Continuum Solvation Model Research Articles

Quantum chemical study of the complexation process of bis-β-d-glucopyranosyl diazacrown derivative with aspirin and paracetamol molecules

1,10-N,N’-bis-(β-d-ureidoglucopyranosyl)-4,7,13-trioxa-1,10-diazacyclopentadecane is studied as a potential carrier of aspirin and paracetamol. The host:drug complexes in stoichiometry 1:1 are investigated in aqueous solution using the quantum chemical method B3LYP-GD2/6-31G(d,p) and the polarizable continuum model of solvent. Five new conformers of the host molecule, which are energetically more stable than the one found in the earlier work, [M. Adamiak, S. Porwański, A. Ignaczak, Tetrahedron 74 (2018) 2166–2173] are presented and their properties are compared to the previous data. For the complexes host:aspirin and host:paracetamol the energies of interaction, deformation and complexation as well as the NMR chemical shifts are analyzed in detail. It is shown that the complexes in stoichiometry 1:1 are stable, having the lowest complexation energy of −26 and −21 kcal/mol. From 1 to 3 moderate hydrogen bonds between host and guest are observed. In the energetically preferred structures neither aspirin nor paracetamol penetrates the area between the glucose units and diazacrown ring, what classifies them as non-inclusion complexes.

Photoabsorption Spectra of Aqueous Oxyluciferin Anions Elucidated by Explicit Quantum Solvent.

Experimental photoabsorption spectra of three possible isomers (phenolate-keto, phenolate-enol, and phenol-enolate) of oxyluciferin anions in aqueous solution were reproduced by first-principles time-dependent density functional theory simulations in which the entire system including the oxyluciferin anion and 64 water molecules were modeled by full quantum mechanics (full QM), unlike the conventional hybrid method, where the surrounding water molecules are modeled by molecular mechanics (MM) or a continuum solvent model. The full QM photoabsorption spectra were calculated from 1000 structures that had been obtained using the first-principles Born-Oppenheimer molecular dynamics simulations, which included the van der Waals correction, to take into account the effect of dynamical fluctuations of the hydration structure. The full QM calculation with CAM-B3LYP functional, which is the most elaborate one and is apparently the most consistent with experiment, is compared to others obtained with different levels of the functional and the solvent model. The amount of charge leakage from the oxyluciferin anions to the aqueous solution is found to differ significantly between the ground and excited states and is strongly dependent on the simulation method. The conventional solvent models do not take this into account, but the QM/MM can do it appropriately when including more than 10 water molecules into the QM region.

Theoretical investigation of the reactivity of bispentamethylcyclopentadienyl uranium(IV) bisthiolate complexes with the heteroallene molecules CS2 and CO2

The insertion reactions of the bispentamethylcyclopentadienyl bisthiolate uranium(IV) complexes [U(Cp*)2(SR)2] (Cp* = η–C5Me5; R = Me (1), tBu (2), iPr (3), Ph (4)) with CO2 or CS2 were investigated using Density Functional Theory (DFT), solvent effects being taken into account using the SMD continuum solvation model. The optimized geometries of the bisthiolate compounds computed at the DFT/B3PW91 level are in good agreement with available X–ray experimental data. The energy profiles of their reactions with CO2 and CS2 were determined. The formation of the products can be explained by a unique reaction mechanism involving an uranium(IV)–bridged heteroallene transition state. The CO2 insertion reactions exhibit lower activation barriers than those of CS2 insertion in accordance with the experiments showing that the CO2 insertion reactions are faster. As expected, compound 2 (R = tBu) was found to be the most difficult to undergo the insertion reaction because of steric hindrance. The geometrical parameters of the CS2 insertion derivative [U(Cp*)2(StBu)(S2CStBu)] (5) and the mixed insertion complex [U(Cp*)2(O2CStBu)(S2CStBu)] (6) obtained after treatment of 5 with CO2 are consistent with those determined by X-ray diffraction. The performed orbital analysis reveal the respective role of the actinide 7s, 6d and 5f orbitals, whereas the Wiberg Bond Indices (WBI) afford a good explanation of the structural variations during the insertion reactions. Finally, the Natural Population Analyses account for the different charge transfers occurring during the insertion processes.

Role of Displacing Confined Solvent in the Conformational Equilibrium of β-Cyclodextrin.

This study investigates the role of hydration and its relationship to the conformational equilibrium of the host molecule β-cyclodextrin. Molecular dynamics simulations indicate that the unbound β-cyclodextrin exhibits two state behavior in explicit solvent due to the opening and closing of its cavity. In implicit solvent, these transitions are not observed, and there is one dominant conformation of β-cyclodextrin with an open cavity. Based on these observations, we investigate the hypothesis that the expulsion of thermodynamically unfavorable water molecules into the bulk plays an important role in controlling the accessibility of the closed macrostate at room temperature. We compare the results of the molecular mechanics analytical generalized Born plus nonpolar solvation approach to those obtained through grid inhomogeneous solvation theory analysis with explicit solvation to elucidate the thermodynamic forces at play. The work illustrates the use of continuum solvent models to tease out solvation effects related to the inhomogeneity and the molecular nature of water and demonstrates the key role of the thermodynamics of enclosed hydration in driving the conformational equilibrium of molecules in solution.

Proton Dissociation and Transfer in Protic Ionic Liquids (PILs)

Protic ionic liquids (PILs) have attracted significant attention due to their promising properties and potential use in various applications. Recent studies revealed exceptionally strong decoupling of proton conductivity from structure relaxation in a mixture of lidocaine with phosphoric acid.1 Proton conductivity in this mixture even exceeds that of phosphoric acid at the same viscosity. Both lidocaine and phosphoric acid have proton donor and acceptor sites that facilitates the formation of a well-connected hydrogen bond network contributing to their high proton diffusivity. Thus, it is necessary to study the effects of the molecular geometry of both the acid and base, the number of the proton donating and accepting sites on the acid and base, and the solvation on the proton dissociation and transfer. In this study, fully optimized structures of pairs and clusters of the phosphoric acids (PAs) with different bases (lidocaine, imidazole, creatinine, and trimethylammonium) were determined through ab initio electronic structure calculations at the B3LYP/6-311G** level of theory in both the gas phase and the SMD model. The molecular binding energies of PA and the base molecules were calculated from both the uncorrected and zero point energies (ZPEs) corrected total electronic energies based on the same level of theory. Subsequently, potential energy surface (PES) scans for the transfer of a proton for pairs and clusters of the acids with various bases were performed at the same level of theory to study the effects of different bases and the number of PAs on the dissociation of PA and the proton transfer energetics. The results reveal that dissociated protons are generally more favorable in the SMD model since the continuum solvation model stabilizes the charge separation. Reference: 1. Z. Wojnarowska, Y. Wang, K. J. Paluch, A. P. Sokolov, M. Paluch, Observation of highly decoupled conductivity in protic ionic conductors. Phys.Chem.Chem.Phys 2014 , 16, 9123-9127.

Improving ligand 3D shape similarity-based pose prediction with a continuum solvent model.

In order to improve the pose prediction performance of docking methods, we have previously developed the pose prediction using shape similarity (PoPSS) method. It identifies a ligand conformation of the highest shape similarity with target protein crystal ligands. The identified ligand conformation is then placed into the target protein binding pocket and refined using side-chain repacking and Monte Carlo energy minimization. Subsequently, we have reported a modification to PoPSS, named as PoPSS-Lite, using a simple grid-based energy minimization for side-chain repacking and Tversky correlation coefficient as the similarity metric. This modification has improved the pose prediction performance and PoPSS-Lite was one of the top performers in D3R GC3. Here we report a further modification to PoPSS that utilizes a continuum solvent model to account for water mediated protein ligand interactions. In this approach, named as PoPSS-PB, the ligand conformation of the highest shape similarity with crystal ligands is refined along with the target protein binding site by incorporating the Poisson-Boltzmann electrostatics. The performance of PoPSS-PB along with PoPSS and PoPSS-Lite was prospectively evaluated in D3R GC4. PoPSS-PB not only demonstrated excellent performance with mean and median RMSDs of 1.20 and 1.13Å but also achieved improved performance over PoPSS and PoPSS-Lite. Furthermore, the comparison with other D3R GC4 pose prediction submissions revealed admirable performance. Our results showed that the binding poses of ligands with unknown binding modes can be successfully predicted by utilizing ligand 3D shape similarity with known crystallographic ligands and that taking the solvation into consideration improves pose prediction.

Probing the pseudocapacitance and energy-storage performance of RuO2 facets from first principles

The energy density of ruthenia (${\mathrm{RuO}}_{2}$) pseudocapacitor electrodes is critically dependent on their surface structure. To understand this dependence, we simulate the electrochemical response of ${\mathrm{RuO}}_{2}$(110), ${\mathrm{RuO}}_{2}$(100), and ${\mathrm{RuO}}_{2}$(101) in aqueous environments using a self-consistent continuum solvation (SCCS) model of the solid-liquid interface. The insertion of protons into the ${\mathrm{RuO}}_{2}$(110) sublayer is found to profoundly affect the voltage-dependent characteristics of the system, leading to a sharp transition from a battery-type to capacitor-type response. The calculated charge-voltage properties for ${\mathrm{RuO}}_{2}$(101) are in qualitative agreement with experiment, albeit with a pseudocapacitance that is significantly underestimated. In contrast, the ${\mathrm{RuO}}_{2}$(100) facet is correctly predicted to be pseudocapacitive over a wide voltage window, with a calculated pseudocapacitance in close agreement with experimental voltammetry. These results establish the SCCS model as a reliable approach to predict and optimize the facet-dependent pseudocapacitance of polycrystalline systems.

Hybrid discrete‐continuum solvation methods

AbstractHybrid discrete‐continuum approaches for solvation have been widely applied for diverse problems in chemistry suck as pKa calculation in aqueous and nonaqueous solvents, activation free energy barriers for ionic processes in solution, and surface reactions. A special version of this approach, the cluster‐continuum quasichemical model, has also been used for establishing a single‐ion solvation free energy scale in different solvents compatible with the tetraphenylarsonium tetraphenylborate assumption. The use of discrete‐continuum solvation methods can lead to meaningful improvement with respect to pure continuum solvation models for modeling diverse chemical process in solution. In the case of pKa calculations, there are cases where the root mean squared error is as large as 7 pKa units with pure continuum solvation model and becomes around 1 pKa unit with the hybrid approach. For complex reactions in solution, errors as large as 10 kcal/mol for activation free energies with the pure continuum approach can be substantially reduced with the inclusion of explicit solvent molecules. A discussion of the theory of hybrid discrete‐continuum methods is also presented and further development is expected in the coming years.This article is categorized under:Structure and Mechanism > Reaction Mechanisms and CatalysisSoftware > Quantum ChemistryMolecular and Statistical Mechanics > Free Energy Methods

CCSD‐PCM Excited State Energy Gradients with the Linear Response Singles Approximation to Study the Photochemistry of Molecules in Solution

AbstractWe present the theory and the implementation for the excited state energy gradients with respect to nuclear displacements for the linear response coupled cluster with single and double excitations (LR‐CCSD) combined with the polarizable continuum model of solvation within the LR formalism and the singles approximation (LR‐PCM‐PTES). This approach allows the exploration of the excited state potential energy surface of solvated molecules for the evaluation of minima and other stationary points, at a computational cost virtually identical to that of gas‐phase LR‐CCSD. The method is applied to the evaluation of vertical absorption and emission energies of 4‐(N,N)‐dimethyl‐aminobenzonitrile (DMABN) in gas phase, cyclohexane, and acetonitrile solutions. The method is able to find the minima for the locally excited and charge transfer states, which are responsible for the dual‐fluorescence of this compound. At the same time, some limitations of the LR and state specific (SS) formalisms for excited state solvation, which suffer from under or overestimation of the solvent effect in excited states, are discussed.

Electrochemical stability and light-harvesting ability of silicon photoelectrodes in aqueous environments.

We study the factors that affect the photoactivity of silicon electrodes for the water-splitting reaction using a self-consistent continuum solvation model of the solid-liquid interface. This model allows us to calculate the charge-voltage response, Schottky barriers, and surface stability of different terminations while accounting for the interactions between the charge-pinning centers at the surface and the depletion region of the semiconductor. We predict that the most stable oxidized surface does not have a favorable Schottky barrier, which further explains the low solar-to-hydrogen performance of passivated silicon electrodes.

PF5 and PCl5 interacting with water – Comparative study at the molecular level

The isomeric structures formed by the interaction of PF5 and PCl5 with up to four water molecules were theoretically examined by employing the MP2 method and the aug-cc-pVDZ basis set. The additional effects of surrounding water molecules were approximated by employing the polarized continuum solvation model (PCM) within a self-consistent reaction field treatment. The calculations indicate that the global minimum resulting from the interaction of PF5 and one H2O molecule corresponds to the PF5–H2O adduct and remains the most stable isomer after addition of second and third H2O, whereas the presence of fourth H2O molecule renders the PF5OH−/H3O+/2H2O structure the most stable. On the contrary, the interaction of PCl5 and a single H2O molecule leads to the global minimum structure corresponding to the PCl3O phosphoryl chloride with two HCl moieties attached. The lowest energy isomers resulting from the interaction of PCl5 with two, three, and four H2O molecules indicate the tendency of PCl3O to subsequent replacement of the Cl ligands with OH groups resulting in formation of H3PO4 (with five surrounding HCl fragments) when the number of available H2O molecules is sufficient. The presence of the competitive isomers containing H3O+ fragments in the case of the PCl5 interacting with water molecules is also predicted and discussed.

11B NMR Chemical Shift Predictions via Density Functional Theory and Gauge-Including Atomic Orbital Approach: Applications to Structural Elucidations of Boron-Containing Molecules.

11B nuclear magnetic resonance (NMR) spectroscopy is a useful tool for studies of boron-containing compounds in terms of structural analysis and reaction kinetics monitoring. A computational protocol, which is aimed at an accurate prediction of 11B NMR chemical shifts via linear regression, was proposed based on the density functional theory and the gauge-including atomic orbital approach. Similar to the procedure used for carbon, hydrogen, and nitrogen chemical shift predictions, a database of boron-containing molecules was first compiled. Scaling factors for the linear regression between calculated isotropic shielding constants and experimental chemical shifts were then fitted using eight different levels of theory with both the solvation model based on density and conductor-like polarizable continuum model solvent models. The best method with the two solvent models yields a root-mean-square deviation of about 3.40 and 3.37 ppm, respectively. To explore the capabilities and potential limitations of the developed protocols, classical boron–hydrogen compounds and molecules with representative boron bonding environments were chosen as test cases, and the consistency between experimental values and theoretical predictions was demonstrated.

Redox Potentials of Small Inorganic Radicals and Hexa-Aquo Complexes of First-Row Transition Metals in Water: A DFT Study Based on the Grand Canonical Ensemble.

The potentials of redox systems involving nitrogen, oxygen, and metal ions of the first-row transition series have been computed according to the general approach of the grand canonical ensemble, which leads to the equilibrium value of the reduction potential via a (complete) sampling of configuration space at a given temperature. The approach is a single configuration approach in the sense that identical molecular structures are sampled for both the oxidized and reduced species considered in water solution. In this study, the solute and a cluster of 11-12 water molecules are treated explicitly at the same level of theory and embedded in a continuum solvent. The molecular energies are computed in the framework of the density functional theory. Our approach is basically different from the approach based on the ThermoDynamic Cycle involving gas-phase calculations of the electron affinity of the oxidized species, corrected by the differential hydration energy (obtained from continuum solvent models only) between oxidized and reduced forms. The calculated redox potentials are in agreement with the available experimental data much closer than other results so far presented in the literature. Our results are very satisfactory also in the case of the 3+/2+ redox states of the first-row transition metals, i.e., systems with a high positive charge for which enhanced effects of the solvent are expected.

Improving Performance of the SMD Solvation Model: Bondi Radii Improve Predicted Aqueous Solvation Free Energies of Ions and pKa Values of Thiols

Calculation of the solvation free energy of ionic molecules is the principal source of errors in the quantum chemical evaluation of pKa values using implicit polarizable continuum solvent models. One of the important parameters affecting the performance of these models is the choice of atomic radii. Here, we assess the performance of the solvation model based on density (SMD) implicit solvation model employing SMD default radii (SMD) and Bondi radii (SMD-B), a set of empirical atomic radii developed based on the crystallographic data. For a set of 112 ions (60 anions and 52 cations), the SMD-B model showed lower mean unsigned error (MUE) for predicted aqueous solvation free energies (4.0 kcal/mol for anions and 2.4 kcal/mol for cations) compared to the standard SMD model (MUE of 5.0 kcal/mol for anions and 2.9 kcal/mol for cations). In particular, usage of Bondi radii improves the aqueous solvation energies of sulfur-containing ions by >5 kcal/mol compared to the SMD default radii. Indeed, for a set of 45 thiols, the SMD-B model was found to dramatically improve the predicted pKa values, with ∼1 pKa unit mean deviation from the experimental values, compared to ∼7 pKa units mean deviation for the SMD model with the default radii. These findings highlight the importance of the choice of atomic radii on the performance of the implicit solvation models.

The mechanisms of isobutene hydration yielding tert-butanol catalyzed by a strong mineral acid (H2SO4) and Lewis-Brønsted superacid (HF/SbF5)

The mechanism of the (CH3)2CCH2+H2O→(CH3)3COH reaction catalyzed by two strong acids (H2SO4 and HSbF6) was investigated theoretically using the ab initio MP2 and CCSD(T) methods and the aug-cc-pVDZ/LANL2DZ and aug-cc-pVTZ/LANL2DZ basis sets. The effects of surrounding solvent molecules were approximated by employing the polarized continuum solvation model. The most important findings include the observation that both acids are capable of catalyzing isobutene hydration but the reaction is predicted to proceed faster when the HSbF6 superacid plays the catalyst role.

Effect of Nitro Groups on Desulfurization Efficiency of Benzyl-Substituted Imidiazolium-Based Ionic Liquids: Experimental and Computational Approach

In the maneuver to achieve desulfurization, we have explored various nitro-substituted positional isomeric imidazolium-based aprotic ionic liquids (ILs). Ortho-, meta-, and para-substituted nitro benzyl group-aided imidazolium-based ILs were synthesized and used to understand the extractive desulfurization (EDS) efficiency of fuels. ILs chosen for the experiment were optimized using the B3LYP method and 6-311(++)g(d,p) of Gaussian 09, and their interactions with thiophene derivatives were analyzed using the integrated electric field polar continuum model solvation. Free energy of solvation provided qualitative information about the ability of ILs to achieve desulfurization. Parameters affecting the efficiency of synthesized ILs were perused, such as the effect of IL volume, concentration, duration of rotation, and other such parameters. Lewis acidity, availability of the Lewis acidic site and π–π interaction influenced the EDS efficiency of ILs.

Theoretical Study of the Adsorption Process of Antimalarial Drugs into Acrylamide-Base Hydrogel Model Using DFT Methods: The First Approach to the Rational Design of a Controlled Drug Delivery System

The interaction between three widely used antimalarial drugs chloroquine, primaquine and amodiaquine with acrylamide dimer and trimer as a hydrogel model, were studied by means of density functional theory calculation in both vacuum and water environments, using the functional wb97xd with 6-31++G(d,p) basis set and polarizable continuum model (C-PCM) of solvent. According to binding energy, around −3.15 to −11.91 kJ/mol, the interaction between antimalarial compounds and hydrogel model are exothermic in nature. The extent of interaction found is primaquine > amodiaquine > chloroquine. The natural bond orbital (NBO) calculation and application of second-order perturbation theory show strong charge transfer between the antimalarial and hydrogel model. In addition, the results suggest these interactions are polar in nature, where hydrogen bonds play a principal role in stabilization of the complex. Comparing with the gas-phase, the complexes in the water environment are also stable, with suitable values of Log P (Partition coefficient), and dipolar momentum. Consequently, these results encourage to test acrylamide hydrogels as antimalarial delivery systems.

Mechanism of the Absorption of CO2 in Ionic Liquid Dimer

The density functional theory (DFT) calculations with the modern continuum solvation model (IEFPCM-SMD) was used to study the mechanism of CO2 absorption at room temperature using ionic liquid such as, [EMIM][BF4] (1-ethyl-3-methylimidazolium tetrafluoroborate) monomer and dimer ionic liquid [IL] dimer comprises two couple of anions and cations, so that more intermolecular interactions are established than in the single IL pair. In this paper, we determined the minimum energy structures and to determine the possible binding sites for CO2 absorption in [EMIM][BF4] monmer and dimer; by comparing the relative minimum energy of [EMIM][BF4] in the presence and in absence of CO2. It was found that CO2 is stabilized by the multiple interactions with several anions. When CO2 penetrates the IL monomer or dimer, through gas-to-liquid diffusion, the O-C-O (CO2)-BF4 intermolecular bond is likely to be formed immediately and bind the CO2 molecule. This result suggests that ionic liquid dimer is suitable for the absorption of CO2.
 Asiat. Soc. Bangladesh, Sci. 45(1): 137-144, June 2019

Influence of surface restructuring on the activity of SrTiO3 photoelectrodes for photocatalytic hydrogen reduction

Perovskite photoelectrodes are being extensively studied in search for photocatalytic materials that can produce hydrogen through water splitting. The solar-to-hydrogen efficiency of these materials is critically dependent on the electrochemical state of their surface. Here, we develop an embedded quantum-mechanical approach using the self-consistent continuum solvation model to predict the relation between band alignment, electrochemical stability, and photocatalytic activity taking into account the long-range polarization of the semiconductor electrode under electrical bias. Using this comprehensive model, we calculate the charge-voltage response of various reconstructions of a solvated ${\mathrm{SrTiO}}_{3}$ surface, revealing that interfacial charge trapping exerts primary control on the electrical response and surface stability of the photoelectrode. Our results provide a detailed molecular-level interpretation of the enhanced photocatalytic activity of ${\mathrm{SrTiO}}_{3}$ upon voltage-induced restructuring of the semiconductor-solution interface.

Computational Insights into Endo/Exo Selectivity of the Diels-Alder Reaction in Explicit Solvent at Ab Initio Quantum Mechanical/Molecular Mechanical Level.

The microscopic insight into the endo/exo stereoselectivity of the Diels-Alder (DA) reaction between cyclopentadiene and methyl vinyl ketone (MVK) has posed a challenge to the computational chemists, which requires an accurate free-energy (FE) landscape. Although ab initio (ai) quantum mechanical/molecular mechanical (QM/MM) calculations are capable of providing accurate conformation energies, they are far too expensive for free-energy calculations, in which large-scale sampling in the phase space is always indispensable. Recently, on the basis of the idea of reference-potential methods, a new approach termed MBAR+wTP method was proposed by us ( Li ; J. Chem. Theory Comput. 2018 , 14 , 5583 ) for the calculations of ai QM/MM FE profiles with a much less computational expense. In this work, we applied this method to investigate the endo/exo stereoselectivity of the Diels-Alder (DA) reaction at B3LYP/MM level and the results indicate that this method can yield more accurate activation free energies than the semiempirical Hamiltonian PM6 and the "sampling-free" quantum mechanical methods at B3LYP and MP2 levels using a polarizable continuous solvent model (PCM). The stereoselectivity mainly comes from the solvation effect. At the transition state, the first peak of the solvent distribution near the oxygen atom in MVK is slightly closer for the endo pathway than that for the exo pathway, whereas the difference at PM6 level is negligible. Nonetheless, in terms of the stereoselectivity, we obtained an endo/exo ratio of 2 with this method, which is still 1 order of magnitude smaller than the experimental measurement. Although the endo/exo ratio from the MP2/PCM calculation agrees well with the experiment, the absolute reaction barriers deviate by about 5 kcal mol-1. This work issues a warning to the use of the computational methods that are routinely employed for the study of organic reactions in the condensed phase, and it also brings a new method that is affordable and more reliable.