Local Reactivity Descriptors Research Articles

Theoretical Study of closo-Borate Anions [BnHn]2− (n = 5–12): Bonding, Atomic Charges, and Reactivity Analysis

This study has focused on the structure, bonding, and reactivity analysis of closo-borate anions [BnHn]2− (n = 5–12). Several descriptors of B–H interactions have been calculated. It has been found that the values of electron density and total energy at bond critical point are the most useful descriptors for investigation of B–H interactions. Using results from the descriptor analysis, one may conclude that orbital interactions in [BnHn]2− increase with increasing the boron cluster size. Several approaches to estimate atomic charges have been applied. Boron atoms in apical positions have more negative values of atomic charges as compared with atoms from equatorial positions. The mean values of boron and hydrogen atomic charges tend to be more positive with the increasing of boron cluster size. Global and local reactivity descriptors using conceptual density functional theory (DFT) theory have been calculated. Based on this theory, the closo-borate anions [BnHn]2− (n = 5–9) can be considered strong and moderate electrophiles, while the closo-borate anions [BnHn]2− (n = 10–12) can be considered marginal electrophiles. Fukui functions for electrophilic attack have been calculated. Fukui functions correlate well with atomic charges of the closo-borate anions. Boron atoms in apical positions have the most positive values of Fukui functions.

Elucidating the therapeutic activity of selective curcumin analogues: DFT-based reactivity analysis

Density functional theory (DFT) has been employed to study the structure, stability and reactivity of curcumin and some of its important analogues by computing HOMO-LUMO energy gap (H-L gap), ionization potential (IP), electron affinity (EA), chemical potential (μ), chemical hardness (η), electrophilicity index (ω) and density of states (DOS). In this study, curcumin is found to be more reactive in dimethyl sulfoxide (DMSO) solvent than in the gas phase in both of its enol and keto isomeric forms. Next, reactivities of the keto-based curcumin analogues are found to follow the order of 1,5-bis(3,4-dimethoxyphenyl)penta-1,4-dien-3-one (GO-035) > 1,5-bis(3,4,5-trimethoxyphenyl)penta-1,4-dien-3-one (GO-Y016) > 1,5-bis[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one (GO-Y031) > 1,5-bis[3,5-dimethoxy-4-(methoxymethoxy)phenyl]penta-1,4-dien-3-one (GO-Y030) > dibenzalacetone (DBA) in both gas and DMSO solvent phases. However, there is enhancement in reactivities of the complexes in DMSO solvent from those in the gas phase. The reactivity order is observed on the basis of H-L gap, IP, μ, η and DOS analyses. Moreover, GO-Y030, GO-Y031 and DBA possess similar electrophilic behaviours as indicated by their comparable EA and ω values, while GO-Y016 and GO-035 behave as the strongest and the weakest electrophiles. Furthermore, the nature of the reactive sites in the curcumin analogues has been identified via local reactivity descriptors and the molecular electrostatic potential (MEP) maps, results of which are consistent with the molecular orbital analyses.

Flavonoid content of the Libyan Onosma Cyrenaicum: isolation, identification, electronic chemical reactivity, drug likeness, docking, and MD study

In this work, an attempt to identify the flavonoid content of the Libyan Onosma Cyrenaicum led to the isolation of three flavonoids 7,8-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one(GE-001), 5,7-dihydroxy-2-(3-hydroxy-4-methoxy phenyl)-4H-chromen-4-one (GE-002) and 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one (GE-003), the isolated compounds were characterized using 1H and 13C-NMR techniques. A further DFT study at ωB97-XD with 6-311++G** basis set in water was conducted to calculate the isolated compounds’ global and local reactivity descriptors and Fukui indices along with their antioxidant activity. The drug-likeness and bioactivity properties of the isolated compounds were estimated and discussed. Finally, GE-001, GE-002, and GE-003 were docked into HCV NS5B polymerase active siteand this was followed by molecular dynamic simulation to certify the obtained docking result and to obtain the MM-GBSA free binding energyy of the isolated compounds. Communicated by Ramaswamy H. Sarma

Growth, spectral, optical, electrical and computational analysis of sodium oxalate single crystals

Single crystals of Sodium Oxalate (SO) were grown by adopting the slow evaporation solution growth approach from aqueous solution. The prominent functional groups seen in the SO crystal were distinctly detected with Fourier transform infrared and FT-Raman spectral analysis. The cut-off wavelength of 230 nm was measured using Ultraviolet -visible spectral analysis. Theoretical quantum chemical computations were done by DFT using Gaussian software package. The different properties such as structural, vibrational and electronic properties of SO was studied at the B3LYP/LanL2DZ level. The chemical activity of SO molecule was revealed by HOMO-LUMO energies. From Topology analysis the chemical significance of the molecules has been enunciated. The electron density centered on local reactivity descriptors like Mulliken atomic charges and Fukui function were calculated to describe the chemical reactivity of the SO compound. The mechanical property of the grown crystal was disclosed from Vicker's micro hardness test carried out on the grown SO crystals and the test confirms the soft nature of the crystal. The dielectric behavior of SO crystal was completely investigated for different temperatures and the activation energies were calculated for different frequencies.

Probing the structural properties, binding mode and intermolecular interactions of herbacetin against H1N1 neuraminidase using vibrational spectroscopic, quantum chemical calculation and molecular docking studies

Herbacetin (HBN) is an antiviral agent of H1N1 influenza virus which was reported to inhibit H1N1 neuraminidase (NA) enzyme with IC50 value of 8.9 μM. The research exploration for HBN was conducted via quantum chemical calculations and spectroscopic techniques. The experimental vibrational FT-IR and FT-Raman spectra of the HBN molecule were obtained, and it was compared with theoretical method utilizing quantum chemical calculations through DFT approach employing basis sets 6-31G(d,p) and 6-311G(d,p). The MEP, NBO, global and local reactivity descriptors were carried out to describe the reactivity, selectivity and stabilization of the HBN molecule. The electronic characteristics namely UV-Vis and HOMO-LUMO were computed through TD-DFT method which was correlated with experimental spectral analysis. The total, partial and overlap population density of states (DOS) were carried out to confirm the molecular orbital contributions. The drug likeness and ADMET predictions were analysed to reveal the biological behaviour of the HBN. Furthermore, the molecular docking investigation is to find the best fit orientation: binding mode, inhibition constant and intermolecular interactions among HBN and NA enzyme. The ligand molecule fits very well in the NA active site cavity. Hence, the HBN molecule exhibits good biological activity, and it can be served as a prospective drug for H1N1 influenza A virus.

Reactivity Dynamics.

The chemical reactivity of a molecule as a whole or of an atom in a molecule varies during a chemical reaction. A variation of global and local reactivity descriptors in the course of a physicochemical process was studied within a quantum fluid density functional theory framework. Effects of a physical confinement and the electronic excitation therein were studied. In this Perspective, we also highlight the direction of a spontaneous chemical reaction in the light of the dynamical variants of the conceptual density functional theory-based electronic structure principles. An exhaustive state-of-the-art dynamical study is warranted in order to understand a chemical reaction from a reactivity perspective augmenting the associated molecular reaction dynamics analysis.

Spectroscopic Investigations and DFT Studies of Synthesized 4- Acetamidophenyl 3,4,5-Trimethoxybenzoate and 4-acetyl phenyl 3,4,5- trimethoxybenzoate a Novel Conjugate of Gallic Acid

Gallic acid is abundantly found in amla (Phyllanthus emblica), a deciduous of the family phyllanthaceae. Gallic acid, the major constituent of the plant, was methylated to 3,4,5 trimethoxy gallic acid, which then underwent steglich esterification first with paracetamol and then with 4-hydroxy acetophenone to yield 4-acetamidophenyl 3,4,5-trimethoxybenzoate and 4-acetyl phenyl 3,4,5-trimethoxybenzoate “respectively”. 1H NMR, 13C NMR, UV, FT-IR and mass spectroscopy were used to characterize the synthesized compounds. Density functional theory (B3YLP) using a 6-31G (d,p) basis set has been used for quantum chemical calculations. AIM (Atom in a molecule) approach depicted weak molecular interactions within the molecules, whereas the reactive site and reactivity within the molecule were examined by global and local reactivity descriptors. The HOMO and LUMO energies and frontier orbital energy gaps were calculated by time dependent DFT approach using the IEFPCM model. A small value for the HOMO-LUMO energy gap indicated that easier charge transfer occurs within compound 4. The nucleophilic and electrophilic reactivity was determined by MEP (molecular electrostatic potential) experiment. Polarizability, dipole moment, and first hyperpolarizability values were calculated to depict the NLO (nonlinear optical) property of both the synthesized compounds. The antimicrobial activity was also carried out and broad-spectrum antibacterial activity against several strains of bacteria and certain unicellular fungi were exhibited by synthesized compound 3.

Design, synthesis, antibacterial evaluation, molecular docking and computational study of 4-alkoxy/aryloxyphenyl cyclopropyl methane oxime derivatives

A series of new 4-alkoxy/aryloxyphenyl cyclopropyl methane oxime derivatives 2(a–k) were synthesized and fully characterized by FT-IR, 1H-NMR, 13C-NMR and Mass spectrometry techniques. All the synthesized compounds 2(a–k) were assayed for in vitro antibacterial activity against a selected bacterial strain and the compound (2 h) and (2k) exerted excellent activity against Staphylococcus aureus, Escherichia coli and Salmonella typhi strains. The potency of inhibitors and possible interaction mechanism of synthetic oxime (2k) with 1GQN enzyme on Salmonella typhi was explored by molecular docking method. Amongst the all synthesized compounds, the quantum chemical calculations were done for Cyclopropyl(4-(pyridin-3-ylmethoxy)phenyl)methanone oxime (2k). The first hyperpolarizability calculation performed in different solvent such as CHCl3, CH2Cl2 and DMSO and compared to the reference compound urea. In addition, natural bond orbital analysis (NBO), local reactivity descriptors, thermodynamic properties, Mulliken charges, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were explored using theoretical calculations.

Molecular interactions and vibrational properties of ricobendazole: Insights from quantum chemical calculation and spectroscopic methods

The structural, spectroscopic (FT-IR and FT-Raman), and physicochemical properties of ricobendazole (RBZ) has been presented with the help of combined experimental and computational approaches. A comparison between the observed and simulated spectra show good agreement with each other. The conformational analysis was performed around eight flexible bonds to predict the most stable conformers, by employing density functional theory (DFT) at B3LYP/6–311++G(d,p) level. The chemical reactivity has been demonstrated in terms of frontier molecular orbitals (HOMO-LUMO) energy gap, molecular electrostatic potential (MEP) surface, and global reactivity. The local reactivity descriptors explored an idea about the donor/acceptor/free radical reactive sites present in the molecule. Natural bond orbital (NBO) analysis was performed to study the interactions between bonding and antibonding orbitals. The intramolecular hydrogen bonding interactions were demonstrated using QTAIM theory. Binding sites against three targets such as Poly [ADP-ribose] polymerase-1, MAP kinase p38 alpha, and Adenosine A2a receptor were identified by molecular docking analysis as RBZ is believed to inhibit against them.

QSAR Classification of Anticancer Heterocyclichydrazones With Reactivity Descriptors

In this study, validated PLS-DA models that discriminate heterocyclichydrazones with potent anticancer activity (GI50/IC50<50x10-6M) from those with low activity (GI50/IC50>=50x10-6M) against the cancer cell lines HCT-116 (colon), OVCAR-8 (human ovary), HL-60 (leukemia), and SF-295 (glioblastoma) were developed. A dataset of 24-a-(N)-heterocyclichydrazones and 14 N-acylhydrazonyl-thienyl and various global and local reactivity descriptors were used for modeling. The best models classified for training and test sets with an accuracy range between 67-100%, a class specificity and sensitivity range between 71-100%, error rate range between 0-0.27, and non-error rate range between 0.73-1.0. An external set of 20 compounds was predicted and the models showed which new compounds are not suggested for further biological investigation. The molecular properties with impact on the modeled endpoints show that the antitumor activity can be improved with electron-acceptor N-acylhydrazonyl-thienyl derivatives and a-(N)-heterocyclichydrazones with moderate electron-donating character.

Conformational analysis and DFT investigations of two triazole derivatives and its halogenated substitution by using spectroscopy, AIM and Molecular docking

Abstract 4-[(E)-(4-Hydroxybenzylidene)amino]-3-(4-chlorobenzyl)-1H-1,2,4-triazole-5(4H) -thione (HTH) and 4-[(E)-(4-Hydroxybenzylidene)amino]-3-(2-chlorobenzyl)-1H-1,2,4-triazole-5(4H)-thione (HAC) were synthesized and characterized using spectral analysis. The fundamental structural aspects of these derivatives have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity and molecular docking analysis. The most stable minimum energy conformer of the title molecules was identified by potential energy surface scan along the rotational bonds. QTAIM study has also been performed to investigate the nature and strength of hydrogen bonding interactions. Halogen substitution on the phenyl ring at different position's are studied. Accordingly global and local chemical reactivity descriptors were investigated. Docking predicts inhibitory activity against tuberculosis and prediction of new anti-TB drug possibility.

Elaborated molecular structure, molecular docking and vibrational spectroscopic investigation of N-((4-aminophenyl)sulfonyl)benzamide with Density functional theory

Abstract The molecule N-((4-aminophenyl)sulfonyl)benzamide was optimized by making use of density functional theory (DFT) with 6-311++G(d,p) basis set. The vibrational frequency and potential energy distribution (PED) of the title compound were calculated and compared with experimental calculations. By using DFT method, the reactivity nature of the molecule was characterized, like as Local reactivity descriptor, Natural bond orbital with a basis set of 6-311++G(d,p), Frontier molecular orbital (FMOs), etc. The electronic properties for HOMO-LUMO, UV-Vis and MEP maps were contemplated by IEFPCM model with various solvation impacts which depends on TD-DFT ((B3LYP for HOMO-LUMO, MEP and M062X for UV)/6-311++G(d,p)) strategies. The Molecular docking analysis reveals the inhibitory nature of title molecule with Aspergillus Niger a fungal protein, SARS CoV-1 and SARS CoV-2 viral proteins. Hence, the present study reveals that the title compound has structural behavior and bioactive (antifungal and antiviral) nature.

Synthesis and spectral analysis of (S)-7-(4-chlorophenyl)-6,7-dihydrothiazolo [4,5-d]pyrimidine-2,5(3H,4H)-dione and study of its quantum chemical properties

In this article, synthesis and quantum chemical properties of novel (S)-7-(4-chlorophenyl)-6,7-dihydrothiazolo[4,5-d]pyrimidine-2,5(3H,4H)-dione (CPTHZ) are described. The aim of this synthesis was to obtain biologically active thiazolidinone scaffolds and correlates its quantum chemical properties with its experimental results. The structure of the compound was characterized by using different spectral analysis. The chemical calculations were computed with the help of DFT level of theory using Becke3–Lee–Yang–Parr (B3LYP)) and Coulomb–Attenuated–Method–Becke3–Lee–Yang–Parr (CAM-B3LYP)/6-31G(d,p) basis set. Thermodynamic properties were calculated at diverse temperatures. Various structural and thermodynamic parameters such as electrophilicity, chemical potential, chemical hardness and maximum amount of electronic charge transfer were done for this compound. The local reactivity descriptors showed that most reactive site for nucleophilic attack was C(7). In addition to it, correlation graphs between experimental and calculated values of 1 HNMR and 13 CNMR were also presented

KID Procedure Applied on the [(PY5Me2)MoO]+ Complex.

The KID (Koopmans in DFT) protocol usually applies in organic molecules of the closed-shell type. We used the KID procedure on an open-shell Mo-based system for the first time to choose the most suitable density functional to compute global and local reactivity descriptors obtained from the conceptual density-functional theory (DFT). From a set of 18 density functionals, spread from the second until the fourth rung of Jacob’s ladder: BLYP, BP86, B97-D, MN12-L, MN15-L, M06-L, M11-L, CAM-B3LYP, PBE0, B3LYP, N12-SX, M06-2X, MN15, MN12-SX, ωB97X-D, M11, LC-ωHPBE, and APFD, we concluded that CAM-B3LYP provides the best outcome, and in the second place, M06-2X. Because the vertical first ionization potential and vertical first electron affinity in the ground state (gs) are defined as follows I = Egs(N – 1) – Egs(N) and A = Egs(N) – Egs(N + 1), where Egs(N – 1), Egs(N), and Egs(N + 1) correspond to energies of the system bearing N, N + 1, and N – 1 electrons, along with Koopmans’ theorem (KT) given by I ≈ −εHOMO (εHOMO, highest occupied molecular orbital energy) and A ≈ −εLUMO (εLUMO, lowest unoccupied molecular orbital energy), the deviation from the KT was performed by the use of the index, such that JI = |Egs(N – 1) – Egs(N) + εHOMO| and JA = |Egs(N) – Egs(N + 1) + εLUMO|, which are absolute deviations from the perspective of I and A, respectively. Furthermore, the εSOMO (SOMO: singly-occupied molecular orbital energy) leads us to another index given by |ΔSL| = |εSOMO – εLUMO|. Therefore, JHL and |ΔSL| are indexes defined to evaluate the quality of the KT when employed within the context of quantum chemical calculations based on DFT and not the Hartree–Fock theory. We propose the index that could be more suitable to choose the most proper density functional because the JHL and |ΔSL| are independent indexes.

Conformational analysis and quantum descriptors of two bifonazole derivatives of immense anti-tuber potential by using vibrational spectroscopy and molecular docking studies

1-[([1,1I-Biphenyl]-4-yl](phenyl)methyl]-1H-imidazolium-2,5-dichloro-3,6-dihydroxy-cyclohexa-2,5-diene-1,4-dione (BCAA) and 1-[([1,1I-Biphenyl]-4-yl](phenyl)methyl]-1H-imidazolium-4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile (BDDQ) were synthesized and characterized using spectral analysis. The fundamental structural aspects of these derivatives have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, and molecular docking analysis. The most stable minimum energy conformer of the title molecules was identified by potential energy surface scan along the rotational bonds. Accordingly, global and local chemical reactivity descriptors were investigated. The wavenumber downshift of different modes is noted. Title molecules exhibit inhibitory activity against different receptors.

Unifying Conceptual Density Functional and Valence Bond Theory: The Hardness-Softness Conundrum Associated with Protonation Reactions and Uncovering Complementary Reactivity Modes.

In this study, we address the long-standing issue—arising prominently from conceptual density functional theory (CDFT)—of the relative importance of electrostatic, i.e., “hard–hard”, versus spin-pairing, i.e., “soft–soft”, interactions in determining regiochemical preferences. We do so from a valence bond (VB) perspective and demonstrate that VB theory readily enables a clear-cut resolution of both of these contributions to the bond formation/breaking process. Our calculations indicate that appropriate local reactivity descriptors can be used to gauge the magnitude of both interactions individually, e.g., Fukui functions or HOMO/LUMO orbitals for the spin-pairing/(frontier) orbital interactions and molecular electrostatic potentials (and/or partial charges) for the electrostatic interactions. In contrast to previous reports, we find that protonation reactions cannot generally be classified as either charge- or frontier orbital-controlled; instead, our results indicate that these two bonding contributions generally interplay in more subtle patterns, only giving the impression of a clear-cut dichotomy. Finally, we demonstrate that important covalent, i.e., spin pairing, reactivity modes can be missed when only a single spin-pairing/orbital interaction descriptor is considered. This study constitutes an important step in the unification of CDFT and VB theory.

Spectroscopic investigations, quantum chemical calculations and molecular docking studies of Mangiferin - an anti-viral agent of H1N1 Influenza virus

Abstract Mangiferin (MFN) is an anti-viral agent of H1N1 influenza virus which was reported to inhibit H1N1 neuraminidase (NA) enzyme with IC50 value of 0.82 μM. The MFN molecule was optimized using DFT method employing 6-31G(d,p) and 6-311G(d,p) basis sets. The experimental FT-IR and FT-Raman were performed for MFN molecule and compared with theoretical value. The MEP, NBO, global and local reactivity descriptors were used to describe the reactivity, selectivity and stability of MFN molecule. The electronic properties like UV-Vis absorption spectra and HOMO-LUMO band gap energy values were computed through TD-DFT approach. The biological activity of lead molecule was examined with the help of drug-likeness and ADMET predictions. A molecular docking investigation was carried out to interpret the binding mode and intermolecular interactions of MFN molecule in the active site of H1N1 NA enzyme. MFN molecule exhibits good biological activity and the observed results are exempt to helpful in drug design.

Chemical reactivity of the ionic liquid tris(2-amino-1,3-thiazolium) hydrogen sulfate sulfate monohydrate (TAHSSM) and surface effects in the TAHSSM/α-Al2O3 system

The chemical reactivity of the ionic liquid tris(2-amino-1,3-thiazolium) hydrogen sulfate sulfate monohydrate (TAHSSM) and its surface interaction with α-Al2O3 support are studied experimentally and theoretically in the current paper. To analyze the chemical reactivity of TAHSSM, molecular electrostatic potential surface, natural charge population analysis, global and local reactivity descriptors are used. A combination of vibrational (FT-IR) and electronic absorption (UV–vis) spectroscopies is applied for investigation the surface effects in TAHSSM/α-Al2O3. The results are connected with the possibility TAHSSM to be used as a catalyst under homogeneous and heterogeneous conditions. It is found that the chemical reactivity of the title compound depends mainly on the SO42− and [HSO4]− fragments. These and the 2-aminothiazolium moieties are involved in the surface interactions between TAHSSM and α-Al2O3. The experimentally registered vibrational modes and absorption wavelengths are compared with the corresponding calculated ones. As a consequence, a good correlation is distinguished. Results revealed that both the vibrational frequencies and the electronic transitions in the supported ionic liquid are notably affected by the observed surface interactions. TAHSSM and TAHSSM/α-Al2O3 samples were referred as promising acid catalytic systems.

Theoretical study of structural effects on reactivity and stability of isomeric pyrano-, thiopyrano-, and selenopyranopyrroles

In this study, global and local DFT reactivity descriptors for isomeric pyrano-, thiopyrano- and selenopyranopyrroles have been calculated. The geometric optimization of the obtained structures was realized with the density functional theory (DFT, B3LYP) at the level of 6-31G(d) and show these isomers have planar configurations. The structural properties such as dipole moments, bond lengths and bond angles of these isomers were calculated. The heats of formation have also been calculated based on the optimized geometry. The energies of HOMO and LUMO molecular orbitals are used to determine several global descriptors as a measure of their electronic properties, relative stabilities and chemical reactivities. These include total energy (E), ionization potential (I), electron affinity (A), chemical hardness (η), chemical softness (S), electronic chemical potentials (μ) and electrophilicity (ω). Selenopyrano[2,3-c]pyrrole possesses the highest electrophilicity and minimum chemical hardness among the calculated isomeric structures. The largest calculated dipole moment belongs to pyrano[3,2-b]pyrrole, while thiopyrano[3,4-b]pyrrole has the lowest.

Microwave-assisted synthesis, biological assessment, and molecular modeling of aza-heterocycles: Potential inhibitory capacity of cholinergic enzymes to Alzheimer's disease

A highly regioselective solvent-free microwave-assisted synthesis of pyrazoles and tetrahydroindazoles based on the condensation of 1,3-diketones with arylhydrazines is described. Compounds were evaluated as cholinesterase inhibitors in order to identify an alternative treatment for Alzheimer's disease. All compounds displayed moderated acetylcholinesterase inhibitory activity and most of the compounds displayed remarkable butyrylcholinesterase inhibitory activity and selectivity. The compounds 3y and 3i with IC50 of 1.65 and 3.59 µM, respectively, were the most active and selective compounds as butyrylcholinesterase inhibitors. Likewise, the compounds were tested as antioxidants agents, results showed that they have the ability to trap free-radicals. Molecular Docking studies showed a key π-π stacking interaction of most of the compounds with residue Trp82 within of butyrylcholinesterase active site. Molecular quantum similarity field, global and local reactivity descriptors, and the Fukui functions were calculated in the Density Functional Theory framework to analyze the reactivity patterns along with the molecular set.