Journal of Computational Chemistry

Cullen, John

doi: 10.1002/jcc.20808pmid: 17663438

The slow computational speed of the generalized valence bond perfect pairing method (GVB‐PP) has been an impediment to its routine use. We have addressed this problem by employing a diatomics in molecules Hamiltonian derived from a second quantization perturbation approach. This results in all three‐ and four‐centered two‐electron integrals being dropped from the traditional GVB‐PP calculation. For moderate sized molecules, as for example C20 computed with a double zeta + polarization basis, there is on average a fifty‐fold decrease in computational times. In this article, we present the theory behind our approach and analyze the accuracy and speed of this approximate GVB‐PP method for several cases where density functional methods have produced ambivalent results. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Fan, Xiao‐Wei; Ju, Xue‐Hai

doi: 10.1002/jcc.20809pmid: 17663437

Density functional theory (DFT) method has been employed to study the geometric and electronic structures of a series of four‐membered ring compounds at the B3LYP/6‐311G** and the B3P86/6‐311G** levels. In the isodesmic reactions designed for the computation of heats of formation (HOFs), 3,3‐dimethyl‐oxetane, azetidine, and cyclobutane were chosen as reference compounds. The HOFs for N3 substituted derivations are larger than those of oxetane compounds with ONO2 and/or NF2 substituent groups. The HOFs for oxetane with ONO2 and/or NF2 substituent groups are negative, while the HOFs for N3 substituted derivations are positive. For azetidine compounds, the substituent groups within the azetidine ring affect the HOFs, which increase as the difluoroamino group being replaced by the nitro group. The magnitudes of intramolecular group interactions were predicted through the disproportionation energies. The strain energy (SE) for the title compounds has been calculated using homodesmotic reactions. For azetidine compounds, the NF2 group connecting N atom in the ring decrease the SE of title compounds. Thermal stability were evaluated via bond dissociation energies (BDE) at the UB3LYP/6‐311G** level. For the oxetane compounds, the ONO2 bond is easier to break than that of the ring CC bond. For the azetidine and cyclobutane compounds, the homolysises of CNX2 and/or NNX2 (X = O, F) bonds are primary step for bond dissociation. Detonation properties of the title compounds were evaluated by using the Kamlet–Jacobs equation based on the calculated densities and HOFs. It is found that 1,1‐dinitro‐3,3‐bis(difluoroamino)‐cyclobutane, with predicted density of ca. 1.9 g/cm3, detonation velocity (D) over 9 km/s, and detonation pressure (P) of 41 GPa that are lager than those of TNAZ, is expected to be a novel candidate of high energy density materials (HEDMs). The detonation data of nitro‐BDFAA and TNCB are also close to the requirements for HEDMs. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Gao, Jiali; Wong, Kin‐Yiu; Major, Dan T.

doi: 10.1002/jcc.20810pmid: 17722009

An integrated Feynman path integral‐free energy perturbation and umbrella sampling (PI‐FEP/UM) method has been used to investigate the kinetic isotope effects (KIEs) in the proton transfer reaction between nitroethane and acetate ion in water. In the present study, both nuclear and electronic quantum effects are explicitly treated for the reacting system. The nuclear quantum effects are represented by bisection sampling centroid path integral simulations, while the potential energy surface is described by a combined quantum mechanical and molecular mechanical (QM/MM) potential. The accuracy essential for computing KIEs is achieved by a FEP technique that transforms the mass of a light isotope into a heavy one, which is equivalent to the perturbation of the coordinates for the path integral quasiparticle in the bisection sampling scheme. The PI‐FEP/UM method is applied to the proton abstraction of nitroethane by acetate ion in water through molecular dynamics simulations. The rule of the geometric mean and the Swain–Schaad exponents for various isotopic substitutions at the primary and secondary sites have been examined. The computed total deuterium KIEs are in accord with experiments. It is found that the mixed isotopic Swain–Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Pitarch‐Ruiz, J.; Sánchez‐Marín, J.; Velasco, A. M.

doi: 10.1002/jcc.20811pmid: 17722010

The all‐electron full configuration interaction (FCI) vertical excitation energies for some low lying valence and Rydberg excited states of BeH are presented in this article. A basis set of valence atomic natural orbitals has been augmented with a series of Rydberg orbitals that have been generated as centered onto the Be atom. The resulting basis set can be described as 4s2p1d/2s1p (Be/H) + 4s4p3d. It allows to calculate Rydberg states up to n= {3,4,5} of the s, p, and d series of Rydberg states. The FCI vertical ionization potential for the same basis set and geometry amounts to 8.298 eV. Other properties such as FCI electric dipole and quadrupole moments and FCI transition dipole and quadrupole moments have also been calculated. The results provide a set of benchmark values for energies, wave functions, properties, and transition properties for the five electron BeH molecule. Most of the states have large multiconfigurational character in spite of their essentially single excited nature and a number of them present an important Rydberg‐valence mixing that is achieved through the mixed nature of the particle MO of the single excitations. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Cruz‐Monteagudo, Maykel; Cordeiro, M. Natália D. S.; Borges, Fernanda

doi: 10.1002/jcc.20812pmid: 17705164

Idiosyncratic drug toxicity (IDT), considered as a toxic host‐dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clinical trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually <1/5000), IDT is often life threatening and is one of the major reasons new drugs never reach the market or are withdrawn post marketing. Computational methodologies, like the computer‐based approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant analysis (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D molecular structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over‐fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross‐validation statistics and predictivity on an external subset of chemicals. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, respectively in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA‐based desirability analysis was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacologically related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, respectively. The computational approach proposed here can be considered as a useful tool in early IDT prognosis. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Yang, Lei; Liu, Jing‐Yao; Wang, Li; He, Hong‐Qing; Wang, Ying; Li, Ze‐Sheng

doi: 10.1002/jcc.20813pmid: 17705163

A dual‐level direct dynamic method is employed to study the reaction mechanisms of CF3CH2OCHF2 (HFE‐245fa2; HFE‐245mf) with the OH radicals and Cl atoms. Two hydrogen abstraction channels and two displacement processes are found for each reaction. For further study, the reaction mechanisms of its products (CF3CH2OCF2 and CF3CHOCHF2) and parent ether CH3CH2OCH3 with OH radical are investigated theoretically. The geometries and frequencies of all the stationary points and the minimum energy paths (MEPs) are calculated at the B3LYP/6‐311G(d,p) level. The energetic information along the MEPs is further refined at the G3(MP2) level of theory. For reactions CF3CH2OCHF2 + OH/Cl, the calculation indicates that the hydrogen abstraction from CH2 group is the dominant reaction channel, and the displacement processes may be negligible because of the high barriers. The standard enthalpies of formation for the reactant CF3CH2OCHF2, and two products CF3CH2OCF2 and CF3CHOCHF2 are evaluated via group‐balanced isodesmic reactions. The rate constants of reactions CF3CH2OCHF2 + OH/Cl and CH3CH2OCH3 + OH are estimated by using the variational transition state theory over a wide range of temperature (200–2000 K). The agreement between the theoretical and experimental rate constants is good in the measured temperature range. From the comparison between the rate constants of the reactions CF3CH2OCHF2 and CH3CH2OCH3 with OH, it is shown that the fluorine substitution decreases the reactivity of the CH bond. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Kenny, Joseph P.; Janssen, Curtis L.; Valeev, Edward F.; Windus, Theresa L.

doi: 10.1002/jcc.20815pmid: 17721922

Sharing low‐level functionality between software packages enables more rapid development of new capabilities and reduces the duplication of work among development groups. Using the component approach advocated by the Common Component Architecture Forum, we have designed a flexible interface for sharing integrals between quantum chemistry codes. Implementation of these interfaces has been undertaken within the Massively Parallel Quantum Chemistry package, exposing both the IntV3 and Cints/Libint integrals packages to component applications. Benchmark timings for Hartree‐Fock calculations demonstrate that the overhead due to the added interface code varies significantly, from less than 1% for small molecules with large basis sets to nearly 10% for larger molecules with smaller basis sets. Correlated calculations and density functional approaches encounter less severe performance overheads of less than 5%. While these overheads are acceptable, additional performance losses occur when arbitrary implementation details, such as integral ordering within buffers, must be handled. Integral reordering is observed to add an additional overhead as large as 12%; hence, a common standard for such implementation details is desired for optimal performance. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Forti, Flavio; Barril, Xavier; Luque, F. Javier; Orozco, Modesto

doi: 10.1002/jcc.20814pmid: 17705247

The need to simulate large‐sized molecules or to deal with large series of compounds is a challenging topic in computational chemistry, which has stimulated the development of accurate semiempirical methods, such as the recently reported Recife Model 1 (RM1; J Comput Chem 2006, 27, 1101). Even though RM1 may prove to be of value simply due to the enhanced quantitative accuracy in gas phase, it is unclear how the new parameters optimized for RM1 affect the suitability of this semiempirical Hamiltonian to study chemical processes in condensed phases. To address this question, we report the parametrization of the MST/RM1 continuum model for neutral solutes in water, octanol, chloroform and carbon tetrachloride, and for ions in water. The results are used to discuss the transferability of the solvation parameters implemented in previous MST/AM1 and MST/PM3 models. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Contreras, M. L.; Alvarez, J.; Guajardo, D.; Rozas, R.

doi: 10.1002/jcc.20816pmid: 17721880

An algorithm based on heuristic rules for topological symmetry perception of organic structures having heteroatoms, multiple bonds, and any kind of cycle, and configuration, is presented. This algorithm identifies topological symmetry planes and sets of equivalent atoms in the structure, named symmetry atom groups (SAGs). This approach avoids both the need to explore the entire graph automorphism groups, and to encompass cycle determination, resulting in a very effective computer processing. Applications to several structures, some of them highly symmetrical such as dendrimers, are presented. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Liu, Aibing; Stuart, Steven J.

doi: 10.1002/jcc.20817pmid: 17786913

Bond‐order potentials provide a powerful class of models for simulating chemically reactive systems with classical potentials. In these models, the covalent bonding interactions adapt to the environment, allowing bond strength to change in response to local chemical changes. However, the non‐bonded interactions should also adapt in response to chemical changes, an effect which is neglected in current bond‐order potentials. Here the AIREBO potential is extended to include adaptive Lennard‐Jones terms, allowing the van der Waals interactions to vary adaptively with the chemical environment. The resulting potential energy surface and its gradient remain continuous, allowing it to be used for dynamics simulations. This new potential is parameterized for hydrocarbons, and is fit to the energetics and densities of a variety of condensed phase molecular hydrocarbons. The resulting model is more accurate for modeling aromatic and other unsaturated hydrocarbon species, for which the original AIREBO potential had some deficiencies. Testing on compounds not used in the fitting procedure shows that the new model performs substantially better in predicting heats of vaporization and pressures (or densities) of condensed‐phase molecular hydrocarbons. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008