Parameter Optimization Method in Multidimensional Umbrella Sampling.

Umbrella sampling (US) is an effective method for calculating free-energy landscapes (FELs). However, the complexity of controlling the sampling positions complicates multidimensional FEL calculations. In this study, we proposed a method for controlling sampling by optimizing the US parameters.

Nudged elastic stiffness band method: A method to solve kinks problems of reaction paths.

The nudged elastic band (NEB) method has been widely employed for reaction path (RP) finding; however, certain NEB calculations do not converge to the minimum energy paths (MEPs) because of the occurrence of kinks, which are caused by the free bending of bands. Thus, we propose an extension of the NEB method, called the nudged elastic stiffness band (NESB) method, which adds the stress of stiffness using a beam theory. Here we present results from three examples: the NFK potential, the RPs of the Witting reaction, and finding saddle points for a set of five chemical reaction benchmarks.

Curvature-weighted nudged elastic band method using the Riemann curvature.

The nudged elastic band (NEB) method is utilized to find reaction paths (RPs) using discretized intermediate structures called "images" between a reactant and a product. In fact, NEB calculations do not always converge because of the bent of RPs. Mathematically, more images are needed for complex curves, and here, we focused on the curvature.

Calculation of the permeability coefficients of small molecules through lipid bilayers by free-energy reaction network analysis following the explicit treatment of the internal conformation of the solute.

Biomembrane permeation represents a major barrier to pharmacokinetics. During preclinical drug discovery, the coefficients of the permeation of molecules through lipid bilayers account for a valuable property of such molecules. Therefore, the control of the permeation of molecules through lipid bilayers is an essential factor in drug design, and the estimation of the permeation phenomena is a crucial study in pharmacy.

Theoretical Design of Blue-Color Phosphorescent Complexes for Organic Light-Emitting Diodes: Emission Intensities and Nonradiative Transition Rate Constants in Ir(ppy)(acac) Derivatives.

Theoretical calculations of phosphorescent spectra and nonradiative transition (NRT) rate constants for S ⇝ T, T ⇝ S, and S ⇝ S were carried out to determine the best candidate for a blue-color phosphorescent complex among several derivatives of bis(2-phenylpyridine)(acetylacetonate)iridium(III). The geometries of the ground state (S), the lowest triplet state (T), and the lowest excited singlet state (S) were optimized at the levels of density functional theory, in which B3LYP functionals and SBKJC+p basis sets were used. The NRT rate constants were derived by using a generating function method within the displaced harmonic oscillator model.

Exploring the Reaction Paths on the Potential Energy Surfaces of the S and T States in Methylenecyclopropane.

The reaction paths of methylenecyclopropane 1 on the potential energy surfaces (PESs) of the lowest triplet (T ) state and the lowest excited singlet (S ) state, as well as that of the ground state (S ), were explored by using the nudged elastic band method at the MRMP2//MCSCF/6-31++G(d,p) and DFT(B3LYP)/6-31++G(d,p) levels of theory. After vertical excitation of 1, three transition states on the PES of the lowest triplet state and one transition state on the S PES were found along the reaction path to produce a carbene, cyclobutylidene 2. All of these transition states are lower in energy than the S state produced by vertical excitation at the S energy minimum in 1.

Theoretical Examination of the Plausible Reaction Process for Stereoselective Synthesis of Hexapole Helicene via a Palladium-Catalyzed [2 + 2 + 2] Cyclotrimerization of [5]Helicenyl Aryne.

The reaction mechanisms of the plausible reaction process for the synthesis of hexapole helicene via a palladium-catalyzed [2 + 2 + 2] cyclotrimerization of [5]helicenyl aryne were examined using a theoretical approach. In a previous experimental study, this reaction selectively produced -symmetrical hexapole helicene, even though the -symmetrical structure is thermodynamically more stable. To clarify the mechanism underlying this reaction, density functional theory (DFT) and transition-state-theory calculations were used to evaluate the reaction profile and kinetic rate constants of the primary reactions.

Spin-Orbit Coupling Constants in Atoms and Ions of Transition Elements: Comparison of Effective Core Potentials, Model Core Potentials, and All-Electron Methods.

The spin-orbit coupling constants (SOCC) in atoms and ions of the first- through third-row transition elements were calculated for the low-lying atomic states whose main electron configuration is [ nd] ( q = 1-4 and 6-9, n = the principal quantum number), using four different approaches: (1) a nonrelativistic Hamiltonian used to construct multiconfiguration self-consistent field (MCSCF) wave functions utilizing effective core potentials and their associated basis sets within the framework of second-order configuration interaction (SOCI) to calculate spin-orbit couplings (SOC) using one-electron Breit-Pauli Hamiltonian (BPH), (2) a nonrelativistic Hamiltonian used to construct MCSCF wave functions utilizing model core potentials and their associated basis sets within the framework of SOCI to calculate SOC using the full BPH, (3) nonrelativistic and spin-independent relativistic Hamiltonians used to construct MCSCF wave functions utilizing all-electron (AE) basis sets within the framework of SOCI to calculate SOC using the full BPH, and (4) a relativistic Hamiltonian given by the exact two-component (X2C) transformation for construction of Kramers-restricted relativistic configuration interaction wave functions. In this investigation, these four approaches are referred to as ECP, MCP, AE, and X2C methods, respectively. The ECP, MCP, and AE methods are so-called two-step approaches (TSA), while the X2C method is a one-step approach (OSA).

Numerical Estimation of the Pseudo-Jahn-Teller Effect Using Nonadiabatic Coupling Integrals in Monocyclic and Bicyclic Conjugated Molecules.

The pseudo-Jahn-Teller (pJT) effect in monocyclic and bicyclic conjugated molecules was investigated by using the state-averaged multiconfiguration self-consistent field (MCSCF) method, together with the 6-31G(d,p) basis sets. Following the perturbation theory, the force constant along a normal mode Q is given by the sum of the classical force constant and the vibronic contribution (VC) resulting from the interaction of the ground state with excited states. The latter is given as the sum of individual contributions arising from vibronic interactions between the ground state and excited states.

Free Energy Contribution Analysis Using Response Kernel Approximation: Insights into the Acylation Reaction of a Beta-Lactamase.

A widely applicable free energy contribution analysis (FECA) method based on the quantum mechanical/molecular mechanical (QM/MM) approximation using response kernel approaches has been proposed to investigate the influences of environmental residues and/or atoms in the QM region on the free energy profile. This method can evaluate atomic contributions to the free energy along the reaction path including polarization effects on the QM region within a dramatically reduced computational time. The rate-limiting step in the deactivation of the β-lactam antibiotic cefalotin (CLS) by β-lactamase was studied using this method.

Amorphous Solid Simulation and Trial Fabrication of the Organic Field-Effect Transistor of Tetrathienonaphthalenes Prepared by Using Microflow Photochemical Reactions: A Theoretical Calculation-Inspired Investigation.

The p-type organic semiconductor (OSC) material tetrathieno[2,3-a:3',2'-c:2″,3″-f:3‴,2‴-h]naphthalene (2TTN) and its alkyl-substituted derivatives C(n)-2TTNs (n = 6, 8, and 10) have been developed based on the results of theoretical calculation-inspired investigation. A hole mobility for amorphous C(n)-2TTNs (10(-2)-10(-3) cm(2) V(-1) s(-1)) was accurately predicted by using a novel statistical method in which the geometric mean of the mobilities for many individual small molecular flocks in an amorphous solid was obtained by using molecular mechanical molecular dynamics simulations and quantum chemical calculations. The simulation also suggests that upon increasing the length of alkyl chains in C(n)-2TTNs the mobilities become smaller as a consequence of a decrease in transfer integral values.

Efficient approach to include molecular polarizations using charge and atom dipole response kernels to calculate free energy gradients in the QM/MM scheme.

An efficient approach to evaluate free energy gradients (FEGs) within the quantum mechanical/molecular mechanical (QM/MM) framework has been proposed to clarify reaction processes on the free energy surface (FES) in molecular assemblies. The method is based on response kernel approximations denoted as the charge and the atom dipole response kernel (CDRK) model that include explicitly induced atom dipoles. The CDRK model was able to reproduce polarization effects for both electrostatic interactions between QM and MM regions and internal energies in the QM region obtained by conventional QM/MM methods.

Synthesis of a double helicene by a palladium-catalyzed cross-coupling reaction: structure and physical properties.

For this study, twisted π-extended helicene 1 and double helicene 2 with a helicene framework were synthesized through palladium-catalyzed C-H arylation or Suzuki-Miyaura coupling reaction. X-ray crystallography revealed grossly twisted structures that were soluble in various conventional organic solvents. Optical properties based on UV/Vis and fluorescence spectra were measured.

Theoretical investigation of the reaction mechanism of ClONO2 + HCl → HNO3 + Cl2 on (H2O)n (n = 0-3) cluster.

Hydrated chlorine nitrate and hydrogen chloride ClONO2·HCl·(H2O)n (n = 0-3) clusters were investigated by using the MP2/aug-cc-pVTZ level of theory to clarify the reaction mechanism of Cl2 production. Isomeric stable structures found in n = 2 and 3 clusters have equivalent binding energies and the reaction barrier drastically decreases to be 2.1 kcal/mol at n = 3.

Toward a new approach for determination of solute's charge distribution to analyze interatomic electrostatic interactions in quantum mechanical/molecular mechanical simulations.

We present an alternative approach to determine "density-dependent property"-derived charges for molecules in the condensed phase. In the case of a solution, it is essential to take into consideration the electron polarization of molecules in the active site of this system. The solute and solvent molecules in this site have to be described by a quantum mechanical technique and the others are allowed to be treated by a molecular mechanical method (QM/MM scheme).

Ab initio electron correlated studies on the intracluster reaction of NO+ (H2O)(n) → H3O+ (H2O)(n-2) (HONO) (n = 4 and 5).

Hydrated nitrosonium ion clusters NO(+)(H(2)O)(n) (n = 4 and 5) were investigated by using MP2/aug-cc-pVTZ level of theory to clarify isomeric reaction pathways for formation of HONO and fully hydrated hydride ions. We found some new isomers and transition state structures in each hydration number, whose lowest activation energies of the intracluster reactions were found to be 4.1 and 3.

Tetrahydrides of third-row transition elements: spin-orbit coupling effects on the stability of rhenium tetrahydride.

The potential energy surfaces of low-lying states in rhenium tetrahydride (ReH(4)) were explored by using the multiconfiguration self-consistent field (MCSCF) method together with the SBKJC effective core potentials and the associated basis sets augmented by a set of f functions on rhenium atom and by a set of p functions on hydrogen atoms, followed by spin-orbit coupling (SOC) calculations to incorporate nonscalar relativistic effects. The most stable structure of ReH(4) was found to have a D(2d) symmetry and its ground state is (4)A(2). It is found that this is lower in energy than the dissociation limit, ReH(2)+H(2), after dynamic correlation effects are taken into account by using second-order multireference Møller-Plesset perturbation (MRMP2) calculations.

A minimal implementation of the AMBER-GAUSSIAN interface for ab initio QM/MM-MD simulation.

For applying to a number of theoretical methodologies based on an ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics method connecting AMBER9 with GAUSSIAN03, we have developed an AMBER-GAUSSIAN interface (AG-IF), which can be one of the simplest architectures. In the AG-IF, only a few subroutines addition is necessary to retrieve the QM/MM energy and forces, obtained by GAUSSIAN, for solving a set of Newtonian equations of motion in AMBER. It is, therefore, easy to be modified for individual applications since AG-IF utilizes most of those functions originally equipped not only in AMBER but also in GAUSSIAN.

Spin-orbit coupling effects in dihydrides of third-row transition elements. II. Interplay of nonadiabatic coupling in the dissociation path of rhenium dihydride.

This is the second paper in a series of investigations on spin-orbit coupling (SOC) effects in dihydrides of third-row transition elements. The dissociation path of rhenium dihydride was explored using the multiconfiguration self-consistent-field method followed by diagonalization of SOC matrices, in which the Stevens-Basch-Krauss-Jasien-Cundari (SBKJC) basis sets were employed after adding one set of polarization functions for each atom. The most stable rhenium dihydride has a linear structure and its ground state is (6)Sigma(g)(+).

Molecular dynamics simulation study on stabilities and reactivities of NADH cytochrome B5 reductase.

Binding free energies between coenzyme (FAD and NADH) and the apoenzyme of NADH-cytochrome b5 reductase (b5R) were estimated by applying the continuum Poisson-Boltzmann (PB) model to structures sampled from molecular dynamics simulations in explicit water molecules. Important residues for the enzymatic catalysis were clarified using a computational alanine scanning method. The binding free energies calculated by applying an alanine scanning method can successfully reproduce the trends of the measured steady-state enzymatic activities kcatNADH/KmNADH.

Magnetic resonance imaging and magnetic resonance myelography in the presurgical diagnosis of lumbar foraminal stenosis.

Study Design: Retrospective case series with a control group.

Objective: To measure the diagnostic performance of magnetic resonance imaging (MRI) and MR myelography (MRM) for symptomatic foraminal stenosis in patients who need surgery.

Summary Of Background Data: MR images are extensively used in the evaluation of foraminal stenosis and are often used to evaluate nerves exiting from the foramen.

Relativistic study on emission mechanism in palladium and platinum complexes.

The present study investigates the spin-orbit coupling (SOC) effects in the radiative processes from the electronically excited states of bis[-2-(2-thienyl)-pyridine] platinum (Pt(thpy)2) and palladium (Pd(thpy)2). The transition probabilities among the low-lying spin-mixed states in these complexes are estimated using the discrete variable representation (DVR) method based on the assumption that the system obeys Fermi's golden rule. It is revealed that the low-lying excited singlets and triplets are strongly mixed with each other by SOC in Pt(thpy)2 and, as a result, a fast nonradiative transition occurs to the low-lying excited spin-mixed states.

Theoretical calculation of structures and proton transfer in hydrated ammonia-hydrogen chloride clusters.

Ab initio molecular orbital calculations have been performed to investigate the structures and quantum effects of the proton motion in NH(3):HCl:(H(2)O)(n) (n = 0-3) clusters using a MP2/aug-cc-pVDZ level of theory. Three new stable structures and one transition-state structure are investigated for these clusters. The detailed analyses of the intermolecular interactions suggest that three-body interactions play an important role to determine the relative stability in each size of cluster.

Molecular dynamics simulation study of the negative correlation in antibody AZ28-catalyzed oxy-cope rearrangement.

The oxy-Cope rearrangement reaction in the antibody AZ28 is investigated using ab initio molecular orbital calculations and molecular mechanical molecular dynamics simulations. This antibody, AZ28, is known as one of the few systems where the mature catalytic antibody shows a negative correlation between the transition state analogue (TSA) binding affinity and the catalytic rate of the oxy-Cope rearrangement compared to the germ line catalytic antibody. The ab initio optimized structure shows that the transition state structure has a more planar configuration than the TSA.