This study shows that the chemical reactivities depend on the orbital energy gaps contributing to the reactions. In the process where a reaction only makes progress through charge transfer with the minimal structural transformation of the reactant, the orbital energy gap gradient (OEGG) between the electron-donating and electron-accepting orbitals is proven to be very low. Using this relation, a normalized reaction diagram is constructed by plotting the normalized orbital energy gap with respect to the normalized intrinsic reaction coordinate. Application of this reaction diagram to 43 fundamental reactions showed that the majority of the forward reactions provide small OEGGs in the initial stages, and therefore, the initial processes of the forward reactions are supposed to proceed only through charge transfer. Conversely, more than 60% of the backward reactions are found to give large OEGGs implying very slow reactions associated with considerable structural transformations. Focusing on the anti-activation-energy reactions, in which the forward reactions have higher barriers than those of the backward ones, most of these reactions are shown to give large OEGGs for the backward reactions. It is also found that the reactions providing large OEGGs in the forward directions inconsistent with the reaction rate constants are classified into S* _{N}*2, symmetric, and methyl radical reactions. Interestingly, several large-OEGG reactions are experimentally established to get around the optimum pathways. This indicates that the reactions can take significantly different pathways from the optimum ones provided no charge transfer proceeds spontaneously without the structural transformations of the reactants. © 2014 Wiley Periodicals, Inc.

Chemical reactivity depends on the orbital energy gap contributing to the reaction in the initial reaction process. This is because the small orbital energy gap gradient indicates the precursory charge transfer process, while the large gradient implies the initial structural transformation. Analyses using a normalized reaction diagram show that large orbital energy gap gradients are given for specific reactions, including several S_{N}2 reactions, which are experimentally established to get around the optimum reaction pathways.

We derive compact expressions of the second-order derivatives of bond length, bond angle, and proper and improper torsion angle potentials, in terms of operators represented in two orthonormal bases. Hereby, simple rules to generate the Hessian of an internal coordinate or a molecular potential can be formulated. The algorithms we provide can be implemented efficiently in high-level programming languages using vectorization. Finally, the method leads to compact expressions for a second-order expansion of an internal coordinate or a molecular potential. © 2014 Wiley Periodicals, Inc.

Compact expressions for the derivatives of a molecular potential are important for use in theoretical and practical applications. In this work, the second-order derivatives are expanded in terms of operators. This leads to a new set of formulas that can be implemented efficiently in high-level programming languages.

Hydrolysis reactions of benzyl chlorides and benzenesulfonyl chlorides were theoretically investigated with the density functional theory method, where the water molecules are explicitly considered. For the hydrolysis of benzyl chlorides (para-ZC_{6}H_{4}CH_{2}Cl), the number of water molecules (*n*) slightly influences the transition-state (TS) structure. However, the para-substituent (Z) of the phenyl group significantly changes the reaction process from the stepwise (S_{N}1) to the concerted (S_{N}2) pathway when it changes from the typical electron-donating group (EDG) to the typical electron-withdrawing one (EWG). The EDG stabilizes the carbocation (MeOC_{6}H_{4}CH_{2}^{+}), which in turn makes the S_{N}1 mechanism more favorable and vice versa. For the hydrolysis of benzenesulfonyl chlorides (para-ZC_{6}H_{4}SO_{2}Cl), both the Z group and *n* influence the TS structure. For the combination of the large *n* value (*n* > 9) and EDG, the S_{N}2 mechanism was preferred. Conversely, for the combination of the small *n* value and EWG, the S_{N}3 one was more favorable. © 2014 Wiley Periodicals, Inc.

Transition states of hydrolysis reactions ZC_{6}H_{4}XCl are investigated with specific water molecules (*n* = 6, 9, 11, 17, 23, and 29), where X = CH_{2}, and SO_{2} and Z = O_{2}N, Cl, H, H_{3}C, and H_{3}CO. In the case of a large *n* value and an electron-donating Z group, the hydrolysis reaction occurs through a S_{N}2 mechanism. However, the combination of a small *n* value and an electron-withdrawing Z group converts the reaction mechanism to S_{N}3.

Virtual screening of a large chemical library for drug lead identification requires searching/superimposing a large number of three-dimensional (3D) chemical structures. This article reports a graphic processing unit (GPU)-accelerated weighted Gaussian algorithm (gWEGA) that expedites shape or shape-feature similarity score-based virtual screening. With 86 GPU nodes (each node has one GPU card), gWEGA can screen 110 million conformations derived from an entire ZINC drug-like database with diverse antidiabetic agents as query structures within 2 s (i.e., screening more than 55 million conformations per second). The rapid screening speed was accomplished through the massive parallelization on multiple GPU nodes and rapid prescreening of 3D structures (based on their shape descriptors and pharmacophore feature compositions). © 2014 Wiley Periodicals, Inc.

A graphic processing unit (GPU)-accelerated weighted Gaussian algorithm for shape and/or pharmacophore features-based molecular superimposing is reported. The algorithm can search more than 55 million three-dimensional structures per second with multiple GPU nodes.

**Almost** (**al**l atom **mo**lecular **s**imulation **t**oolkit) is an open source computational package for structure determination and analysis of complex molecular systems including proteins, and nucleic acids. **Almost** has been designed with two primary goals: to provide tools for molecular structure determination using various types of experimental measurements as conformational restraints, and to provide methods for the analysis and assessment of structural and dynamical properties of complex molecular systems. The methods incorporated in **Almost** include the determination of structural and dynamical features of proteins using distance restraints derived from nuclear Overhauser effect measurements, orientational restraints obtained from residual dipolar couplings and the structural restraints from chemical shifts. Here, we present the first public release of **Almost**, highlight the key aspects of its computational design and discuss the main features currently implemented. **Almost** is available for the most common Unix-based operating systems, including Linux and Mac OS X. **Almost** is distributed free of charge under the GNU Public License, and is available both as a source code and as a binary executable from the project web site at http://www.open-almost.org. Interested users can follow and contribute to the further development of **Almost** on http://sourceforge.net/projects/almost. © 2014 Wiley Periodicals, Inc.

“**Almost**” (all atom molecular simulation toolkit) is an open source computational package for the structure determination and analysis of biomolecules. **Almost** provides tools for the molecular structure determination using various types of experimental measurements as conformational restraints and methods for the analysis of structural and dynamical properties of complex molecular systems.

The concept of “electron deformation orbitals” (EDOs) is used to investigate the electric response of conducting metals and oligophenyl chains. These orbitals and their eigenvalues are obtained by diagonalization of the deformation density matrix (difference between the density matrices of the perturbed and unperturbed systems) and can be constructed as linear combinations of the unperturbed molecular orbitals within “frozen geometry” conditions. This form of the EDOs allows calculating the part of the electron deformation density associated to an effective electron transfer from occupied to virtual orbitals (valence to conduction band electron transfer in the band model of conductivity). It is found that the “electron deformation” orbitals pair off, displaying the same eigenvalue but opposite sign. Each pair represents an amount of accumulation/depletion of electron charge at different molecular regions. In the oligophenyl systems investigated only one pair contributes effectively to the charge flow between molecular ends, resulting from the promotion of electrons from occupied orbitals to close in energy virtual orbitals of appropriate symmetry and overlapping. Analysis of this pair along explains the differences in conductance of olygophenyl chains based on phenyl units. © 2014 Wiley Periodicals, Inc.

Electron deformation orbitals and occupied-virtual electron transfer induced by a constant external electric perturbation provide an orbital picture of the charge transfer process. The proposed methodology is qualitatively related to the band model of conductivity and allows discernment between good and poor unimolecular conductors in terms of their electronic structure.

In hybrid particle models where coarse-grained beads and atoms are used simultaneously, two clearly separate time scales are mixed. If such models are used in molecular dynamics simulations, a multiple time step (MTS) scheme can therefore be used. In this manuscript, we propose a simple MTS algorithm which approximates for a specific number of integration steps the slow coarse-grained bead–bead interactions with a Taylor series approximation while the atom–atom ones are integrated every time step. The procedure is applied to a previously developed hybrid model of a melt of atactic polystyrene (di Pasquale, Marchisio, and Carbone, *J. Chem. Phys*. 2012, 137, 164111). The results show that structure, local dynamics, and free diffusion of the model are not altered by the application of the integration scheme which can confidently be used to simulate multiresolved models of polymer melts. © 2014 Wiley Periodicals, Inc.

In the dual-resolved model, bead–bead and atom–atom interactions are sampled with two different timestep values. For *k* timesteps, bead–bead forces are approximated with their Taylor expansion:

An assessment of the orbital-optimized coupled-electron pair theory [or simply “optimized CEPA(0),” OCEPA(0)] [Bozkaya and Sherrill, *J. Chem. Phys*. 2013, 139, 054104] for thermochemistry and kinetics is presented. The OCEPA(0) method is applied to closed- and open-shell reaction energies, barrier heights, and radical stabilization energies (RSEs). The performance of OCEPA(0) is compared with those of the MP2, CEPA(0), OCEPA(0), CEPA(1), coupled-cluster singles and doubles (CCSD), and CCSD(T) methods [at complete basis set limits employing cc-pVTZ and cc-pVQZ basis sets]. For the most of the test sets, the OCEPA(0) method performs better than CEPA(0), CEPA(1), and CCSD, and provides accurate results. Especially, for open-shell reaction energies and barrier heights, the OCEPA(0)–CEPA(1) and OCEPA(0)–CCSD differences become obvious. Similarly, for barrier heights and RSEs, the OCEPA(0) method improves on CEPA(0) by 1.6 and 2.3 kcal mol^{−1}. Our results demonstrate that the CEPA(0) method dramatically fails when the reference wave function suffers from the spin-contamination problem. Conversely, the OCEPA(0) method can annihilate spin-contamination in the unrestricted-Hartree–Fock initial guess orbitals and can yield stable solutions. For overall evaluation, we conclude that the OCEPA(0) method is quite helpful not only for problematic open-shell systems and transition-states but also for closed-shell molecules. Hence, one may prefer OCEPA(0) over CEPA(0), CEPA(1), and CCSD as an
method, where *N* is the number of basis functions, for thermochemistry and kinetics. As discussed previously, the cost of the OCEPA(0) method is as much as of CCSD and CEPA(1) for energy computations. However, for analytic gradient computations, the OCEPA(0) method is two times less expensive than CCSD and CEPA(1). Further, the stationary properties of the OCEPA(0) method making it promising for excited state properties via linear response theory. © 2014 Wiley Periodicals, Inc.

An assessment of the orbital-optimized coupled-electron pair theory [or simply “optimized CEPA(0)”, OCEPA(0)] [Bozkaya and Sherrill, *J. Chem. Phys*., 2013, **139**, 054104] for thermochemistry and kinetics is presented. Our results demonstrate that the OCEPA(0) method is quite helpful for problematic open-shell systems and transition-states as well as for closed-shell molecules.

An ultrafast shape-recognition technique was used to analyze the phase transition of finite-size clusters, which, according to our research, has not yet been accomplished. The shape of clusters is the unique property that distinguishes clusters from bulk systems and is comprehensive and natural for structural analysis. In this study, an isothermal molecular dynamics simulation was performed to generate a structural database for shape recognition of AgCu metallic clusters using empirical many-body potential. The probability contour of the shape similarity exhibits the characteristics of both the specific heat and Lindemann index (bond-length fluctuation) of clusters. Moreover, our implementation of the substructure to the probability of shapes provides a detailed observation of the atom/shell-resolved analysis, and the behaviors of the clusters were reconstructed based on the statistical information. The method is efficient, flexible, and applicable in any type of finite-size system, including polymers and nanostructures. © 2014 Wiley Periodicals, Inc.

An ultrafast shape recognition technique was applied to analyze the phase transition of finite-size clusters. The shape of clusters is the unique property that distinguishes clusters from bulk systems, and is comprehensive and natural for structural analysis. The probability contour and the implementation of the substructure provide insightful atom/shell-resolved perspectives. The method can considerably simplify the tedious trajectory analysis and is efficient in any type of finite-size system, including polymers and nanostructures.

In this work, first-principles density functional theory (DFT) is used to predict oxygen adsorption on two types of hybrid carbon and boron-nitride nanotubes (CBNNTs), zigzag (8,0), and armchair (6,6). Although the chemisorption of O_{2} on CBNNT(6,6) is calculated to be a thermodynamically unfavorable process, the binding of O_{2} on CBNNT(8,0) is found to be an exothermic process and can form both chemisorbed and physisorbed complexes. The CBNNT(8,0) has very different O_{2} adsorption properties compared with pristine carbon nanotubes (CNTs) and boron-nitride nanotube (BNNTs). For example, O_{2} chemisorption is significantly enhanced on CBNNTs, and O_{2} physisorption complexes also show stronger binding, as compared to pristine CNTs or BNNTs. Furthermore, it is found that the O_{2} adsorption is able to increase the conductivity of CBNNTs. Overall, these properties suggest that the CBNNT hybrid nanotubes may be useful as a gas sensor or as a catalyst for the oxygen reduction reaction. © 2014 Wiley Periodicals, Inc.

Hybrid carbon nanotube and boron-nitride nanotube materials have been recently synthesized in the lab. Here, DFT calculations indicate that molecular oxygen adsorption is significantly enhanced on these hybrid carbon and boron-nitride nanotube materials, versus on pristine nanotubes. Furthermore, the large change in the band gap upon oxygen adsorption may provide unique sensing capabilities, in addition to other catalytic properties, motivating further experimental investigations.

We have developed a new hybrid (MPI+OpenMP) parallelization scheme for molecular dynamics (MD) simulations by combining a cell-wise version of the midpoint method with pair-wise Verlet lists. In this scheme, which we call the midpoint cell method, simulation space is divided into subdomains, each of which is assigned to a MPI processor. Each subdomain is further divided into small cells. The interaction between two particles existing in different cells is computed in the subdomain containing the midpoint cell of the two cells where the particles reside. In each MPI processor, cell pairs are distributed over OpenMP threads for shared memory parallelization. The midpoint cell method keeps the advantages of the original midpoint method, while filtering out unnecessary calculations of midpoint checking for all the particle pairs by single midpoint cell determination prior to MD simulations. Distributing cell pairs over OpenMP threads allows for more efficient shared memory parallelization compared with distributing atom indices over threads. Furthermore, cell grouping of particle data makes better memory access, reducing the number of cache misses. The parallel performance of the midpoint cell method on the K computer showed scalability up to 512 and 32,768 cores for systems of 20,000 and 1 million atoms, respectively. One MD time step for long-range interactions could be calculated within 4.5 ms even for a 1 million atoms system with particle-mesh Ewald electrostatics. © 2014 Wiley Periodicals, Inc.

A new hybrid (MPI+OPENMP) parallelization scheme is developed for molecular dynamics (MD) simulations introducing a cell-wise version of the midpoint method, named the “midpoint cell method.” This method retains the advantages of the original midpoint method for MPI parallelization, and it allows efficient shared memory parallelization by grouping particle data cell-wise and distributing cell pairs over OPENMP threads. The parallel performance of the midpoint cell method on a K computer shows scalability up to 32,768 cores for a system of 1 million atoms. One MD step with long-range interaction can be calculated within 4.5 ms.

Elastic network models (ENM) are based on the idea that the geometry of a protein structure provides enough information for computing its fluctuations around its equilibrium conformation. This geometry is represented as an elastic network (EN) that is, a network of links between residues. A spring is associated with each of these links. The normal modes of the protein are then identified with the normal modes of the corresponding network of springs. Standard approaches for generating ENs rely on a cutoff distance. There is no consensus on how to choose this cutoff. In this work, we propose instead to filter the set of all residue pairs in a protein using the concept of alpha shapes. The main alpha shape we considered is based on the Delaunay triangulation of the Cα positions; we referred to the corresponding EN as EN(*∞*). We have shown that heterogeneous anisotropic network models, called αHANMs, that are based on EN(*∞*) reproduce experimental B-factors very well, with correlation coefficients above 0.99 and root-mean-square deviations below 0.1 Å^{2} for a large set of high resolution protein structures. The construction of EN(*∞*) is simple to implement and may be used automatically for generating ENs for all types of ENMs. © 2014 Wiley Periodicals, Inc.

The image shows a comparison of the elastic networks generated by the conventional cutoff-based approach (top) and alpha shape theory (bottom). The protein's Protein Data Bank code is 1LTU. The figure shows the detailed spring connections for the protrusion part of the protein, as elastic network models based on cutoffs have difficulty in accurately reproducing the experimental B-factors in this region. Excellent agreement with the experimental B-factor is achieved after removing a few pairwise connections according to the alpha shape theory.

The analysis of chemical bonding in Zintl anions and complexes thereof is mostly based on frontier molecular orbital (FMO) analysis. While this approach delivers remarkable insights, it falls short of providing quantitative measures for chemical bonding in these compounds. Here, we investigate the organozinc-ligated Zintl anions [Sn_{2}E^{15}_{2}(ZnPh)]^{−} (E^{15} = Sb, Bi) and [Sn_{2}Sb_{5}(ZnPh)_{2}]^{3-} with charge and energy analysis methods. Partial charge analysis confirms that natural population analysis is more reliable than the Hirshfeld method for the diffuse charge density of the Zintl anions. In a subsequent step, the combined method energy decomposition analysis with natural orbitals for chemical valence is used to deliver quantitative results for the chemical bond between the organozinc fragment and the Zintl anionic cage. From this analysis, we conclude that the shared-electron description represents the chemical bonding in these compounds more appropriate. The bonding is characterized by a σ-type bond polarized toward the ZnPh fragment and a strong π-donation (15–20% of orbital interaction) into the p-orbitals at zinc. Electrostatic contributions, which are not considered in FMO analyses, make up around two-thirds of the attractive metal–ligand interaction and should not be neglected in the discussion of chemical bonding in these compounds. Usage of ligands with better σ- or π-accepting ability might thus serve to further stabilize the interesting class of compounds with multinary Zintl anions in the future. © 2014 Wiley Periodicals, Inc.

Density functional theory based analysis of the chemical bonding in ternary Sn/(Sb,Bi)/Zn Zintl anions outlines the importance of π-bonding contributions, polarized σ-bonding and significant electrostatic effects. This leads to a quantitative description of the metal–ligand interaction in this interesting compound class and has implications on ligand design for the stabilization of Zintl cages.

To get deep insights into the structure–reactivity relationship for ring-opening oligomerization reactions toward targeted design of novel main-chain boron-containing materials, detailed DFT B97D/TZVP calculations are carried out to compare the ring-opening oligomerization of both unsubstituted and *tert*-butyl (*t*Bu)-substituted 9*H*−9-borafluorenes. In contrast to substituent exchange between normal boranes, such reactions are initiated by substituent exchanges involving double BCB bridged intermediates. On *t*Bu-substitution, the BCB, and BHB bridged dimer intermediate is stabilized mainly due to enhanced barrier of 18.1 kcal/mol toward further trimerization channel and higher isomerization barrier of 22.5 kcal/mol toward the double BHB bridged dimer. In good agreement with available experiments, it is clearly shown that various product channels can be efficiently controlled by bulky substitution and by reaction temperatures, pointing out the way toward desired higher oligomers with improved thermal stability. © 2014 Wiley Periodicals, Inc.

The remarkable substituent effects of the bulky *tert*-butyl-substitution on the ring-opening oligomerization reactivity of 9*H*−9-borafluorene compounds are mainly due to the evidently increased trimerization barrier from intermediate **G** on substitution. Both **G** and **H** are actually formed from ring-opening aryl exchange through double BCB bridges and, thus, cannot support the Köster's postulate. Experimentally desired polymerization channels are expected at a controlled heating, opening the way toward higher oligomers with improved thermal stability.

Ligand-protected metal clusters are difficult to describe within density functional theory due to the need to treat the electronic structure of the cluster, possible charge-transfer between the ligands and the cluster, and weak ligand–ligand interactions. On page 986 (DOI: 10.1002/jcc.23578), Doreen Mollenhauer and Nicola Gaston demonstrate the use of an appropriate, stepwise benchmarking process that accounts for the non-additivity of these different contributions to stability and catalytic activity. The performance of density functional theory is thereby tested for gold phosphine clusters and their different components, with increasing system size, open and closed shell systems, and for different charged states.

The cover illustrates how atomic basins allow splitting of the bond electronic distribution (BED) between attached atoms. On page 978 (DOI: 10.1002/jcc.23574), David Ferro-Costas, Ignacio Pérez-Juste, and Ricardo A. Mosquera introduce a novel electronegativity estimator, the *g*_{AH} index, based on dividing (by means of quantum theory of atoms in molecules [QTAIM] basins) the BED of hydrogen-containing compounds described by natural localized molecular orbitals or electron localization function disynaptic basins. The periodic trends exhibited by this new estimator are shown for second and third periods. Its values are compared with the most popular electronegativity scales.

In recent years, the basic problem of understanding chemical bonding, nonbonded, and/or van der Waals interactions has been intensively debated in terms of various theoretical methods. We propose and construct the potential acting on one electron in a molecule-molecular orbital (PAEM-MO) diagram, which draws the PAEM inserted the MO energy levels with their major atomic orbital components. PAEM-MO diagram is able to show clear distinction of chemical bonding from nonbonded and/or vdW interactions. The rule for this is as follows. Along the line connecting two atoms in a molecule or a complex, the existence of chemical bonding between these two atoms needs to satisfy two conditions: (a) a critical point of PAEM exists and (b) PAEM barrier between the two atoms is lower in energy than the occupied major valence-shell bonding MO which contains in-phase atomic components (positive overlap) of the two considered atoms. In contrast to the chemical bonding, for a nonbonded interaction or van der Waals interaction between two atoms, both conditions (a) and (b) do not be satisfied at the same time. This is demonstrated and discussed by various typical cases, particularly those related to helium atom and HH bonding in phenanthrene. There are helium bonds in HHeF and HeBeO molecules, whereas no HH bonding in phenanthrene. The validity and limitation for this rule is demonstrated through the investigations of the curves of the PAEM barrier top and MO energies versus the internuclear distances for He_{2}, H_{2}, and He_{2}^{+} systems. © 2014 Wiley Periodicals, Inc.

The potential acting on one electron in a molecule-molecular orbital (PAEM-MO) diagram is proposed. The PAEM-MO diagram can show clear distinctions of chemical bonding from nonbonded and/or van der Waals interactions. The existence of chemical bonding between two atoms in a molecule or a complex needs to satisfy two conditions: a critical point of PAEM exists; and the major valence-shell bonding MO is higher in energy than the PAEM barrier.

The electron localization function, natural localized molecular orbitals, and the quantum theory of atoms in molecules have been used all together to analyze the bond electron density (BED) distribution of different hydrogen-containing compounds through the definition of atomic contributions to the bonding regions. A function, *g _{AH}*, obtained from those contributions is analyzed along the second and third periods of the periodic table. It exhibits periodic trends typically assigned to the electronegativity (

Entities related to bonds, such as natural localized molecular orbitals, are susceptible to being partitioned into atomic contributions. This partition, which can be carried out by using the quantum theory of atoms in molecules basin limits, provides a procedure for analyzing how the bond electron density is distributed between the corresponding bonded atoms. Magnitudes arising from such an analysis can be related to the electronegativity difference between the atoms of the bond.

Ligand-protected metal clusters are difficult to describe within density functional theory due to the need to treat the electronic structure of the cluster, possible charge transfer between the ligands and the cluster, and weak ligand–ligand interactions in a balanced manner. We demonstrate the use of an appropriate, stepwise benchmarking process that accounts for the nonadditivity of these different contributions to stability and catalytic activity. We consider both open- and closed-shell clusters, differently charged systems, and ligands of increasing complexity for gold phosphine systems. The use of a dispersion correction to density functional calculations was found to be crucial for both structure optimization and the calculation of binding energies. We find that PBE-D3 performs well with a variation in energetics of 0.7–10.9 kcal/mol, PBE0-D3 better with 0.0–3.3 kcal/mol, and B2PLYP-D3 the best with 0.2–2.4 kcal/mol, when compared to the best available benchmark [CCSD(T) or SCS-MP2]. Our systematic procedure clarifies that these functionals all give accurate results for certain cases, but for the total performance over a range of interactions, they perform in accordance with Jacob's ladder. © 2014 Wiley Periodicals, Inc.

Ligand-protected metal clusters are difficult to describe within density functional theory due to the need to treat the electronic structure of the cluster, possible charge-transfer between the ligands and the cluster, and weak ligand–ligand interactions. This study demonstrates the use of an appropriate, stepwise benchmarking process that accounts for the nonadditivity of these different contributions to stability and catalytic activity.

Transition metal complexes with terminal oxo and dioxygen ligands exist in metal oxidation reactions, and many are key intermediates in various catalytic and biological processes. The prototypical oxo-metal [(OC)_{5}CrO, (OC)_{4}FeO, and (OC)_{3}NiO] and dioxygen-metal carbonyls [(OC)_{5}CrOO, (OC)_{4}FeOO, and (OC)_{3}NiOO] are studied theoretically. All three oxo-metal carbonyls were found to have triplet ground states, with metal-oxo bond dissociation energies of 77 (CrO), 74 (FeO), and 51 (NiO) kcal/mol. Natural bond orbital and quantum theory of atoms in molecules analyses predict metal-oxo bond orders around 1.3. Their featured *ν*(MO, M = metal) vibrational frequencies all reflect very low IR intensities, suggesting Raman spectroscopy for experimental identification. The metal interactions with O_{2} are much weaker [dissociation energies 13 (CrOO), 21 (FeOO), and 4 (NiOO) kcal/mol] for the dioxygen-metal carbonyls. The classic parent compounds Cr(CO)_{6}, Fe(CO)_{5}, and Ni(CO)_{4} all exhibit thermodynamic instability in the presence of O_{2}, driven to displacement of CO to form CO_{2}. The latter reactions are exothermic by 47 [Cr(CO)_{6}], 46 [Fe(CO)_{5}], and 35 [Ni(CO)_{4}] kcal/mol. However, the barrier heights for the three reactions are very large, 51 (Cr), 39 (Fe), and 40 (Ni) kcal/mol. Thus, the parent metal carbonyls should be kinetically stable in the presence of oxygen. © 2014 Wiley Periodicals, Inc.

The classic parent compounds Cr(CO)_{6}, Fe(CO)_{5}, and Ni(CO)_{4} all exhibit thermodynamic instability in the presence of O_{2}, driving the displacement of CO to form CO_{2} and viable oxo-metal carbonyls.

We develop an efficient method to extract site–site bridge functions from molecular simulations. The method is based on the inverse solution of the reference site interaction model. Using the exact long-range asymptotics of site–site direct correlation functions defined by the site–site Ornstein–Zernike equations, we regularize the ill-posed inverse problem, and then calculate site–site bridge functions and effective pair potentials for ambient water, methanol, and ethanol. We have tested the proposed algorithm and checked its performance. Our study has revealed various peculiarities of the site–site bridge functions, such as long-range behavior, strong dependence on the electrostatic interactions. Using the obtained data, we have calculated thermodynamic properties of the solvents, namely, isothermal compressibility, internal energy, and Kirkwood-Buff integrals. The obtained values are in excellent agreement not only with molecular simulations but also with available experimental data. Further extensions of the method are discussed. © 2014 Wiley Periodicals, Inc.

A method is developed to extract site–site bridge functions from molecular simulations, based on the inverse solution of the reference site interaction model. Site–site bridge functions and effective pair potentials are calculated for ambient water, methanol, and ethanol.

The evaluation of the free energy is essential in molecular simulation because it is intimately related with the existence of multiphase equilibrium. Recently, it was demonstrated that it is possible to evaluate the Helmholtz free energy using a single statistical ensemble along an entire isotherm by accounting for the “chemical work” of transforming each molecule, from an interacting one, to an ideal gas. In this work, we show that it is possible to perform such a free energy perturbation over a liquid vapor phase transition. Furthermore, we investigate the link between a general free energy perturbation scheme and the novel nonequilibrium theories of Crook's and Jarzinsky. We find that for finite systems away from the thermodynamic limit the second law of thermodynamics will always be an inequality for isothermal free energy perturbations, resulting always to a dissipated work that may tend to zero only in the thermodynamic limit. The work, the heat, and the entropy produced during a thermodynamic free energy perturbation can be viewed in the context of the Crooks and Jarzinsky formalism, revealing that for a given value of the ensemble average of the “irreversible” work, the minimum entropy production corresponded to a Gaussian distribution for the histogram of the work. We propose the evaluation of the free energy difference in any free energy perturbation based scheme on the average irreversible “chemical work” minus the dissipated work that can be calculated from the variance of the distribution of the logarithm of the work histogram, within the Gaussian approximation. As a consequence, using the Gaussian ansatz for the distribution of the “chemical work,” accurate estimates for the chemical potential and the free energy of the system can be performed using much shorter simulations and avoiding the necessity of sampling the computational costly tails of the “chemical work.” For a more general free energy perturbation scheme that the Gaussian ansatz may not be valid, the free energy calculation can be expressed in terms of the moment generating function of the “chemical work” distribution. © 2014 Wiley Periodicals, Inc.

The link between free energy perturbation schemes and modern nonequilibrium theories is investigated. It is possible to evaluate free energy in molecular simulations by accounting for the chemical work of transforming each interacting molecule into an ideal gas, over a liquid–vapor phase transition. A Gaussian model is proposed for the chemical work distribution, which dramatically reduces the computational cost by avoiding the necessity of sampling the tails of the distribution.

A database of environmentally hazardous chemicals, collected and modeled by QSAR by the Insubria group, is included in the updated version of QSARINS, software recently proposed for the development and validation of QSAR models by the genetic algorithm-ordinary least squares method. In this version, a module, named QSARINS-Chem, includes several datasets of chemical structures and their corresponding endpoints (physicochemical properties and biological activities). The chemicals are accessible in different ways (CAS, SMILES, names and so forth) and their three-dimensional structure can be visualized. Some of the QSAR models, previously published by our group, have been redeveloped using the free online software for molecular descriptor calculation, PaDEL-Descriptor. The new models can be easily applied for future predictions on chemicals without experimental data, also verifying the applicability domain to new chemicals. The QSAR model reporting format (QMRF) of these models is also here downloadable. Additional chemometric analyses can be done by principal component analysis and multicriteria decision making for screening and ranking chemicals to prioritize the most dangerous. © 2014 Wiley Periodicals, Inc.

QSARINS-Chem is a module implemented in the new version of QSARINS, the software for OLS-GA QSAR models that includes a database of various environmental pollutants and new validated PaDEL-Descriptor models on several end points. The chemicals can be accessed by CAS, SMILES, and name, obtaining the structure and available end points. The new PaDEL-Descriptor models, accompanied by the QSAR model reporting format for REACH, can be applied for the prediction of unavailable data, verifying the applicability domain to new chemicals.