Evidences of noncovalent interactions between indole and dichloromethane under different solvent conditions.

CONTEXT: Theoretical investigation of indole (IND) and its binary combination with dichloromethane (DC) in various solvents were computed to track the impact of molecular interactions on spectral characteristics. When transitioning from plain drug to complexes, different modes of IND display a substantial shift in peak location. The 3561.26 cm-1 band shows (~15.58 cm-1) red shift upon dilution. The geometry in various solvents was calculated using quantum chemical calculation utilizing density functional theory (DFT). The highest ALIE values are located at the indole skeleton and on complexation with DC, and the ring atoms become more electron rich. The atom-centered density matrix propagation (ADMP) molecular dynamic (MD) calculation shows that the geometries optimized through the DFT calculation match the global minima effectively. MD simulations indicate that indole is more stable in water and methanol. METHODS: DFT studies have been employed to study the interaction between indole and dichloromethane. CAM-B3LYP/6-311++G(d)(6D,7F) level of theory was employed using Gaussian 16 W suite. Quantum topological descriptors were discussed using quantum theory of atoms in molecules (QTAIM) with the help of Multiwfn software. Reduced density gradient (RDG) plot describes the nature of the interaction, while average local ionization energy (ALIE) explained the variation in local ionization energy of the molecular surface before and after complexation.

Study of Non-Covalent Interactions Present in the Tapinarof-Ethanol System with Special Emphasis on Hydrogen-Bonding Interactions.

In this study, the effect of non-covalent interaction in the tapinarof-EtOH systems is evaluated, particularly the hydrogen-bonding interaction using density functional theory in a gas phase. From the optimization results and the binding energy calculated thereafter, it is concluded that interaction in the employed system occurs between the O-H groups on tapinarof and the oxygen atom of EtOH molecules existing in the vicinity of the O-H group. These interactions were concluded to be those of the weak hydrogen bonds by carrying out the reduced gradient approach and QTAIM analysis, which are basically electron-density-based topological analyses. The charge localization between the donor-acceptor moieties was analyzed using the NBO analysis. Using the LED analysis, the binding energy between the tapinarof and EtOH was partitioned into different energy terms centered on a domain-based local pair natural orbital coupled cluster method. Thus, the electronic environment of the tapinarof-EtOH systems is evaluated.

Synthesis and Biological Evaluation of Octahydroquinazolinones as Phospholipase A2, and Protease Inhibitors: Experimental and Theoretical Exploration.

Phospholipase A2 (PLA2) promotes inflammation via lipid mediators and releases arachidonic acid (AA), and these enzymes have been found to be elevated in a variety of diseases, including rheumatoid arthritis, sepsis, and atherosclerosis. The mobilization of AA by PLA2 and subsequent synthesis of prostaglandins are regarded as critical events in inflammation. Inflammatory processes may be treated with drugs that inhibit PLA2, thereby blocking the COX and LOX pathways in the AA cascade. To address this issue, we report herein an efficient method for the synthesis of a series of octahydroquinazolinone compounds (4a-h) in the presence of the catalyst Pd-HPW/SiO2 and their phospholipase A2, as well as protease inhibitory activities. Among eight compounds, two of them exhibited overwhelming results against PLA2 and protease. By using FT-IR, Raman, NMR, and mass spectroscopy, two novel compounds were thoroughly studied. After carefully examining the SAR of the investigated compounds against these enzymes, it was found that compounds (4a, 4b) containing both electron-donating and electron-withdrawing groups on the phenyl ring exhibited higher activity than compounds with only one of these groups. DFT studies were employed to study the electronic nature and reactivity properties of the molecules by optimizing at the BLYP/cc-pVDZ. Natural bond orbitals helped to study the various electron delocalizations in the molecules, and the frontier molecular orbitals helped with the reactivity and stability parameters. The nature and extent of the expressed biological activity of the molecule were studied using molecular docking with human non-pancreatic secretory phospholipase A2 (hnps-PLA2) (PDB ID: 1DB4) and protease K (PDB ID: 2PWB). The drug-ability of the molecule has been tested using ADMET, and pharmacodynamics data have been extracted. Both the compounds qualify for ADME properties and follow Lipinski's rule of five.

Adsorption of a thione derivative on carbon, AlN, and BN nanotubes: a detailed DFT and MD investigation.

The performance of nanotubes (NT) of carbon (CC), aluminium-nitrogen (AlN), and boron-nitrogen (BN) as a sensor and nanocarrier for mercaptopurine (MCP) was investigated by means of a theoretical approach. The calculated negative values of adsorption energy showed the interaction and adsorption of MCP. Highest-occupied molecular orbital (HOMO) and lowest-unoccupied molecular orbital (LUMO) distributions were only found on the NT counter portion of the drug-nanotube not on MCP for AlN-NT and BN-NT while HOMO is over MCP and LUMO is over NT for CC-NT. The polarizability of MCP-NTs is greater than that of MCP. Raman wavenumbers of MCP are enhanced in NTs, and hence, NTs can act as a sensor for the detection of MCP. Solvent dependency on adsorption behaviour is also presented in the manuscript, where we found that the AlN nanotube showed exceptionally high free energy of adsorption over other nanotubes in all solvent mediums. Solvation-free energies were also reported. Noncovalent interaction scattered plot also showed significant intermolecular interaction between AlN nanotubes and the mercaptopurine when compared to other nanotubes under study. To find the antiviral activity of MCP and MCP-NTs against antiviral activities, docking and molecular dynamics simulations were performed with 1HMP PDB. Recovery times show that MCP desorption occurs quickly. The MD simulations and docking results show that BN and CC-NTs with MCP show good activity as drug carriers.

Synthesis and investigation of anti-COVID19 ability of ferrocene Schiff base derivatives by quantum chemical and molecular docking.

The recent outbreak of coronavirus disease (COVID-19) has rampaged the world with more than 236 million confirmed cases and over 4.8 million deaths across the world reported by the world health organization (WHO) till Oct 5, 2021. Due to the advent of different variants of coronavirus, there is an urgent need to identify effective drugs and vaccines to combat rapidly spreading virus varieties across the globe. Ferrocene derivatives have attained immense interest as anticancer, antifungal, antibacterial, and antiparasitic drug candidates. However, the ability of ferrocene as anti-COVID-19 is not yet explored. Therefore, in the present work, we have synthesized four new ferrocene Schiff bases (L1-L4) to understand the active sites and biological activity of ferrocene derivatives by employing various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential, and molecular electrostatic potential (MEP). A theoretical insight on synthesized ferrocene Schiff bases was accomplished by molecular docking, frontier molecular orbitals energies, active sites, and molecular descriptors which were further compared with drugs being currently used against COVID-19, i.e., dexamethasone, hydroxychloroquine, favipiravir (FPV), and remdesivir (RDV). Moreover, through the molecular docking approach, we recorded the inhibitions of ferrocene derivatives on core protease (6LU7) protein of SARS-CoV-2 and the effect of substituents on the anti-COVID activity of these synthesized compounds. The computational outcome indicated that L1 has a powerful 6LU7 inhibition of SARS-CoV-2 compared to the currently used drugs. These results could be helpful to design new ferrocene compounds and explore their potential application in the prevention and treatment of SARS-CoV-2.

Evidence of cluster formation of croconic acid with Ag, Au and Cu cages, enhancement of electronic properties and Raman activity.

Investigation of the adsorption properties croconic acid (CCA) with metal clusters (mC: Ag, Au and Cu) are reported using DFT method. CCA is found to form stable cluster with transition metal clusters of copper, silver and gold. The drug-cluster complexaton energy is slightly more for the copper nanocluster-drug complex. Non-covalent interaction analysis indicated that strong interactions and weak van der Waal interaction is present between drug and metal clusters. Dipole moment of the drug-gold cluster is found to be higher than that of the other systems. SERS studies demonstrates improved Raman signals for multiple wavenumbers of all CCA-metal cluster complexes. Mulliken charge analysis show that all CCA oxygen atom's charge changes due to the interactions with the mCs. Clustering of CCA with metal cages enhances the medicinal properties and the metal nanoclusters will act as a drug carrier of CCA.

Energy and reactivity profile and proton affinity analysis of rimegepant with special reference to its potential activity against SARS-CoV-2 virus proteins using molecular dynamics.

Rimegepant is a new medicine developed for the management of chronic headache due to migraine. This manuscript is an attempt to study the various structural, physical, and chemical properties of the molecules. The molecule was optimized using B3LYP functional with 6-311G + (2d,p) basis set. Excited state properties of the compound were studied using CAM-B3LYP functional with same basis sets using IEFPCM model in methanol for the implicit solvent atmosphere. The various electronic descriptors helped to identify the reactivity behavior and stability. The compound is found to possess good nonlinear optical properties in the gas phase. The various intramolecular electronic delocalizations and non-covalent interactions were analyzed and explained. As the compound contain several heterocyclic nitrogen atoms, they have potential proton abstraction features, which was analyzed energetically. The most important result from this study is from the molecular docking analysis which indicates that rimegepant binds irreversibly with three established SARS-CoV-2 proteins with ID 6LU7, 6M03, and 6W63 with docking scores - 9.2988, - 8.3629, and - 9.5421 kcal/mol respectively. Further assessment of docked complexes with molecular dynamics simulations revealed that hydrophobic interactions, water bridges, and π-π interactions play a significant role in stabilizing the ligand within the binding region of respective proteins. MMGBSA-free energies further demonstrated that rimegepant is more stable when complexed with 6LU7 among the selected PDB models. As the pharmacology and pharmacokinetics of this molecule are already established, rimegepant can be considered as an ideal candidate with potential for use in the treatment of COVID patients after clinical studies.

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.

Structural investigations, quantum mechanical studies on proton and metal affinity and biological activity predictions of selpercatinib.

Cancer of the lungs and thyroid is particularly difficult to manage and treat. Notably, selpercatinib has recently been suggested as an effective drug to combat these diseases. The entire world is currently tackling the pandemic caused by the SARS-CoV-19 virus. Numerous pharmaceuticals have been evaluated for the management of the disease caused by SARS-CoV-19 (i.e., COVID-19). In this study, selpercatinib was proposed as a potential inhibitor of different SARS-CoV-19 proteins. Several intriguing effects of the molecule were found during the conducted computational investigations. Selpercatinib could effectively act as a proton sponge and exhibited high proton affinity in solution. Moreover, it was able to form complexes with metal ions in aqueous solutions. Specifically, the compound displayed high affinity towards zinc ions, which are important for the prevention of virus multiplication inside human cells. However, due to their charge, zinc ions are not able to pass the lipid bilayer and enter the cell. Thus, it was determined that selpercatinib could act as an ionophore, effectively transporting active zinc ions into cells. Furthermore, various quantum mechanical analyses, including energy studies, evaluation of the reactivity parameters, examination of the electron localisation and delocalisation properties, as well as assessment of the nonlinear optical (NLO) properties and information entropy, were conducted herein. The performed docking studies (docking scores -9.3169, -9.1002, -8.1853 and -8.1222 kcal mol-1) demonstrated that selpercatinib strongly bound with four isolated SARS-CoV-2 proteins.

Adsorption of the drug bempedoic acid over different 2D/3D nanosurfaces and enhancement of Raman activity enabling ultrasensitive detection: First principle analysis.

The nanocluster-based drug delivery system is of much importance, now days. This manuscript studies the interaction of pristine/substituted/doped GQDs, fullerene, helicene and CNT with bempedoic acid, which is an effective alternative of statins in the treatment of hypercholesteremia. The adsorption energies are calculated at B3LYP-D3/6-311G+(2d,p) level in order to study the adsorption of bempedoic acid over the surfaces of the nanoclusters incorporating Grimme's dispersion correction. Surface enhanced Raman scattering (SERS), which is a sound approach to vibrational spectroscopy, is used in order to detect bempedoic acid. All the studies signify that bempedoic acid can be detected with these nanoclusters and the negative adsorption energies advocate for the possible use of these nanoclusters as effective drug delivery system in case of bempedoic acid. Adsorption energy of bempedoic acid over helicene was found to be the most negative among the mentioned nanocluster systems, while adsorption on the surface of CNT was found to be the least negative.

Excited-state electronic properties, structural studies, noncovalent interactions, and inhibition of the novel severe acute respiratory syndrome coronavirus 2 proteins in Ripretinib by first-principle simulations.

Ripretinib is a recently developed drug for the treatment of adults with advanced gastrointestinal stromal tumors. This paper reports an attempt to study this molecule by electronic modeling and molecular mechanics to determine its composition and other specific chemical features via the density-functional theory (DFT), thereby affording sufficient information on the electronic properties and descriptors that can enable the estimation of its molecular bioactivity. We explored most of the physico-chemical properties of the molecule, as well as its stabilization, via the studies of the natural bond orbitals and noncovalent interactions. The electronic excitation, which is a time-dependent process, was examined by the time-dependent DFT with a CAM-B3LYP functional. The molecular docking study indicated that Ripretinib strongly docks with three known novel severe acute respiratory syndrome coronavirus 2 (SARS-n-CoV-2) proteins with a reasonably good docking score.

Structural study of letrozole and metronidazole and formation of self-assembly with graphene and fullerene with the enhancement of physical, chemical and biological activities.

Letrozole and metronidazole are two commonly used drugs for the management of breast cancer and parasitic infections, respectively. This manuscript attempts to study their structure, geometry, search for stable conformers using relaxed potential energy scan, spectral properties, quantum mechanical properties like energy and reactivity descriptors, intra molecular electron transfer properties, non-linear properties etc using various computational tools. It is found that these compounds will form a self-assembly with graphene sheets and fullerenes and exhibit a surface-enhanced Raman spectra and enhancement in non-linear optical properties when compared to the single molecule. The electronic absorption behavior of the compounds was studied using TD-DFT method. Global chemical reactivity descriptors and activity sites toward electrophilic and nucleophilic attack have been discussed. Studies of intra molecular electron transfer gave information about the relative stability of the compounds. Molecular docking studies indicate that the pure compounds and their self-assemblies with graphene have excellent biological activities.Communicated by Ramaswamy H. Sarma.

Modelling the structural and reactivity landscapes of tucatinib with special reference to its wavefunction-dependent properties and screening for potential antiviral activity.

HER-2 type breast cancer is one of the most aggressive malignancies found in women. Tucatinib is recently developed and approved as a potential medicine to fight this disease. In this manuscript, we present the gross structural features of this compound and its reactivity and wave function properties using computational simulations. Density functional theory was used to optimise the ground state geometry of the molecule and molecular docking was used to predict biological activity. As the electrons interact with electromagnetic radiations, electronic excitations between different energy levels are analysed in detail using time-dependent density functional theory. Various intermolecular and intermolecular interactions are analysed and reaction sites for attacking electrophiles and nucleophiles identified. Information entropy calculations show that the compound is inherently stable. Docking with COVID-19 proteins show docking score of - 9.42, - 8.93, - 8.45 and - 8.32 kcal/mol respectively indicating high interaction between the drug and proteins. Hence, this is an ideal candidate to study repurposing of existing drugs to combat the pandemic.

Spectral analysis and detailed quantum mechanical investigation of some acetanilide analogues and their self-assemblies with graphene and fullerene.

Spectroscopic analysis and different quantum mechanical studies of four pharmaceutically active compounds phenacetin, p-acetanisidide, 4'-butoxyacetanilide, and 4'-(3-chloropropoxy)acetanilide are reported in this manuscript. Simulated IR spectrum of these compounds was compared with experimentally available data, and essential functional group assignments were made. We also report the frontier orbital properties and other derived local energy descriptors which talks about the relative stability and reactivity. Photovoltaic efficiency of the compounds was studied from the simulated electronic spectra. The compound was found to interact with graphene and fullerene, to form molecular self-assembly. These self-assemblies showed tremendous enhancement in various physicochemical properties when compared with its constituents. The nature of the interactions between studied chemical species was discussed with the help of chemical reactivity principles. Biological activity of the compounds was predicted using molecular docking studies. It is interesting to see that on adsorption with a graphene/fullerene surface, all adsorbed complex shows enhancement in the Raman activity giving surface enhanced Raman spectra (SERS). This can be used for the detection of these drugs in a pharmacological or biological sample. Interestingly the graphene/fullerene drug molecular assembly shows enhanced biological activity when compared with individual drug molecules. Graphical abstract.

Structural and physico-chemical evaluation of melatonin and its solution-state excited properties, with emphasis on its binding with novel coronavirus proteins.

Melatonin is a natural hormone from the pineal gland that regulates the sleep-wake cycle. We examined the structure and physico-chemical properties of melatonin using electronic structure methods and molecular-mechanics tools. Density functional theory (DFT) was used to optimise the ground-state geometry of the molecule from frontier molecular orbitals, which were analysed using the B3LYP functional. As its electrons interacted with electromagnetic radiation, electronic excitations between different energy levels were analysed in detail using time-dependent DFT with CAM-B3LYP orbitals. The results provide a wealth of information about melatonin's electronic properties, which will enable the prediction of its bioactivity. Molecular docking studies predict the biological activity of the molecules against the coronavirus2 protein. Excellent docking scores of -7.28, -7.20, and -7.06 kcal/mol indicate that melatonin can help to defend against the viral load in vulnerable populations. Hence it can be investigated as a candidate drug for the management of COVID.

Cocrystals of hydrochlorothiazide with picolinamide, tetramethylpyrazine and piperazine: quantum mechanical studies, docking and modelling of the photovoltaic efficiency for DSSC.

Cocrystals are of immense applications in crystal engineering and pharmaceutical chemistry. Hydrochlorothiazide is found to form cocrystals with picolinamide (H1), tetramethylpyrazine (H2) and piperazine (H3). It was characterized using IR spectra, and quantum mechanical calculations for geometry and other properties. Frontier orbital energies are used to predict the energy properties and model the possible charge transfer between the constituents of the cocrystal. The frontier molecular orbital analysis indicates chemical reactivity and bioactivity of the cocrystals. The MEP surface reveals the various reactive surfaces in the cocrystal system, which is very important in deciding various biological activities. The UV-Vis spectra show the possible electronic transitions of the molecules. Simulated electronic spectra using TDDFT method with CAM-B3LYP functional were used to investigate the suitability of the cocrystals to be used in DSSC. Moreover, the molecular docking analysis proves that the cocrystals can act as potential inhibitors and paves the way for developing effective drugs.

Detailed molecular structure (XRD), conformational search, spectroscopic characterization (IR, Raman, UV, fluorescence), quantum mechanical properties and bioactivity prediction of a pyrrole analogue.

Pyrroles are an exciting class of organic compounds with immense medicinal activities. This manuscript presents the structural and quantum mechanical studies of 1-(2-aminophenyl) pyrrole using X-Ray diffraction and various spectroscopic methods like Infra-Red, Raman, Ultra-violet and Fluorescence spectroscopy and its comparison with theoretical simulations. The single-crystal X-ray diffraction values and optimized geometry parameters also were within the agreeable range. A fully relaxed potential energy scan revealed the stability of the possible conformers of this molecule. We present the density functional theory results and assignment of the vibrational modes in the infrared spectrum. The experimental and scaled simulated vibrations matched when density functional theory simulations (B3LYP functional with 6-311++G∗∗). The electronic spectrum was simulated using time-dependent density functional theory with CAM-B3LYP functional in dimethylsulphoxide solvent. The fluorescence spectrum of the compound was studied at different excitation wavelengths in the dimethylsulphoxide solvent. The stability of the molecule by intramolecular electron transfer by hyperconjugation was studied with the natural bond orbital analysis. Frontier molecular orbitals and molecular electrostatic potentials of the compound gave an idea about the reactive behaviour of the compounds. Prediction of activity spectral studies followed by docking analysis indicated that the molecule is active against arylacetonitrilase inhibitor.

Spectroscopic and TDDFT investigation of highly selective fluoride sensors by substituted acyl hydrazones.

In this work, we report the synthesis of two receptors for fluoride ions based on acyl hydrazone, such as N'-[(1Z)-1-(4-fluorophenyl)ethylidene]benzohydrazide (R1) and N'-[(1Z)-1-(2-hydroxyphenyl)ethylidene]benzohydrazide (R2). The receptors R1 and R2 were synthesized from the corresponding ketones and benzoic acid hydrazide and characterized spectroscopically by UV-visible, IR and 1HNMR techniques. The response of R1 and R2 towards different anions was studied colourimetrically in acetonitrile. The receptors exhibited a specific response towards fluoride ions. Further studies of 1:1 composition of receptors, R1/R2:fluoride ions by different spectroscopic techniques such as UV-Visible, IR and 1HNMR spectroscopy indicated the participation of -NH proton of the receptors in the sensing action through the hydrogen bonding. To understand the mechanism, Time-Dependent Density Functional Theory (TD-DFT) studies were done using the CAM-B3LYP/6311G++ (3df,2p) with Grimme's D3BJ empirical dispersion basis set. The studies supported the role of hydrogen bonding interaction of -NH and-OH protons of the receptors with the fluoride ions.

Exploring the detailed spectroscopic characteristics, chemical and biological activity of two cyanopyrazine-2-carboxamide derivatives using experimental and theoretical tools.

This article represents the spectroscopic and computational studies of two new pyrazine compounds. In order to establish the structure and functional nature of the compounds, we have employed Fourier transformed infrared (FT-IR) and Raman spectra, nuclear magnetic resonance (NMR) spectra, and ultraviolet (UV) absorptions and have compared them with the simulated computational spectra and found that they are in the agreeable range. Simulated hyperpolarisability values are used to obtain the nonlinear optic (NLO) activity of the compound, to be used in organic electronic materials. The charge transfer and related properties was investigated by the simulation of electronic spectrum with time dependent density functional theory (TD-DFT). Natural transition orbitals (NTO) provides information about which region of the molecules are more involved in the electronic transitions and the charge transfer properties for the lowest energy excitation have been analyzed on the basis of electron density variation. Molecular dynamics simulations provide information about the behavior of the molecule in solutions. Frontier orbital analysis and study of various reactivity descriptors like ALIE and Fukui provided deep knowledge on the reactivity side. Molecular docking has been also performed to investigate the interaction between title molecules and exhibits inhibitory activity against Pseudomonas aeruginosa Enoyl-Acyl carrier protein reductase (Fabl).