A comprehensive understanding of structure–reactivity relationships is critical to the design and optimization of cysteine-targeted covalent inhibitors. Herein, we report glutathione (GSH) reaction rates for N-phenyl acrylamides with varied substitutions at the α- and β-positions of the acrylamide moiety. We find that the GSH reaction rates can generally be understood in terms of the electron donating or withdrawing ability of the substituent. When installed at the β-position, aminomethyl substituents with amine pK a’s > 7 accelerate, while those with pK a’s < 7 slow the rate of GSH addition at pH 7.4, relative to a hydrogen substituent. Although a computational model was able to only approximately capture experimental reactivity trends, our calculations do not support a frequently invoked mechanism of concerted amine/thiol proton transfer and C–S bond formation and instead suggest that protonated aminomethyl functions as an electron-withdrawing group to reduce the barrier for thiolate addition to the acrylamide.

In this paper we present embedded-cluster calculations on singly charged and neutral oxygen vacancies (or F centres) in the oxide perovskite BaTiO3. The simulations include Hartree-Fock theory with MP2 corrections and density-functional-theory calculations for a central quantum defect cluster and a pair-potential description of the embedding lattice. All important defect-induced lattice distortions are taken into account in this way. We discuss the possible electronic states of charged F centres and the effects of nearby acceptor-type defects. It is shown that isolated oxygen vacancies induce electronic deep-gap levels. Scenarios are discussed to account for shallow-gap levels observed experimentally.

Optimization of a transition state typically requires both a good initial guess of the molecular structure and one or more computationally demanding Hessian calculations to converge reliably. Often, the transition state being optimized corresponds to the barrier in a chemical reaction where bonds are being broken and formed. Utilizing the geometries and bonding information for reactants and products, an algorithm is outlined to reliably interpolate an initial guess for the transition state geometry. Additionally, the change in bonding is also used to increase the reliability of transition state optimizations that utilize approximate and updated Hessian information. These methods are described and compared against standard transition state optimization methods.

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The development of algorithms to optimize reaction pathways between reactants and products is an active area of study. Existing algorithms typically describe the path as a discrete series of images (chain of states) which are moved downhill toward the path, using various reparameterization schemes, constraints, or fictitious forces to maintain a uniform description of the reaction path. The Variational Reaction Coordinate (VRC) method is a novel approach that finds the reaction path by minimizing the variational reaction energy (VRE) of Quapp and Bofill. The VRE is the line integral of the gradient norm along a path between reactants and products and minimization of VRE has been shown to yield the steepest descent reaction path. In the VRC method, we represent the reaction path by a linear expansion in a set of continuous basis functions and find the optimized path by minimizing the VRE with respect to the linear expansion coefficients. Improved convergence is obtained by applying constraints to the spacing of the basis functions and coupling the minimization of the VRE to the minimization of one or more points along the path that correspond to intermediates and transition states. The VRC method is demonstrated by optimizing the reaction path for the Müller-Brown surface and by finding a reaction path passing through 5 transition states and 4 intermediates for a 10 atom Lennard-Jones cluster.

Classical shell-model-and embedded-cluster-rype cdculuians are employed in order to supply thearetical arguments in favour of hale bipolarons in BaTiOx which have recently been speculated to exist in this photorefractive material. Our investigations concern the geometrical structure of hole bipolaram trapped at acceptor defects, their spin state and hole ionization energies. In particular the embedded-cluster modelling studies, which explicitly include the local electronic defect strncture. suggest the importance of lattice relaxation and electron correlation terms in order to stabilize diamosetic 0:-molecules (bipolaram) in BaTiO3. Our simulations show that hole bipalnrans arc predominantly bound at Ti-site acceptor defects. A trapping of bipolarons at Ba-site acceptors is in most cases unfavourable. Finally. by extrapolating OUT present results to the high-T, superconducting oxides we qualitatively discuss the possible r6le of small hole (perouy) bipolamns in these materials.

Reaction path optimization is being used more frequently as an alternative to the standard practice of locating a transition state and following the path downhill. The Variational Reaction Coordinate (VRC) method was proposed as an alternative to chain-of-states methods like nudged elastic band and string method. The VRC method represents the path using a linear expansion of continuous basis functions, allowing the path to be optimized variationally by updating the expansion coefficients to minimize the line integral of the potential energy gradient norm, referred to as the Variational Reaction Energy (VRE) of the path. When constraints are used to control the spacing of basis functions and to couple the minimization of the VRE with the optimization of one or more individual points along the path (representing transition states and intermediates), an approximate path as well as the converged geometries of transition states and intermediates along the path are determined in only a few iterations. This algorithmic efficiency comes at a high per-iteration cost due to numerical integration of the VRE derivatives. In the present work, methods for incorporating redundant internal coordinates and potential energy surface interpolation into the VRC method are described. With these methods, the per-iteration cost, in terms of the number of potential energy surface evaluations, of the VRC method is reduced while the high algorithmic efficiency is maintained.

Defect electrons (holes) play an important role in most technologically important complex oxides. In this contribution we present the first detailed characterization of localized hole states in such materials. Our investigations employ advanced embedded-cluster calculations which consistently include electron correlations and defect-induced lattice relaxations. This is necessary in order to account for the variety of possible hole-state manifestations.PACS numbers: 71.55Ht, 71.50.+t I. INTRODUCTIONThe basic structural building units of solid oxides are MO 6 metal-oxygen octahedra and, possibly, additional MO 4 tetrahedra. The complete crystal structure is built up of corner-, face-and/or edge-sharing connections of these structural elements. Additional cations (A) can be incorporated at interstitial lattice sites. These are increasingly formed, the more open-structured the whole network of MO n units appears to be. Generally, open crystal structures imply high formal M-cation charge states (referring to formal O 2− anions) leading to mixed ionic-covalent (or semiionic) material properties. The M-cations are in most cases transition-metal (TM) ions. Examples of such complex materials are given by AMO 3 perovskite-structured oxides such as barium titanate (BaTiO 3 ). Perovskite oxides are frequently ferroelectric and possess important electrooptic applications based on the photorefractive effect. Also high-T C oxides resemble the perovskite structure.Charge carriers, either valence-band (VB) holes or conduction-band (CB) electrons, are created by doping with impurities, annealing treatments or by light-induced charge-transfer excitations which, for example, take place during photorefractive processes in the appropriate oxides. Combined optical-absorption-and electron-spin-resonance measurements (Photo-ESR) [1] proved that the created and afterwards trapped holes influence the light-induced charge-transfer reactions in photorefractive BaTiO 3 . These holes, which are either para-or diamagnetic, probably induce the observed sublinear dependence of photoconductivity on the light intensity (e.g. [2]). A further example highlighting the relevance of holes refers to high-T C oxides: Pairs of doped holes give rise to superconductivity in these materials. The possible pairing scenarios are still a matter of active debate.The present work initiates a systematic and detailed characterization of localized hole states in complex oxides. Our investigations employ real-space embedded-cluster calculations, which consistently combine electron correlations and defect-induced lattice relaxations. This procedure is indispensable in order to predict the richness of possible hole states. Here, we demonstrate simulations for trapped holes in BaTiO 3 , but many results, ranging from stabilization of cationic charge states to the formation of bipolarons, can be extrapolated to other oxides.The trapping of holes at acceptor defects leads to a localization of hole states, which is further aided by defectinduced lattice distortions. In near-...