul 2006

DOI:10.1039/B608069C

We have explored possible mechanisms for the formation of the catalytically active Nia–S state of the enzyme, nickel iron hydrogenase, from the Ni*r (ready) or Ni*u (unready) state, by reaction with H2, using density functional theory calculations with the BP86 functional in conjunction with a DZVP basis set. We find that for the reaction of the ready state, which is taken to have an –OH bridge, the rate determining step is the cleavage of H2 at the Ni3+ centre with a barrier of ∼15 kcal mol−1. We take the unready state to have a –OOH bridge, and find that reaction with H2 to form the Nir–S state can proceed by two possible routes. One such path has a number of steps involving electron transfer, which is consistent with experiment, as is the calculated barrier of ∼19 kcal mol−1. The alternative pathway, with a lower barrier, may not be rate determining. Overall, our predictions give barriers in line with experiment, and allow details of the mechanism to be explored which are inaccessible from experiment.

Active site structures and the redox properties of blue copper proteins: atomic resolution structure of azurin II and electronic structure calculations of azurin, plastocyanin and stellacyanin

Co-reporter:Konstantinos Paraskevopoulos, Mahesh Sundararajan, Rajeev Surendran, Michael A. Hough, Robert R. Eady, Ian H. Hillier and S. Samar Hasnain

Dalton Transactions 2006 (Issue 25) pp:3067-3076

Publication Date(Web):23 Feb 2006

DOI:10.1039/B513942B

Understanding how the active site structures of blue copper proteins determine their redox properties is the central structure–function relationship question of this important class of protein, also referred to as cupredoxins. We here describe both experimental and computational studies of azurin, plastocyanin and stellacyanin designed to define more accurately the geometric structures of the active site of the reduced and oxidized species, and thus to understand how these structures determine the redox potentials of these proteins. To this end the crystal structure of reduced azurin II has been determined at an atomic resolution of 1.13 Å and is presented here. Co-ordinates and structure factors have been deposited in the RCSB Protein Data Bank with accession codes 2ccw and r2ccwsf respectively. The improved accuracy provided by the atomic resolution for the metal stereochemistry are utilised in conjunction with the EXAFS data for theoretical calculations. Multilevel calculations involving density functional theory and molecular mechanical potentials are used to predict both the geometric and electronic structure of the active sites of azurin, plastocyanin and stellacyanin and to estimate the relative redox potentials of these three proteins. We have also compared the relative energies of the structures obtained from experiment at varying resolutions, and from the isolated and embedded cluster calculations. We find significant energy differences between low and high (atomic) resolution structures arising primarily due to inaccuracies in the Cu–ligand distances in the lower resolution structures, emphasising the importance of accurate, very high resolution structural information. QM/MM structures are only ∼1 kcal mol−1 lower in energy than the 1.13 Å structure while the optimized gas phase structure is 13.0 kcal mol−1 lower in energy.

The solvated fluoride anion can be a good nucleophile

Co-reporter:Mark A. Vincent and Ian H. Hillier

Chemical Communications 2005 (Issue 47) pp:5902-5903

Publication Date(Web):20 Oct 2005

DOI:10.1039/B510477G

Computations show how the solvated fluoride ion can be a good nucleophile in spite of its high solvation energy.

The nature and function of the catalytic centres of the DMSO reductases

Co-reporter:Jonathan P. McNamara, Ian H. Hillier, Tarnjeet S. Bhachu and C. David Garner

Dalton Transactions 2005 (Issue 21) pp:3572-3579

Publication Date(Web):20 Sep 2005

DOI:10.1039/B507206A

Density functional theory calculations have been performed to probe aspects of the function of the reaction centres of the DMSO reductase enzymes, in respect of catalysis of oxygen atom transfer (OAT). The first comparison between Mo and W at the active site of these enzymes has been accomplished by a consideration of the reaction profile for OAT from DMSO to [MoIV(OMe)(S2C2H2)2]1−versus that for the corresponding reaction with [WIV(OMe)(S2C2H2)2]1−. Both reaction profiles involve two transition states separated by a well-defined intermediate; however, whilst the second transition state (TS2) is clearly rate-limiting for the Mo system, the two transition states have a similar energy for the W system. The activation energy for OAT from DMSO to [WIV(OMe)(S2C2H2)2]1− is ca. 23 kJ mol−1 lower for the corresponding reaction with Mo, consistent with the significantly faster rate of reduction of DMSO by Rhodobacter capsulatus W–DMSO reductase than by its Mo counterpart. Consistent with the principle of the entatic state, the geometrical constraints imposed by the protein on the metal centre of the Mo– and W–DMSO reductases facilitate OAT by favouring a trigonal prismatic geometry for the transition state TS2 that is close to that observed for the metal in the oxidised form of each of these enzymes. The effects of different tautomers of a simplified form of the pyran ring-opened, dihydropterin state of the molybdopterin cofactor on the reaction profile for OAT have been considered. The major effect, a significant lowering of the activation barrier associated with TS2, is observed for a protonated form of a tautomer that involves conjugation between the pyrazine and metallodithiolene rings.

Forming a ruthenium isomerisation catalyst from Grubbs II: a DFT study

Co-reporter:Allan Young, Mark A. Vincent, Ian H. Hillier, Jonathan M. Percy and Tell Tuttle

Dalton Transactions 2014 - vol. 43(Issue 22) pp:NaN8498-8498

Publication Date(Web):2014/04/14

DOI:10.1039/C4DT00464G

Which density functional should be used to study actinyl complexes?

Co-reporter:Jonathan P. Austin, Neil A. Burton, Ian H. Hillier, Mahesh Sundararajan and Mark A. Vincent

Physical Chemistry Chemical Physics 2009 - vol. 11(Issue 8) pp:NaN1145-1145

Publication Date(Web):2009/01/09

DOI:10.1039/B821577D

QM/MM studies of Ni–Fe hydrogenases: the effect of enzyme environment on the structure and energies of the inactive and active states

Co-reporter:Prabha Jayapal, Mahesh Sundararajan, Ian H. Hillier and Neil A. Burton

Physical Chemistry Chemical Physics 2008 - vol. 10(Issue 29) pp:NaN4257-4257

Publication Date(Web):2008/06/11

DOI:10.1039/B804035D

High level ab initio and DFT calculations of models of the catalytically active Ni–Fe hydrogenases

Co-reporter:Prabha Jayapal, David Robinson, Mahesh Sundararajan, Ian H. Hillier and Joseph J. W. McDouall

Physical Chemistry Chemical Physics 2008 - vol. 10(Issue 13) pp:NaN1738-1738

Publication Date(Web):2008/02/15

DOI:10.1039/B719980E

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

Co-reporter:Rajesh K. Raju, Anitha Ramraj, Ian H. Hillier, Mark A. Vincent and Neil A. Burton

Physical Chemistry Chemical Physics 2009 - vol. 11(Issue 18) pp:NaN3416-3416

Publication Date(Web):2009/03/02

DOI:10.1039/B822877A

Semi-empirical molecular orbital methods including dispersion corrections for the accurate prediction of the full range of intermolecular interactions in biomolecules

Co-reporter:Jonathan P. McNamara and Ian H. Hillier

Physical Chemistry Chemical Physics 2007 - vol. 9(Issue 19) pp:NaN2370-2370

Publication Date(Web):2007/03/22

DOI:10.1039/B701890H

Mapping the potential energy surfaces for ring-closing metathesis reactions of prototypical dienes by electronic structure calculations

Co-reporter:Ian H. Hillier, Shanthi Pandian, Jonathan M. Percy and Mark A. Vincent

Dalton Transactions 2011 - vol. 40(Issue 5) pp:NaN1072-1072

Publication Date(Web):2010/12/15

DOI:10.1039/C0DT01314E

The mechanism of the reduction of [AnO2]2+ (An = U, Np, Pu) in aqueous solution, and by Fe(II) containing proteins and mineral surfaces, probed by DFT calculations

Co-reporter:Mahesh Sundararajan, Rajeev S. Assary, Ian H. Hillier and David J. Vaughan

Dalton Transactions 2011 - vol. 40(Issue 42) pp:NaN11163-11163

Publication Date(Web):2011/08/11

DOI:10.1039/C1DT10700C

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

Co-reporter:Ian W. Ashworth, Ian H. Hillier, David J. Nelson, Jonathan M. Percy and Mark A. Vincent

Chemical Communications 2011 - vol. 47(Issue 19) pp:NaN5430-5430

Publication Date(Web):2011/04/11

DOI:10.1039/C1CC11230A

Modelling the binding of HIV-reverse transcriptase and nevirapine: an assessment of quantum mechanical and force field approaches and predictions of the effect of mutations on binding

Co-reporter:Rajesh K. Raju, Neil A. Burton and Ian H. Hillier

Physical Chemistry Chemical Physics 2010 - vol. 12(Issue 26) pp:NaN7125-7125

Publication Date(Web):2010/05/17

DOI:10.1039/C001384F

The interaction of carbohydrates and amino acids with aromatic systems studied by density functional and semi-empirical molecular orbital calculations with dispersion corrections

Co-reporter:Raman Sharma, Jonathan P. McNamara, Rajesh K. Raju, Mark A. Vincent, Ian H. Hillier and Claudio A. Morgado

Physical Chemistry Chemical Physics 2008 - vol. 10(Issue 19) pp:NaN2774-2774

Publication Date(Web):2008/02/27

DOI:10.1039/B719764K

Can the DFT-D method describe the full range of noncovalent interactions found in large biomolecules?

Co-reporter:Claudio Morgado, Mark A. Vincent, Ian H. Hillier and Xiao Shan

Physical Chemistry Chemical Physics 2007 - vol. 9(Issue 4) pp:NaN451-451

Publication Date(Web):2006/12/06

DOI:10.1039/B615263E

The DFT-D method is shown to yield interaction energies between biologically important groups to an accuracy comparable to that obtained using state-of-the-art ab initio methods.

The binding of nitric oxide at the Cu(I) site of copper nitrite reductase and of inorganic models: DFT calculations of the energetics and EPR parameters of side-on and end-on structures

Co-reporter:Ganga Periyasamy, Mahesh Sundararajan, Ian H. Hillier, Neil A. Burton and Joseph J. W. McDouall

Physical Chemistry Chemical Physics 2007 - vol. 9(Issue 20) pp:NaN2506-2506

Publication Date(Web):2007/03/23

DOI:10.1039/B701083D

The non-covalent functionalisation of carbon nanotubes studied by density functional and semi-empirical molecular orbital methods including dispersion corrections

Co-reporter:Jonathan P. McNamara, Raman Sharma, Mark A. Vincent, Ian H. Hillier and Claudio A. Morgado

Physical Chemistry Chemical Physics 2008 - vol. 10(Issue 1) pp:NaN135-135

Publication Date(Web):2007/10/25

DOI:10.1039/B711498B

The structure and interaction energies of the weak complexes of CHClF2 and CHF3 with HCCH: a test of density functional theory methods

Co-reporter:Mark A. Vincent and Ian H. Hillier

Physical Chemistry Chemical Physics 2011 - vol. 13(Issue 10) pp:NaN4392-4392

Publication Date(Web):2011/01/18

DOI:10.1039/C0CP02626C

The effects of perfluorination on carbohydrate–π interactions: computational studies of the interaction of benzene and hexafluorobenzene with fucose and cyclodextrin

Co-reporter:Rajesh K. Raju, Ian H. Hillier, Neil A. Burton, Mark A. Vincent, Slimane Doudou and Richard A. Bryce

Physical Chemistry Chemical Physics 2010 - vol. 12(Issue 28) pp:NaN7967-7967

Publication Date(Web):2010/06/02

DOI:10.1039/C002058C

The geometric structures, vibrational frequencies and redox properties of the actinyl coordination complexes ([AnO2(L)n]m; An = U, Pu, Np; L = H2O, Cl−, CO32−, CH3CO2−, OH−) in aqueous solution, studied by density functional theory methods

Co-reporter:Jonathan P. Austin, Mahesh Sundararajan, Mark A. Vincent and Ian H. Hillier

Dalton Transactions 2009(Issue 30) pp:NaN5909-5909

Publication Date(Web):2009/04/22

DOI:10.1039/B901724K

The geometric and electronic structures of the aqua, chloro, acetato, hydroxo and carbonato complexes of U, Np and Pu in both their (VI) and (V) oxidation states, and in an aqueous environment, have been studied using density functional theory methods. We have obtained micro-solvated structures derived from molecular dynamics simulations and included the bulk solvent using a continuum model. We find that two different hydrogen bonding patterns involving the axial actinyl oxygen atoms are sometimes possible, and may give rise to different An–O bond lengths and vibrational frequencies. These alternative structures are reflected in the experimental An–O bond lengths of the aqua and carbonato complexes. The variation of the redox potential of the uranyl complexes with the different ligands has been studied using both BP86 and B3LYP functionals. The relative values for the four uranium complexes having anionic ligands are in surprisingly good agreement with experiment, although the absolute values are in error by ∼1 eV. The absolute error for the aqua species is much less, leading to an incorrect order of the redox potentials of the aqua and chloro species.