Polarizable Continuum Method Research Articles

A Novel Computational Approach for Development of Highly Selective Fenitrothion Imprinted Polymer: Theoretical Predictions and Experimental Validations

The quality of molecularly imprinted recognition sites depend on the mechanisms and the extent of the functional monomer-template interactions present in the prepolymerization mixture. Thus, an understanding of the physical parameters governing these interactions is key for producing a highly selective molecularly imprinted polymer (MIP). In this paper, novel molecular modeling studies were performed to optimize the conditions for the molecular imprinting of fenitrothion. Four possible functional monomers were evaluated. Five porogenic solvents were investigated employing the polarizable continuum method. The MIP based in methacrylic acid (MAA-MIP) synthesized in the presence of toluene shown to be the most thermodynamically stable complex. Contrarily, MIP based in p-vinylbenzoic acid (PVB-MIP) had the lowest binding energy. According to the adsorption parameters fitted by the Langmuir-Freundlich isotherm, MAA-MIP presented twice the number of binding sites compared to PVB-MIP (103.35 and 53.77 µmol g-1, respectively).

A DFT Study on Tautomer Stability of 4-Hydroxyquinoline Considering Solvent Effect and NBO Analysis

Computational calculations at B3LYP/6-311++G (d,p) level were employed in the study of the predominant tautomeric of 4-hydroxyquinoline derivatives (5-H, 5-NO 2, 5-Cl, 5-OH, 5-CH 3, 6-NO 2, 6-Cl, 6-OH, 6-CH 3, 7-NO 2, 7-Cl, 7-OH, 7-CH 3, 8-NO 2, 8-Cl, 8-OH, 8-CH 3,) in the gas phase and selected solvents (benzene (non-polar solvent), tetrahydrofuran (THF) (polar aprotic solvent) and water (protic solvent)). The tautomers were also optimized in solvents according to the polarisable continuum method (PCM). For electron withdrawing and releasing derivatives the order of stability is X1 >X2 >X3 and X1 form is a more stable and dominant form. An exception in the gas phase is X2 isomer of (8-OH) which has two forms. In one, the hydrogen bond between hydroxyl substituted with nitrogen isn't formed, but in another it is formed. If the hydrogen bond is formed, X2 isomer is more stable than X1. In addition variation of dipole moments and charges on atoms in the solvents are studied.

Role of Solvent on Charge Transfer in 7-Aminocoumarin Dyes: New Hints from TD-CAM-B3LYP and State Specific PCM Calculations.

Time-dependent B3LYP and CAM-B3LYP calculations have been used to investigate the absorption and emission energies as well as to shed light on the formation of the twisted intramolecular charge transfer state (TICT) in Coumarin-152 (C152) embedded in cyclohexane, acetonitrile, and water solvents. The bulk solvent effects have been included by using the linear-response (LR) and State-Specific (SS) models in the framework of the so-called polarizable continuum method (PCM). The results demonstrate that the choice of the exchange-correlation functional and of the PCM model is critical to reproduce the experimental data in the most accurate way. In particular, it has been observed that both the solvatochromic and Stokes' shifts are well reproduce by CAM-B3LYP/SSPCM calculations performed on the S0 and S1 geometries of C152 optimized at the B3LYP/LRPCM level of theory, whereas not accurate Stokes' shifts are computed with CAM-B3LYP/SSPCM calculations carried out on the CAM-B3LYP/LRPCM optimized structures. This is attributed to the incorrect (underestimated) solvation energy provided by LRPCM, which could lead to misleading results especially for charge-transfer excited state structures in polar solvents. Instead, B3LYP/LRPCM excited state optimizations seem to provide a reasonable geometry for a simple 'error cancellation' effect due to the balance among the B3LYP overstabilization of charge transfer states and the LRPCM underestimation of the solute-solvent binding energy when the former is in a polar solvent. Finally, CAM-B3LYP/SSPCM calculations, in very good agreement with experimental evidence, show that the formation of an accessible TICT state is possible for C152 and that the crossing between S0 and S1 states at a dihedral angle of around 70° occurs only in polar solvents.

Tautomerism and spectroscopic properties of the immunosuppressant azathioprine

The molecular structure and the relative stabilities of the four possible tautomers of the immunosuppressant azathioprine (AZA) are calculated by DFT/B3LYP method using different basis sets. The results of the energy analysis and thermodynamic treatment of the obtained data are used to predict the relative stabilities of the AZA tautomers. The effect of solvents such as DMSO and water on the stability of the AZA tautomers was studied using the polarized continuum method (PCM) at the same level of theory. The calculation predicted that, the total energies of all tautomers are decreased indicating that all tautomers are more or less stabilized by the solvent effect. The vibrational spectra of AZA are calculated using the same level of theory and the results are compared with the experimentally measured FTIR spectra. Good correlation is obtained between the experimental and calculated vibrational frequencies (R2=0.997). The electronic spectra of AZA in gas phase and in methanol as solvent are calculated using the TD-DFT method. The calculations predicted bathochromic shift in all the spectral bands in presence of solvent compared to the gas phase. Also the NMR spectra of all tautomers are calculated and the results are correlated with the experimental NMR chemical shifts where the most stable tautomer gives the best correlation coefficient (R2=0.996).

Theoretical investigation on tautomerism and NBO analysis of 3-hydroxy-1,2,5-thiadiazole derivatives: solvent and substituent effects

Abstract Thiadiazole compounds including 3-hydroxy-4-substituted-1,2,5-thiadiazole are known as non-nucleoside inhibitors of HIV-1. Density functional calculations at the B3LYP/6-311++G(d,p) level were employed to determine the stability, tautomerism, and substituent effects of 1,2,5-thiadiazole, a widely used skin-whitening, antibrowning, and antibacterial agent, and its derivatives (4-NO2, 4-CN, 4-F, 4-H, 4-Me, 4-NH2), in the gas phase and solution using the polarizable continuum method model. Some selected IR frequencies, molecular parameters, charges on atoms, and dipole moment results were analyzed.

Competitive hydrogen bonding in aspirin-aspirin and aspirin-leucine interactions

Aspirin-aspirin and aspirin-leucine interactions are studied by the density functional theory (DFT) and high level ab initio calculations with second order Moller-Plesset perturbation theory (MP2). The rotational isomers of aspirin are identified by their relative stability both in gaseous phase and in water using the polarizable continuum method (PCM). Local minima of aspirin monomers in water are found to be all highly populated compared to the gas phase behavior. Homodimers of aspirin form hydrogen bonds with bond energies of 10 kcal/mol. Weak hydrogen bonds utilizing phenyl and methyl groups are also found. The interaction between aspirin and leucine is stronger with relatively short bond lengths compared to homodimeric aspirin interactions. The potential energy surface has several minima with comparable stability. This study shows the significance of diverse bonding schemes, which are important for understanding complete interaction mechanisms of aspirin.

A higher energy conformer of ( S)-proline is the active catalyst in intermolecular aldol reaction: Evidence from DFT calculations

Full catalytic cycle of the stereoselective ( S)-proline catalyzed aldol reaction of acetone and acetaldehyde in DMSO solvent has been investigated using three different DFT methods, viz. B3LYP, MPWB1K and B97D in conjunction with the polarizable continuum (PCM) method. At all the levels of theory, one of the higher energy conformers of the catalyst, 1b showed higher activity than the most stable conformer, 1a. On the basis of Δ G # of 39.8 kcal/mol observed for the reaction of 1a with acetone, 1a is considered to be inactive in the catalytic cycle while the same reaction with 1b showed 22.7 kcal/mol (B97D-PCM level) lower value for Δ G # than 1a. All the possibilities for enamine formation and C–C bond formation step have been considered for describing the most appropriate stereoselective catalytic cycle which showed that the full cycle is made up of a relay of eight proton transfer steps and the reaction is categorized under hydrogen bond catalysis. The hydration across the iminium bond of the second nucleophilic adduct – an intermediate formed subsequent to the aldehyde addition to the enamine – is the rate limiting step of the reaction with Δ G # = 21.7 kcal/mol (B97D-PCM level).

Asymmetric ImineN-Inversion in 3-Methyl-4-pyrimidinimine. Molecular Dipole Analysis of Solvation Effects

The thermal (E)/(Z)-isomerization of 3-methyl-4-pyrimidinimine, 3MePMI, has been studied in the gas phase at MP2/6-31G* and with the inclusion of medium effects using the polarizable continuum method, PCM(MP2/6-31G*), and the solvation model density method, SMD(MP2/6-31G*). For the free molecule and for 3MePMI in each of 14 solvents, the structures were determined of the (E)- and (Z)-isomers, of the transition state structure for isomerization ITS by asymmetric N-inversion, and of the second-order saddle point structure (SOSP) associated with in-plane N-inversion. The results predict a reduction of the (E)-isomer preference energy of 3MePMI, an increase of the deformation energy ΔE(def) = E(SOSP) - E(ITS), and an increase of the activation barrier E(act)(Z → E) with increasing solvent polarity. Electronic effects associated with N-inversion are analyzed using molecular orbital theory, results of population analysis, and electrostatic potential maps. The molecular dipole moments are superior parameters for the description of electronic relaxation in the imine basin during N-inversion. In particular, the analysis of dipole moments explains the compatibility of the increase of local CN polarity during N-inversion with the negative solvation effect on the activation barrier.

Theoretical studies of the solvent effect on conformational equilibria and atomic charges for isolated and hydrogen-bonded dimethoxy thiadiazoles

Thiadiazoles and their dimethoxy derivatives are substructure motifs for specific muscarinic agonist ligands under development in this laboratory. The B3LYP/aug-cc-pvtz and MP2/aug-cc-pvtz optimized geometric parameters for the four isomeric thiadiazole rings were close to the experimental values in the gas phase. Relative free energies were calculated for 11 conformers of the isomeric dimethoxy thiadiazoles in the gas phase, in tetrahydrofuran, and water solvent. In-solution calculations were performed using the IEF-PCM polarizable continuum method at the B3LYP/6-31G ∗ and B3LYP/aug-cc-pvtz levels. In aqueous solution, a main conformation with at least 95% of the total population was calculated for each of the dimethoxy-1,2,3- and 1,2,5-thiadiazoles, whereas a second conformation with populations of 14–18% was predicted to be present in aqueous solution for the 1,2,4- and 1,3,4-thiadiazole derivatives. Net atomic charges obtained by the CHELPG fit to the in-solution molecular electrostatic potential indicated only a moderate solvent effect on the derived values. The IEF-PCM/B3LYP/6-31G ∗-derived charges provide a reasonable alternative to those from IEF-PCM/B3LYP/aug-cc-pvtz calculations and could be applied in molecular dynamics and Monte Carlo simulations for thiadiazole ligand – receptor complexes. Consideration of the charge transfer for hydrogen-bonded complexes of the dimethoxy 1,2,4-thiadiazole and amino acid side-chain mimics is, however, a key issue throughout MC/FEP calculations. The applied charge sets affect the calculated binding constant by a factor up to 40–80 at T = 310 K. A re-parameterization for the amino acid residues has been suggested in such cases so that the ligand + amino acid residue maintain together an integer value net charge.

Physico-chemical characterization of flavonol molecularly imprinted polymers

Along the last decade considerable interest has been focused in deciphering the binding recognition process and the heterogeneity nature of binding sites in molecularly imprinted polymers (MIPs). Density Functional Theory (DFT) was employed at B3LYP/6-31+G ** level of theory, to investigate the intermolecular interactions between the template flavonol and the functional monomer (methacrylic acid). The solvent effect energy stabilization of the monomer and template in different solvents was investigated by using the polarizable continuum method (PCM). The MIP against flavonol prepared using methacrylic acid as functional monomer was then characterized in terms of specific bindings by using Scatchard plot analysis. The rebinding properties were analyzed by equilibrium/rebinding batch experiments using the Langmuir, Bi-Langmuir, Freundlich, Langmuir-Freundlich, Jovanovich, Bi-Jovanovich and Jovanovich-Freundlich isotherms. The imprinted polymer was also characterized by continuous flow experiments, SEM and BET surface area measurements. Parallel studies were carried out with the non-imprinted polymer as control material.

Liquid–liquid equilibrium in ternary ionic liquid systems by UNIFAC: New volume, surface area and interaction parameters. Part II

Ionic liquids are potential solvents for liquid extraction processes; thermodynamic modeling of liquid–liquid equilibrium (LLE) data is essential for the optimization and operation of these processes. Therefore, ternary LLE data in systems involving ionic liquids have been investigated by several years. In most of the cases, the thermodynamic modeling of these systems has been made using the NRTL model; in some cases, the UNIQUAC model has also been used. The structural parameters of UNIQUAC for ionic liquids have been determined either by empirical correlations or, more recently, through quantum mechanics calculation. This work is a continuation of a recent paper, in which the structural group volume and area parameters for the group-contribution UNIFAC method have been calculated for five ionic liquids following the quantum mechanics approach. In order to optimize the molecular geometry and to calculate the area and volume, the Density Functional Theory (DFT) and the Polarizable Continuum Method (PCM) were used, respectively. The obtained parameters were used to correlate LLE data for fifteen ternary systems, totalizing 155 tie-lines. New interaction parameters were also estimated between the solvent and the ionic liquid functional groups. The results are very satisfactory, with root mean square deviations 0.0037 between experimental and calculated equilibrium mole fractions.

Liquid–liquid equilibrium in ternary ionic liquid systems by UNIFAC: New volume, surface area and interaction parameters. Part I

Ternary liquid–liquid equilibria (LLE) data in systems involving ionic liquids has been investigated by several years, mainly due to the innovative role of ionic liquids as extraction solvents. The thermodynamic modeling of these systems has been performed almost invariably with the well-known NRTL model. In recent years, the UNIQUAC model has also been used, with structural parameters for ionic liquids determined either by empirical correlations or, more recently, through quantum mechanics calculations. In this work, the structural group volume and area parameters for the group-contribution UNIFAC method have been calculated for six ionic liquids following the quantum mechanics approach. The Density Functional Theory (DFT) was used to optimize the molecular geometry and the Polarizable Continuum Method (PCM) was used to calculate the area and volume. The obtained parameters were used to correlate LLE data for twenty-four ternary systems, totalizing 169 tie-lines. New interaction parameters were also estimated between the solvent and ionic liquid functional groups. The results are very satisfactory, with root mean square deviations between experimental and calculated compositions about 1.6%.

UNIQUAC correlation of liquid–liquid equilibrium in systems involving ionic liquids: The DFT–PCM approach. Part II

In this work, new UNIQUAC structural parameters r and q for the ionic liquids were determined by quantum chemistry calculations performed with the Gaussian 03 and GAMESS 7.1 packages, including the density functional theory (DFT) for the optimization of the structures and the polarizable continuum method (PCM) for the calculation of molecular areas and volumes. Data liquid–liquid equilibrium (LLE) of 41 ternary systems involving 15 different ionic liquids, comprising 379 experimental tie-lines, was correlated by the UNIQUAC model for the activity coefficient. The results, expressed by deviations between experimental and calculated compositions, are very satisfactory, with deviation values about 1.93%.

Alanine: Then There Was Water

An ab initio study of the addition of successive water molecules to the amino acid l-alanine in both the nonionized (N) and zwitterionic (Z) forms are presented. The main focus is the number of waters needed to stabilize the Z form and how the solvent affects conformational preference. The solvent is modeled by ab initio electronic structure theory, the EFP (effective fragment potential) model, and the isotropic dielectric PCM (polarizable continuum method) bulk solvation techniques. The EFP discrete solvation model is used with a Monte Carlo algorithm to sample the configuration space to find the global minimum. Bridging structures are predicted to be the lowest energy Z minima after 3-5 discrete waters are included in the calculations, depending on the level of theory. Second-order perturbation theory and PCM stabilize the Z structures by approximately 3-6 and 7 kcal/mol, respectively, relative to the N global minimum through the addition of up to 8 waters. Subsequently, the contributions of each are approximately 1 kcal/mol relative to the N global minimum. The presence of 32 waters appears to be close to converging the N-Z enthalpy difference, DeltaH(N-Z).

UNIQUAC correlation of liquid–liquid equilibrium in systems involving ionic liquids: The DFT–PCM approach

In this work, the liquid–liquid equilibrium (LLE) of fifty ternary systems involving twelve different ionic liquids, comprising 408 experimental tie-lines, was correlated by the UNIQUAC model for the activity coefficient. New UNIQUAC structural parameters r and q for the ionic liquids were determined by quantum chemistry calculations performed with the Gaussian 03 and GAMESS 7.1 packages, including the Density Functional Theory (DFT) for the optimization of the structures and the Polarizable Continuum Method (PCM) for the calculation of molecular areas and volumes. The results, expressed by deviations between experimental and calculated compositions, are very satisfactory, with deviation values about 1.75%.

Quantum-Chemical Calculations of the Electronic Properties of Pyrrole Oligomers

The electrochemical pyrrole polymerization mechanism at initial stages is theoretically studied through sequential monomer units coupling to obtain 2 to 9 oligomer formation. The relevance of these oligomers lies on their solubility in water as well as on the influence in uniformity of the final polymer film. The dependence of the growing chain electronic properties has been studied by the Polarizable Continuum Method (PCM) taking into account the influence of water as solvent effect. It was observed that the |HOMO-LUMO| energy difference, defined as Eg, decreases as the delocalization (resonance) of the π-electrons increases within the 5-member rings, which occur while the length of the oligomer molecule increases in line with literature reported experimental observation. The improvement in electron conduction of the stepwise oligomer product as a function of its chemical structure is also discussed.

A theoretical approach to the solvation of brassinosteroids

The interaction of three different brassinosteroids with water was studied by the Multiple Minima Hypersurface (MMH) procedure to model molecular interactions explicitly. The resulting thermodynamic data give useful information on properties of molecular association with water. This application can serve as a tool for future investigations and modelling concerning interactions of brassinosteroids with receptor proteins in plants. DFT/B3LYP calculations were also made in order to correlate and test the performance of the current AM1 Hamiltonian calculations of these complexes, which are inherent to MMH routine. Diol functionalities located in ring A and lateral chain appears as the sites that show the highest affinity to water. The oxalactone group does not appear to be a key structural requirement in the association with water. Parallel calculations with a “polarizable continuum method” (PCM) agreed with the reported experimental order of biological activities, where Brassinolide exhibited the best solubility features.

Electronic structures and spectroscopic properties of rhenium (I) tricarbonyl photosensitizer: [Re(4,4′-(COOEt) 2-2,2′-bpy)(CO) 3py]PF 6

The ground state and lowest triplet-state structures of [Re(4,4′-(COOEt) 2-2,2′-bpy)(CO) 3py]PF 6 photosensitizer (bpy = bipyridine, py = pyridine) have been studied with density functional theory (DFT). Time-dependent density functional theory (TD-DFT) was carried out to predict the photophysical properties of the photosensitizer. The effects of the solvents were evaluated using the conductor-like polarizable continuum (CPCM) method in dichloromethane, chloroform, acetonitrile, acetone, ethanol and dimethylsulfoxide. The electronic transition energies computed with BLYP, MPWPW91, B3LYP and MPW1PW91 functionals are compared with the experimental spectra. Based on the calculated excited energies, the experimental absorption maximum is assigned as metal-to-ligand charge transfer (MLCT) and ligand-to-ligand charge transfer (LLCT) mixed transition, and the luminescence originates from the lowest triplet state that is ascribed as the mixed transition of MLCT/LLCT.

Quantitative evaluation of the aqueous dihydronitroxide nitrogen hyperfine coupling constant from QM/MM//MD computations

A sequential molecular dynamics + hybrid quantum mechanical/molecular mechanical (QM/MM//MD) approach is presented and applied to the determination of the nitrogen hyperfine coupling constant in the dihydronitroxide radical solvated in water. The model relies on a sophisticated polarizable force-field featuring a many-body hydrogen bond potential, whose parameters have been carefully fitted to QM calculations with special attention paid to the nitrogen out-of-plane angle. It involves also an electronic embedding of the QM subsystem thanks to the ElectroStatic Potential Fitted (ESPF) operator method which is shown to be superior to continuum methods like the polarizable continuum method when anisotropic electrostatic interactions take place between the QM subsystem and its classical surroundings.

Theoretical studies on tautomerism of dihydropyrimidine tautomers

The second-order Moller–Plesset (MP2) and density functional theory (DFT) calculations have been carried out using 6-311++G(d, p) basis set to investigate the tautomerism of all five tautomers of dihydropyrimidine in the gas phase and in the solution. In the gas phase the order of stability was found as: B > C > A > E > D, however changing to more polar solvents this order was changed using polarisable continuum method (PCM). In addition variation of dipole moments and charges on atoms are studied in the gas phase and in solvents. NBO analysis shows that there is a strong interaction between nitrogen lone pairs and double bonds. Specific solvent effect induced slight changes in geometry of rings but the order of stability remained.