SMD Solvation Model Research Articles

Theoretical inclusion of deprotonated 2,4-D and dicamba pesticides in ß-cyclodextrin

In the present work the SMD solvation model and distinct functionals (PBE0, B97-D and M06-2X) were applied to investigate the best approach to study CD inclusion compounds. Within this work 2,4D and dicamba inclusion compounds were used as reference to test the theoretical methodology. Molecular Dynamics simulations were also performed. The Gibbs free energy in condensed phase accounted for the experimental findings for B97-D and M06-2X being the former outcomes in best agreement to experimental data. Molecular dynamics simulations did not produce any reliable information for the inclusion compounds under investigation in function of the huge fluctuations identified.

Computational Study of the Radical Mediated Mechanism of the Formation of C8, C5, and C4 Guanine:Lysine Adducts in the Presence of the Benzophenone Photosensitizer

The oxidation of guanine by triplet benzophenone in the presence of lysine has been shown to produce mono- and dilysine-substituted spiroiminodihydantion products, 8-Lys-Sp and 5,8-diLys-Sp. The potential energy surfaces for C8, C5, and C4 nucleophilic addition have been mapped out using the B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d,p) level of density functional theory with the SMD solvation model and employing methylamine as a model for the side chain of lysine. Enthalpies, barrier heights, pKa's, and reduction potentials were calculated for intermediates to find the lowest energy paths. For neutral methylamine plus guanine radical and neutral methylamine radical plus guanine, the barrier for addition at C8 is ca. 10 kcal/mol lower than that for addition at C5 and C4. The barriers for water addition at C8, C5, and C4 of guanine radical are 13-20 kcal/mol higher than that for methylamine addition at C8. Further oxidation and loss of a proton leads to 8-methylaminoguanine, the methylamino analogue of 8-oxo-7,8-dihydroguanine (8-oxoG). The barrier for the addition of a second methylamine at C5 of 8-methylaminoguanine is 4.5 kcal/mol lower than that for the corresponding addition of water. Nevertheless, if the concentration of methylamine (or lysine) is very low, water addition could be competitive with methylamine addition. This would lead to comparable fractions of 8-monosubstituted-Sp and 5-8-disubstituted-Sp, in agreement with the experimental observations.

Predicting cyclohexane/water distribution coefficients for the SAMPL5 challenge using MOSCED and the SMD solvation model

We present blind predictions using the solubility parameter based method MOSCED submitted for the SAMPL5 challenge on calculating cyclohexane/water distribution coefficients at 298K. Reference data to parameterize MOSCED was generated with knowledge only of chemical structure by performing solvation free energy calculations using electronic structure calculations in the SMD continuum solvent. To maintain simplicity and use only a single method, we approximate the distribution coefficient with the partition coefficient of the neutral species. Over the final SAMPL5 set of 53 compounds, we achieved an average unsigned error of [Formula: see text] log units (ranking 15 out of 62 entries), the correlation coefficient (R) was [Formula: see text] (ranking 35), and [Formula: see text] of the predictions had the correct sign (ranking 30). While used here to predict cyclohexane/water distribution coefficients at 298K, MOSCED is broadly applicable, allowing one to predict temperature dependent infinite dilution activity coefficients in any solvent for which parameters exist, and provides a means by which an excess Gibbs free energy model may be parameterized to predict composition dependent phase-equilibrium.

Prediction of pH Effect on the Octanol–Water Partition Coefficient of Ionizable Pharmaceuticals

The octanol–water partition coefficient (KOW) is a measure of the relative hydrophobicity and hydrophilicity of a chemical. Knowledge regarding how this value changes with the acidity (pH value) in the aqueous phase is important for understanding many biological activities. In this work, we develop a computational method to predict the effect of pH on the partition coefficient of ionizable drugs. In particular, three dissociation mechanisms were examined based on four relevant properties: the acid dissociation constant (pKa), and the octanol–water partition coefficient of the molecule in the neutral form (KOW,N), in the form of free ions (KOW,I) and in the form of an ion pair (KOW,IP). The values of KOW,N, KOW,I, and KOW,IP are predicted based on the COSMO-SAC activity coefficient model, and the value of pKa is determined using the SMD solvation model. The root-mean-square (RMS) error in the predicted log KOW,N, log KOW,IP, and pKa for 41 pharmaceuticals are found to be 0.636, 0.816, and 2.59, respectivel...

Двохелектронне відновлення нітроароматичних сполук флавінмононуклеотидом. ТФГ розрахункове дослідження

The mechanism for reduction of nitroaromatic compounds by flavin mononucleotide (FMN) was examined at MPWB1K/tzvp level. The solvent effects were calculated using a PCM(Pauling) and SMD(Pauling) solvation models for ions and neutral molecules, respectively. Calculated thermodynamics of the reduction of nitro group to nitroso group suggests consequtive four-steps’ process (electron–proton–electron–proton transfer) where the first proton comes from solution, while the second one – from FMN. Water molecule releases during fourth step of the process. Electron attachment to nitrocompound and electron lose by reduced FMN facilitate the breaking of N–O bond and proton release, respectively. Calculations show that reduction of nitro group to nitroso group in studied nitrocompounds is a thermodynamically feasible with 56–59 kcal/mol Gibbs free energy release. The most easy electron transfer proceeds for TNT (2,4,6-trinitrotoluene) and NTO (5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one). While the most energy release occurs during proton transfer in case of ANTA (5-amino-3-nitro-1H-1,2,4-triazole).

Prediction of pKa values using the PM6 semiempirical method.

The PM6 semiempirical method and the dispersion and hydrogen bond-corrected PM6-D3H+ method are used together with the SMD and COSMO continuum solvation models to predict pKa values of pyridines, alcohols, phenols, benzoic acids, carboxylic acids, and phenols using isodesmic reactions and compared to published ab initio results. The pKa values of pyridines, alcohols, phenols, and benzoic acids considered in this study can generally be predicted with PM6 and ab initio methods to within the same overall accuracy, with average mean absolute differences (MADs) of 0.6–0.7 pH units. For carboxylic acids, the accuracy (0.7–1.0 pH units) is also comparable to ab initio results if a single outlier is removed. For primary, secondary, and tertiary amines the accuracy is, respectively, similar (0.5–0.6), slightly worse (0.5–1.0), and worse (1.0–2.5), provided that di- and tri-ethylamine are used as reference molecules for secondary and tertiary amines. When applied to a drug-like molecule where an empirical pKa predictor exhibits a large (4.9 pH unit) error, we find that the errors for PM6-based predictions are roughly the same in magnitude but opposite in sign. As a result, most of the PM6-based methods predict the correct protonation state at physiological pH, while the empirical predictor does not. The computational cost is around 2–5 min per conformer per core processor, making PM6-based pKa prediction computationally efficient enough to be used for high-throughput screening using on the order of 100 core processors.

Density Functional Theory Calculation of pKa's of Thiols in Aqueous Solution Using Explicit Water Molecules and the Polarizable Continuum Model.

The pKa's of substituted thiols are important for understanding their properties and reactivities in applications in chemistry, biochemistry, and material chemistry. For a collection of 175 different density functionals and the SMD implicit solvation model, the average errors in the calculated pKa's of methanethiol and ethanethiol are almost 10 pKa units higher than for imidazole. A test set of 45 substituted thiols with pKa's ranging from 4 to 12 has been used to assess the performance of 8 functionals with 3 different basis sets. As expected, the basis set needs to include polarization functions on the hydrogens and diffuse functions on the heavy atoms. Solvent cavity scaling was ineffective in correcting the errors in the calculated pKa's. Inclusion of an explicit water molecule that is hydrogen bonded with the H of the thiol group (in neutral) or S(-) (in thiolates) lowers error by an average of 3.5 pKa units. With one explicit water and the SMD solvation model, pKa's calculated with the M06-2X, PBEPBE, BP86, and LC-BLYP functionals are found to deviate from the experimental values by about 1.5-2.0 pKa units whereas pKa's with the B3LYP, ωB97XD and PBEVWN5 functionals are still in error by more than 3 pKa units. The inclusion of three explicit water molecules lowers the calculated pKa further by about 4.5 pKa units. With the B3LYP and ωB97XD functionals, the calculated pKa's are within one unit of the experimental values whereas most other functionals used in this study underestimate the pKa's. This study shows that the ωB97XD functional with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and the SMD solvation model with three explicit water molecules hydrogen bonded to the sulfur produces the best result for the test set (average error -0.11 ± 0.50 and +0.15 ± 0.58, respectively). The B3LYP functional also performs well (average error -1.11 ± 0.82 and -0.78 ± 0.79, respectively).

Air–water partition coefficients for a suite of polycyclic aromatic and other C10 through C20 unsaturated hydrocarbons

ABSTRACTThe air–water partition coefficients (Kaw) for 86 large polycyclic aromatic hydrocarbons and their unsaturated relatives were estimated using high-level G4(MP2) gas and aqueous phase calculations with the SMD, IEFPCM-UFF, and CPCM solvation models. An extensive method validation effort was undertaken which involved confirming that, via comparisons to experimental enthalpies of formation, gas-phase energies at the G4(MP2) level for the compounds of interest were at or near thermochemical accuracy. Investigations of the three solvation models using a range of neutral and ionic compounds suggested that while no clear preferential solvation model could be chosen in advance for accurate Kaw estimates of the target compounds, the employment of increasingly higher levels of theory would result in lower Kaw errors. Subsequent calculations on the polycyclic aromatic and unsaturated hydrocarbons at the G4(MP2) level revealed excellent agreement for the IEFPCM-UFF and CPCM models against limited available experimental data. The IEFPCM-UFF-G4(MP2) and CPCM-G4(MP2) solvation energy calculation approaches are anticipated to give Kaw estimates within typical experimental ranges, each having general Kaw errors of less than 0.5 log10 units. When applied to other large organic compounds, the method should allow development of a broad and reliable Kaw database for multimedia environmental modeling efforts on various contaminants.

Ozonolysis mechanism of heterocyclic organic sulfides: A computational study

The reaction mechanism of the ozonation of benzothiophene (BT) and its derivatives was explored by using the density functional theory (DFT) considering the solvation effect in acetonitrile using both the COSMO implicit solvent approach and SMD solvent model with and without D3 corrections. Two pathways are proposed for ozonation of BT. The path through Criegee mechanism was found to be more favorable. Furthermore, we also calculated the ozonation of the derivatives of BT such as dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT). The reaction mechanisms of DBT and 4,6-DMDBT are different from that of BT. Based on the activation energies, the reactivity of BT and its derivatives to ozone are in the following order: BT>4, 6-DMDBT>DBT.

Reaction Mechanisms of the Initial Oligomerization of Aluminophosphate

The mechanisms of aluminophosphate oligomerization were investigated using density functional theory with the SMD solvation model. Two aluminum species, Al(OH)4(-) and Al(H2O)6(3+), and four phosphorus species, H3PO4, H2PO4(-), HPO4(2-), and PO4(3-), were considered as the monomers for polycondensation reactions. It was found that the most favorable pathway to dimerization was a Lewis acid-base reaction: the aprotic oxygen of phosphoric acid (P═O) performs a nucleophilic attack on the central aluminum atom of Al(OH)4(-). Using this mechanism as a pattern, plausible dimerization mechanisms were investigated by varying the proticity and hydration of the phosphorus and aluminum monomers, respectively. The relative reaction rates of each mechanism were estimated under different pH conditions. The chain growth of aluminophosphates to trimers, tetramers, and pentamers and the cyclization of a linear tetramer were also investigated. For oligomerization reactions beyond dimer formation, it is found that cluster growth favors the addition of the phosphoric monomers rather than aluminum monomers.

Conformation of six fentanyls revisited

Conformation of fentanyl and its five derivatives was studied at the B3LYP/6-31G∗∗ level. Two stereoisomers for α-methyl-β-hydroxy fentanyl and four for the ohmefentanyl were taken into account. Conformation in the gas phase and water, simulated using the IEF-PCM and SMD implicit models of solvents, was independently optimized using 27 starting structures resulted from rotations about the most important three torsion angles. The role of the Grimme’s D3 correction for the dispersion forces was additionally considered for each medium. The correction appeared to influence more the gas phase than water dissolved structures. Moreover, the correction influences more the conformations of N-phenylpropionamide group than those of the modified phenylethyl substituent. In water solution simulated by the IEF-PCM and SMD solvation models, the conformers connected to the phenylethyl moiety, are substantially different only for the two derivatives, for which indications coming from different computational variants are the most vague. However, for the conformers connected to the N-phenylpropionamide group, the IEF-PCM model favors the t conformation for three derivatives while SMD prefers sum of the g+ and g− conformations for the other three derivatives. For the ohmefentanyl stereoisomers, irrespectively, the solvation or presence of the D3 correction, all the methods concordingly predict the N-phenylpropionamide group conformation twisted by either −120° or to 120°.

Density functional theory investigation of the ruthenium-catalyzed cycloisomerization of silicon-tethered 1,7-enynes

Density functional theory calculations at the M06-2X/6-31G(d,p) (RECPs for Ru) level of theory are performed to explore the reaction mechanism for the cycloisomerization of silicon-tethered 1,7-enynes using CpRuCl as a catalyst. The solvent effect is taken into account by M06-2X/6-311++G (d,p) single-point calculations with SMD solvation model in toluene. The calculation results indicate that the reactions of the ruthenium-catalyzed cycloisomerization of 1,7-enynes occur through the possible mechanisms and get five-membered ring or six-membered ring products, respectively. The process of forming six-membered ring product is more favored kinetically with the barrier of 13.6kcal/mol for Ph group, while the energy barrier for five-membered ring product becomes relatively higher of 34.3kcal/mol. The above reaction mechanism indicates that the ruthenium-catalyzed cycloisomerization of silicon connected 1,7-enynes has high regioselectivity, which is consistent with the experimental observations of Kaminsky and Clark.

A Combined Computational and Experimental Study of Copolymerization Propagation Kinetics for 1‐Ethylcyclopentyl methacrylate and Methyl methacrylate

The crosspropagation of 1‐ethylcyclopentyl methacrylate (ECPMA) and methyl methacrylate (MMA) has been studied using a combination of quantum chemistry calculations and experiment. Our computational work utilizes a trimer‐to‐tetramer reaction model, coupled with an ONIOM (B3LYP/6‐31G(2df,p): B3LYP/6‐31G(d)) method for geometry optimization and an M06‐2X/6‐311+G(2df,p) method plus SMD solvation model for single point energy calculations. The results show several trends: the identity of the ultimate unit of a trimer radical affects not only the preferred conformation of the region where the reaction takes place, but also the reactivity of the radical; the addition of an ECPMA monomer to the radicals is generally favored compared to an MMA monomer; the pen‐penultimate unit of a trimer radical shows a nonnegligible entropic effect; the penultimate unit effect is implicit for the ECPMA–MMA copolymer system. Finally, terminal model reactivity ratios fitted based on the explicit rate coefficients calculated from the quantum chemical results are compared with those from experimental measurements. The computations not only agree qualitatively with experimentally derived results in terms of the selectivity of ECPMA–MMA crosspropagation, but also give reasonable quantitative predictions of reactivity ratios. image

Quantum mechanical based approaches for predicting pKavalues of carboxylic acids: evaluating the performance of different strategies

The FP method is recommended for estimating pKavalues of carboxylic acids for which this information is still unknown, especially in combination with the PBE0 functional (MUE = 0.26) and the SMD solvent model.

Solvation enthalpies and Gibbs energies of the proton and electron: Influence of solvation models

A comprehensive examination of the solvation enthalpies and Gibbs energies of the proton and electron in twenty solvents of different polarities was carried. Eleven quantum mechanical methods were applied in conjunction with the 6-311++G(d,p) basis set and C-PCM solvation model. It was found that different methods produce consistent values for the solvation enthalpy and Gibbs energy of the proton in all solvents, while the corresponding values for the electron are mutually notably different. The fact that the Minnesota functionals often produced inconsistent solvation enthalpy and Gibbs energy values of the electron indicates their unreliable performance without the corresponding SMD solvation model, whereas other studied methods only slightly depend on solvation models. A comparison of the results of the present investigation to those obtained by employing SMD reveals that C-PCM produces slightly more negative (less positive) solvation enthalpies and Gibbs energies of the electron, and less negative values for the proton. These results are also in accord with the literature data where the IEF-PCM solvation model was used.

Synthesis and characterization of ML and ML2 metal complexes with amino acid substituted bis(2-picolyl)amine ligands.

Metal complexes with ML or ML2 stoichiometry have been isolated in the reaction of Zn(NO3)2, ZnBr2 or M(NO3)2/NaBF4, M = Zn(ii), Co(ii) or Ni(ii), with either amino acid or amine substituted tridentate nitrogen ligands based on bis(2-picolyl)amine (bpa) or bis(2-quinaldyl)amine (bqa). The stoichiometry (M : L = 1 : 1 or 1 : 2) and stereochemistry (mer, trans-fac or cis-fac) of the products have been studied by NMR and IR spectroscopy, X-ray single crystal analysis and quantum-chemical calculations with an implicit SMD solvation model.

Theoretical and Experimental Investigation of Thermodynamics and Kinetics of Thiol-Michael Addition Reactions: A Case Study of Reversible Fluorescent Probes for Glutathione Imaging in Single Cells.

Density functional theory (DFT) was applied to study the thermodynamics and kinetics of reversible thiol-Michael addition reactions. M06-2X/6-31G(d) with the SMD solvation model can reliably predict the Gibbs free energy changes (ΔG) of thiol-Michael addition reactions with an error of less than 1 kcal·mol(-1) compared with the experimental benchmarks. Taking advantage of this computational model, the first reversible reaction-based fluorescent probe was developed that can monitor the changes in glutathione levels in single living cells.

Crystallographic and Computational Study on Cationic Triply Hydrogen-Bonded Nucleobases without Direct Anionic Stabilization

[(1MeCH)(1MeC)](I3)·2H2O (1MeC = 1-methylcytosine) (1) displays a single hemicytosinium i-motif, which is surrounded by four water molecules and interestingly does not exhibit direct interactions with anions. Quantum chemical calculations in water (SMD solvent model) reproduce accurately the geometry of the “water-submerged” cation 1. Furthermore, we performed stabilization and proton transfer studies, as well as an evaluation and rationalization of the influence of surrounding molecules enclosing lone electron pairs on triply hydrogen-bond connected nucleobases.

Revisiting the solvation enthalpies and free energies of the proton and electron in various solvents

In scientific literature there are only several values for solvation enthalpies and free energies of the proton and electron, the quantities from which the enthalpies and free energies of the solvated proton and electron can be issued. The latter quantities are of significance in thermodynamic modeling of antioxidative properties in the media where the reactions really occur. This work fills this gap in scientific literature. Namely, a systematic investigation of the solvation enthalpies and free energies of the proton and electron in twenty commonly used solvents of different polarities was performed. For this purpose eleven ab initio and DFT methods were used in combination with the 6-311++G(d,p) basis set and SMD solvation model. Due to very good overall performance, B3LYP was selected for further computations with larger basis sets. The thermodynamic values obtained at the B3LYP/Aug-cc-pVTZ level of theory are in very good agreement with the existing several values for solvation enthalpies of the proton and electron, and they are recommended for application in the examinations of antioxidative activity in different solvents.

Bio-Inspired Electroactive Organic Molecules for Aqueous Redox Flow Batteries. 1. Thiophenoquinones

Redox flow batteries (RFB) utilizing water-soluble organic redox couples are a new strategy for low-cost, eco-friendly, and durable stationary electrical energy storage. Previous studies have focused on benzoquinones, napthoquinones, and anthraquinones as the electroactive species. Here, we explore a new class of molecules—thiophenoquinones—specifically focusing on the caldariellaquinone-, sulfolobusquinone-, and benzodithiophenoquinone-like frameworks that are used for metabolic processes in thermophilic aerobic Sulfolobus archaebacteria. We demonstrated that B3LYP/6-311+G(d,p) thermochemical calculations (using the SMD solvation model) reproduce experimental reduction potentials to within ±0.04 V. We then studied the effect of amine, hydroxyl, methyl, fluoro, phosphonic acid, sulfonic acid, carboxylic acid, and nitro functional group modifications on the reduction potential and Gibbs energy of solvation in water (using density functional theory) and aqueous solubility (using cheminformatics). Next we enumerated all of the 10 611 possible combinations of functional group substitutions on these frameworks and identified 1056 potential molecules with solubilities exceeding 2 mol/L; of these, 36 molecules have reduction potentials below 0.25 V and 15 molecules above 0.95 V (versus the standard hydrogen electrode (SHE)). The combination of high solubility and wide voltage range makes these molecules promising candidates for high performance aqueous RFB applications. Finally, using our data set of ab initio reduction potentials, we developed a cheminformatics model that predicts ab initio reduction potentials to within ±0.09 V based solely on molecular connectivity. We found that a model trained with as few as 200 examples generates rank-ordered predictions allowed us to identify the highest performance candidates with half the number of ab initio calculations. This offers a strategy for improving the tractability of future computational searches for high performance RFB molecules.