Solvation Model Density Research Articles

A “Turn‐On” Fluorescent Probe for the Visual Detection of Total Iron in Wine

ABSTRACTA turn‐on fluorescent sensor (E)‐4‐((4‐(5‐fluoro‐1H‐benzo[d]imidazol‐2‐yl)benzylidene)amino)phenol (FBAP) for the detection of Fe3+/2+ was synthesized. The fluorescence intensity of probe FBAP solution gradually increased with increased Fe3+ concentration. The low detection limit (LOD) was calculated to be 0.17 nM. The optimized structure and luminescent properties of FBAP were calculated by time‐dependent density functional theory (TD‐DFT) and Solvation Model Density (SMD). The rotation of the dihedral angle and ICT in the imine probe turned off the emission of the benzimidazole, which was restored upon cleaving the imine. Probe FBAP was successfully applied to determine whether Fe3+/2+ in wine exceeded the standard by phone and the rapid detection of Fe3+/2+ in the form of test strips was also conducted.

Hybrid Cluster-Continuum Method for Single-Ion Solvation Free Energy in Acetonitrile Solvent.

A new hybrid discrete-continuum approach named the cluster-continuum static approximation (CCSA) has been proposed for acetonitrile solvent. The continuum part uses the conductor-like polarizable continuum model for electrostatic and a surface area-dependent term for nonelectrostatic solvation. The CCSA includes only one explicit acetonitrile solvent molecule and a damping function, which makes the CCSA method reduce to pure continuum solvation in the case of weaker potential of mean force for solute-solvent interaction. The performance of the model was tested for 22 anions and 22 cations, including challenge species that cannot be adequately described by pure continuum solvation. A comparison was done with the widely used solvent model density (SMD) model. For anions, the CCSA reduces to pure continuum solvation and the method has the same performance as the SMD model, with a standard deviation of the mean signed error (SD-MSE) of 2.7 kcal mol-1 for both models. However, the CCSA method for cations considerably outperforms the SMD model, with an SD-MSE of 3.3 kcal mol-1 for the former and 8.4 kcal mol-1 for the latter. The method can be automated, and the present study suggests that continuum solvation models could be parameterized taking into account the explicit solvation as proposed in this work.

Neighbor effect on conformational spaces of alanine residue in azapeptides

The conformational properties of Alanine (Ala) residue have been investigated to understand protein folding and develop force fields. In this work, we examined the neighbor effect on the conformational spaces of Ala residue using model azapeptides, Ac-Ala-azaGly-NHMe (3, AaG), and Ac-azaGly-Ala-NHMe (4, aGA1). Ramachandran energy maps were generated by scanning (φ, ψ) dihedral angles of the Ala residues in models with the fixed dihedral angles (φ = ±90°, ψ = ±0° or ±180°) of azaGly residue using LCgau-BOP and LCgau-BOP + LRD functionals in the gas and water phases. The integral-equation-formalism polarizable continuum model (IEF-PCM) and a solvation model density (SMD) were employed to mimic the solvation effect. The most favorable conformation of Ala residue in azapeptide models is found as the polyproline II (βP), inverse γ-turn (γ′), β-sheet (βS), right-handed helix (αR), or left-handed helix (αL) depending on the conformation of neighbor azaGly residue in isolated form. Solvation methods exhibit that the Ala residue favors the βP, δR, and αR conformations regardless of its position in azapeptides 3 and 4 in water. Azapeptide 5, Ac-azaGly-Ala-NH2 (aGA2), was synthesized to evaluate the theoretical results. The X-ray structure showed that azaGly residue adopts the polyproline II (βP) and Ala residue adopts the right-handed helical (αR) structure in aGA2. The conformational preferences of aGA2 and the dimer structure of aGA2 based on the X-ray structure were examined to assess the performance of DFT functionals. In addition, the local minima of azapeptide 6, Ac-Phe-azaGly-NH2 (FaG), were compared with the previous experimental results. SMD/LCgau-BOP + LRD methods agreed well with the reported experimental results. The results suggest the importance of weak dispersion interactions, neighbor effect, and solvent influence in the conformational preferences of Ala residue in model azapeptides.

Predicting the propene stereoselectivity on transition metal catalysts: A daunting task for density functional theory.

Thanks to recent developments in hardware and software, quantum chemical methods are increasingly used for interpreting the complex mechanisms underlying polymerization reaction by homogeneous catalysis. Unfortunately, the dimensions of even the smallest realistic models are too large to permit the use of state-of-the-art composite wave function methods. Under these circumstances, density functional theory still offers the best compromise between cost and accuracy. However, comprehensive benchmarks of different functionals are not yet available for this important research field. The main aim of the present paper is to fill this gap by performing an unbiased comparison of several density functionals and continuum solvent models for the stereo-control in the propylene polymerization on prototypical catalysts inducing different reaction mechanisms. While it was not possible to define a unique computational protocol providing the best results in all the situations, the B3PW91 functional in conjunction with D3 empirical dispersions and the solvent model density solvent model performs remarkably well for three out of the four investigated catalysts. Under such circumstances, it is recommended to compare the results delivered by different models when approaching additional classes of catalysts.

Computational Investigation of Conformational Properties of Short Azapeptides: Insights from DFT Study and NBO Analysis.

Azapeptides have gained much attention due to their ability to enhance the stability and bioavailability of peptide drugs. Their structural preferences, essential to understanding their function and potential application in the peptide drug design, remain largely unknown. In this work, we systematically investigated the conformational preferences of three azaamino acid residues in tripeptide models, Ac-azaXaa-Pro-NHMe [Xaa = Asn (4), Asp (5), Ala (6)], using the popular DFT functionals, B3LYP and B3LYP-D3. A solvation model density (SMD) was used to mimic the solvation effect on the conformational behaviors of azapeptides in water. During the calculation, we considered the impact of the amide bond in the azapeptide models on the conformational preferences of models 4-6. We analyzed the effect of the HB between the side-chain main chain and main-chain main-chain on the conformational behaviors of azapeptides 4-6. We found that the predicted lowest energy conformation for the three models differs depending on the calculation methods. In the gas phase, B3LYP functional indicates that the conformers tttANP-1 and tttADP-1 of azapeptides 4 and 5 correspond to the type I of β-turn, the lowest energy conformation with all-trans amide bonds. Considering the dispersion correction, B3LYP-D3 functional predicts the conformers tctANP-2 and tctADP-3 of azapeptide 4 and 5, which contain the cis amide bond preceding the Pro residue, as the lowest energy conformation in the gas phase. The results imply that azaAsx and Pro residues may involve cis-trans isomerization in the gas phase. In water, the predicted lowest energy conformer of azapeptides 4 and 5 differs from the gas phase results and depends on the calculational method. For azapeptide 6, regardless of calculation methods and phases, tttAAP-1 (β-I turn) is predicted as the lowest energy conformer. The results imply that the effect of the side chain that can form HBs on the conformational preferences of azapeptides 4 and 5 may not be negligible. We compared the theoretical results of azaXaa-Pro models with those of Pro-azaXaa models, showing that incorporating azaamino acid residue in peptides at different positions can significantly impact the folding patterns and stability of azapeptides.

DFT Study on the Mechanisms of Iron-Catalyzed Ortho C–H Homoallylation of Aromatic Ketones with Methylenecyclopropanes

The mechanisms of iron-catalyzed ortho C–H homoallylation of aromatic ketones with methylenecyclopropanes are calculated using density functional theory calculations with B3LYP-D3BJ functionals and solvation model density (cyclohexane) model. Our results show that the catalytic cycle includes C–H bond oxidative addition, insertion of C–C double bond, ring-opening reaction, reductive elimination, ligand exchange, and the catalyst regeneration. Two possible catalytic cycles are calculated, where Path A is where the iron active catalyst first combined with 2,2-dimethyl-1-[4-(trifluoromethyl) phenyl]-propan-1-one and Path B is where the iron active catalyst initially attacked 2-phenyl-1-methylenecyclopropane. Our calculated results show that the rate-determining step in the whole catalytic cycle for the favored Path A is the C–H bond oxidation addition step, where Gibbs free energy in solvent cyclohexane, ΔGsol, is 10.8 kcal/mol.

DFT Study on the Molecular Mechanism, Thermodynamic and Kinetic Parameters of Cycloaddition Reaction of Aziridine with CO2 in the Presence of Organocatalysts (TBD and 7-Azaindole)

The catalytic conversions of CO2 into value added chemicals have attracted the interest of many visionary researchers. In this work, the coupling reaction of aziridine with CO2 has been investigated in the absence and presence of organocatalysts (TBD and 7-azaindole) computationally using density functional theory method. The kinetic and thermodynamic parameters of each mechanism were calculated at B3LYP/6-31G (d) level. The results show that, the TBD and 7-azaindole catalyzed reactions of aziridine with CO2 have significantly lower the energy barrier compared to a single step concerted non-catalyzed one. In TBD catalyzed reaction, mechanism I in which the TBD catalyst first interact with CO2 to form TBD-CO2 adduct (zwitterion) and then the zwitterion formed facilitated the ring opening of aziridine to form intermediate is the favorable path. In the case of 7-azaindole catalyzed reaction, mechanism 1 is the most favorable pathway in both gas phase and water phase. However, these parameters were significantly affected in the presence of water using Solvent Model Density (SMD).

Nile Red solvatochromy. TD-DFT calculations and experimental data

The problem of theoretical (quantum chemical) description of electronic absorption spectra and, in particular, solvatochromism, for a well-known Nile Red dye has been investigated. In particular, we consider the use of the time-dependent density functional theory TD-DFT. A number of popular functionals have been investigated, including B3LYP, CAM-B3LYP, M06-L, M06-2X, PBE, BMK, and wB97XD. The standard AO basis set with polarization and diffusion functions 6-31+G(d,p) was used. To describe the effects of the media, three common models based on the polarization-continuum approach were considered. These models include the State Specific (SS) method, the Linear Response (LR) method, and the so-called universal solvation model (Solvation Model Density, SMD). It was found that, in general, the bulk of the functionals are able to qualitative description of the spectral properties of the dye. For the studied system, the best results of the solvation effects descriptions were achieved using the SMD method with the M06-L and B3LYP functionals.

Understanding the Kinetics and Topological Events Within the Thione‐to‐Thiol Rearrangement of Xanthates

AbstractThe heating of O‐furfuryl S‐methyl xanthate in p‐xylene solvent that is known from the literature to yield in parallel S‐furfuryl S‐methyl dithiocarbonate and furfuryl methyl sulfide via the thione‐to‐thiol rearrangement and carbon oxysulfide extrusion, respectively, have been studied theoretically. The CBS‐QB3 energies in conjugation with the solvation model density and B3LYP/6‐311G(2d,d,p) monodeterminantal wave functions have been used to investigate the kinetics of the parallel reaction by means of canonical transition state theory and molecular mechanism of the thione‐to‐thiol rearrangement by means of topological approaches. According to the supplied kinetic data the considered reactions are assisted strongly by the solvent molecules implying implicit solvent model cannot account properly the effect of solvent media. The cross topological analysis of the thione‐to‐thiol rearrangement via [1,3]‐sigmatropic rearrangement revealed that the electron density flow along the reaction is not concerted and the sequence of catastrophes can be summarized as 4‐EF†C‐0. In simple chemical term, chemical events through the reaction are heterolytic breaking of C−O bond, formation of pseudoradical center on the C atom, and creation of a new chemical C−S bond via the C‐to‐S coupling of pseudoradical centers, respectively.

Synthesis, spectral analysis, and theoretical investigations of diphenyl fumarate

Diphenyl fumarate is synthesized from maleic anhydride and phenol under solvent-free conditions. The structure of the product is characterized by FTIR, 1H NMR, and 13C NMR. The molecular structure is optimized using the density functional theory approach at the B3LYP/6-311G(d,p) level and the structural parameters are analyzed. Theoretical vibrational frequencies are investigated at the same level; the 1H NMR and 13C NMR are simulated using the default gauge-independent atomic orbital method at the B3LYP/6-31G(d) level and the solvation model density implicit continuum solvation model for chloroform; chemical shifts are scaled using scaling factors available on the cheshirenmr.info website (accessed 12 September 2021). In addition, the UV-Vis absorption and fluorescence emission are simulated using the time-dependent method at the PBE38/6-311G(d,p) level. All the calculated spectral values are compared with the experimental data. A generally good agreement between the experimental and theoretical results is found. The results reveal diphenyl fumarate as a candidate substrate for small-molecule organic fluorophores with a large Stokes shift. This work provides a detailed experimental and theoretical study on the structural and spectral properties of diphenyl fumarate, and thus provides proof for the novel applications of diphenyl fumarate and its derivatives.

DFT study on the mechanisms of α‐C cross coupling of π‐bonds catalyzed by iron complexes

AbstractThe mechanisms of α‐C cross coupling of π‐bonds catalyzed by iron complexes have been investigated using density functional theory (DFT) calculations with the B3LYP‐D3BJ in solvation model density (SMD) (dichloromethane). The results show that the overall catalytic cycle includes the deprotonation of α‐position of alkynes, electrophilic functionalization, protonation and BF3 departure, alkynes exchange, and catalyst regeneration. The deprotonation step of α‐position of alkynes is the rate‐determining step in the whole catalytic cycle where the energy barrier ΔGsol in dichloromethane solution is 11.6 kcal/mol. Our results also show that the product is in a racemic form, which keeps consistent with the experimental results.

Molecular design and experimental study of cellulose conversion to 5-hydroxymethylfurfural catalyzed by different ratios of Brønsted/Lewis acid ionic liquids

Cellulose conversion into 5-hydroxymethylfurfural (5-HMF) is difficult because of the strong hydrogen bonding existed in cellulose chains. Brønsted/Lewis (B/L) biacidic functionalized ionic liquids (ILs) have great advantages in acid-catalyzed tandem reactions, but the catalytic effect of ILs differs considerably depending on B/L acid ratios. Therefore, this work designed a series of reactions with different proportions of biacidic ILs for the preparation of 5-HMF from cellulose. The tandem reaction is often performed in the presence of a solvent, and the activity of the catalyst is also affected by the solvent. Therefore, in this work, the solvation model density(SMD) model was introduced into the quantum chemical calculation method for molecular design to predict the catalytic effect and explore the catalytic mechanism. The calculation results and experiments jointly showed that [(HSO3-P)2im]Cl·ZnCl2 had the highest efficiency, with a 5-HMF yield of 65.66%. This study facilitates the directional optimization design of the catalyst.

Interaction of Sulforaphane with Cis-Platin: A Theoretical Study

Both sulforaphane (SF) and cisplatin (CP) are well-known anticancer drugs and in some cases, they are used simultaneously for the treatment of a wide range of cancers. SF is the main component of cruciferous vegetables such as broccoli. CP is a four-coordinated complex of platinum, Pt(NH3)Cl2. The interaction of SF with CP is important since a ligand of this inorganic complex might be replaced by SF. In this work, the complexation of SF with CP has been studied theoretically using an accurate high-level ab initio method, together with a reliable method of density functional theory method. Calculations are extended to solution phase by means of solvation model density. Different functional groups of SF are investigated so that the most active site of SF in reaction with CP is determined from both thermodynamics and kinetics points of view. Derivatives of SF have been also studied in order to improve their solbilities in aqueous solution. The results of this work show that SF can form a stable complex with CP and interactions of these two compounds should be considered.

Performance of molecular dynamics simulation for predicting of solvation free energy of neutral solutes in methanol

Abstract In this study, molecular dynamics simulation was applied for calculating solvation free energy of 16 solute molecules in methanol solvent. The thermodynamic integration method was used because it was possible to calculate the difference in free energy in any thermodynamic path. After comparing results for solvation free energy in different force fields, COMPASS force field was selected since it had the lowest error compared to experimental result. Group-based summation method was used to compute electrostatic and van der Waals forces at 298.15 K and 1 atm. The results of solvation free energy were obtained from molecular dynamics simulation and were compared to the results from Solvation Model Density (SMD) and Universal Continuum Solvation Model (denoted as SM8), which were obtained from other research works. Average square-root-error for molecular dynamics simulation, SMD and SM8 models were 0.096091, 0.595798, and 0.70649. Furthermore, the coefficient of determination (R 2) for molecular dynamics simulation was 0.9618, which shows higher accuracy of MD simulation for calculating solvation free energy comparing to two other models.

Theoretical DFT Studies on Free Base, Cationic and Hydrochloride Species of Narcotic Tramadol Agent in Gas Phase and Aqueous Solution

Theoretical studies based on the density functional theory (DFT) have been performed to study structural and vibrational properties of the free base, cationic, and hydrochloride species of narcotic tramadol agent in the gas phase and aqueous solution. In both media, B3LYP/6-31G* calculations were used while in solution, the self-consistent reaction field (SCRF) method together with the integral equation formalism variant polarised continuum (IEFPCM) and universal solvation model density (SMD) models have been employed because these models consider the solvent effects. The vibrational studies have revealed that the species cationic is present in the solid phase because the most intense band predicted for the hydrochloride in infrared and Raman spectra is not observed in the experimental spectra. The harmonic force fields, together with the normal internal coordinates and scaling factors, have allowed the complete vibrational assignments of 126, 129, and 132 vibration modes expected for the free base, cationic, and hydrochloride species, respectively, by using the SQMFF methodology. The cationic species evidence the most negative solvation energy and higher hydration in solution in agreement with its lower stability, while the hydrochloride species is the most reactive in solution. MK charges and NBO and AIM studies support cationic species' instability due to the positive charge on N atom. Comparisons of the experimental UV spectrum of hydrochloride tramadol with the predicted for the three species suggest that the free base, cationic, and hydrochloride species can be present in solution. Comparisons of predicted infrared, Raman, 1H, and 13C NMR and electronic spectra for the free base, cationic, and hydrochloride species of tramadol with the corresponding experimental ones have evidenced reasonable correlations for the cationic species showing that this species present in the solid phase and in solution.

Stabilization of glyphosate zwitterions and conformational/tautomerism mechanism in aqueous solution: insights from ab initio and density functional theory-continuum model calculations.

In this work, a comparative theoretical conformational analysis of the commercially most successful herbicide compound, glyphosate (N-phosphonomethylglycine), has been made at various quantum chemical levels of theory, in the gas phase and aqueous solution, using the integral equation-formalism polarizable continuum model (IEFPCM) and the solvation model density (SMD) approaches. The stable conformers of non-ionized (NE) and ionized or zwitterionic (ZW) neutral forms of glyphosate and the inter-conversions between them are described. Calculations revealed that several NE conformers of glyphosate exist in the gas phase but the zwitterionic form (ZW) is unstable in vacuo at all levels of theory. In aqueous solution, the stabilization of the zwitterion form of glyphosate was unable to be predicted satisfactorily within the equilibrated framework of the IEFPCM polarizable continuum model and using the standard UFF-radii cavity. However, the calculation with the density-based solvation model (SMD) was consistent with the experimental findings and led to the identification of the phosphonate zwitterionic (ZWP) structure as the global minimum energy in aqueous solution. The ZWP ⇋ NE tautomeric equilibrium between the non-ionized and zwitterionic forms of glyphosate was studied in aqueous solution at the SMD-B3LYP-D3/6-311++(2d,2p) level. Zwitterion formation in solution could occur by means of a concerted intramolecular proton transfer from the nitrogen to the oxygen of the phosphonate group. An analysis of the intermolecular mechanism shows that the addition of one water molecule favours the process either thermodynamically or kinetically. The possibility that the tautomerization process of glyphosate via a nonconcerted mechanism with zwitterion carboxylate (ZWC) as the intermediate can be excluded and the ZWP → ZWC proton transfer conversion can be a nearly barrierless process in PES and FES surfaces. comparison with similarly related biologically active systems was made.

On the Accuracy of the Direct Method to Calculate pKa from Electronic Structure Calculations.

The direct method (HA(soln) ⇌ A(soln)– + H(soln)+) for calculating pKa of monoprotic acids is as efficient as thermodynamic cycles. A selective adjustment of proton free energy in solution was used with experimental pKa data. The procedure was analyzed at different levels of theory. The solvent was described by the solvation model density (SMD) model, including or not explicit water molecules, and three training sets were tested. The best performance under any condition was obtained by the G4CEP method with a mean absolute error close to 0.5 units of pKa and an uncertainty around ±1 unit of pKa for any training set including or excluding explicit solvent molecules. PM6 and AM1 performed very well with average absolute errors below 0.75 units of pKa but with uncertainties up to ±2 units of pKa, using only the SMD solvent model. Density functional theory (DFT) results were highly dependent on the basis functions and explicit water molecules. The best performance was observed for the local spin density approximation (LSDA) functional in almost all calculations and under certain conditions, as high as those obtained by G4CEP. Basis set complexity and explicit solvent molecules were important factors to control DFT calculations. The training set molecules should consider the diversity of compounds.

Structural Study and Vibrational Assignments of Anticonvulsant Topiramate by using DFT calculations and Two Harmonic Force Fields

B3LYP/6-311++G** calculations have been combined with the scaled quantum mechanical force field (SQMFF) methodology to study structural and vibrational properties of anticonvulsant topiramate (TPM) agent. The 123 vibration modes expected for TPM were completely assigned, considering two harmonic force fields. In one case, C2V symmetries were considered for both SO2 and NH2 groups, while in the other one C2V and C3V symmetries for the NH2 and SO3 groups, respectively. The calculated harmonic vibrational frequencies are consistent with the experimental IR and Raman spectra in the solid phase. Very good concordances were found between the theoretical structures in gas phase and aqueous solution and the corresponding experimental reported. Thus, the fused five-membered ring in TPM produces that the pyranose ring adopts distorted twist-boat conformation, as was experimentally observed. In solution, all calculations were performed with the self-consistent reaction force (SCRF) method by the integral equation formalism variant polarised continuum (IEFPCM) and universal solvation model density (SMD) models. The corrected solvation energy value for TPM in aqueous solution by total non-electrostatic terms and by ZPVE is -1066.10 kJ/mol. The bond orders have evidenced that the three O atoms are not linked of the same form to S atom. Hence, the S atom of TPM is practically tetra-coordinate in both media, as evidenced by the high negative MK and NPA charges on the O atoms linked to it. The AIM study supports the higher stability of TPM in the gas phase while the NBO calculations suggest higher stability in solution. Gap values support the higher reactivity of TPM in solution than in the gas phase. The scaled force constant for both cases are reported for the first time. Comparisons of predicted 1H- and 13C-NMR spectra with the corresponding experimental ones reveal very good concordances.

Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives.

We report on the density functional theory (DFT) modelling of structural, energetic and NMR parameters of uracil and its derivatives (5-halogenouracil (5XU), X = F, Cl, Br and I) in vacuum and in water using the polarizable continuum model (PCM) and the solvent model density (SMD) approach. On the basis of the obtained results, we conclude that the intramolecular electrostatic interactions are the main factors governing the stability of the six tautomeric forms of uracil and 5XU. Two indices of aromaticity, the harmonic oscillator model of aromaticity (HOMA), satisfying the geometric criterion, and the nuclear independent chemical shift (NICS), were applied to evaluate the aromaticity of uracil and its derivatives in the gas phase and water. The values of these parameters showed that the most stable tautomer is the least aromatic. A good performance of newly designed xOPBE density functional in combination with both large aug-cc-pVQZ and small STO(1M)−3G basis sets for predicting chemical shifts of uracil and 5-fluorouracil in vacuum and water was observed. As a practical alternative for calculating the chemical shifts of challenging heterocyclic compounds, we also propose B3LYP calculations with small STO(1M)−3G basis set. The indirect spin–spin coupling constants predicted by B3LYP/aug-cc-pVQZ(mixed) method reproduce the experimental data for uracil and 5-fluorouracil well.

Understanding the Formation of 5-(Diethylammoniothio)-1,3-dimethylbarbituric Acid: Crystal Structure and DFT Studies

5-(Diethylammoniothio)-1,3-dimethylbarbituric acid (8) was obtained in good yield from the reaction of 5-bromo-1,3-dimethylbarbituric acid (5) and 1,3-diethylthiourea. The obtained product has been characterized using different techniques including single-crystal X-ray diffraction, FTIR, MS and NMR spectroscopy. For this reaction, a detailed computational study of the reaction steps has been performed using density functional theory (DFT). Both thermodynamic and kinetic parameters were calculated. Step B is the most favorable reaction with an activation energy of 33 kJ mol−1 using the solvation model that based on the solvent model density (SMD) calculated at B3LYP/6-31G(d). The rate-determining step of the most plausible mechanism involves the formation of C-S bond via proton transfer to oxygen (intramolecular attraction) with an activation barrier of 33 kJ mol-1 using the solvation model that based on density (SMD) solvent model calculated at B3LYP/6-31G(d).