Mixed implicit/explicit solvation models in quantum mechanical calculations of binding enthalpy for protein–ligand complexes

An approach to quantum mechanical investigation of interactions in protein–ligand complexes has been developed that treats the solvation effect in a mixed scheme combining implicit and explicit solvent models. In this approach, the first solvation shell of the solvent around the solute is modeled with a limited number of hydrogen bonded explicit solvent molecules. The influence of the remaining bulk solvent is treated as a surrounding continuum in the conductor‐like screening model (COSMO). The enthalpy term of the binding free energy for the protein–ligand complexes was calculated using the semiempirical PM3 method implemented in the MOPAC package, applied to a trimmed model of the protein–ligand complex constructed with special rules. The dependence of the accuracy of binding enthalpy calculations on size of the trimmed model and number of optimized parameters was evaluated. Testing of the approach was performed for 12 complexes of different ligands with trypsin, thrombin, and ribonuclease with experimentally known binding enthalpies. The root‐mean‐square deviation (RMSD) of the calculated binding enthalpies from experimental data was found as ～1 kcal/mol over a large range. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Ureases: quantum chemical calculations on cluster models

Herein, we present results from a computational study of dinickel complexes that are relevant to the catalytic hydrolysis of urea exerted by the urease enzymes. The B3LYP density functional is used to characterize the equilibrium geometry, electronic and magnetic properties, and energies for a series of realistic complexes modeling the active site of ureases. The analysis of the theoretical results gives new insight into the structure, substrate binding, and catalytic mechanism. The water bridge between the two Ni(II) ions observed in the crystallographic structures of the ureases was assigned to a hydroxide bridge in agreement with the observed small antiferromagnetic coupling. Both monodentate and bidentate urea-bound complexes, in which urea had favorable orientations for catalysis, were characterized. Finally, two reaction mechanisms were investigated starting from the monodentate and bidentate urea-bound complexes, respectively. Both a Ni1...Ni2 bridging hydroxide and a Ni2-bound water molecule play crucial roles in the two mechanisms.     

FTIR and quantum chemical study of LiBr solvation in acetonitrile solutions

FTIR spectroscopy and quantum chemical calculations at the RTF + MP2/6-311G** level of theory with solvation model density (SMD) corrections were used to study ion solvation and association in LiBr/acetonitrile solutions. The aim of this study was to establish the composition and geometry of the predominant ionic species solvated by acetonitrile molecules and to analyse their spectroscopic signatures. The results obtained make it possible to propose an equilibrium between Li⁺Br⁻(CH₃CN)₃, Li⁺(CH₃CN)₄, and anionic Br⁻(CH₃CN)_n complexes with an undetermined n value and bent coordination of the solvent molecules. The calculated wavenumbers and the geometric parameters of the solvated ionic species were found to be in excellent agreement with the experimental data.     

A microscopic model for calculations of chemical processes in aqueous solutions

A new microscopic model for calculations of chemical processes in aqueous solutions is presented. The model, referred to here as the “surface constrained soft sphere dipoles” (SCSSD) model avoids the problems of the continuum models by explicitly including the solvent molecules. Each solvent molecule is represented as a point dipole attached to the center of a soft sphere. The solvation energy is evaluated by minimizing the solute-solvent energy with respect to the orientations and positions of those dipoles while constraining the surface dipoles to have the orientations and positions of the bulk solvent. The model is demonstrated by calculating the energetic of charge separation in aqueous solution and evaluating the corresponding dielectric constant. The SCSSD model can be used for quantitative studies of ionic reactions in solutions. This is demonstrated by calculation of the potential surface for the dissociation of formic acid in aqueous solution.     

Modeling the solvation shell of complexes in solution for quantum chemical calculations of electronic spectra

A procedure that allows for solvation effects is suggested; it is designed for quantum chemical calculations of the electronic spectra of complex compounds. Based on Monte Carlo (MC) simulation of the solvation shell one can calculate the electrostatic potential created by the solvation shell at the sites of all atoms of the complex; appropriate corrections are added to the diagonal elements of the Fock matrix and to the matrix elements of the Hamiltonian in the configuration interaction method. The method suggested has been implemented based on the semiempirical (CINDO) version of the CI (configuration interaction) technique and tested on the following compounds: [Ru(NH₃)₅(py)]²⁺, [Ru(NH₃)₅(pyz)]²⁺, [Ru(bpy)(CN)₄]^2?, [Ru(NO)(py)₄-NC-Ru(py)₄(CN)]³⁺.     

Real and chemical solvation energies of individual ions in solution

On the basis of the proposed concept of real thermodynamic properties for individual ions in solution, the real thermodynamic properties of transport (resolvation) for various ions (sodium, potassium, chloride, bromide, and iodide) from water to mixtures of water with ethyl, n-propyl, and isopropyl alcohols, acetone, acetonitrile, dimethylsulfoxide, and dimethylformamide are determined by the method of Volta potential differences. Values of the chemical thermodynamic properties of transport of the ions under investigation are determined on the basis of previously calculated values of surface potentials of the solvents mentioned above. A comparative analysis of the values obtained is carried out, and characteristics of the solvation of ions of different sign are established as functions of their nature relative to the physicochemical and structural properties of the solvents. The satisfactory agreement of the data obtained on the basis of the total Gibbs energy of transport of the ions under investigation in the indicated solvents with literature data is the criterion of correctness for the scientific material presented in this paper.     

Bond dissociation energies for removal of the hydroxyl group in some alcohols from quantum chemical calculations

In this theoretical work, 22 alcohols and their geometric structure properties have been investigated employing quantum chemical methods to calculate the C? OH equilibrium bond distances and bond dissociation energies (BDEs). Since DFT methods have been researched to have low basis sets sensitivity for small and medium molecules in our previous work (Zhao et al., J Mol Struct, 2006, 766, 87), 22 title compounds have been studied by employing the hybrid density functional theory (B3LYP, B3PW91, B3P86, PBE1PBE) in conjunction with the 6‐311G** basis set and the complete basis set (CBS–Q) method. Comparison with the available experimental data shows that CBS–Q and B3P86 methods calculated results agree very well with the experimental values, with the average absolute errors of 1.3 kcal/mol and 3.5 kcal/mol, respectively. So considering the expensive computational time, CBS–Q method can be chosen as a satisfactory method of predicting the accurate BDEs for removal of the OH group in small and medium size alcohols. And B3P86 method may give accurate BDEs for larger alcohols we haven't studied. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Coupled semiempirical quantum mechanics and molecular mechanics (QM/MM) calculations on the aqueous solvation free energies of ionized molecules

The aqueous solvation free energies of ionized molecules were computed using a coupled quantum mechanical and molecular mechanical (QM/MM) model based on the AM1, MNDO, and PM3 semiempirical molecular orbital methods for the solute molecule and the TIP3P molecular mechanics model for liquid water. The present work is an extension of our model for neutral solutes where we assumed that the total free energy is the sum of components derived from the electrostatic/polarization terms in the Hamiltonian plus an empirical “nonpolar” term. The electrostatic/polarization contributions to the solvation free energies were computed using molecular dynamics (MD) simulation and thermodynamic integration techniques, while the nonpolar contributions were taken from the literature. The contribution to the electrostatic/polarization component of the free energy due to nonbonded interactions outside the cutoff radii used in the MD simulations was approximated by a Born solvation term. The experimental free energies were reproduced satisfactorily using variational parameters from the vdW terms as in the original model, in addition to a parameter from the one-electron integral terms. The new one-electron parameter was required to account for the short-range effects of overlapping atomic charge densities. The radial distribution functions obtained from the MD simulations showed the expected H-bonded structures between the ionized solute molecule and solvent molecules. We also obtained satisfactory results by neglecting both the empirical nonpolar term and the electronic polarization of the solute, i.e., by implementing a nonpolarization model. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1028–1038, 1999     

Perfluoropoly-ether/peroxide compounds: spectroscopic studies and quantum chemical calculations

Perfluoropolyethers (PFPEs) are a class of high performance materials used in a wide range of applications (refrigeration, lubrication, semiconductor industry, etc.). PFPEs containing peroxidic units are intermediate materials for the preparation of commercial end products. In this work we study the spectroscopic properties of ether and peroxides linkages in this class of compounds; nuclear magnetic resonance (NMR) spectra are discussed, FT-Raman data presented. Quantum chemical calculations on model molecules were used as a tool for the interpretation of the Raman experimental data and physical-chemical properties.     

Microscopic solvation of NaBO2 in water: anion photoelectron spectroscopy and ab initio calculations

We investigated the microscopic solvation of NaBO(2) in water by conducting photoelectron spectroscopy and ab initio studies on NaBO(2)(-)(H(2)O)(n) (n = 0-4) clusters. The vertical detachment energy (VDE) of NaBO(2)(-) is estimated to be 1.00 ± 0.08 eV. The photoelectron spectra of NaBO(2)(-)(H(2)O)(1) and NaBO(2)(-)(H(2)O)(2) are similar to that of bare NaBO(2)(-), except that their VDEs shift to higher electron binding energies (EBE). For the spectra of NaBO(2)(-)(H(2)O)(3) and NaBO(2)(-)(H(2)O)(4), a low EBE feature appears dramatically in addition to the features observed in the spectra of NaBO(2)(-)(H(2)O)(0-2). Our study shows that the water molecules mainly interact with the BO(2)(-) unit in NaBO(2)(-)(H(2)O)(1) and NaBO(2)(-)(H(2)O)(2) clusters to form Na-BO(2)(-)(H(2)O)(n) type structures, while in NaBO(2)(-)(H(2)O)(3) and NaBO(2)(-)(H(2)O)(4) clusters, the water molecules can interact strongly with the Na atom, therefore, the Na-BO(2)(-)(H(2)O)(n) and Na(H(2)O)(n)···BO(2)(-) types of structures coexist. That can be seen as an initial step of the transition from a contact ion pair (CIP) structure to a solvent-separated ion pair (SSIP) structure for the dissolution of NaBO(2).     

Understanding solvation in hydrofluoroalkanes: ab initio calculations and chemical force microscopy

Understanding solvation in hydrofluoroalkane (HFA) propellants is of great importance for the development of novel pressurized metered-dose inhaler (pMDI) formulations. HFA-based pMDIs are not only the most widely used inhalation therapy devices for treating lung diseases, but they also hold promise as vehicles for the systemic delivery of biomolecules to and through the lungs. In this work we propose a combined microscopic experimental and computational approach to quantitatively relate the chemistry of moieties to their HFA-philicity. Binding energy calculations are used to determine the degree of interaction between a propellant HFA and candidate fragments. We define a new quantity, the enhancement factor E, which also takes into account fragment-fragment interactions. This quantity is expected to correlate well with the solubility and the ability of the moieties of interest to impart stability to colloidal dispersions in HFAs. We use a methyl-based (CH) segment and its fluorinated analog (CF) to test our approach. CH is an important baseline case since it represents the tails of surfactants in FDA-approved pMDIs. CF was chosen due to the improved solubility and ability of this chemistry to stabilize aqueous dispersions in HFAs. Adhesion force from Chemical Force Microscopy (CFM) is used as an experimental analog to the binding energy calculations. The force of interaction between a chemically modified AFM tip and substrate is measured in a model HFA, which is a liquid at ambient conditions. Silanes with the same chemistry as the fragments used in the ab initio calculations allow for direct comparison between the two techniques. The CFM results provide an absolute scale for HFA-philicity. Single molecule (pair) forces calculated from the CFM experiments are shown to be in very good agreement to the E determined from the ab initio calculations. The ab initio calculations and CFM are corroborated by previous experimental studies where propellants HFAs are seen to better solvate the CF functionality.     

Vibrational study of fluorobenzene and its solvation with methanol via polarized Raman measurements and quantum chemical calculations

Raman spectra of neat fluorobenzene (C₆H₅F, FB) and its binary mixtures with methanol (CH₃OH, M) at varying mole fractions of FB from 0.1 to 0.9 were recorded in order to understand the influence of intermolecular interaction on spectral features corresponding to some selected vibrational bands of FB in the region 1200-450 cm⁻¹. Only few vibrational bands of fluorobenzene show a significant change in their peak position in going from neat liquid to the complexes. The 803, 829 and 994 cm⁻¹ bands show blue shift upon complexation which indicates significant amount of charge transfer between the reference molecule and the solvent. However, the linewidths do not show any appreciable change. Density functional theory (DFT) calculations were performed employing B3LYP method and high level basis set 6-311++G(d,p) to obtain the ground state geometry of neat FB and its hydrogen bonded complexes with methanol in gas phase. In order to account for the solvent effect and also to realize a condition quite close to the experiment, polarizable continuum model (PCM) calculations considering bulk solvation as well as explicit (specific plus bulk) solvation approaches were also performed. A detailed vibrational assignment of the various normal modes has been performed on the basis of potential energy distribution (PED) calculations. Depolarization ratios for the different vibrational bands were calculated and the values match nicely with the depolarization ratio determined from the experimental data.     

CO2 absorption in aqueous solutions of alkanolamines: mechanistic insight from quantum chemical calculations

DFT and high-level ab initio calculations (among them B3LYP and G3MP2B3) have been used to describe molecular reactions relevant for CO2 absorption in aqueous (alkanol)amine solutions. Reaction mechanisms for various reactions of CO2 with ammonia, monoethanolamine (MEA), and diethanolamine (DEA) to carbamic acid and ion pair products have been investigated and interpreted in light of experimental observations. Additional water, ammonia, MEA, and DEA molecules have also been added to the molecular complexes to simulate microsolvation effects. These extra molecules may act as catalysts for the desired reactions, and in several cases they have a large impact on activation and reaction energies. Solvent effects were estimated by applying electrostatic continuum models for selected systems. Our calculated transition state energies agree well with experimental activation energies.     

Particle formation and surface processes on atmospheric aerosols: A review of applied quantum chemical calculations

Aerosols significantly influence atmospheric processes such as cloud nucleation, heterogeneous chemistry, and heavy-metal transport in the troposphere. The chemical and physical complexity of atmospheric aerosols results in large uncertainties in their climate and health effects. In this article, we review recent advances in scientific understanding of aerosol processes achieved by the application of quantum chemical calculations. In particular, we emphasize recent work in two areas: new particle formation and heterogeneous processes. Details in quantum chemical methods are provided, elaborating on computational models for prenucleation, secondary organic aerosol formation, and aerosol interface phenomena. Modeling of relative humidity effects, aerosol surfaces, and chemical kinetics of reaction pathways is discussed. Because of their relevance, quantum chemical calculations and field and laboratory experiments are compared. In addition to describing the atmospheric relevance of the computational models, this article also presents future challenges in quantum chemical calculations applied to aerosols.     

Prediction of Henry's law constants of triazine derived herbicides from quantum chemical continuum solvation models

The Henry's law constants (H) for triazine derived herbicides are calculated using quantum chemical solvation models, SM2, SM3, PCM-DFT, and CPCM-DFT, and their performances are discussed. The results show considerable differences in performance among the different levels of theory. The values of H calculated by the semiempirical methods agree much better with the experimental values than those obtained at the DFT level. The differences are discussed in terms of the different contributions, electrostatic and no-electrostatic, to Gibbs free energy of solvation. In addition, the Henry's law constants of some triazine derived herbicides whose values have not been reported earlier are predicted as well.