Calculation Of Solvent Effects Research Articles

Investigation on itraconazole solubility in aqueous solutions based on models, solvent effect, thermodynamic analysis and quantum chemical calculations

The mole-fraction solubility of itraconazole in four aqueous blends of ethanol/isopropanol/DMSO/methanol within the temperature range of 283.15 to 323.15 K was experimentally obtained using the isothermal shake-flask method. Under the identical temperature and ethanol/isopropanol/DMSO/methanol composition, itraconazole solubility in DMSO+water is much higher than that in ethanol/isopropanol/methanol + water. At the same temperature, the solubility increases monotonically with organic solvent concentration. X-ray power diffraction analysis demonstrated that over the course of the investigations, there was no crystal transition or solvate formation. The modified van’t Hoff-Jouyban-Acree and Jouyban-Acree models adequately related the solubility to solvent composition and temperature, with relative average deviations (RADs) not exceeding 7.65 %. Furthermore, the extended Hildebrand solubility approach was utilized to quantitatively characterize the solubility behavior at 298.15 K for the mixtures of ethanol/isopropanol/DMSO/methanol plus water. In both instances, the RADs were maintained below 4.12 %. The solubility parameter and dipolarity-polarizability of solutions have a major impact on the solubility fluctuation, as indicated by the analysis of the linear solvation energy relationship. The preferential solvation of itraconazole at 298.15 K was examined using the efficient approach of inverse Kirkwood-Buff integrals. The preferred solvation parameters showed positive values in blends within rich and moderate ethanol/isopropanol/DMSO/methanol composition regions. This suggests that the organic solvents preferentially solvated itraconazole. When itraconazole dissolved in the blends, thermodynamic analysis of the entropy-enthalpy compensation and dissolution parameters revealed both an endothermic and an enthalpy-driven mechanism. Furthermore, the microscopic electrostatic characteristics of basicity and acidity were effectively demonstrated by means of the electrostatic potential of molecular surface. The −C=O and −N=groups of the itraconazole molecule, which link the five-membered ring, are the primary targets of the electrophilic attack. An independent gradient model based on Hirshfeld partition analysis was used to demonstrate the weak interactions between itraconazole and solvents.

Mutual synergistic regulation of chloride anion and cesium cation binding using a new designed macrocyclic multi-functional sites receptor: A case of DFT computational prediction.

The mutual synergistic regulation of the multi-functional sites on a single receptor molecule for ion-binding/recognition is vital for the new receptor design and needs to be well explored from experiment and theory. In this work, a new macrocyclic ion receptor (BEBUR) with three functional zones, including two ether holes and one biurea groups, is designed expecting to mutually enhance the ion-binding performance. The binding behaviors of BEBUR mainly for Cl- and Cs+ are deeply investigated by using density functional theoretical calculations. It is found that Cl-/Cs+ binding can be mutually enhanced and synergistically regulated via corresponding conformational changes of the receptor, well reflecting an electrical complementary matching and mutual reinforcement effect. Moreover, solvent effect calculations indicate that BEBUR may be an excellent candidate structure for Cl--binding with the enhancement of counter ion (Cs+) in water and toluene. In addition, visualization of intermolecular noncovalent interaction is used for analysis on the nature of the binding interactions between receptor and ions.

Synergistic regulation of chloride anion recognition using a triple-functional sites receptor with two different cationic effectors.

The synergistic regulation of the multi-functional sites on one receptor molecule with different cationic effectors for anion recognition is scarce to be well understood from the experiment and theory. In this work, a new anion receptor with three functional zones including ether hole, biurea and double bipyridine groups (EUPR) is designed expecting to enhance the chloride anion recognition together with a rational synthesis path being proposed based on four simple and mature organic reaction steps. The conformational structures of the designed receptor EUPR and the binding behaviors for three kinds of ions (Cl-, Na+, and Ag+) are deeply investigated by using density functional theoretical calculations. It is found that Cl- binding via the hydrogen bond interaction can be significantly enhanced and synergistically regulated by the two kinds of cations and the corresponding conformational changes of receptor EUPR. Especially, the conformational pre-organization of receptor caused by the encapsulation of sodium ion into ether hole is benefit to the binding for Cl- in both thermodynamics and kinetics. Na+ binding, in turn, can ever be enhanced by chloride anion, whereas it seems that Ag+ binding cannot always be enhanced by chloride anion, reflecting an electrical complementary matching and mutual enhancement effect for different counter ions. Moreover, solvent effect calculations indicate that EUPR may be an ideal candidate structure for Cl- recognition by strategy of counter ion enhancement in water. Additionally, a visual study of intermolecular noncovalent interaction (NCI) and molecular electrostatic potential (ESP) are used for the analysis on the nature of interactions between receptor and bound ions.

The Importance of Solvent Effects in Calculations of NMR Coupling Constants at the Doubles Corrected Higher Random-Phase Approximation

In this work, 242 NMR spin–spin coupling constants (SSCC) in 20 molecules are calculated, either with correlated wave function methods, SOPPA and HRPA(D), or with density functional theory based on the B3LYP, BHandH, or PBE0 functionals. The calculations were carried out with and without treatment of solvation via a polarizable continuum model in both the geometry optimization step and/or the SSCC calculation, and thereby, four series of calculations were considered (the full-vacuum calculation, the full-solvent calculation, and the two cross combinations). The results were compared with experimental results measured in a solvent. With the goal of reproducing experimental values, we find that the performance of the PBE0 and BHandH SSCCs improves upon including solvation effects. On the other hand, the quality of the B3LYP SSCCs worsens with the inclusion of solvation. Solvation had almost no effect on the performance of the SOPPA and HRPA(D) calculations. We find that the PBE0-based calculations of the spin–spin coupling constants have the best agreement with the experimental data.

Synergistic Effect of Coordination Fields and Hydrosolvents on the Single-Atom Catalytic Property in H2O2 Synthesis: A Density Functional Theory Study

The design of high-performance single-atom catalysts (SACs) for two-electron oxygen reduction reaction (2e– ORR) is of great importance for the large-scale commercial application of H2O2 electrosynthesis. Herein, utilizing the combination of density functional theory (DFT) calculation and ab initio molecular dynamic (AIMD) simulation, an effective computational framework was built to identify the critical role of coordination fields and hydrosolvents in the 2e– ORR catalytic properties of SAC-based two substrates [pristine γ-type graphyne (γ-GY) and B-doped γ-GY]. The screening calculations of 168 TM@(B-doped) γ-GY (TM = transition metal) revealed that both Co@B1-2-γ-GY and Pd@B3-2-γ-GY feature outstanding catalytic properties with low overpotentials (0.06, 0.02 V) and excellent stability. The electronic structure results uncovered that viewing from the coordination field, electron-deficient boron atoms can manipulate the electron back-donation effect (d → π2p*) of the TM–O bond to mediate the H2O2 property. Solvent effect calculations revealed that the hydrogen-bond (H-bond) framework plays an important role in the high selectivity of H2O2 by facilitating the H transfer from water (>99.9 and 98.6% for Co@B1-2-γ-GY and Pd@B3-2-γ-GY), shedding light on the higher accuracy of an explicit solvent than that of an implicit one. This work will provide one way to better design high-selectivity SACs for H2O2 synthesis effectively.

Relativistic frozen density embedding calculations of solvent effects on the nuclear magnetic resonance shielding constants of transition metal nuclei

AbstractNuclear magnetic resonance shielding constants of transition metals in solvated complexes are computed at the relativistic density functional theory (DFT) level. The solvent effects evaluated with subsystem‐DFT approaches are compared with the reference solvent shifts predicted from supermolecular calculations. Two subsystem‐DFT approaches are analyzed—in the standard frozen density embedding (FDE) scheme the transition metal complexes are embedded in an environment of solvent molecules whose density is kept frozen, in the second approach the densities of the complex and of its environment are relaxed in the “freeze‐and‐thaw” procedure. The latter approach improves the description of the solvent effects in most cases, nevertheless the FDE deficiencies are rather large in some cases.

Host–guest complex properties of calix[4]arene derivatives: a DFT study of adsorption and sensing of an anticancer drug, 5-fluorouracil

In this study, it has been reported the host–guest complex properties of calix[4]arene compounds (the 3rd generation supramolecule) against the 5-fluorouracil (5-FU) anticancer drug by density functional theory calculations at room temperature. The B3LYP hybrid method was used to determine the optimized structures of the host and guest molecules and their complexes. The adsorption energy changes of the complexes formed between calix[4]arene compounds and 5-FU drug were calculated to be negative values. The strongest interaction was determined for the water-soluble calix[4]arene compound with sulfonyl (–SO3H) groups (ΔE = − 98 kJ/mol and ΔH = − 100.5 kJ/mol). Moreover, it was determined that HOMO–LUMO gaps of all calix[4]arene compounds decreased. The charge transfer has occurred between the four calix[4]arene compounds and the drug molecule. The work function values of calix[4]arene compounds have been changed. These results indicate that calix[4]arene derivatives can be used as well-suited 5-FU sensor at room temperature. Solvent effect calculations have stated that the interaction of 5-FU molecule with the calix[4]arene compound with sulfonyl (–SO3H) groups weakens and the ΔE becomes less negative value (− 71.6 kJ/mol).

Coordination of methylene blue to group 11 and 12 transition metals: A DFT study

Density functional theory (DFT) was used to investigate the possible coordination modes of the methylene blue ligand (MB+) to transition metal cations with the d10 configuration in groups 11 and 12 of the periodic table. Calculations were done in the gas phase and with a water solvent effect. The results showed that MB+ is not a good ligand and can only form complexes by coordination to metals using the N atom of a tricyclic ring. The bond by the S atom makes MB+ act only as a counter-ion in purely electrostatic bonding. Complex formation for Cu and Ag metals were observed only in solvent effect calculations, showing that external factors are needed for the structure’s formation. The relative Gibbs free energy values of the structures showed that there was competition between the complexes and their respective salt isomers, making the formation of both species possible. For other metals, the results showed that the formation of (MB)[MCl2] and (MB)[MCl3] salt types are the only ones possible. However, the absolute Gibbs free energy values for all structures showed that the reactions are favorable in gas phase and unfavorable with solvent effect, and the Cu complex is more easily accessible than the others.

Modelling absorption and emission of a meso-aniline-BODIPY based dye with molecular mechanics.

Absorption and emission spectra of 8-(4-dimethylaminophenyl)-1,3,5,7-tetramethyl-BODIPY have been calculated using Coupled Cluster (CC) approaches, Time-Dependent Density Functional Theory (TD-DFT) and a QM-informed MM approach. In the case of TD-DFT calculations solvent effects were included using the linear-response (LR), corrected linear response (cLR) and state specific (SS) Polarizable Continuum Model (PCM). We show that range-separated functionals give results in reasonable agreement with coupled cluster methods but both tend to overestimate excitation energies. Furthermore, we show that the SS-PCM approach is unable to provide a quantitative description of solvent effects in these systems, especially for the highly challenging charge-separated charge-transfer state. In contrast, the QM-informed MM approach gives results in good agreement with experiment and we propose a scheme which can be used to directly compare theoretically obtained spectra with experimental ones.

Conformational studies of 3-[(2,2-dimethylhydrazinyl)methylene]-pentane-2,4-dione using vibrational and NMR spectra, X-ray analysis and ab initio calculations

The conformers of push–pull 3-[(2,2-dimethylhydrazinyl)methylene]-pentane-2,4-dione (CH3)2NNHCHC(COCH3)2 (DMHMP) have been studied experimentally by NMR and vibrational spectroscopy and theoretically by ab initio calculations at MP2 and DFT B3LYP levels in various basis sets. The NMR spectra were obtained in chloroform and dimethylsulfoxide and the IR and Raman spectra of DMHMP as a solid and as a solute in various less and more polar solvents at room temperature have been recorded.DMHMP was prepared as a pure solid and the data from X-ray analysis revealed that DMHMP exists in solid state as EZa conformer with an intramolecular hydrogen bond. The geometries and relative energies of possible conformers of DMHMP were evaluated at the both levels of theory in several basis sets and compared with the data from X-ray analysis.According to the NMR spectra the studied compound exists as a single entity. On the other hand vibrational spectra revealed that in less polar DMHMP solutions the presence of the second less polar ZZa conformer is possible, whereas in more polar solvent only one EZa conformer is observed. The influence of the environment polarity on this conformational equilibrium is discussed with respect to the SCRF solvent effect calculations using IEFPCM model. The observed IR and Raman bands were compared with calculated MP2/cc-pVTZ harmonic vibrational frequencies and assigned on the basis of potential energy distribution.

Structure ofH2GeFMgFand its insertion reactions withRH(R=F,OH,NH2)

The structures of the germylenoid H2GeFMgF and its insertion reactions with RH ( R = F , OH , NH2) were studied using the DFT B3LYP and QCISD approaches for the first time. The geometries of all of the stationary points were optimized at the B3LYP/6-311+G (d, p) level of theory. And then the QCISD/6-311++G (d, p) single-point energies were calculated. The solvent effects on the geometries and insertion reactions were also computed using the PCM model. The calculated results suggested that H2GeFMgF had three equilibrium configurations, in which the p-complex structure had the lowest energy and was the most stable structure. The isomerization reactions among the three complexes had been studied. For the insertion reactions of H2GeFMgF with RH ( R = F , OH , NH2), along the potential energy surface, there were one transition state and one intermediate which connected the reactants and the products. For the three insertion reactions the mechanisms are identical. However, under the same conditions the insertion reactions should occur easily in the order of H - F > H - OH > H - NH2. The solvent effect calculations suggested the larger the solvent polarity is, the easier the reaction will be.

Density Functional Theory Calculations on Ni—Ligand Bond Dissociation Enthalpies

The formation and breaking of Ni—L (L=N-heterocyclic carbene, tertiary phosphine etc.) bond is involved in many Ni-catalyzed/mediated reactions. The accurate prediction of Ni—L bond dissociation enthalpies (BDEs) is potentially important to understand these Ni-complex involving reactions. We assess the accuracy of different DFT functionals (such as B3LYP, M06, MPWB1K, etc.) and different basis sets, including both effective core potentials for Ni and the all electron basis sets for all other atoms in predicting the Ni-L BDE values reported recently by Nolan et al. [J. Am. Chem. Soc. 125, 10490 (2003) and Organometallics 27, 3181 (2008)]. It is found that the MPWB1K/LanL2DZ:6-31+G(d,p)//MPWB1K/LanL2DZ:6-31G(d) method gives the best correlations with the experimental results. Meanwhile, the solvent effect calculations (with CPCM, PCM, and SMD models) indicate that both CPCM and PCM perform well.

Isomerizational and conformational study of 3-fluorophenylamino-2-acetyl propenenitrile (FPAAPN)

The isomers and conformers of push–pull 3-fluorophenylamino-2-acetyl propenenitrile (FH4C6)NHCHC(CN)(COCH3) (FPAAPN) have been studied experimentally by NMR and vibrational spectroscopy and theoretically by ab initio calculations at MP2 and DFT B3LYP levels in various basis sets. The IR and Raman spectra of FPAAPN as a solid and as a solute in various solvents have been recorded. The NMR spectra were obtained in chloroform, acetone, acetonitrile and dimethylsulfoxide at room temperature.FPAAPN was prepared as a pure Z-isomer with an intramolecular hydrogen bond. According to the NMR spectra in chloroform the studied compound exists as a single ZZa entity. On the other hand, in more polar solvents the isomerization process occured and an additional EZa confomer was detected. The influence of the environment polarity on this conformational equilibrium is discussed with respect to the SCRF solvent effect calculations using IEFPCM model.The observed IR and Raman bands were compared with calculated MP2/6-311G∗∗ harmonic vibrational frequencies and assigned on the basis of potential energy distribution.

Comparative study of copper complexes with different anchoring groups by molecular modeling and its application to dye-sensitized solar cells

Copper complexes with different anchoring groups (based on biquinoline ligands with acetylacetone, catechol, hydroxamic acid, phosphonic acid and thiocarboxylic acid groups) have been studied by Density Functional Theory and Time-Dependent Density Functional Theory, also the integral equation formalism of the polarizable continuum model has been extended to the calculation of solvent effects. Maximum absorption wavelength reaches the highest value for the complex with hydroxamic acid as anchoring group but a low oscillator strength; the rest of the complexes fulfill both properties. In general, the molecular orbitals energy levels and the schematic representation of them suppose an appropriate electron transfer between the sensitizer and the semiconductor (TiO2), emphasizing more clearly for the copper complex with the thiocarboxylic acid. Chemical reactivity parameters like chemical hardness shows similitude for all molecular systems; but not so in the case of the electrophilicity index and electroaccepting power.

Theoretical study of antioxidative ability and antioxidative mechanism of norathyriol in solution

A quantum mechanical approach has been used to shed light on the antioxidative mechanism for scavenging OOH and OH radicals by norathyriol in the solution phase. Density functional theory (DFT) calculations at the B3LYP and UB3LYP/6-311+G(d,p) level are used to optimize norathyriol and its different radical forms. Analysis of the theoretical bond dissociation enthalpy (BDE) values for all OH sites of norathyriol in solution clearly shows the importance of the B-ring and the 6-OH and 7-OH groups in the antioxidant activity. We have also investigated the spin density of the radicals to determine the delocalization possibilities. The results of the calculations show that the oxidation of norathyriol by both the OOH and OH radical is an exothermic reaction. In all calculations solvent effects are considered using a polarized continuum model (PCM).

Electronic confinement effects on the reaction field type calculations of solvent effects

We analyze some procedures to introduce the effect of confining the electrons of the hydrogen atoms in cavitation spheres like those used in the self‐consistent reaction field models for studying the solvent influence on molecular properties [as polarizable continuum model (PCM), or conductor screening model (COSMO)]. We have found that the boundary conditions to be applied have an important effect on the system energy that by no means should be neglected in this type of calculations. We have found as well that “‐nG” expansion technique could be applicable in this kind of calculations (even at the very simple “‐3G” level) and lead us to a relatively simple form of applying the theory. Moreover, we have found a way to define the cavitation radius of PCM calculations, by minimizing the system energy with respect to this parameter, which could be a more satisfactory procedure—at least from a theoretical point of view—than the use of empirical values characteristic of most of the PCM or COSMO standard calculations. © 2013 Wiley Periodicals, Inc.

Investigation of solute–solvent interactions in phenol compounds: accurate ab initio calculations of solvent effects on 1H NMR chemical shifts

Accurate (1)H chemical shifts of the -OH groups of polyphenol compounds can be calculated, compared to experimental values, using a combination of DFT, polarizable continuum model (PCM) and discrete solute-solvent hydrogen bond interactions. The study focuses on three molecular solutes: phenol, 4-methylcatechol and the natural product genkwanin in DMSO, acetone, acetonitrile, and chloroform. Excellent linear correlation between experimental and computed chemical shifts (with the GIAO method at the DFT/B3LYP/6-311++G(2d,p) level) was obtained with minimization of the solvation complexes at the DFT/B3LYP/6-31+G(d) and DFT/B3LYP/6-311++G(d,p) level of theory with a correlation coefficient of 0.991. The use of the DFT/B3LYP/6-31+G(d) level of theory for minimization could provide an excellent means for the accurate prediction of the experimental OH chemical shift range of over 8 ppm due to: (i) strong intramolecular and solute-solvent intermolecular hydrogen bonds, (ii) flip-flop intramolecular hydrogen bonds, and (iii) conformational effects of substituents of genkwanin. The combined use of ab initio calculations and experimental (1)H chemical shifts of phenol -OH groups provides a method of primary interest in order to obtain detailed structural, conformation and electronic description of solute-solvent interactions at a molecular level.

Solvatochromism and Nonradiative Decay of Intramolecular Charge‐Transfer Excited States: Bands‐of‐Energy Model, Thermodynamics, and Self‐Organization

The fluctuations of orientation and induction interactions in solution and their impact on the broadening of absorption and fluorescence spectra are considered in terms of a bands-of-energy model. Also covered is the application of principles of thermodynamics and self-organization of systems for calculation of solvatochromic shift, among them a component owing to the work on electronic polarization of solvent at the instant of electronic transition in the solute. The findings on solvatochromic shift and spectral broadening open the way to the calculation of solvent effects on the rate constant of nonradiative transitions. As demonstrated herein for 15 fluorophores, the novel theory of nonradiative decay of the intramolecular charge-transfer excited states is carried out for dyes and organic compounds of different nature, both for polar and nonpolar media.

Implementation of the Solvent Macromolecule Boundary Potential and Application to Model and Realistic Enzyme Systems

The implementation of the solvent macromolecule boundary potential (SMBP) by Benighaus and Thiel (J. Chem. Theory Comput. 2009, 5, 3114) into the program package CHARMM is presented. The SMBP allows for the efficient calculation of solvent effects for large macromolecules using irregularly shaped dielectric boundaries. In contrast to the generalized solvent boundary potential (GSBP) by Roux et al. (J. Chem. Phys. 2001, 114, 2924) from which it is derived, the SMBP is targeted for quantum mechanical/molecular mechanical (QM/MM) setups using ab initio methods for the QM part. After presenting benchmark results for simple model systems, applications of the SMBP for the calculation of geometries, reaction energy barriers, and vibrational frequencies for an alkaline phosphatase (AP) enzyme are discussed. Although the effect of the boundary potential on optimized structures (including the transition state) and vibrational frequencies is relatively small, the energetics of the phosphoryl transfer catalyzed by AP depend significantly on the boundary potential. Finally, to emphasize a unique feature of our implementation, we apply both SMBP and GSBP to the calculation of the energy barrier for a proton transfer reaction in a simple model channel, where the effect of an external transmembrane potential is studied. Due to the dipolar response of the polar environment, the effective charge displacement estimated based on the effect of the membrane potential on the proton transfer energetics deviates from the net charge that passes the membrane.

Role of Noncoplanar Conformation in Facilitating Ground State Hole Transfer in Oxidized Porphyrin Dyads

We employ density functional theory to investigate ground state hole transfer in covalently linked oxidized zinc-zinc porphyrin ([ZnZn](+)) and zinc-free-base porphyrin ([ZnFb](+)) dyads in both coplanar and noncoplanar (tilted) conformations. We obtain reactant, product, and transition state (TS) for the hole transfer reaction in the [ZnZn](+) system. The hole is localized on a single porphyrin unit in the reactant and product states while delocalized in the TS, implying the dominance of superexchange mechanism in the hole transfer reaction. A metastable as well as stable states are located for the [ZnFb](+) system while no TS is found, indicating a barrierless hole transfer reaction. The hole lifetimes are calculated to be 15.80 and 0.034 ns for [ZnZn](+) in the coplanar and tilted conformation, respectively, and 14.45 and 0.313 ns for [ZnFb](+). The hole transfer rates are found to be several orders of magnitude faster in the tilted conformation than in the coplanar conformation for both dyads, showing the importance of noncoplanar conformation between the two porphyrin pigments in facilitating the hole transfer process. We also show that inclusion of solvent effects in calculations plays an important role in the proper ground state hole localization in oxidized dyads. These results provide an unconventional insight into the hole transfer mechanism in porphyrin arrays and are relevant to design of artificial photoharvesting materials.