Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives

The structure assignment and conformational analysis of the thiosemicarbazones, DKI21 and DKI24, were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-ROESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations, using Functional Density Theory (DFT). In addition, utilizing a combination of 2D-NOESY and 2D-ROESY spectra an exo structure was established for both of the analogs. This experimental results were confirmed by theoretical mechanistic studies, as the lowest minima conformations derived through DFT calculations were compatible with the spatial correlations observed in the 2D-NOESY and 2D-ROESY spectra. Finally, molecular binding experiments were performed to detect the potential targets for DKI21 and DKI24, derived from SwissAdme. In silico molecular binding experiments showed favorable binding energy values for the most of the enzymes studied. The ADMET calculations, using the preADMET and pKCSm software, showed that the two molecules appear as possible drug leads.     

Structural and spectroscopic characterization of 2,3-difluorobenzoic acid and 2,4-difluorobenzoic acid with experimental techniques and quantum chemical calculations

In this study, the molecular conformation, vibrational and electronic transition analysis of 2,3-difluorobenzoic acid and 2,4-difluorobenzoic acid (C7H4F2O2) were presented using experimental techniques (FT-IR, FT-Raman and UV) and quantum chemical calculations. FT-IR and FT-Raman spectra in solid state were recorded in the region 4000-400 cm(-1) and 4000-5 cm(-1), respectively. The UV absorption spectra of the compounds that dissolved in ethanol were recorded in the range of 200-800 nm. The structural properties of the molecules in the ground state were calculated using density functional theory (DFT) and second order M?ller-Plesset perturbation theory (MP2) employing 6-311++G(d,p) basis set. Optimized structure of compounds was interpreted and compared with the earlier reported experimental values. The scaled vibrational wavenumbers were compared with experimental results. The complete assignments were performed on the basis of the experimental data and total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. A study on the electronic properties, such as absorption wavelength, excitation energy, dipole moment and frontier molecular orbital energy, were performed by time dependent DFT (TD-DFT) approach. Based on the UV spectra and TD-DFT calculations, the electronic structure and the assignments of the absorption bands of steady compounds were discussed. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecules.     

镧系水合离子的密度泛函理论研究

用密度泛函理论(DFT)方法研究了镧系水合离子[Ln(H2O9)]^3+(Ln=Ce,Pr,Nd,Pm,Ho,Er,Tm,Yb)的几何构型、电荷分布和Ln^3+与水的结合能,计算结果与实验基本符合,表明DFT方法也适用于计算镧系离子与中性配体形成的化合物,对计算结果的分析表明,Ln^3+与H2O之间主要通过Ln5d轨道与氧孤对电子相互作用成键而结合,其余轨道起的作用比较小,用镧系化合物成键模型解释了镧系离子与水的结合能从La到Lu逐渐增加的事实。     

Investigate oxoazolidine-2,4-dione based eutectic mixture via DFT calculations and SAR

In this work, DFT calculations for the designed eutectic mixtures (EMs) using oxoazolidine 2,4-dione (OZD) and zinc chloride (ZnCl2) are done. The interaction between the hydrogen bond donor and hydrogen bond acceptor at atomic level to get EMs are studied using DFT calculations. At room temperature, the stability of these various systems have been investigated using thermodynamic values or parameters such as enthalpy, free energy and others. DFT calculations is used to investigate the possibility of forming the systems (EMs). Further, the impact of varying the temperature on each system was also investigated (323K, 348K). Various other thermodynamic parameters are studied like dipole moment, hardness, chemical potential of the systems (individual molecules and EMs) at different temperatures. The results of the calculations showed that O1Z4 and O4Z1 have maximum dipole moment having values 8.1291, 9.8801 respectively, indicating maximum polarizability. Change in free energy for O1Z4 is least and was found to be ?37.2496 kcal/ mol. Further on changing the temperature, the parameters do not show much variation. Additionally, we have analyzed structure activity relationship (SAR) method to understand the physico-chemical properties of designed EMs and predict their regression and correlation to optimized energy. From the calculated values of pOE model, the value of r² is 0.9995 confirms the validity of the equation obtained. The results of this study suggest a link between the structures that have been utilized to describe the intermolecular interaction between the hydrogen bond donor and acceptor, as well as the stability of the EMs.     

13C and (15)N chemical shift tensors in adenosine,guanosine dihydrate, 2'-deoxythymidine,and cytidine

The (13)C and (15)N chemical shift tensor principal values for adenosine, guanosine dihydrate, 2'-deoxythymidine, and cytidine are measured on natural abundance samples. Additionally, the (13)C and (15)N chemical shielding tensor principal values in these four nucleosides are calculated utilizing various theoretical approaches. Embedded ion method (EIM) calculations improve significantly the precision with which the experimental principal values are reproduced over calculations on the corresponding isolated molecules with proton-optimized geometries. The (13)C and (15)N chemical shift tensor orientations are reliably assigned in the molecular frames of the nucleosides based upon chemical shielding tensor calculations employing the EIM. The differences between principal values obtained in EIM calculations and in calculations on isolated molecules with proton positions optimized inside a point charge array are used to estimate the contributions to chemical shielding arising from intermolecular interactions. Moreover, the (13)C and (15)N chemical shift tensor orientations and principal values correlate with the molecular structure and the crystallographic environment for the nucleosides and agree with data obtained previously for related compounds. The effects of variations in certain EIM parameters on the accuracy of the shielding tensor calculations are investigated.     

An In Silico investigation for acyclovir and its derivatives to fight the COVID-19: Molecular docking,DFT calculations,ADME and td-Molecular dynamics simulations

In the present work, we have designed three molecules, acyclovir (A), ganciclovir (G) and derivative of hydroxymethyl derivative of ganciclovir (CH₂OH of G, that is D) and investigated their biological potential against the Mpro of nCoV via in silico studies. Further, density functional theory (DFT) calculations of A, G and D were performed using Gaussian 16 on applying B3LYP under default condition to collect the information for the delocalization of electron density in their optimized geometry. Authors have also calculated various energies including free energy of A, G and D in Hartree per particle. It can be seen that D has the least free energy. As mentioned, the molecular docking of the A, G and D against the Mpro of nCoV was performed using iGemdock, an acceptable computational tool and the interaction has been studied in the form of physical data, that is, binding energy for A, G and D were calculated in kcal/mol. It can be seen the D showed effective binding, that is, maximum inhibition that A and G. For a better understanding for the inhibition of the Mpro of nCoV by A, G and D, temperature dependent molecular dynamics simulations were performed. Different trajectories like RMSD, RMSF, Rg and hydrogen bond were extracted and analyzed. The results of molecular docking of A, G and D corroborate with the td-MD simulations and hypothesized that D could be a promising candidate to inhibit the activity of Mpro of nCoV.     

Theoretical determination of standard oxidation and reduction potentials of chlorophyll-a in acetonitrile

QM/MM calculations were performed on ethyl chlorophyllide-a and its radical cation and anion, by using the density functional (DF) B3LYP method to determine the molecular characteristics, and a molecular mechanics (MM) method to simulate the solvating medium. The presence of the solvent was accounted for during the optimization of the geometry of the 85-atom chlorophyll-a system by using an ONIOM methodology. A total of 24 solvent molecules were explicitly considered during the optimization process, and these were treated by the universal force field (UFF) method. Initially, the split-valence 3-21G basis set was used for optimizing the geometry of the 85-atom species, neutral, cation and anion. Electronic energies were then determined for the optimized species by making use of the polarized 6-31G(d) basis set. The ionization energy calculated (6.0 eV) is in very good agreement with the observed one (6.1 eV). The MM+ force field was used to investigate the dynamics of the acetonitrile molecules around the neutral species as well as the radical ions of chlorophyll. The required atomic charges on all the atoms were obtained from calculations on all involved molecules at the DFT/6-31G(d) level. Randomly sampled configurations were used to determine the first solvation layer contribution to the free energy of solvation of various species. A truncated 46-atom model of ethyl chlorophyllide-a was used to evaluate the thermal energies of neutral chlorophyll molecule relative to its two radical ions in the gas phase. Born energy, Onsager energy, and the Debye-Huckel energy of the chlorophyll-solvent aggregate were added as perturbative corrections to the free energy of solvation that was initially obtained through molecular dynamics method for the same complex. These calculations yield the oxidation potential as 0.75 +/- 0.32 V and the reduction potential -1.18 +/- 0.31 V at 298.15 K. The calculated values are in good agreement with the experimental midpoint potentials of +0.76 and -1.04 V, respectively.     

Probing the bent bonds in cyclopropane systems for gas storage and separation process: A computational study

The hydrogen, carbon dioxide, and carbon monoxide gas adsorption and storage capacity of lithium-decorated cyclopropane ring systems were examined with quantum chemical calculations at density functional theory, DFT M06-2X functional using 6-31G(d) and cc-pVDZ basis sets. To examine the reliability of M06-2X DFT functional, a few representative systems are also examined with complete basis set CBS-QB3 method and CCSD-aug-cc-pVTZ level of theory. The cyclopropane systems can bind to one Li⁺ ion; however, the corresponding the methylated systems can bind with two Li⁺ ions. The cyclopropane systems can adsorb six hydrogen molecules with an average binding energy of 3.8 kcal/mol. The binding free energy (ΔG) values suggest that the hydrogen adsorption process is feasible at 273.15 K. The calculation of desorption energies indicates the recyclable property of gas adsorbed complexes. The same number of CO₂ and CO gas molecules can also be adsorbed with an average binding energy of −14.4 kcal/mol and −10.7 kcal/mol, respectively. The carbon dioxide showed ~3–4 kcal/mol better binding energy as compared to carbon monoxide and hence such designed systems can function as a potential candidate for the separation of these flue gas molecules. The nature of interactions in complexes was examined with atoms in molecules analysis revealed the electrostatic nature for the interaction of Li⁺ ion with cyclopropane rings. The chemical hardness and electrophilicity calculations showed that the gas adsorbed complexes are rigid and therefore robust as gas storage materials.     

Molecular parameterization and determination of the electrode potentials of anticoagulant derivatives: Electrochemical and quantum chemical study

This research presents calculations and computation of two anticoagulant derivatives electrode potentials in methanol. For this purpose, the ab initio molecular orbital calculations (HF) and density functional theory (DFT) together with the 6-31G(d) basis set were utilized. The calculated values were compared with the experimental values obtained by linear sweep voltammetry. The observed and the calculated changes in the reduction potential of the anticoagulant derivatives differed from those of the reference compound (catechol), being less than 20 mV. In this way, a method was provided, by which the reduction potentials of the related molecules could be predicted very accurately. Actually, the resulting data illustrated that the method was likely to be useful for the prediction of biomolecules electrode potentials in different aprotic solvents. The bond lengths, bond angles and dipole moment of the studied compounds were calculated in two different solvents and the solvent effects were discussed.     

Density functional theory calculations of the internal rotations and vibrational spectra of 2-, 3- and 4-formyl pyridine

The torsional potentials, molecular conformations and vibrational spectra, of 2-, 3- and 4-formyl pyridine have been investigated using density functional theory (DFT) method with 6-31+G* basis set. From the calculations, 2-formyl pyridine and 3-formyl pyridine were predicted to exist predominantly in cis conformation with the cis-trans rotational barrier of 9.38 kcal/mol and 8.55 kcal/mol, respectively. The two equivalent planar structures of 4-formyl pyridine are separated by an energy barrier of 7.18 kcal/mol. The vibrational wavenumbers and the corresponding vibrational assignments of molecules in C(s) symmetry were examined theoretically and the calculated Infrared of the molecules in the cis conformation was plotted. Observed wavenumbers for normal modes were compared with those calculated from normal mode coordinate analysis carried out on the basis of DFT force fields using the standard 6-31+G* basis set of the theoretical optimized geometry.     

Computational structural determination and energy landscape analysis of the hepatic carcinogen 2-(acetylamino)fluorene

 2-(Acetylamino)fluorene (AAF), a potent mutagen and a prototypical example of the mutagenic aromatic amines, forms covalent adducts to DNA after metabolic activation in the liver. A benchmark study of AAF is presented using a number of the most widely used molecular mechanics and semiempirical computational methods and models. The results are compared to higher-level quantum calculations and to experimentally obtained crystal structures. Hydrogen bonding between AAF molecules in the crystal phase complicates the direct comparison of gas-phase theoretical calculations with experiment, so Hartree–Fock (HF) and Becke–Perdew (BP) density functional theory (DFT) calculations are used as benchmarks for the semiempirical and molecular mechanics results. Systematic conformer searches and dihedral energy landscapes were carried out for AAF using the SYBYL and MMFF94 molecular mechanics force fields; the AM1, PM3 and MNDO semiempirical quantum mechanics methods; HF using the 3-21G*and 6-31G* basis sets; and DFT using the nonlocal BP functional and double numerical polarization basis sets. MMFF94, AM1, HF and DFT calculations all predict the same planar structures, whereas SYBYL, MNDO and PM3 all predict various nonplanar geometries. The AM1 energy landscape is in substantial agreement with HF and DFT predictions; MMFF94 is qualitatively similar to HF and DFT; and the MNDO, PM3 and SYBYL results are qualitatively different from the HF and DFT results and from each other. These results are attributed to deficiencies in MNDO, PM3 and SYBYL. The MNDO, PM3 and SYBYL models may be unreliable for compounds in which an amide group is immediately adjacent to an aromatic ring. Received: 26 May 2002 / Accepted: 12 December 2002 / Published online: 14 February 2003     

SAMPL6 host–guest challenge: binding free energies via a multistep approach

In this effort in the SAMPL6 host–guest binding challenge, a combination of molecular dynamics and quantum mechanical methods were used to blindly predict the host–guest binding free energies of a series of cucurbit[8]uril (CB8), octa-acid (OA), and tetramethyl octa-acid (TEMOA) hosts bound to various guest molecules in aqueous solution. Poses for host–guest systems were generated via molecular dynamics (MD) simulations and clustering analyses. The binding free energies for the structures obtained via cluster analyses of MD trajectories were calculated using the MMPBSA method and density functional theory (DFT) with the inclusion of Grimme’s dispersion correction, an implicit solvation model to model the aqueous solution, and the resolution-of-the-identity (RI) approximation (MMPBSA, RI-B3PW91-D3, and RI-B3PW91, respectively). Among these three methods tested, the results for OA and TEMOA systems showed MMPBSA and RI-B3PW91-D3 methods can be used to qualitatively rank binding energies of small molecules with an overbinding by 7 and 37 kcal/mol respectively, and RI-B3PW91 gave the poorest quality results, indicating the importance of dispersion correction for the binding free energy calculations. Due to the complexity of the CB8 systems, all of the methods tested show poor correlation with the experimental results. Other quantum mechanical approaches used for the calculation of binding free energies included DFT without the RI approximation, utilizing truncated basis sets to reduce the computational cost (memory, disk space, CPU time), and a corrected dielectric constant to account for ionic strength within the implicit solvation model.     

Molecular Recognition of Pyromellitic Imide-azacyclophane to Organic Pollutant

Anion can be identified by pyromellitic imide-azacyclophane which is one of the host compounds.This article investigated the interaction between the host and organic pollution compounds.The host and other eight compounds were optimized by DFT(density functional theory) B3LYP/6-31G level and the energy of compounds was corrected using Boys-Bemardi method.On the basis of B3LYP/6-31G optimized geometries,the RDG function and sign(λ2(r))ρ(r) function values of space points were calculated,and color RDG isosurface map was drawn.3He chemical shift was calculated by the B3LYP/6-31G method.The results showed that the eight organic pollution molecules with the host one shaped stable configurations by hydrogen bonds,respectively.The stabilization energy of complexes 4 and 7 showed repulsion(steric effects) of cyclophane cage observably affecting the stability of the complexes.The location,intensity and the type of interaction in complex 1 were analyzed through color-filled RDG isosurface map.Aromaticity calculations showed that the weak interaction reduced the transverse induction ring current in the host rings,and deteriorated the aromaticity of compounds.     

Chelate Coordination Compounds as a New Class of High-Energy Materials: The Case of Nitro-Bis(Acetylacetonato) Complexes

The existence of areas of strongly positive electrostatic potential in the central regions of the molecular surface of high-energy molecules is a strong indicator that these compounds are very sensitive towards detonation. Development of high-energy compounds with reduced sensitivity towards detonation and high efficiency is hard to achieve since the energetic molecules with high performance are usually very sensitive. Here we used Density Functional Theory (DFT) calculations to study a series of bis(acetylacetonato) and nitro-bis(acetylacetonato) complexes and to elucidate their potential application as energy compounds with moderate sensitivities. We calculated electrostatic potential maps for these molecules and analyzed values of positive potential in the central portions of molecular surfaces in the context of their sensitivity towards detonation. Results of the analysis of the electrostatic potential demonstrated that nitro-bis(acetylacetonato) complexes of Cu and Zn have similar values of electrostatic potential in the central regions (25.25 and 25.06 kcal/mol, respectively) as conventional explosives like TNT (23.76 kcal/mol). Results of analysis of electrostatic potentials and bond dissociation energies for the C-NO₂ bond indicate that nitro-bis(acetylacetonato) complexes could be used as potential energetic compounds with satisfactory sensitivity and performance.     

Determination of structural and vibrational spectroscopic properties of 2-, 3-, 4-nitrobenzenesulfonamide using FT-IR and FT-Raman experimental techniques and DFT quantum chemical calculations

In this work, the molecular conformation and vibrational analysis of 2-, 3-, 4-nitrobenzenesulfonamide (abbreviated as 2-, 3-, 4-NBSA) were presented for the ground state using experimental techniques (FT-IR and FT-Raman) and density functional theory (DFT) employing B3LYP exchange correlation with the 6-311++G(d,p) basis set. The complete assignments of fundamental vibrations were performed on the basis of the experimental results and total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. The effects of the nitro group substituent on the characteristic benzene sulfonamides bands in the spectra were discussed. Raman activities calculated by DFT method have been converted to the corresponding Raman intensities using Raman scattering theory. Optimized structure of compounds were interpreted and compared with the earlier reported experimental values for studied molecules. The observed and the calculated geometric parameters and vibrational wavenumbers were compared and found to be in good agreement.     

Binding energies of hydrogen molecules to isoreticular metal-organic framework materials

Recently, several novel isoreticular metal-organic framework (IRMOF) structures have been fabricated and tested for hydrogen storage applications. To improve our understanding of these materials, and to promote quantitative calculations and simulations, the binding energies of hydrogen molecules to the MOF have been studied. High-quality second-order Moller-Plesset (MP2) calculations using the resolution of the identity approximation and the quadruple zeta QZVPP basis set were used. These calculations use terminated molecular fragments from the MOF materials. For H2 on the zinc oxide corners, the MP2 binding energy using Zn4O(HCO2)6 molecule is 6.28 kJ/mol. For H2 on the linkers, the binding energy is calculated using lithium-terminated molecular fragments. The MP2 results with coupled-cluster singles and doubles and noniterative triples method corrections and charge-transfer corrections are 4.16 kJ/mol for IRMOF-1, 4.72 kJ/mol for IRMOF-3, 4.86 kJ/mol for IRMOF-6, 4.54 kJ/mol for IRMOF-8, 5.50 and 4.90 kJ/mol for IRMOF-12, 4.87 and 4.84 kJ/mol for IRMOF-14, 5.42 kJ/mol for IRMOF-18, and 4.97 and 4.66 kJ/mol for IRMOF-993. The larger linkers are all able to bind multiple hydrogen molecules per side. The linkers of IRMOF-12, IRMOF-993, and IRMOF-14 can bind two to three, three, and four hydrogen molecules per side, respectively. In general, the larger linkers have the largest binding energies, and, together with the enhanced surface area available for binding, will provide increased hydrogen storage. We also find that adding up NH2 or CH3 groups to each linker can provide up to a 33% increase in the binding energy.     

Computer simulation of the interaction of Cu(I) with cys residues at the binding site of the yeast metallochaperone Cu(I)-Atx1

The copper binding site and electronic structure of the metallochaperone protein Atx1 were investigated using the combination of quantum mechanics methods and molecular mechanics methods in the ONIOM(QM:MM) scheme at the density functional theory (DFT) B3LYP/ 6-31G(d):AMBER level. The residues in the binding site, -Met13-Thr14-Cys15-Cu(I)-Cys18-Gly17-Ser16-, were modeled with QM and the rest of the residues with MM. Our results indicate that the structure for Cu(I)-Atx1 has the copper atom coordinated to two sulfur atoms from Cys15 (2.110 A) and Cys18 (2.141 A) with an angle S-Cu(I) -S of 166 degrees . The potential energy surface of the copper atom is used to estimate its binding energy and the force field for the copper ligands. The potential surface is shallow for the bending mode S-Cu-S, which explains the origin of the disorder observed in crystallographic and nuclear magnetic resonance studies. Using molecular dynamics for Cu(I)-Atx1 in a box of water molecules and in vacuum, with the force field derived in this work, we observed a correlated motion between the side chains of Thr14 and of Lys65 which enhances distortions in the S-Cu-S geometry. The results are compared with recent experiments and the previous models. The vibrational spectra for the copper ligands and for the residues in the binding site were computed. The localized modes for the copper ligands and the amide bands were assigned. The presence of the copper atom affects the amide bands' frequencies of the residues Cys15 and Cys18, giving resolved bands that can be used to sense changes in the binding site upon translocation of copper atom or interaction with target proteins. Furthermore, the EXAFS (extended X-ray absorption fine structure) spectrum of the proposed structure for Cu(I)-Atx1 was calculated and reproduced the experiments fairly well.     

Speciation of uranyl ions in fulvic acid and humic acid: a DFT exploration

The speciation of uranyl ions in fulvic acid (FA) and humic acid (HA), based on models of larger sizes, is systematically studied using density functional theory (DFT). Four uranyl binding sites are suggested for FA and based on their energetics, the preferential binding sites are proposed. The computed binding sites include two chelating types, one through the carboxylate group and one via the hydroxo group. A systematic way to attain the possible structure for Stevenson's HA model is carried out using a combined molecular dynamics (MD) and quantum chemical approach. Calculated structures and energetics reveal many interesting features such as conformational flexibility of HA and binding of hydrophobic molecules in agreement with the experimental suggestions. Five potential binding sites are proposed for uranyl binding to HA and the calculated geometries correlate nicely with the experimental observations. Our binding energy calculations reveal that apart from uranyl binding at the carboxylate functional group, binding at other functional groups such as those involving quinone and hydroxo sites are also possible. Finally, based on our cluster calculations the strength of uranyl binding to HAs and FAs is largely influenced by neighbouring groups via hydrogen bonding interactions.     

Molecular structures and vibrational frequencies of 2-, 3- and 4-pyridine carboxaldehydes by ab initio Hartree-Fock and density functional theory calculations

The optimised molecular structures, vibrational frequencies and corresponding vibrational assignments of the cis and trans conformers of 2-, 3- and 4-pyridine carboxaldehydes have been calculated using ab initio Hartree-Fock (HF) and density functional theory (B3LYP) methods with 6-311++G(d, p) basis set. The calculations were adapted to the C(S) symmetries of all the molecules. The mean vibrational deviations between the vibrational frequency values of the two conformers of all the compounds have been seen to increase while the relative energies increase and it was concluded the more different the molecular structure of the two conformers is the higher the relative energy is between them, and thus a bigger mean vibrational deviation.     

共轭CN与非共轭CF3吸电子取代基对PPV类衍生物分子结构及光电性质的影响

运用密度泛函DFT B3LYP／6-31G(d)方法对CN和CF3吸电子基团取代的PPV类衍生物的三聚体进行了几何构型优化,并采用含时密度泛函TD-DFT、B3LYP／6-31G(d)方法计算了其相应化合物的紫外吸收光谱．通过对CN和CF3取代的PPV类衍生物的分子几何结构、前线分子轨道能级、电子云分布规律的分析,从理论上解释了共轭CN与非共轭CF3吸电子取代基对其光谱性质影响的差异：前者使相应PPV类衍生物的吸收光谱发生红移,后者则发生蓝移．计算结果还表明用TD-DFT方法计算该体系的紫外吸收光谱值与实验数据吻合得很好;另外引入CN和CF3基团之后,使其相应的PPV衍生物的LUMO能级降低,电子亲合势增加,都是很好的电子传输材料．