Natural Bond Orbital Theory Research Articles

Study of the Torquoselectivity of a Set of Unusual Ring‐Opening Electrocyclic Reactions: Determination of the Electronic Bonding Structure Through the Methodologies of Natural Bond Orbital Analysis and Quantum Theory of Atoms in Molecules, and Analysis of the Electronic Reaction Mechanism Through Bond Reactivity Descriptors

ABSTRACTIn this work, we have studied the torquoselectivity of a set of unusual ring‐opening electrocyclic reactions that have not been successfully rationalized using models based on orbital symmetry nor have they been explained by steric hindrance. Firstly, the corresponding transition states have been obtained, and it has been verified that the intrinsic reaction coordinates associated with these transition states are consistent with the reactants and products of the reactions studied. This has allowed us to theoretically calculate the reaction barriers (with their corresponding thermal corrections) and compare them with the corresponding experimental values. In a second step, we have analyzed the electronic bonding structure using the methodologies of Natural Bond Orbital Analysis and Quantum Theory of Atoms in Molecules, searching for interactions that may significantly stabilize the transition states. Finally, we have analyzed the reactivity using a recent model that has allowed us to calculate the corresponding bond reactivity descriptors.

Theoretical Study of the Effects of Different Coordination Atoms (O/S/N) on Crystal Structure, Stability, and Protein/DNA Binding of Ni(II) Complexes with Pyridoxal-Semi, Thiosemi, and Isothiosemicarbazone Ligand Systems

Nickel transition metal complexes have shown various biological activities that depend on the ligands and geometry. In this contribution, six Ni(II) nitrate complexes with pyridoxal-semi, thiosemi, and isothiosemicarbazone ligands were examined using theoretical chemistry methods. The structures of three previously reported complexes ([Ni(PLSC)(H2O)3]∙2NO3−, [Ni(PLTSC)2] ∙2NO3−∙H2O, and [Ni(PLITSC)(H2O)3]∙2NO3−) were investigated based on Hirshfeld surface analysis, and the most important stabilization interactions in the crystal structures were outlined. These structures were optimized at the B3LYP/6-311++G(d,p)(H,C,N,O,(S))/LanL2DZ(Ni) level of theory, and the applicability was checked by comparing theoretical and experimental bond lengths and angles. The same level of theory was applied for the optimization of three additional structures, ([Ni(PLSC)2]2+, [Ni(PLTSC)(H2O)3]2+, and [Ni(PLITSC)2]2+). The interactions between selected ligands and Ni(II) were examined using the Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) approaches. Particular emphasis was placed on interactions between oxygen, sulfur, and nitrogen donor atoms and Ni(II). Human Serum Albumin (HSA) and the DNA-binding properties of these complex cations were assessed using molecular docking simulations. The presence of water molecules and various substituents in the thermodynamics of the processes was demonstrated. The results showed significant effects of structural parameters on the stability and reactivity towards important biomolecules.

Study of chemical reactivity and molecular interactions of the hydrochlorothiazide-4-aminobenzoic acid cocrystal using spectroscopic and quantum chemical approaches

In this study, the molecular, electronic, and chemical properties of the drug hydrochlorothiazide (HCTZ) are determined after cocrystallization with 4-aminobenzoic acid (4-ABA). Analysis has been performed to understand how those variations lead to alteration of physical properties and chemical reactivity in the cocrystal HCTZ-4ABA. IR and Raman characterizations were performed along with quantum chemical calculations. A theoretical investigation of hydrogen bonding interactions in HCTZ-4ABA has been conducted using two functionals: B3LYP and wB97X-D. The results obtained by B3LYP and wB97X-D are compared which leads to the conclusion that B3LYP is the best applied function (density functional theory) to obtain suitable results for spectroscopy. The chemical reactivity descriptors are used to understand various aspects of pharmaceutical properties. Natural bond orbital (NBO) analysis and quantum theory of atoms (QTAIM) are used to analyze nature and strength of hydrogen bonding in HCTZ-4ABA. QTAIM analyzed moderate role of hydrogen bonding interactions in HCTZ-4ABA. The calculated HOMO-LUMO energy gap shows that HCTZ-4ABA is chemically more active than HCTZ drug. These chemical parameters suggest that HCTZ-4ABA is chemically more reactive and softer than HCTZ. The results of this study suggest that cocrystals can be a good alternative for enhancing physicochemical properties of a drug without altering its therapeutic properties.

The Perfluoro-o-phenylene-mercury Trimer [Hg(o-C6F4)]3 - a Textbook Example of Phase-Dependent Structural Differences.

The geometric and electronic structure of [Hg(o-C6F4)]3 (1) in the gas phase, i. e. free of intermolecular interactions, was determined by a synchronous gas-phase electron diffraction/mass spectrometry experiment (GED/MS), complemented by quantum chemical calculations. 1 is stable up to 498 K and the gas phase contains a single molecular form: the trimer [Hg(o-C6F4)]3. It has a planar structure of D3h symmetry with a Hg-C distance of 2.075(5) Å and a Hg-Hg distance of 3.614(7) Å (both rh1). Structural differences between the crystalline and gaseous state have been analyzed. Different DFT functional-basis combinations were tested, demonstrating the importance to consider the relativistic effects of the mercury atoms. The combination PBE0/MWB(Hg),cc-pVTZ(C,F) turned out to be the most appropriate for the geometry optimization of such organomercurials. The electronic structure of 1, the nature of the chemical bonding in C-Hg-C fragments and the nature of the Hg⋅⋅⋅Hg interactions have been analyzed in terms of the Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) approaches. The influence of the nature of halogen substitution on the structure of the molecules in the series [Hg(o-C6H4)]3, [Hg(o-C6F4)]3, [Hg(o-C6Cl4)]3, [Hg(o-C6Br4)]3 was also analyzed.

Exploring the structural and electronic characteristics of phenethylamine derivatives: a density functional theory approach

Accurate structure elucidation of biologically active molecules is crucial for designing and developing new drugs, as well as for analyzing their pharmacological activity. In this study, density functional theory calculations are applied to explore the electronic structure and properties of phenethylamine derivatives, including Amphetamine, Methamphetamine, and Methylene Dioxy Methamphetamine(MDMA). The investigation encompasses various aspects such as geometry optimization, vibrational analysis, electronic properties, Molecular Electrostatic Potential analysis, and local and global descriptor analysis. Additionally, the study utilizes Natural Bond Orbital analysis and Quantum Theory of Atoms in Molecules to investigate the chemical bonding and charge density distributions of these compounds. Experimental techniques such as Fourier transform infrared (FT-IR) and Raman spectroscopic analysis are employed in the range of 4000-400 cm-1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$cm^{-1}$$\\end{document} and 4000-50 cm-1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$cm^{-1}$$\\end{document}, respectively. Theoretical vibrational analysis with Potential Energy Distribution(PED) assignments is conducted, and the resulting frequencies are compared to experimental spectral data, revealing good agreement. By correlating various structural parameters with the pharmacological activity of each derivative, computational structure elucidation aids in understanding the unique actions of phenethylamine derivatives. The obtained results offer a comprehensive understanding of the molecular behavior and properties of these drugs, facilitating the development of new drugs and therapies for addiction and related disorders.

Theory guided engineering of zeolite adsorbents for acaricide residue adsorption from the environment.

Zeolites have attracted attention for their potential in adsorbing environmental contaminants. However, contaminants, such as acaricides used extensively in livestock production to control ticks and mites, have received limited exploration regarding their adsorption onto zeolite surfaces. This study aimed to identify the most appropriate zeolite frameworks for the adsorption of acaricide residues, deduce the mechanism underlying the adsorption process, and evaluate the impact of surface modification on the adsorption capabilities of zeolites. Grand Canonical Monte Carlo (GCMC) was used to screen the entire zeolite database to analyze their adsorption properties, where the cloverite zeolite framework (CLO) exhibits the highest adsorption capacity (percentage weight, 54%). Machine learning was employed to rank structural feature importance on adsorption. Density and helium void fraction appeared to be the most important structural features. Thus, engineering these features is of utmost significance in harvesting the desired acaricides. The second step involved engineering the structural and electronic properties of the shortlisted zeolite frameworks via cation substitution with suitable atoms. DFT calculations involving natural bond orbital (NBO) analysis and quantum theory of atoms in molecules (QTAIM) have been done to understand the influence of cation substitution on the electronic structure.

Exploring the Nature of Chemical Bonding between Noble Gases and Hypercoordinate Group 13 Compounds: Beyond Boron.

In this article, we systematically study the stability and chemical bond nature of EH4Ng+ compounds (E = Al-Tl; Ng = He-Rn) at the CCSD(T) and ωB97XD levels of theory. Thermochemical calculations obtained by exploring different dissociation pathways show that these compounds could be stable at low temperatures. In addition, studied compounds have a strong E-Ng bond, which has been characterized using different methodologies such as quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) theory, and natural energy decomposition analysis (NEDA). Results indicate that the nature of the chemical bond is predominantly covalent, especially in the case those including the heavier gases (Ar-Rn), occurring through a charge transfer from the noble gas to the group 13 element. However, the electrostatic contribution is also important in the stabilization of this bond. This study extends the universe of group 13 molecules containing noble gas bonds beyond boron and other elements from the second period.

Quantum Chemical-Based Investigations and Lipophilicity Evaluations on Some Structurally Related Quinazoline Derivatives

This work was chiefly conceived to explore the substituent effects on thermodynamic, electronic and lipophilic characteristics of some quinazoline derivatives (Q1-Q4) from theoretical aspects. The variations caused by methyl, ethyl, chlorine and bromine substituents on the same carbon of the aromatic ring were evaluated with a computational approach. In accordance with this purpose, simultaneously, DFT-based calculations were performed for vacuum and two different surroundings (DMSO and water) on methaqualone (Q1), etaqualone (Q2), mecloqualone (Q3), and mebroqualone (Q4) compounds by using the B3LYP functional and 6-311++G(d, p) split-valence triple zeta basis set. The computed thermodynamic quantities revealed that the halogen substitution was more preferable. The effect of substituent modification on electrostatic surface features was evaluated visually by molecular electrostatic potential (MEP) mapping technique. To shed light on the chemical reactivity behaviors of the Q1-Q4, DFT-based reactivity identifiers were computed. Also, the intramolecular interactions affected by substitution were evaluated on the basis of the Natural Bond Orbital (NBO) theory. The NBO results revealed that π-π* interactions predominate for each compound. The lipophilic character analyzes of the mentioned compounds were evaluated both numerically and visually. The data of both methods support each other.

(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand.

The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the "piano stool" type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.

Electronic properties and collision cross sections of AgOkHm± (k, m = 1-4) aerosol ionic clusters.

Experimental evidence shows that hydroxylated metal ions are often produced during cluster synthesis by atmospheric pressure spark ablation. In this work, we predict the ground state equilibrium structures of AgOkHm± clusters (k and m = 1-4), which are readily produced when spark ablating Ag, using the coupled cluster with singles and doubles (CCSD) method. The stabilization energy of these clusters is calculated with respect to the dissociation channel having the lowest energy, by accounting perturbative triples corrections to the CCSD method. The interatomic interactions in each of the systems have been investigated using the frontier molecular orbital (FMO), natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) methods. Many of the ground states of these ionic clusters are found to be stable, corroborating experimental observations. We find that clusters having singlet spin states are more stable in terms of dissociation than the clusters that have doublet or triplet spin states. Our calculations also indicate a strong affinity of the ionic and neutral Ag atom towards water and hydroxyl radicals or ions. Many 3-center, 4-electron (3c/4e) hyperbonds giving rise to more than one resonance structure are identified primarily for the anionic clusters. The QTAIM analysis shows that the O-H and O-Ag bonds in the clusters of both polarities are respectively covalent and ionic. The FMO analysis indicates that the anionic clusters are more reactive than the cationic ones. Using the cluster structures predicted by the CCSD method, we calculate the collision cross sections of the AgOkHm± family, with k and m ranging from 1 to 4, by the trajectory method. In turn, we predict the electrical mobilities of these clusters when suspended in helium at atmospheric pressure and compare them with experimental measurements.

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors.

Halogen bonding permeates many areas of chemistry. A wide range of halogen-bond donors including neutral, cationic, monovalent, and hypervalent have been developed and studied. In this work we used density functional theory (DFT), natural bond orbital (NBO) theory, and quantum theory of atoms in molecules (QTAIM) to analyze aryl halogen-bond donors that are neutral, cationic, monovalent and hypervalent and in each series we include the halogens Cl, Br, I, and At. Within this diverse set of halogen-bond donors, we have found trends that relate halogen bond length with the van der Waals radii of the halogen and the non-covalent or partial covalency of the halogen bond. We have also developed a model to calculate ΔG of halogen-bond formation by the linear combination of the % p-orbital character on the halogen and energy of the σ-hole on the halogen-bond donor.

Synthesis, Characterizations, and Quantum Chemical Investigations on Imidazo[1,2-a]pyrimidine-Schiff Base Derivative: (E)-2-Phenyl-N-(thiophen-2-ylmethylene)imidazo[1,2-a]pyrimidin-3-amine.

In this study, (E)-2-phenyl-N-(thiophen-2-ylmethylene)imidazo[1,2-a]pyrimidin-3-amine (3) is synthesized, and detailed spectral characterizations using 1H NMR, 13C NMR, mass, and Fourier transform infrared (FT-IR) spectroscopy were performed. The optimized geometry was computed using the density functional theory method at the B3LYP/6-311++G(d,p) basis set. The theoretical FT-IR and NMR (1H and 13C) analysis are agreed to validate the structural assignment made for (3). Frontier molecular orbitals, molecular electrostatic potential, Mulliken atomic charge, electron localization function, localized orbital locator, natural bond orbital, nonlinear optical, Fukui functions, and quantum theory of atoms in molecules analyses are undertaken and meticulously interpreted, providing profound insights into the molecular nature and behaviors. In addition, ADMET and drug-likeness studies were carried out and investigated. Furthermore, molecular docking and molecular dynamics simulations have been studied, indicating that this is an ideal molecule to develop as a potential vascular endothelial growth factor receptor-2 inhibitor.

Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes.

Pyridoxylidene-aminoguanidine (PLAG) and its transition metal complexes are biologically active compounds with interesting properties. In this contribution, three new metal-PLAG complexes, Zn(PLAG)(SO4)(H2O)].∙H2O (Zn-PLAG), [Co(PLAG)2]SO4∙2H2O (Co-PLAG), and [Fe(PLAG)2]SO4∙2H2O) (Fe-PLAG), were synthetized and characterized by the X-ray crystallography. The intermolecular interactions governing the stability of crystal structure were compared to those of Cu(PLAG)(NCS)2 (Cu-PLAG) within Hirshfeld surface analysis. The structures were optimized at B3LYP/6-31+G(d,p)(H,C,N,O,S)/LanL2DZ (Fe,Co,Zn,Cu), and stability was assessed through Natural Bond Orbital Theory and Quantum Theory of Atoms in Molecules. Special emphasis was put on investigating the ligand's stability and reactivity. The binding of these compounds to Bovine and Human serum albumin was investigated by spectrofluorometric titration. The importance of complex geometry and various ligands for protein binding was shown. These results were complemented by the molecular docking study to elucidate the most important interactions. The thermodynamic parameters of the binding process were determined. The binding to DNA, as one of the main pathways in the cell death cycle, was analyzed by molecular docking. The cytotoxicity was determined towards HCT116, A375, MCF-7, and A2780 cell lines. The most active compound was Cu-PLAG due to the presence of PLAG and two thiocyanate ligands.

Effect of α-Substitution on the Reactivity of C(sp3)-H Bonds in Pd0-Catalyzed C-H Arylation.

We report mechanistic studies on the reactivity of different α-substituted C(sp3)-H bonds, -CHnR (R = H, Me, CO2Me, CONMe2, OMe, and Ph, as well as the cyclopropyl and isopropyl derivatives -CH(CH2)2 and -CHMe2) in the context of Pd0-catalyzed C(sp3)-H arylation. Primary kinetic isotope effects, kH/kD, were determined experimentally for R = H (3.2) and Me (3.5), and these, along with the determination of reaction orders and computational studies, indicate rate-limiting C-H activation for all substituents except when R = CO2Me. This last result was confirmed experimentally (kH/kD ∼ 1). A reactivity scale for C(sp3)-H activation was then determined: CH2CO2Me > CH(CH2)2 ≥ CH2CONMe2 > CH3 ≫ CH2Ph > CH2Me > CH2OMe ≫ CHMe2. C-H activation involves AMLA/CMD transition states featuring intramolecular O → H-C H-bonding assisted by C-H → Pd agostic bonding. The "AMLA coefficient", χ, is introduced to quantify the energies associated with these interactions via natural bond orbital 2nd order perturbation theory analysis. Higher barriers correlate with lower χ values, which in turn signal a greater agostic interaction in the transition state. We believe that this reactivity scale and the underlying factors that determine this will be of use for future studies in transition-metal-catalyzed C(sp3)-H activation proceeding via the AMLA/CMD mechanism.

The Electronic Effects of 3-Methoxycarbonylcoumarin Substituents on Spectral, Antioxidant, and Protein Binding Properties.

Coumarin derivatives are a class of compounds with pronounced biological activities that depend primarily on the present substituents. Four 3-methoxycarbonylcoumarin derivatives with substituents of different electron-donating/electron-withdrawing abilities (Br, NO2, OH, and OMe) were investigated structurally by NMR, IR, and UV-VIS spectroscopies and density functional theory methods. The appropriate level of theory (B3LYP-D3BJ/6-311++G(d,p) was selected after comparing similar compounds' experimental and theoretical structural parameters. The natural bond orbital and quantum theory of atoms in molecules were employed to investigate the intramolecular interactions governing stability. The electronic effects of substituents mostly affected the aromatic ring that the substituents are directly attached to. The antioxidant properties were investigated by electron paramagnetic resonance spectroscopy towards HO•, and the percentages of reduction were between 13% (6-Br) and 23% (6-OMe). The protein binding properties towards transport proteins were assessed by spectrofluorimetry, molecular docking, and molecular dynamics (MD). The experimentally determined binding energies were well reproduced by molecular docking, showing that the spontaneity of ibuprofen binding was comparable to the investigated compounds. The flexibility of HSA in MD simulations depended on the substituents. These results proved the importance of electronic effects for the protein binding affinities and antioxidant properties of coumarin derivatives.

Photophysical and nonlinear optical properties of para-substituted nitrobenzofurazan: A comprehensive DFT investigation

We investigate the ability of the 4-chloro-7-nitrobenzofurazan (NBD-Cl) to append Pyrrolidine (Pyrr), a secondary amine, acting as a nucleophile group in SNAr reactions resulting in the fluorescent NBD-Pyrr compound. Their electrochemical and photo-physical responses have been thoroughly investigated using Cyclic Voltammetry (CV), UV–Visible, photoluminescence (cw-PL) and time resolved photoluminescence (TR-PL) spectroscopies. The intra-molecular charge transfer associated to nonlinear optical (NLO) properties of NBD-Pyrr molecule has reported, for the first time. Important NLO parameters such as dipole moment (μ), polarizability (α), anisotropy of polarizability (Δα) and first and second order hyperpolarizabilities (β and γ) are calculated at the B3LYP/6–31 + g(d,p) level of theory as well. Additionally, natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM), Hirshfeld surface (HS), Electron Localization Function (ELF), and Localized orbital locator (LOL) analyses have been used to illustrate structure and bonding in the NBD-Pyrr molecule.

Synthesis, structural and spectral investigations of an optically active E-N′-(3,4-dimethoxybenzylidene)− 4-fluorobenzohydrazide crystal

Hydrazines represent a group of compounds with pronounced pharmacological activities, along with their possible use of optically active materials. In this contribution, E-N′-(3,4-dimethoxybenzylidene)− 4-fluorobenzohydrazide (DBF) was synthesized and chemically characterized by X-ray crystallography, IR, Raman, UV–VIS, and NMR spectroscopies. The intermolecular interactions governing the stability of the crystal were investigated by the Hirshfeld surface analysis. The structure optimization was performed starting from a crystallographic one. The highest resemblance between experimental and theoretical bond lengths and angles was obtained for the structure at M06–2X/6–311 + +G(d,p) level of theory. The Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) analyses outlined the most important intramolecular interactions. The IR and Raman spectra vibrational peaks were assigned based on the Potential Energy Distribution (PED) analysis. Theoretical methods with high correlation factors and low mean absolute error reproduced the NMR chemical shifts. The excited state optimization of DBF with a difference of several nm modelled the peak at 330 nm in the experimental UV–VIS spectrum. The Condensed Fukui functions outlined the most active positions for electrophilic, neutrophilic, and radical attacks. The non-linear optical (NLO) Z-scan experiment determined the absorption coefficient and nonlinear refractive index, concluding that DBF can be used as NLO material. The ECOSAR prediction of toxicity showed that the material could be potentially dangerous for aquatic organisms.

Computational study of inclusion complexes of V-type nerve agents (VE, VG, VM, VR and VX) with β-cyclodextrin

The effective detoxification of organophosphate (OP) nerve agents (OPNAs) is a challenging issue for scientists. The host–guest inclusion complexes of five V-type nerve agents (VE, VG, VM, VR and VX) with β-cyclodextrin (β-CD) have been studied by combining quantum mechanical (QM) calculations and molecular dynamics (MD) simulations. The frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) have been analyzed to describe the reactivity parameters and electronic properties. The obtained results clearly reveal that stable complexes were formed in both vacuum and water media, and the complexation process occurred spontaneously. To understand non-covalent interactions, natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) have been used. IR and Raman spectra have been calculated to confirm the formation of complexes and also thermodynamic parameters have been investigated. It was demonstrated that in addition to van der Waals interactions, the presence of intermolecular hydrogen bonds enhances the stability of these complexes. Furthermore, MD simulations were carried out to get a better insight into the inclusion process of the above complexes. From MD simulations, all simulated systems reached full equilibration at 1000 ps and the V-agent molecules consistently remained in the β-CD cavity and only had vibrational motion inside the cavity. More importantly, MD simulations support the findings of QM calculations and indicate that hydrogen bonding can help the leaving groups of V-agents to be released and them to be hydrolyzed. All results have shown that the VR agent formed the most stable complex with β-CD molecule than that of other agents. Communicated by Ramaswamy H. Sarma

Molecular Structure, Hydrogen Bonding Interactions and Docking Simulations of Nicotinamide (Monomeric and Trimeric Models) by Using Spectroscopy and Theoretical Approach

The present work focuses on the structural properties, spectroscopic signatures, intermolecular hydrogen bonding interactions, chemical and biological activity of nicotinamide (NIC) based on its monomeric and trimeric models using density functional theory and vibrational spectroscopy. FT-IR and FT-Raman spectra were obtained using the double-side forward-backward acquisition mode under vacuum. UV-Vis absorption spectra were recorded in methanol and compared with the calculated values. Geometry optimization and vibrational wavenumbers were obtained with the aid of Gaussian 09 program packages. The structural analysis of NIC revealed that the trimeric model was in better agreement with the experimental values than the monomer due to the incorporation of nearest hydrogen bond interactions. Spectroscopic results showed that NH2 and C = O groups of NIC were involved in intermolecular interactions in the trimeric model. The natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses determined the presence, strength as well as nature of the hydrogen bonds were partially covalent. The lesser value of the HOMO-LUMO energy gap for the trimeric model indicated higher reactivity than monomer. Moreover, chemical reactivity was calculated using molecular electrostatic potential surface (MESP) and reactivity descriptors. The docking studies for NIC with several targets explored its biological activity.

Sulfur-arene interactions: the S⋯π and S-H⋯π interactions in the dimers of benzofuran⋯sulfur dioxide and benzofuran⋯hydrogen sulfide.

Non-covalent interactions between sulfur centers and aromatic rings play important roles in biological chemistry. We examined here the sulfur-arene interactions between the fused aromatic heterocycle benzofuran and two prototype sulfur divalent triatomics (sulfur dioxide and hydrogen sulfide). The weakly-bound adducts were generated in a supersonic jet expansion and characterized with broadband (chirped-pulsed) time-domain microwave spectroscopy. The rotational spectrum confirmed the detection of a single isomer for both heterodimers, consistent with the computational predictions for the global minima. The benzofuran⋯sulfur dioxide dimer exhibits a stacked structure with sulfur closer to benzofuran, while in benzofuran⋯hydrogen sulfide the two S-H bonds are oriented towards the bicycle. These binding topologies are similar to the corresponding benzene adducts, but offer increased interaction energies. The stabilizing interactions are described as S⋯π or S-H⋯π, respectively, using a combination of density-functional theory calculations (dispersion corrected B3LYP and B2PLYP), natural bond orbital theory, energy decomposition and electronic density analysis methods. The two heterodimers present a larger dispersion component, but nearly balanced by electrostatic contributions.