Polarizable Continuum Method Research Articles

Estudo QSPR sobre os coeficientes de partição: descritores mecânico-quânticos e análise multivariada

Quantum chemistry and multivariate analysis were used to estimate the partition coefficients between n-octanol and water for a serie of 188 compounds, with the values of the q 2 until 0.86 for crossvalidation test. The quantum-mechanical descriptors are obtained with ab initio calculation, using the solvation effects of the Polarizable Continuum Method. Two different Hartree-Fock bases were used, and two different ways for simulating solvent cavity formation. The results for each of the cases were analised, and each methodology proposed is indicated for particular case.

Density functional theory gas- and solution-phase study of nucleophilic substitution at di- and trisulfides

Density functional calculations indicate that nucleophilic substitution in the thiolate–disulfide and thiolate–trisulfide exchange reactions proceeds by an addition–elimination pathway. Solution calculations were performed using B3LYP/6-31+G* and the polarized continuum method. These solution-phase calculations indicate that for the reactions where the sulfur under attack bears a hydrogen atom, the substitution proceeds via an addition–elimination mechanism; however, when a methyl group is attached to the sulfur under attack, the SN2 mechanism is predicted.

The Prediction of Protein pKa's Using QM/MM: The pKa of Lysine 55 in Turkey Ovomucoid Third Domain

A computational methodology for pKa predictions of small molecules based on an ab initio quantum mechanics (QM) description of the acid and a linearized Poisson−Boltzmann equation (LPBE) description of bulk solvation using the polarized continuum method is presented. This QM/LPBE method is capable of reproducing the pKa's of several functional groups found in amino acid residues with a root-mean-square deviation from experiment of 0.6 pH units. The practical applicability of the QM/LPBE method is extended to proteins by using a QM description of the ionizable residue and an effective fragment potential (MM) description of the rest of the protein. This QM/MM/LPBE method is used to predict a pKa of the Lys55 residue in turkey ovomucoid third domain of 11.0, which is in good agreement with the experimental value of 11.1.

Calculation of aqueous dissociation constants of 1,2,4-triazole and tetrazole: A comparison of solvation models

The aqueous acidity constants of 1,2,4-triazole and tetrazole have been calculated using quantum chemical methods with four solvation models. Gas-phase proton transfer reaction energies and enthalpies of formation were calculated at the G3 level of theory. For tetrazole, the G3 energies all differ from the experimental values by more than 10 kJ mol−1, while for 1,2,4-triazole the agreement is significantly better. Solvation energies were calculated using the semi-empirical quantum mechanical method SM5.42R/A, the iterative Langevin dipole method iLD, the ab initio quantum mechanical polarisable continuum method IEF-PCM and the Poisson–Boltzmann method PB. The PB method consistently provided better agreement with experiment than the other methods when applied to the G3 energies, although the difference in pKa was as large as 2.6 for tetrazole. The acidity constants obtained using PB and iLD solvation energies applied to the experimental gas-phase proton dissociation energies are in good agreement with experiment.

Solvent dependence of the di- tert-butyl nitroxide (DTBN) hyperfine tensors: an experimental and computational study

The di- tert-butyl nitroxide (DTBN) hyperfine tensors are computed in a reasonable time frame using the UB1LYP method and Barone's electron paramagnetic resonance EPR-III basis sets. The effects of six solvents on the 14N hyperfine splittings are calculated using the polarizable continuum method and reproduce the experimental trends. Further improvement in the accuracy is obtained when one extra water molecule is made to interact with the NO moiety. All the DTBN atoms are not magnetically equivalent since the molecule has C 1 symmetry. This must be taken into consideration when simulating the EPR line shapes of randomly oriented DTBN molecules isolated in an argon matrix.

Solvent effects on the relative stability of 4-nitro-1H-imidazole and 5-nitro-1H-imidazole. Ab initio and density functional theory calculations

Ab initio and density functional theory (DFT) calculations were carried out to investigate the relative stability of 4-nitro-1H-imidazole (1) and 5-nitro-1H-imidazole (2) in the gas phase and in solutions with different polarities. Solvent effects were examined by means of both the self-consistent isodensity polarized continuum method (SCI-PCM) and the self-consistent reaction field (SCRF) method. In the gas phase, both QCISD(T)/6-311++G∗∗ and CCSD(T)/6-311++G∗∗ single point calculations at the MP2/6-311++G∗∗ optimized geometries estimated that 1 is more stable than 2 by 0.7kcal/mol. On the other hand, B3LYP calculations, even with the 6-311++G(3df, 3pd) basis set, predicted that 2 is more stable than 1 by about 0.3–0.8kcal/mol. In solutions, all the calculations employed in this study agreed that the relative stability of 1 over 2 gets significantly larger as the solvent becomes more polar. However, the relative stability calculated by the SCRF method was substantially larger than those computed by the SCI-PCM method. Origins of the solvent effects were examined by analyzing the changes of: (1) electrostatic potentials; and (2) the dipole moments due to the change of a solvent polarity.

Effects of electron correlation and the environment on the conformational preferences of the β-alanine dipeptide

The conformational preferences of the β-alanine dipeptide have been determined in the gas-phase using HF/6-31G(d) and MP2/6-31G(d) geometry optimizations. The conformational energy of the six resulting minima was estimated by single point calculations at both the HF/6-311G(d,p) and MP2/6-311G(d,p) levels. Self-consistent reaction field calculations using the polarizable continuum method were performed in order to evaluate the effect of the solvent on the relative stability of the different minima. Furthermore, the theoretical results obtained for the dipeptide have been compared with the conformational preferences found for the β-alanine residue in small peptides by examination of the Cambridge Structural Data Base. The influence of both electron correlation and the environment on the conformational energies is discussed.

The influence of axial ligands on the reduction potential of blue copper proteins.

The reduction potentials of blue copper sites vary between 180 and about 1000 mV. It has been suggested that the reason for this variation is that the proteins constrain the distance between the copper ion and its axial ligands to different values. We have tested this suggestion by performing density functional B3LYP calculations on realistic models of the blue copper proteins, including solvent effects by the polarizable continuum method. Constraining the Cu-S(Met) bond length to values between 245 and 310 pm (the range encountered in crystal structures) change the reduction potential by less than 70 mV. Similarly, we have studied five typical blue copper proteins spanning the whole range of reduction potentials: stellacyanin, plastocyanin, azurin, rusticyanin, and ceruloplasmin. These studies included the methionine (or glutamine) ligand as well as the back-bone carbonyl oxygen group that is a ligand in azurin and is found at larger distances in the other proteins. The active-site models of these proteins show a variation in the reduction potential of about 140 mV, i.e., only a minor part of the range observed experimentally (800 mV). Consequently, we can conclude that the axial ligands have a small influence on the reduction potentials of the blue copper proteins. Instead, the large variation in the reduction potentials seems to arise mainly from variations in the solvent accessibility of the copper site and in the orientation of protein dipoles around the copper site.

Theoretical Study on the Thermodynamics of the Elimination of Formic Acid in the Last Step of the Hydrogenation of CO2 Catalyzed by Rhodium Complexes in the Gas Phase and Supercritical CO2

How coordination of a CO2 molecule can assist in the release of HCOOH from the [P2Rh(HCOOH)] complex in the last step of the hydrogenation of CO2 catalyzed by rhodium complexes has been investigated by density functional methods. The effect of a supercritical CO2 solution has been included using the polarizable continuum method. It has been found that the presence of a CO2 molecule in the model of the active site favors the thermodynamics of the HCOOH dissociation from the [P2Rh(HCOOH)] species.

Molecular Vibrations of Solvated Uracil. Ab Initio Reaction Field Calculations and Experiment

Harmonic vibrational frequencies and transition strengths in uracil have been calculated in self-consistent reaction fields of low (ε = 1.53) and high (ε = 78.54) dielectric constant using ab initio Hartree−Fock and density functional theory methods at the 6-31+G* level of theory. Uniformly scaled frequencies calculated in low dielectric medium agree well with infrared spectra of uracil in argon matrix, Δν(avg) = 2.2 cm-1, although only partial agreement is obtained for individual matrix-induced frequency shifts and intensity changes. Reaction field calculations with a tighter spherical cavity or solute cavity determined by the isodensity polarizable continuum method yield better match with experiment for certain vibrations. In a polar protic medium, the vibrational analysis is extended beyond neutral uracil to its (de)protonation derivatives selected by reaction field calculations. Unscaled vibrational frequencies, as well as infrared and Raman intensities of the uracil-4-ol cation, neutral uracil, uracil N1-anion, and uracil N1,3-dianion calculated in continuous high dielectric medium are found to agree fairly well with vibrational spectra of uracil in aqueous media recorded over a wide pH range. The deficiencies of the reaction field model, like hydrogen bonding and ion−solvent interactions, are highlighted and their contributions quantitatively estimated.

Conformational Preferences of the Asparagine Residue. Gas-Phase, Aqueous Solution, and Chloroform Solution Calculations on the Model Dipeptide

The conformational preferences of the asparagine dipeptide have been determined in the gas phase using ab initio calculations at the HF/6-31G(d) and MP2/6-31G(d) levels. Geometry optimizations lead to 17 different minima, the lowest energy structure being characterized by a C7,eq backbone orientation and a gauche conformation for the side chain. Self-consistent reaction-field (SCRF) calculations using a polarized continuum method have been performed in order to evaluate the effects of the solvent on the conformational preferences of the compound under study. Water and chloroform were the solvents chosen for this purpose. Results show that water solvent exerts a larger influence on the conformational properties of the asparagine dipeptide than chloroform solvent. However, in both solvents the lowest energy structure is the same as that in the gas phase. Finally, the side chain conformations of the characterized minima have been analyzed and compared with experimental data. The gauche was the most populated...

Ab initio quantum mechanical gas phase and reaction field solvation study on the proton abstraction from hydroxyacetaldehyde by formate: implications for enzyme catalysis

Proton abstraction from a model carbon acid hydroxyacetaldehyde by formate has been studied using ab initio quantum mechanical calculations up to the MP4(SDQ)/6-31+G**//HF/6-31+G* level. Solvation effects are included using the polarisable continuum method. The calculated energies of several intermediates and transition states of the proton transfer reaction are found to be in reasonable agreement with the available experimental data. Calculations show that the α-carbon, which loses a proton in the reaction, retains a substantial amount of sp3 character in the transition state of the reaction. Therefore the resonance-stabilised enolate anion product, in which the α-carbon is sp2 hybridised, develops after the transition state has been passed. Inclusion of solvation energies moves the transition state to an earlier point on the reaction profile. This indicates that in the case of enzyme-catalysed reaction, in which the protein environment presumably can stabilise an enolate-like structure more efficiently than water does, the transition state would be even less enolate-like unless enzymes had other means of enhancing the reaction and making the transition state occur later. We discuss how lowering of the intrinsic reaction barrier and proton tunnelling may move the transition state of the enzyme-catalysed proton abstraction reaction to a later point on the reaction profile.

A semiempirical study on the ring-opening process for the cyclopropanone, 2,2-dimethylcyclopropanone,trans-2,3-di-tert-butylcyclopropanone, and spiro(bicyclo[2.2.1]heptane-2.1?-cyclopropan)-2?-one systems in solution

The molecular mechanisms for the ring openings of cyclopropanone, 2,2-dimethylcyclopropanone, trans-2,3-di-tert-butylcyclopropanone, and spiro(bicyclo[2.2.1]heptane-2.1′-cyclopropan)-2′-one systems were studied at the PM3 semiempirical level in the gas phase and including solvent effects. The behavior of the solvent polarity was considered by using the SCRF polarizable continuum method. Six solvents were selected: hexane, ether, tetrahydrofuran, pyridine, acetone, and acetonitrile. An extensive exploration of the potential energy surface using analytical gradient techniques allows the characterization of stationary points associated to the stereomutation conversion. Along a disrotatory ring-opening mechanism, cyclopropanone, 2,2-dimethylcyclopropanone and trans-2,3-di-tert-butylcyclopropanone are intraconverted via an oxyallyl intermediate. The epimeric forms of the spiro(bicyclo[2.2.1]heptane-2.1′-cyclopropan)-2′-one intraconvert along two competitive pathways correspond to two-step processes by a disrotatory ring-opening mechanism. Two oxyallyl intermediates and four transition structures were obtained and the corresponding transition vectors are associated to the carbon–carbon bond-breaking process and the dihedral angle measuring the conrotatory movement of the plane defined by the three carbon atoms of the cyclopropanone ring. The oxyallyl intermediates and the transition structures for the four model systems present similar structures and energies and they are located on a rather flat region. The analysis of the theoretical results shows that the solvent reaction field decreases the energy barriers for the ring-opening processes and a stabilization of the oxyallyl intermediates takes place. The calculated relative barrier heights are in good agreement with the experimental data available, and the trends in the kinetics can be explained primarily by steric interactions. Nevertheless, for the spiro(bicyclo[2.2.1]heptane-2.1′-cyclopropan)-2′-one system, it is necessary to include a specific interaction of a discrete molecule of the nucleophilic solvent on the quantum mechanical representation to explain the experimental behavior. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 65: 729–738, 1997

Hybrid supermolecule-polarizable continuum approach to solvation: Application to the mechanism of the Stevens rearrangement

Semiempirical molecular orbital theory has been used to study the effects of solvation by acetonitrile on the Stevens rearrangement of methylammonium formylmethylide to 2-aminopropanal. Three methods of solvation have been used to investigate both the electrostatic and specific solvent–solute effects of solvation: a supermolecule calculation involving the complete geometry optimization of up to six solvent molecules about the solute, the conductor-like screening model (COSMO) polarizable continuum method which allows for geometry optimization of the solute in a solvent defined by its dielectric constant, and a hybrid method in which up to five solvent molecules are incorporated inside the solute cavity and complete geometry optimization of the complex is carried out within the polarizable continuum. A comparison of the calculated geometries, rearrangement activation energies, and enthalpies of solvation from these approaches is presented, and the explicit versus bulk solvation effects are discussed. The overall effect of all methods for incorporating solvation effects is that the radical pair pathway is perferred over the concerted mechanism. © 1996 by John Wiley & Sons, Inc.

Speciation in Aqueous Zinc Chloride. An ab Initio Hybrid Microsolvation/Continuum Approach

The structure and energetics of zinc chlorides (ZnCln2-n, n = 0−4) in aqueous solution are studied by ab initio molecular orbital methods. The first solvation shell is included explicitly, the remainder of the solvent being modeled by the polarizable continuum method. The species Zn(H2O)62+, ZnCl2(H2O)2, ZnCl3(H2O)-, and ZnCl42- are predicted to occur in an aqueous environment. The predictions are consistent with the limited structural and energetic data available. A comparison with the predictions of the continuum model alone shows the necessity of including the first solvation shell explicitly to model solvation energies, although the continuum model is successful in predicting structural changes of ZnCl+ and ZnCl2 upon hydration.

A theoretical model of solvation in continuum anisotropic dielectrics

A new formulation of the polarizable continuum method (PCM) is presented to describe the electrostatic interaction between molecular solutes and anisotropic media (e.g., liquid crystals, crystalline matrices). The main features of the PCM (ab initio treatment of solute, cavity of arbitrary shape, dielectric reaction described with apparent charges) are maintained, though in this case polarization charges are present both on the cavity surface and in the bulk of the dielectric. A simplified method, saving about half of the computational time, is also presented.

Solute—solvent electrostatic interactions with non-homogeneous radial dielectric functions

Distance-dependent permitivity functions, ϵ( r), allow the description of ionic or dipolar solutes more accurately than the usual homogeneous Onsager model. We present an extension of the polarizable continuum method (PCM) which is able to calculate solute—solvent electrostatic interactions in the case of a non-homogeneous dielectric constant. Every functional form for ϵ( r) can be implemented in this extended PCM version: some results using the Block-Walker permittivity function are reported.

Assessment of quantum mechanical continuum models of solvation: the prediction of tautomer equilibria, partition coefficients and amine basicity

Quantum mechanical continuum models of solvation, the self-consistent reaction field (SCRF), and polarizable continuum method, are used at the ab initio SCF level, to study tautomer equilibria, partition coefficients and amine basicity. The predictions are compared both with experimental data and with results from free energy perturbation (FEP) studies. In the SCRF studies, the description of the solute charge distribution beyond the dipole level does not lead to a significant improvement in the accuracy of the predictions. For the range of properties studied, the quality of predictions by these continuum models rivals that obtained by traditional molecular dynamics calculations.

Evaluation of complexation energies between aspartic protease of HIV-1 and its hexapeptide inhibitors including the effect of solvation

The complexation energy and their individual contributions between the Aspartic Protease enzyme (AP) of human immunodeficiency virus and hexapeptide inhibitors(I) with CH 2NH reduced peptide bond have been first evaluated using the method of molecular mechanics. Then the evaluation of solvation energies for individual species AP:I, AP and I has been done by polarizable continuum method. As to the complexation itself, the dominant role for the electrostatic interaction is found. Various replacements of P3…..P3′ inhibitor residues have been modelled with the goal to design inhibitors with the high affinity towards AP enzyme. Solvation energy modifies the order of stability of complexes depending on the solvent polarity. New, hypothetically more active structures have been forwarded for synthesis and testing.

Nonequilibrium solvation: An ab initio quantum-mechanical method in the continuum cavity model approximation

The electrostatic relationships necessary for the quantum-mechanical evaluation of the properties of a solute experiencing sudden changes in its internal charge distribution are here presented in a form suitable to perform accurate quantum-mechanical calculations of the solute properties. Attention has been paid to express the boundary conditions in the most convenient form and to avoid further constraints on the elaboration of the computational procedures. The approach exploits the separation of orientational (inertial) and electronic (inertialess) components of the polarization and complements the polarizable continuum method [Chem. Phys. 65, 239 (1982)], usually employed for static descriptions. Examples of application of the method to photoionization and electronic transitions processes are shown.