Jeremy N. Harvey

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Organization: University of Bristol , England

Department: School of Chemistry

Title: Professor(PhD)

TOPICS

Physical Chemistry

Inorganic Chemistry

Chemicals
References

Electronic Structure and Formation of Simple Ferryloxo Complexes: Mechanism of the Fenton Reaction

Co-reporter:Alban S. Petit, Robert C. R. Pennifold, and Jeremy N. Harvey

Inorganic Chemistry 2014 Volume 53(Issue 13) pp:6473-6481

Publication Date(Web):May 1, 2014

DOI:10.1021/ic500379r

The Fenton reaction is a famous reaction in inorganic chemistry, with relevance to topics such as bioinorganic oxidation and fundamental redox chemistry of water and oxygen. It is also a reaction concerning which there has been very extensive mechanistic debate, with experimental and computational work leading to extensive evidence concerning its mechanism—not all of which is consistent. Here, we use this reaction as a challenge to modern electronic structure theory methods and show that density functional theory, when validated by accurate ab initio methods, can yield a picture of this reaction that is consistent with experiment. The article also highlights some of the challenges in accurate studies of reaction mechanisms of ionic species in water solution.

Computed ligand effects on the oxidative addition of phenyl halides to phosphine supported palladium(0) catalysts

Co-reporter:Claire L. McMullin, Natalie Fey and Jeremy N. Harvey

Dalton Transactions 2014 vol. 43(Issue 36) pp:13545-13556

Publication Date(Web):05 Aug 2014

DOI:10.1039/C4DT01758G

The manifold of reaction pathways for the oxidative addition of phenyl bromide and phenyl chloride substrates to phosphine-modified palladium(0) complexes has been investigated with dispersion-corrected density functional theory (B3LYP-D2) for a range of synthetically relevant ligands, permitting the evaluation of ligand, substrate and method effects on calculated predictions. Bulky and electron-rich ligands PtBu3 and SPhos can access low-coordinate complexes more easily, facilitating formation of the catalytically active species throughout the cycle. While the bisphosphine oxidative addition step is reasonably facile for the smaller PCy3 and PPh3 ligands, the dissociation of these ligands to generate reactive palladium complexes becomes more important and the catalyst is more likely to become trapped in unreactive intermediates. This study demonstrates the feasibility of exploring the catalytic manifold for synthetically relevant ligands with computational chemistry, but also highlights the remaining challenges.

Computational Kinetics of Cobalt-Catalyzed Alkene Hydroformylation

Co-reporter:Laura E. Rush;Dr. Paul G. Pringle ;Dr. Jeremy N. Harvey

Angewandte Chemie 2014 Volume 126( Issue 33) pp:8816-8820

Publication Date(Web):

DOI:10.1002/ange.201402115

Abstract

Density functional theory, coupled-cluster theory, and transition state theory are used to build a computational model of the kinetics of phosphine-free cobalt-catalyzed hydroformylation and hydrogenation of alkenes. The model provides very good agreement with experiment, and enables the factors that determine the selectivity and rate of catalysis to be determined. The turnover rate is mainly determined by the alkene coordination step.

Computational Kinetics of Cobalt-Catalyzed Alkene Hydroformylation

Co-reporter:Laura E. Rush;Dr. Paul G. Pringle ;Dr. Jeremy N. Harvey

Angewandte Chemie International Edition 2014 Volume 53( Issue 33) pp:8672-8676

Publication Date(Web):

DOI:10.1002/anie.201402115

Abstract

Influence of Cyclopentadienyl Ring-Tilt on Electron-Transfer Reactions: Redox-Induced Reactivity of Strained [2] and [3]Ruthenocenophanes

Co-reporter:Dr. Andrew D. Russell; Joe B. Gilroy; Kevin Lam;Dr. Mairi F. Haddow; Jeremy N. Harvey; William E. Geiger; Ian Manners

Chemistry - A European Journal 2014 Volume 20( Issue 49) pp:16216-16227

Publication Date(Web):

DOI:10.1002/chem.201403512

Abstract

In contrast to ruthenocene [Ru(η⁵-C₅H₅)₂] and dimethylruthenocene [Ru(η⁵-C₅H₄Me)₂] (7), chemical oxidation of highly strained, ring-tilted [2]ruthenocenophane [Ru(η⁵-C₅H₄)₂(CH₂)₂] (5) and slightly strained [3]ruthenocenophane [Ru(η⁵-C₅H₄)₂(CH₂)₃] (6) with cationic oxidants containing the non-coordinating [B(C₆F₅)₄]⁻ anion was found to afford stable and isolable metalmetal bonded dicationic dimer salts [Ru(η⁵-C₅H₄)₂(CH₂)₂]₂[B(C₆F₅)₄]₂ (8) and [Ru(η⁵-C₅H₄)₂(CH₂)₃]₂[B(C₆F₅)₄]₂ (17), respectively. Cyclic voltammetry and DFT studies indicated that the oxidation potential, propensity for dimerization, and strength of the resulting RuRu bond is strongly dependent on the degree of tilt present in 5 and 6 and thereby degree of exposure of the Ru center. Cleavage of the RuRu bond in 8 was achieved through reaction with the radical source [(CH₃)₂NC(S)SSC(S)N(CH₃)₂] (thiram), affording unusual dimer [(CH₃)₂NCS₂Ru(η⁵-C₅H₄)(η³-C₅H₄)C₂H₄]₂[B(C₆F₅)₄]₂ (9) through a haptotropic η⁵–η³ ring-slippage followed by an apparent [2+2] cyclodimerization of the cyclopentadienyl ligand. Analogs of possible intermediates in the reaction pathway [C₆H₅ERu(η⁵-C₅H₄)₂C₂H₄][B(C₆F₅)₄] [E=S (15) or Se (16)] were synthesized through reaction of 8 with C₆H₅EEC₆H₅ (E=S or Se).

Quantum Mechanics/Molecular Mechanics Modeling of Regioselectivity of Drug Metabolism in Cytochrome P450 2C9

Co-reporter:Richard Lonsdale ; Kerensa T. Houghton ; Jolanta Żurek ; Christine M. Bathelt ; Nicolas Foloppe ; Marcel J. de Groot ; Jeremy N. Harvey ;Adrian J. Mulholland

Journal of the American Chemical Society 2013 Volume 135(Issue 21) pp:8001-8015

Publication Date(Web):May 3, 2013

DOI:10.1021/ja402016p

Cytochrome P450 enzymes (P450s) are important in drug metabolism and have been linked to adverse drug reactions. P450s display broad substrate reactivity, and prediction of metabolites is complex. QM/MM studies of P450 reactivity have provided insight into important details of the reaction mechanisms and have the potential to make predictions of metabolite formation. Here we present a comprehensive study of the oxidation of three widely used pharmaceutical compounds (S-ibuprofen, diclofenac, and S-warfarin) by one of the major drug-metabolizing P450 isoforms, CYP2C9. The reaction barriers to substrate oxidation by the iron-oxo species (Compound I) have been calculated at the B3LYP-D/CHARMM27 level for different possible metabolism sites for each drug, on multiple pathways. In the cases of ibuprofen and warfarin, the process with the lowest activation energy is consistent with the experimentally preferred metabolite. For diclofenac, the pathway leading to the experimentally observed metabolite is not the one with the lowest activation energy. This apparent inconsistency with experiment might be explained by the two very different binding modes involved in oxidation at the two competing positions. The carboxylate of diclofenac interacts strongly with the CYP2C9 Arg108 side chain in the transition state for formation of the observed metabolite—but not in that for the competing pathway. We compare reaction barriers calculated both in the presence and in the absence of the protein and observe a marked improvement in selectivity prediction ability upon inclusion of the protein for all of the substrates studied. The barriers calculated with the protein are generally higher than those calculated in the gas phase. This suggests that active-site residues surrounding the substrate play an important role in controlling selectivity in CYP2C9. The results show that inclusion of sampling (particularly) and dispersion effects is important in making accurate predictions of drug metabolism selectivity of P450s using QM/MM methods.

Understanding the reactivity bottleneck in the spin-forbidden reaction FeO+ + H2 → Fe+ + H2O

Co-reporter:Jeremy N. Harvey, David P. Tew

International Journal of Mass Spectrometry 2013 Volumes 354–355() pp:263-270

Publication Date(Web):15 November 2013

DOI:10.1016/j.ijms.2013.07.011

•Accurate coupled-cluster energies are reported for the title reaction.•The crossing point between quartet and sextet surfaces is located.•Non-adiabatic statistical rate theory calculations are performed.•The HH bond splitting transition state is predicted to be rate-limiting.New coupled cluster theory calculations, including extrapolation to the complete basis set limit, are reported for key species on the [Fe,O,H2]+ potential energy surfaces. Test calculations including Bruecker orbital methods suggest that the single-reference coupled-cluster approach is reliable for this system. The minimum energy crossing point (MECP) between the sextet and quartet states has been found to lie close in energy and structure to the quartet reactant complex 4FeO+H2. Non-adiabatic transition state theory is used to calculate the rate constant for hydrogen oxidation, and is found to agree reasonably well with experiment, considering the remaining uncertainties in the ab initio energies and the kinetic modelling. The isotope effects are reproduced fairly well also. The transition state theory calculations suggest that the bottleneck to reaction is an adiabatic quartet transition state for insertion of FeO+ into the HH bond. Spin state change at the MECP is calculated to be considerably faster, even allowing for errors in the relative energies.

Spin-forbidden hydrogen atom transfer reactions in a cobalt biimidazoline system

Co-reporter:Virginia W. Manner, Alex D. Lindsay, Elizabeth A. Mader, Jeremy N. Harvey and James M. Mayer

Chemical Science 2012 vol. 3(Issue 1) pp:230-243

Publication Date(Web):16 Sep 2011

DOI:10.1039/C1SC00387A

Described here are hydrogen atom transfer (HAT) reactions from high-spin cobalt(II) tris(2,2′-bi-2-imidazoline) (CoIIIIH22bim) to the hydrogen atom acceptors, 2,2,6,6-tetramethyl-1-piperidinyl-oxyl (TEMPO), 2,4,6-tri-tert-butylphenoxyl radical (tBu3ArO˙), and benzoquinone (BQ). The cobalt product is the oxidized and deprotonated, low-spin cobalt(III) complex (CoIIIIIIHbim), and the organic products are TEMPOH, tBu3ArOH, or hydroquinone, respectively. These reactions are formally spin forbidden because the spin state of the reactants is different from that of the products. For instance, quartet CoIIIIH22bim plus doublet RO˙ can have a triplet or quintet ground state, while the CoIIIIIIHbim + ROH product state is a singlet. Kinetics measured in the forward and reverse directions and thermochemical measurements provide a detailed picture of the reactions. The reactions are quite slow: the reaction of 10 mM CoIIIIH22bim with excess TEMPO requires roughly a day at ambient temperatures to reach equilibrium. This is 3400 times slower than the related reaction of the iron analogue FeIIIIH22bim, which is 2 kcal mol−1 more uphill. Mechanistic analyses show that the TEMPO reaction occurs by hydrogen atom transfer (HAT), and this is likely for the tBu3ArO˙ and BQ reactions as well. This is an unusually well defined spin-forbidden HAT system, which serves as a model for more complex multi-spin state HAT processes such as those suggested to occur in cytochrome P450 and metal-oxo model systems. In principle, HAT could occur before, after, or concerted with spin change. Computational studies indicate a reaction mechanism involving pre-equilibrium spin state interconversion of quartet 44CoIIIIH22bim to its doublet excited state 22CoIIIIH22bim, followed by spin-allowed HAT to the organic acceptor. This mechanism is consistent with the available kinetic, thermochemical and spectroscopic measurements. It indicates that the slow rates are due to the large change in geometry between CoIIIIH22bim and CoIIIIIIHbim, rather than any inherent difficulty in changing spin state. The implications of these results for other spin-forbidden or ‘two-state’ HAT processes are discussed.

Effects of Dispersion in Density Functional Based Quantum Mechanical/Molecular Mechanical Calculations on Cytochrome P450 Catalyzed Reactions

Co-reporter:Richard Lonsdale, Jeremy N. Harvey, and Adrian J. Mulholland

Journal of Chemical Theory and Computation 2012 Volume 8(Issue 11) pp:4637-4645

Publication Date(Web):August 21, 2012

DOI:10.1021/ct300329h

Density functional theory (DFT) based quantum mechanical/molecular mechanical (QM/MM) calculations have provided valuable insight into the reactivity of the cytochrome P450 family of enzymes (P450s). A failure of commonly used DFT methods, such as B3LYP, is the neglect of dispersion interactions. An empirical dispersion correction has been shown to improve the accuracy of gas phase DFT calculations of P450s. The current work examines the effect of the dispersion correction in QM/MM calculations on P450s. The hydrogen abstraction from camphor, and hydrogen abstraction and C–O addition of cyclohexene and propene by P450cam have been modeled, along with the addition of benzene to Compound I in CYP2C9, at the B3LYP-D2/CHARMM27 level of theory. Single point energy calculations were also performed at the B3LYP-D3//B3LYP-D2/CHARMM27 level. The dispersion corrections lower activation energy barriers significantly (by ∼5 kcal/mol), as seen for gas phase calculations, but has a small effect on optimized geometries.These effects are likely to be important in modeling reactions catalyzed by other enzymes also. Given the low computational cost of including such dispersion corrections, we recommend doing so in all B3LYP based QM/MM calculations.

Boron Incorporation at a Diamond Surface: A QM/MM Study of Insertion and Migration Pathways during Chemical Vapor Deposition

Co-reporter:James C. Richley, Jeremy N. Harvey, and Michael N. R. Ashfold

The Journal of Physical Chemistry C 2012 Volume 116(Issue 34) pp:18300-18307

Publication Date(Web):August 9, 2012

DOI:10.1021/jp305773d

Quantum mechanical and hybrid quantum mechanical/molecular mechanical (QM/MM) cluster models have been used to investigate the energetics of (i) B atom and BH radical insertion reactions into surface C–H and C–C bonds during chemical vapor deposition (CVD) of B-doped diamond and (ii) BH group migration on the C{100}:H 2 × 1 and C{111}:H surfaces and at step edges between these surfaces. B and BH insertions into surface C–H bonds are shown to be energetically feasible routes to forming surface-bound BHx species under typical CVD conditions but are likely to be of minor importance compared with the alternative process, wherein a gas-phase BHx species adds to a surface radical site. BH migration on and between the C{100}:H 2 × 1 and C{111}:H surfaces involves passage through ring-closed intermediate structures. These are generally more stable than those involved in analogous CH2 migration reactions, with the result that BH groups are likely to be less migratory and to incorporate nearer the point where they initially accommodate on the diamond surface – most particularly at concave step-edges.

CH2 Group Migration between H-Terminated 2 × 1 Reconstructed {100} and {111} Surfaces of Diamond

Co-reporter:James C. Richley ; Jeremy N. Harvey ;Michael N. R. Ashfold

The Journal of Physical Chemistry C 2012 Volume 116(Issue 14) pp:7810-7816

Publication Date(Web):March 19, 2012

DOI:10.1021/jp300454r

Successful growth of diamond by chemical vapor deposition requires that chemisorbed hydrocarbon species, most notably CH2 groups, are able to migrate on the growing surface. Quantum mechanical and hybrid quantum mechanical/molecular mechanical (QM/MM) cluster models are here used to investigate the energetics of CH2 migration on the C{111}:H surface and between C{100}:H 2 × 1 terraces separated by a region of C{111}:H surface. Many migration pathways of this type proceeding via structures involving 3-, 4-, and 5-membered rings are found to have relatively low barriers, so that migration should be relatively facile at typical diamond growth temperatures. In contrast, CH2 migration via one particular C{111}:H/C{100}:H 2 × 1 step-edge geometry results in the formation of a very stable 6-membered ring intermediate. The energetics suggest that this process will be irreversible and should thus result in incorporation. This type of step-edge also occurs in the limiting case of two C{100}:H 2 × 1 terraces separated by a monolayer step, and migration of CH2 species along the lower C{100}:H 2 × 1 terrace toward such step edges is predicted to favor incorporation. These findings offer a rationale for the deduced propensity for step-flow growth and the observation of stepped {100} terraces in CVD diamond samples.

MetalMetal Bond Formation Between [n]Metallocenophanes: Synthesis and Characterisation of a Dicarba[2]ruthenocenophanium Dimer

Co-reporter:Andrew D. Russell;Dr. Joe B. Gilroy;Dr. Kevin Lam;Mairi F. Haddow;Dr. Jeremy N. Harvey;Dr. William E. Geiger;Dr. Ian Manners

Chemistry - A European Journal 2012 Volume 18( Issue 26) pp:8000-8003

Publication Date(Web):

DOI:10.1002/chem.201201129

Nitrogen Atom Transfer from Iron(IV) Nitrido Complexes: A Dual-Nature Transition State for Atom Transfer

Co-reporter:Jeremiah J. Scepaniak, Charles G. Margarit, Jeremy N. Harvey, and Jeremy M. Smith

Inorganic Chemistry 2011 Volume 50(Issue 19) pp:9508-9517

Publication Date(Web):September 8, 2011

DOI:10.1021/ic201190c

The mechanism of nitrogen atom transfer from four-coordinate tris(carbene)borate iron(IV) nitrido complexes to phosphines and phosphites has been investigated. In the absence of limiting steric effects, the rate of nitrogen atom transfer to phosphines increases with decreasing phosphine σ-basicity. This trend has been quantified by a Hammett study with para-substituted triarylphosphines, and is contrary to the expectations of an electrophilic nitrido ligand. On the basis of electronic structure calculations, a dual-nature transition state for nitrogen atom transfer is proposed, in which a key interaction involves the transfer of electron density from the nitrido highest occupied molecular orbital (HOMO) to the phosphine lowest unoccupied molecular orbital (LUMO). Compared to analogous atom transfer reactions from a 5d metal, these results show how the electronic plasticity of a 3d metal results in rapid atom transfer from pseudotetrahedral late metal complexes.

Organometallic reactivity: the role of metal–ligand bond energies from a computational perspective

Co-reporter:Natalie Fey, Benjamin M. Ridgway, Jesús Jover, Claire L. McMullin and Jeremy N. Harvey

Dalton Transactions 2011 vol. 40(Issue 42) pp:11184-11191

Publication Date(Web):19 Aug 2011

DOI:10.1039/C1DT10909J

The association and dissociation of ligands plays a vital role in determining the reactivity of organometallic catalysts. Computational studies with density functional theory often fail to reproduce experimental metal–ligand bond energies, but recently functionals which better capture dispersion effects have been developed. Here we explore their application and discuss future challenges for computational studies of organometallic catalysis.

How Important Is Backbonding in Metal Complexes Containing N-Heterocyclic Carbenes? Structural and NBO Analysis

Co-reporter:Aleix Comas-Vives

European Journal of Inorganic Chemistry 2011 Volume 2011( Issue 32) pp:5025-5035

Publication Date(Web):

DOI:10.1002/ejic.201100721

Abstract

DFT calculations have been used to analyze the degree of metal-to-ligand backbonding in a range of model transition metal complexes of N-heterocyclic carbenes. Two new methods of analysis have been introduced for this purpose. The first is structural and involves comparing the variation of the C–N bond length and N–C–N angle in complexes in which σ-donation is dominant (e.g. complexes with BF₃) and others in which backbonding might be expected. The second uses the perturbative natural bonding orbital (NBO) method. Both methods lead to the firm conclusion that backbonding is significant in these compounds – as large or even larger than in the corresponding phosphane complexes. This is partly due to the very strong σ-donor nature of the ligand, which makes typical metal acceptor centers very electron-rich and hence very apt to undergo backbonding.

Strain-Induced Cleavage of Carbon−Carbon Bonds: Bridge Rupture Reactions of Group 8 Dicarba[2]metallocenophanes

Co-reporter:David E. Herbert ; Joe B. Gilroy ; Anne Staubitz ; Mairi F. Haddow ; Jeremy N. Harvey ;Ian Manners

Journal of the American Chemical Society 2010 Volume 132(Issue 6) pp:1988-1998

Publication Date(Web):January 22, 2010

DOI:10.1021/ja9087049

Thermal treatment of dicarba[2]ferrocenophanes [Fe(η5-C5H4)2(CMe2)2] (1), rac-[Fe(η5-C5H4)2(CHiPr)2] (rac-5), and meso-[Fe(η5-C5H4)2(CHtBu)2] (meso-7) at 240−300 °C in the melt led to cleavage of the carbon−carbon bond in the bridge. Compounds 1 and rac-5 underwent intramolecular abstraction of H• and yielded ring-opened, vinyl-substituted 1,1ˈ-metallocenes, while meso-7 thermally converted to the more thermodynamically stable rac isomer. The corresponding dicarba[2]ruthenocenophanes [Ru(η5-C5H4)2(CMe2)2] (10), rac-[Ru(η5-C5H4)2(CHiPr)2] (rac-12), and meso-[Ru(η5-C5H4)2(CHtBu)2] (meso-15) underwent analogous thermal carbon−carbon bond cleavage but more readily, consistent with a higher degree of ring strain. In the case of 7 and 15, the stability of the rac isomers relative to the respective meso isomers was confirmed by DFT studies, despite the former species exhibiting slightly higher tilt angles (α/deg) between the two cyclopentadienyl (Cp) rings. Theoretical investigations were used to explore the mechanism of carbon−carbon bond cleavage in dicarba[2]metallocenophanes, confirming the validity of the proposed homolytic bond cleavage mechanism. In addition, the potential role of bis-fulvene metal(0) and ‘tuck-in’ complexes in the bond-cleavage mechanism was assessed. This study also provides insight into the mechanism of the thermal ring-opening polymerization of −CH2CH2− bridged dicarba[2]metallocenophanes and, for the first time, supports a homolytic carbon−carbon bond cleavage pathway.

Accurate modelling of Pd(0) + PhX oxidative addition kinetics

Co-reporter:Claire L. McMullin, Jesús Jover, Jeremy N. Harvey and Natalie Fey

Dalton Transactions 2010 vol. 39(Issue 45) pp:10833-10836

Publication Date(Web):20 Oct 2010

DOI:10.1039/C0DT00778A

We have used dispersion-corrected DFT (DFT-D) together with solvation to examine possible mechanisms for reaction of PhX (X = Cl, Br, I) with Pd(PtBu3)2 and compare our results to recently published kinetic data (F. Barrios-Landeros, B. P. Carrow and J. F. Hartwig, J. Am. Chem. Soc., 2009, 131, 8141–8154).1 The calculated activation free energies agree near-quantitatively with experimentally observed rate constants.

Computational study of PtBu3 as ligand in the palladium-catalysed amination of phenylbromide with morpholine

Co-reporter:Claire L. McMullin, Bastian Rühle, Maria Besora, A. Guy Orpen, Jeremy N. Harvey, Natalie Fey

Journal of Molecular Catalysis A: Chemical 2010 324(1–2) pp: 48-55

Publication Date(Web):

DOI:10.1016/j.molcata.2010.02.030

A computational study of phosphine ligand effects in Suzuki–Miyaura coupling

Co-reporter:Jesús Jover, Natalie Fey, Mark Purdie, Guy C. Lloyd-Jones, Jeremy N. Harvey

Journal of Molecular Catalysis A: Chemical 2010 324(1–2) pp: 39-47

Publication Date(Web):

DOI:10.1016/j.molcata.2010.02.021

Superelectrophilic Intermediates in Nitrogen-Directed Aromatic Borylation

Co-reporter:Timothy S. De Vries ; Aleksandrs Prokofjevs ; Jeremy N. Harvey ;Edwin Vedejs

Journal of the American Chemical Society 2009 Volume 131(Issue 41) pp:14679-14687

Publication Date(Web):September 28, 2009

DOI:10.1021/ja905369n

The first examples of borylation under conditions of borenium ion generation from hydrogen-bridged boron cations are described. The observable H-bridged cations are generated by hydride abstraction from N,N-dimethylamine boranes Ar(CH2)nNMe2BH3 using Ph3C+ (C6F5)4B− (TrTPFPB) as the hydride acceptor. In the presence of excess TrTPFPB, the hydrogen-bridged cations undergo internal borylation to afford cyclic amine borane derivatives with n = 1−3. The products are formed as the corresponding cyclic borenium ions according to reductive quenching experiments and 11B and 1H NMR spectroscopy in the case with Ar = C6H5 and n = 1. The same cyclic borenium cation is also formed from the substrate with Ar = o-C6H4SiMe3 via desilylation, but the analogous system with Ar = o-C6H4CMe3 affords a unique cyclization product that retains the tert-butyl substituent. An ortho-deuterated substrate undergoes cyclization with a product-determining isotope effect of kH/kD 2.8. Potential cationic intermediates have been evaluated using B3LYP/6-31G* methods. The computations indicate that internal borylation from 14a occurs via a C−H insertion transition state that is accessible from either the borenium π complex or from a Wheland intermediate having nearly identical energy. The Ar = o-C6H4SiMe3 example strongly favors formation of the Wheland intermediate, and desilylation occurs via internal SiMe3 migration from carbon to one of the hydrides attached to boron.

Building ligand knowledge bases for organometallic chemistry: Computational description of phosphorus(III)-donor ligands and the metal–phosphorus bond

Co-reporter:Natalie Fey, A. Guy Orpen, Jeremy N. Harvey

Coordination Chemistry Reviews 2009 Volume 253(5–6) pp:704-722

Publication Date(Web):March 2009

DOI:10.1016/j.ccr.2008.04.017

Changing the coordinated ligands is a powerful and synthetically convenient way of modifying and fine-tuning the properties of transition metal complexes, especially those active in homogeneous catalysis. Parameters capturing such changes in the steric and electronic characteristics of complexes have played a key role in improving our understanding of ligand effects on the kinetic, thermodynamic, spectroscopic and structural behaviour of such species. Such ligand parameters can be useful for interpreting experiments, but they can also guide the discovery of novel ligands from ligand maps and allow the prediction of ligand effects before further experimentation. The latter aims especially are best served if such parameters can be determined before ligands and complexes have been synthesised, and here we review calculated descriptors for phosphorus(III) ligands as widely used in organometallic and coordination chemistry. We also discuss the application of such ligand descriptors in models, maps and predictions of ligand effects, describe related computational studies of the metal–phosphorus bond, and provide an overview of the statistical methods used.

On the Role of Carbon Radical Insertion Reactions in the Growth of Diamond by Chemical Vapor Deposition Methods

Co-reporter:James C. Richley, Jeremy N. Harvey and Michael N. R. Ashfold

The Journal of Physical Chemistry A 2009 Volume 113(Issue 42) pp:11416-11422

Publication Date(Web):September 24, 2009

DOI:10.1021/jp906065v

Potential energy profiles for the insertion of gas phase C atoms, and CH, CH2, C2, C2H, and C3 radicals, into C−H and C−C bonds on a 2 × 1 reconstructed, H-terminated diamond {100} surface have been explored using both quantum mechanical (density functional theory) and hybrid quantum mechanical/molecular mechanical (QM/MM) methods. Both sets of calculations return minimum energy pathways for inserting a C atom, or a CH(X), C2(X), or CH2(a) radical into a surface C−H bond that are essentially barrierless, whereas the barriers to inserting any of the investigated species into a surface C−C bond are prohibitively large. Reactivity at the diamond surface thus parallels behavior noted previously with alkanes, whereby reactant species that present both a filled σ orbital and an empty p(π) orbital insert readily into C−H bonds. Most carbon atoms on the growing diamond surface under typical chemical vapor deposition conditions are H-terminated. The present calculations thus suggest that insertion reactions, particularly reactions involving C(3P) atoms, could make a significant contribution to the renucleation and growth of ultrananocrystalline diamond (UNCD) films.

Computational Analysis of Amine−Borane Adducts as Potential Hydrogen Storage Materials with Reversible Hydrogen Uptake

Co-reporter:Anne Staubitz ; Maria Besora ; Jeremy N. Harvey ;Ian Manners

Inorganic Chemistry 2008 Volume 47(Issue 13) pp:5910-5918

Publication Date(Web):May 24, 2008

DOI:10.1021/ic800344h

Amine−borane adducts are promising compounds for use in hydrogen storage applications, and the efficient catalytic release of hydrogen from these systems has been recently demonstrated. However, if hydrogen storage is to be of practical use, it is necessary that, once hydrogen has been removed from the material, it can be put back into the system to recharge the appliance. In order to develop such systems, we computationally screened a range of amine−borane adducts for their thermodynamic dehydrogenation properties. Structural trends, which lay the foundation for the possible design of amine−borane systems that exhibit reversible dihydrogen uptake, are established. We found that it is mainly the strengths of the dative bonds in both starting materials and products that govern the thermodynamic parameters of the dehydrogenation reactions. Thus, in general, electron-donating groups on nitrogen and electron-withdrawing groups on boron lead to more favorable systems. It is also possible to design promising systems whose thermodynamic parameters are a consequence of different steric strain in starting materials and products.

Computational Descriptors for Chelating P,P- and P,N-Donor Ligands1

Co-reporter:Natalie Fey, Jeremy N. Harvey, Guy C. Lloyd-Jones, Paul Murray, A. Guy Orpen, Robert Osborne and Mark Purdie

Organometallics 2008 Volume 27(Issue 7) pp:1372-1383

Publication Date(Web):March 13, 2008

DOI:10.1021/om700840h

The ligand knowledge base approach has been extended to capture the properties of 108 bidentate P,P- and P,N-donor ligands. This contribution describes the design of the ligand set and a range of DFT-calculated descriptors, capturing ligand properties in a variety of chemical environments. New challenges arising from ligand conformational flexibility and donor asymmetry are discussed, and descriptors are related to other parameters, such as the ligand bite angle. A novel map of bidentate ligand space, potentially useful in catalyst design and discovery, has been derived from principal component analysis of the resulting LKB-PP descriptors. In addition, a range of multiple linear regression models have been derived for both experimental and calculated data, considering ligand bite angles in square-planar palladium complexes and ligand dissociation energies from octahedral chromium complexes, respectively. These data sets were fitted with models based on LKB descriptors to explore the transferability of descriptors to different coordination environments and to illustrate potential applications of such models in catalyst design, allowing predictions about novel or untested ligands.

Origin of Enantioselective Hydrogenation of Ketones by RuH2(diphosphine)(diamine) Catalysts: A Theoretical Study

Co-reporter:Tom Leyssens, Daniel Peeters and Jeremy N. Harvey

Organometallics 2008 Volume 27(Issue 7) pp:1514-1523

Publication Date(Web):March 14, 2008

DOI:10.1021/om700940m

The origin of the enantioselective hydrogenation of acetophenone by the (S-BINAP)RuH2(S,S-cydn) (cydn = 1,2-cyclohexanediamine) catalyst has been investigated by a theoretical DFT study. Computations for hydrogenation of acetone and acetophenone by the model system RuH2(PH3)2(en) (en = 1,2 ethylenediamine) confirm the previously proposed mechanism. These calculations show that reaction involving two of the four NH protons, which adopt a pseudoaxial orientation in the catalyst, is favored by ca. 2 kcal/mol over reaction involving the other two pseudoequatorial protons. The results for the model system reacting with acetophenone show that approach of the ketone with the phenyl group oriented away from the phosphine ligands (“out” approach) is favored by weak hydrogen bonding between the ketone phenyl group and one of the ruthenium-coordinated NH2 groups. In the full (S-BINAP)RuH2(S,S-cydn) catalyst, steric interactions also contribute to establishing the R selectivity in hydrogenation, and the magnitude of this selectivity is reproduced semiquantitatively. Study of the mismatched (S-BINAP)RuH2(R,R-cydn) also semiquantitatively reproduces the much reduced R selectivity of this catalyst and contributes to rationalizing it. Transfer of the less favored pseudoequatorial NH2 proton plays a key role in this case. It is shown that the results can also be used to discuss selectivity in other related systems.

Studies of Carbon Incorporation on the Diamond {100} Surface during Chemical Vapor Deposition using Density Functional Theory

Co-reporter:Andrew Cheesman, Jeremy N. Harvey and Michael N. R. Ashfold

The Journal of Physical Chemistry A 2008 Volume 112(Issue 45) pp:11436-11448

Publication Date(Web):October 7, 2008

DOI:10.1021/jp8034538

Accurate potential energy surface calculations are presented for many of the key steps involved in diamond chemical vapor deposition on the {100} surface (in its 2 × 1 reconstructed and hydrogenated form). The growing diamond surface was described by using a large (∼1500 atoms) cluster model, with the key atoms involved in chemical steps being described by using a quantum mechanical (QM, density functional theory, DFT) method and the bulk of the atoms being described by molecular mechanics (MM). The resulting hybrid QM/MM calculations are more systematic and/or at a higher level of theory than previous work on this growth process. The dominant process for carbon addition, in the form of methyl radicals, is predicted to be addition to a surface radical site, opening of the adjacent C−C dimer bond, insertion, and ultimate ring closure. Other steps such as insertion across the trough between rows of dimer bonds or addition to a neighboring dimer leading to formation of a reconstruction on the next layer may also contribute. Etching of carbon can also occur; the most likely mechanism involves loss of a two-carbon moiety in the form of ethene. The present higher-level calculations confirm that migration of inserted carbon along both dimer rows and chains should be relatively facile, with barriers of ∼150 kJ mol−1 when starting from suitable diradical species, and that this step should play an important role in establishing growth of smooth surfaces.

Understanding the kinetics of spin-forbidden chemical reactions

Co-reporter:Jeremy N. Harvey

Physical Chemistry Chemical Physics 2007 vol. 9(Issue 3) pp:331-343

Publication Date(Web):20 Nov 2006

DOI:10.1039/B614390C

Many chemical reactions involve a change in spin-state and are formally forbidden. This article summarises a number of previously published applications showing that a form of Transition State Theory (TST) can account for the kinetics of these reactions. New calculations for the emblematic spin-forbidden reaction HC + N2 are also reported. The observed reactivity is determined by two factors. The first is the critical energy required for reaction to occur, which in spin-forbidden reactions is often defined by the relative energy of the Minimum Energy Crossing Point (MECP) between potential energy surfaces corresponding to the different spin states. The second factor is the probability of hopping from one surface to the other in the vicinity of the crossing region, which is largely defined by the spin–orbit coupling matrix element between the two electronic wavefunctions. The spin-forbidden transition state theory takes both factors into account and gives good results. The shortcomings of the theory, which are largely analogous to those of standard TST, are discussed. Finally, it is shown that in cases where the surface-hopping probability is low, the kinetics of spin-forbidden reactions will be characterised by unusually unfavourable entropies of activation. As a consequence, reactions involving a spin-state change can be expected to compete poorly with spin-allowed reactions at high temperatures (or energies).

Is phenyl a good migrating group in the rearrangement of organoborates generated from sulfur ylides?

Co-reporter:Raphaël Robiette, Guang Yu Fang, Jeremy N. Harvey and Varinder K. Aggarwal

Chemical Communications 2006 (Issue 7) pp:741-743

Publication Date(Web):05 Jan 2006

DOI:10.1039/B514987H

Calculations show that the unexpected low phenyl migratory aptitude observed in reactions of mixed alkyl–aryl boranes with benzylic sulfur ylides can be attributed to (1) a conformational issue, (2) the reduction of the usual neighbouring effect of the phenyl in the transition state by the benzylic nature of the migrating terminus, (3) steric hindrance suffered by the larger phenyl group migrating to the hindered migrating terminus and this despite (4) the increase in the barrier to alkyl migration by the presence of a ‘non-migrating’ phenyl on the boron atom.

Mechanisms of reaction in cytochrome P450: hydroxylation of camphor in P450cam

Co-reporter:Jolanta Zurek, Nicolas Foloppe, Jeremy N. Harvey and Adrian J. Mulholland

Organic & Biomolecular Chemistry 2006 vol. 4(Issue 21) pp:3931-3937

Publication Date(Web):03 Oct 2006

DOI:10.1039/B611653A

The fundamental nature of reactivity in cytochrome P450 enzymes is currently controversial. Modelling of bacterial P450cam has suggested an important role for the haem propionates in the catalysis, though this finding has been questioned. Understanding the mechanisms of this enzyme family is important both in terms of basic biochemistry and potentially in the prediction of drug metabolism. We have modelled the hydroxylation of camphor by P450cam, using combined quantum mechanics/molecular mechanics (QM/MM) methods. A set of reaction pathways in the enzyme was determined. We were able to pinpoint the source of the discrepancies in the previous results. We show that when a correct ionization state is assigned to Asp297, no spin density appears on the haem propionates and the protein structure in this region remains preserved. These results indicate that the haem propionates are not involved in catalysis.

QM and QM/MM studies of selectivity in organic and bioorganic chemistry

Co-reporter:Jeremy N. Harvey;Varinder K. Aggarwal;Christine M. Bathelt;José-Luis Carreón-Macedo;Timothy Gallagher;Nicole Holzmann;Adrian J. Mulholl and;Raphaël Robiette

Journal of Physical Organic Chemistry 2006 Volume 19(Issue 8‐9) pp:608-615

Publication Date(Web):24 APR 2006

DOI:10.1002/poc.1030

Electronic structure methods are used to explore the origin of selectivity in a number of organic, organometallic and bioorganic processes. Diastereoselectivity in reactions of sulfur and phosphorus ylides is shown to arise during a variety of different elementary steps, and is due to steric and electronic effects. Unusual rearranged products from Heck reaction of o-bromo biphenyl derivatives are shown to result from an unusual electrophilic addition step. Predicting selectivity in oxidation of aromatic substrates by cytochrome P450 isoforms is a challenging problem, which can be tackled using hybrid QM/MM methods. Differences in the electronic structure of the Compound I active intermediates of different cytochrome P450 isoforms do not appear to be large enough to explain the different selectivity of these different isoforms. Copyright © 2006 John Wiley & Sons, Ltd.

Development of a Ligand Knowledge Base, Part 1: Computational Descriptors for Phosphorus Donor Ligands

Co-reporter:Natalie Fey Dr.;Athanassios C. Tsipis Dr.;Stephanie E. Harris Dr. Dr.;A. Guy Orpen Dr.;Ralph A. Mansson Dr.

Chemistry - A European Journal 2006 Volume 12(Issue 1) pp:

Publication Date(Web):9 NOV 2005

DOI:10.1002/chem.200500891

A prototype collection of knowledge on ligands in metal complexes, termed a ligand knowledge base (LKB), has been developed. This contribution describes the design of DFT-calculated descriptors for monodentate phosphorus(III) donor ligands in a range of representative complexes. Using the resulting data, a ligand space is mapped and predictive models are derived for metal complexes. Important characteristics, including chemical, computational and statistical robustness for the generation and exploitation of such an LKB are described. Chemical robustness ensures transferability of the descriptors, as well as comprehensive sampling of ligand space. To make the calculations amenable to automation in an e-science setting, a reliable, well-defined computational approach has been sought from which the descriptors can be readily extracted. The LKB has been explored with multivariate statistical methods. Principal component analysis (PCA) is used for the mapping of chemical space, projecting multiple descriptors into scatter plots which illustrate the clustering of chemically similar ligands. Interpretation of the resulting principal components in terms of established steric and electronic properties and the importance of its statistical robustness to variations in the ligand set are discussed. Multiple linear regression (MLR) models have been derived, demonstrating the versatility of the descriptors for modeling varied experimentally determined parameters (bond lengths, reaction enthalpies and bond-stretching frequencies). The importance of re-sampling methods for testing the robustness of predictions is highlighted. A strategy for the construction of a robust LKB suitable for the modeling of ligand and complex behavior is outlined based on these observations.

A computational study of the atmospheric oxidation of nopinone

Co-reporter:Peter J. Lewis, Katherine A. Bennett and Jeremy N. Harvey

Physical Chemistry Chemical Physics 2005 vol. 7(Issue 8) pp:1643-1649

Publication Date(Web):07 Mar 2005

DOI:10.1039/B418909D

Electronic structure calculations are used to derive the overall rate coefficient for hydrogen atom abstraction by the hydroxyl radical from a typical volatile organic compound, nopinone. The branching ratios for abstraction from the seven possible different positions are also obtained. Abstraction from the bridgehead position 1 is found to be important, with a branching ratio of 23%. This prediction differs from that derived using a structure-activity relationship, which suggests much less oxidation in this position, but is in agreement with available experimental evidence, showing formation of significant amounts of products such as 1-hydroxynopinone during terpene oxidation. Calculated rate coefficients are derived from standard transition state theory, with energy barriers, vibrational frequencies and rotational constants for reactants and transition states obtained using density functional theory with the KMLYP functional. This approach was calibrated by calculating the well-known rate coefficients for the simpler volatile organic compounds methane, ethane, propane, cyclobutane and acetone. High-level G3 calculations are possible and were carried out for these simpler systems, giving barrier heights in good agreement with KMLYP. Transition state theory gives surprisingly good results for the rate coefficients, probably in part due to error cancellation. This validates the use of the same relatively low level of theory for exploring reactivity and selectivity in oxidation of complex molecules such as nopinone.

Insight into metal–phosphorus bonding from analysis of the electronic structure of redox pairs of metal–phosphine complexes

Co-reporter:Tom Leyssens, Daniel Peeters, A. Guy Orpen and Jeremy N. Harvey

New Journal of Chemistry 2005 vol. 29(Issue 11) pp:1424-1430

Publication Date(Web):07 Sep 2005

DOI:10.1039/B508219F

Density functional theory calculations reproduce the changes in geometry which are observed experimentally upon oxidation of a range of metal phosphine complexes. Removal of one electron from the metal leads to an increase in the M–P bond length, along with a decrease in pyramidalization at the phosphorus atom. These changes had previously been used to suggest that π back-bonding from the metal to the P–R σ* antibonding orbitals plays a role even in complexes of simple alkyl- and aryl-phosphines. Similar changes in geometry are found upon one electron oxidation of the simple model species Cr(CO)5(PR3) and Mo(CO)5(PR3) (R = H or Me). The analogous ammonia complexes instead undergo a decrease of the M–N bond length upon ionization, consistent with stronger σ-bonding upon increasing the charge on the metal atom. Analysis of the electron density in the neutral and cationic species, and of the change in density (this is the finite difference Fukui function) also shows evidence of π back-bonding in the neutral species, and much less in the cationic form.

On the Importance of Leaving Group Ability in Reactions of Ammonium, Oxonium, Phosphonium, and Sulfonium Ylides

Co-reporter:Varinder K. Aggarwal, Jeremy N. Harvey,Raphaël Robiette

Angewandte Chemie International Edition 2005 44(34) pp:5468-5471

Publication Date(Web):

DOI:10.1002/anie.200501526

On the Importance of Leaving Group Ability in Reactions of Ammonium, Oxonium, Phosphonium, and Sulfonium Ylides

Co-reporter:Varinder K. Aggarwal Dr.;Raphaël Robiette Dr.

Angewandte Chemie 2005 Volume 117(Issue 34) pp:

Publication Date(Web):1 AUG 2005

DOI:10.1002/ange.200501526

Was lenkt die Reaktivität von Yliden? Theoretische Studien zeigen, dass der Verlauf der im Schema gezeigten Reaktionen hauptsächlich vom Austrittsvermögen der Onium-Abgangsgruppen bestimmt wird. Dieses nimmt aus sowohl kinetischen wie auch thermochemischen Gründen in der Reihe O>S>N>P ab. Die Ergebnisse bestätigen experimentelle Befunde und erklären, warum nur wenige Beispiele für solche Reaktionen mit Phosphor-yliden existieren.

Accurate modelling of Pd(0) + PhX oxidative addition kinetics

Co-reporter:Claire L. McMullin, Jesús Jover, Jeremy N. Harvey and Natalie Fey

Dalton Transactions 2010 - vol. 39(Issue 45) pp:NaN10836-10836

Publication Date(Web):2010/10/20

DOI:10.1039/C0DT00778A

Organometallic reactivity: the role of metal–ligand bond energies from a computational perspective

Co-reporter:Natalie Fey, Benjamin M. Ridgway, Jesús Jover, Claire L. McMullin and Jeremy N. Harvey

Dalton Transactions 2011 - vol. 40(Issue 42) pp:NaN11191-11191

Publication Date(Web):2011/08/19

DOI:10.1039/C1DT10909J

Computed ligand effects on the oxidative addition of phenyl halides to phosphine supported palladium(0) catalysts

Co-reporter:Claire L. McMullin, Natalie Fey and Jeremy N. Harvey