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Tea is a very important source of the terepenoid [Formula: see text]-ionone, which is much appreciated as a medicinal beverage. Schiff bases are a very important class of organic compounds usually formed by the condensation of carbonyl compounds with amines. [Formula: see text]-ionone is a carbonyl terpenoid obtained from Schiff bases on condensation with nucleobases like adenine and cytosine and the amino acid [Formula: see text]-leucine. We synthesized these three Schiff bases and characterized them using UV, FTIR, and H1 and C13-NMR spectra. The molecules were optimized using B3LYP/6-311+G(2d,p) level followed by the simulation of FT-IR spectra, of which the simulated and experimental spectra showed complete agreement. The UV spectra were simulated using TD-DFT, and the electronic excitations were carefully analyzed. Natural bond orbitals provided an analysis of the stability of the compound, which is supplemented by the data from frontier molecular orbital analysis. Detailed wavefunction analysis is reported which predicts the active centers, reactivity profile, and the extent of non-covalent interactions. PASS indicated that compounds show antieczemic properties and antiarthritic properties, which is confirmed with the help of molecular docking results.

Lung cancer is one of the major classes of cancer affecting men. Capmatinib is developed and approved as a medicine to fight non-small lung cancer. Even though the compound is developed for the management of cancer, it may be of several other applications. To tune the property of molecules to fit diverse functions, the study of the electronic structure and other quantum mechanical properties is very important. Literature survey indicates that the detailed structure and reactivity profile of this compound was not reported. We use molecular modeling using DFT and TD-DFT methods using B3LYP/CAM-B3LYP/aug-cc-pVDZ level to study the structure, reactivity, and other Physico-chemical properties of this compound. The optical properties of the compound are compared with standard materials. Different useful indices from molecular wave function analysis present the reactivity and stability of the compound in detail. A qualitative study of non-covalent interactions was also reported along with many useful local information entropy studies, which showed that the molecule is stable with low uncertainty of electrons in spatial distribution.

This manuscript aims to look at the structure and the other physical and chemical properties of solriamfetol, which is used to treat excessive sleepiness, using electronic structure methods. Densit...

Dermal fibrosis and Parkinson's disease are two chronic syndromes affecting a large population leading to systematic morbidity. The mechanisms of these diseases are well debated, and many medicines...

Cenobamate, which is a voltage-gated sodium channel (VGSC) blocker, finds its full application in several anti-epileptic medications. This manuscript tries to look at the structure and other physicochemical properties of this compound with electronic structure methods and molecular mechanics tools. Density functional theory was used to optimise the ground-state geometry of the molecule using dispersion-corrected ω-B97XD functional using aug-cc-pVDZ basis sets, from which frontier molecular orbitals were studied. This study gave a myriad of information about the electronic properties and descriptors that are well enough to predict the bioactivity of the molecule. Electronic excitations between different energy levels, resulting from the interaction between the electrons and electromagnetic radiation, were analysed using time-dependent density functional theory with CAM-B3LYP functional. Numerous parameters like Fukui, ALIE and MESP provided an ample amount of information about the reactivity preferences of the molecule. Molecular docking studies predicted the biological activity of the molecule and its possible use as an anti-depressant. As it was found to show biological activity, its liquid-state behaviour in different solvents was mapped using molecular dynamics simulations.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00894-021-04885-z.

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.

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., Organic chemistry, Theoretical chemistry, Pharmaceutical chemistry, 1-(2-Aminophenyl) pyrrole(2APP), XRD, FT-IR, Fluorescence, UV-VIS, DFT.

The incorporation of quinolines into drugs is critical for accomplishing important tasks and acting as an active ingredient in a variety of treatments. In the present investigation, N-aryl-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-carboxamides (5a–c) were prepared substituted coumarin (3) and substituted phenyl ureas (4a–c). The newly synthesized derivatives were characterized by infrared (IR), nuclear magnetic resonance (1H/13C NMR) and mass spectroscopic techniques. The geometric parameters of compounds 5a–c were computed by density functional theoryat the level of B3LYP/aug-cc-pVDZand energies of highest occupied/lowest unoccupied molecular orbitals (HOMO/LUMO) were analyzed. Anticancer activity was tested against 60 NCI cancer cell lines at 10 µM. N-(4-Fluorophenyl)-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-carboxamides (5a) showed the most promising anticancer activity against HOP-92, UO-31, CAKI 1, and PC-3 with percent growth inhibitions (%GIs) of 22.77, 21.30, 8.04, and 5.42, respectively. This compound also exhibited promising antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay with an IC50 value of 15.06 ± 1.01 µM. In order to rationalize the anticancer activity of the synthesized compounds, molecular docking study was performed with epidermal growth factor receptor (EGFR) using AutoDock Vina program. Docked ligands 5a–c efficiently bound to the active site of the EGFR. Key interacting residues affording polar interactions include Met793 and Asp855 whereas Leu718, Phe723, Val726 and Leu844 were involved in hydrophobic contacts with the receptor.

Two new self-adjustable acyclic diiminodipyrromethane Schiff‘s bases of composition [(Ph)(CH3)C(2,6-iPr2C6H3-N = CH-C4H2NH)2] (L1) and [(Ph)(CH3)C(Ph3C-N = CH-C4H2NH)2] (L2) their zinc complexes of chemical composition [Zn{(Ph)(CH3)C(2,6-iPr2C6H3-N = CH-C4H2N)(2,6-iPr2C6H3-N = CH-C4H2NH)}2] (1) and [ZnCl2{(Ph)(CH3)C(Ph3C-NH = CH-C4H2N)2}] (2) are screened for their biological activity such as in-vitro cytotoxicity, antibacterial and antifungal activity by using various cancer cell lines, bacterial and fungal strains respectively. Density Functional Theory (DFT) calculations are made to understand more insight of the self-adjustable coordination behavior of the both ligands (L1 and L2) and structural stability of the zinc complexes (1 and 2). The experimental biological importance of zinc complexes (1 and 2) further investigated by using molecular docking simulations with human breast cancer (2ING and 3PXC), cervical cancer (5J6R), and lung cancer (5WD6) protein strains. Molecular docking studies showed both zinc complexes have significant amount of hydrogen bonding interactions with binding energy from −6.80 to −8.20 kcal/mol (for1) and −8.30 to −10.30 kcal/mol (for 2). In addition to strong hydrogen bonding interactions, significant amount of non-covalent interactions such as pi-pi stacked, pi-piT-shaped, pi-alkyl, pi-cation, pi-anion, pi-sigma and pi-donor interactions have also been observed in the case of zinc complexes (1 and 2) which make them unique and useful anticancer agents.

A novel series of dinitrophenylpyrazole bearing triazole scaffolds were designed and synthesized with appreciable yields. The structures of all the target molecules (9a–j) were confirmed and characterized by 1H NMR, 13C NMR, FT-IR and HR-MS spectral techniques. These novel molecules were tested for their anti-cancer activity (in vitro) using three tumor cell lines indicating breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), and human epithelial colorectal adenocarcinoma (Caco-2) via the MTT approach. Compounds 9e, 9f, and 9 h showed the high potency growth inhibitory activity against the HeLa cell line (IC50 = 4.0 μM, 5.0 μM and 6.0 μM) higher than that of Combretastatin-A4 (IC50 = 9.0 μM) as reference drug. Besides, compound 9 h was found to be highly potent against MCF-7 cell line IC50 value of 8.0 μM. Additionally, in this manuscript, the structure-activity relationship (SAR) analysis is reported. Molecular docking studies also confirm the experimental findings and explains the most probable interaction pattern.

Hexanal, a naturally phytochemical known to inhibit phospholipase-D and facilitates extension of shelf-life of fruits, vegetables and flower during storage. We attemped to synthesise three quasi liquid Schiff bases using hexanal as the aldehyde component and other three natural biomolecules like adenine, cytosine and l-leucine as the amine counterpart and characterised them using different spectroscopic methods like FTIR, FT-NMR, UV–VIS etc. Detailed vibrational and electronic spectral explanation are reported using experimental spectra and theoretically simulated spectra. The compound was optimised using DFT- B3LYP/6–311 + G(2d,p) and electronic spectra was generated using CAM-B3LYP functional and same basis sets. Schiff base from cytosine was found to show excellent light harvesting properties (99.99%). Analysis of wave function based properties like electrostatic potential, ALIE, non-covalent interactions etc provide information about the reactivity and stability features. PASS and subsequent docking studies predicts that the first Schiff base shows DNA Lyase inhibition and the other two shows anti-eczematic properties.

Trans-2-hexenal, a naturally compound found to be present abundantly in tea. We synthesized imines/Schiff bases by the condensation of trans-2-hexenal with bioactive molecules like cytosine and l-leucine. We characterized the Schiff bases using various spectroscopic methods like FT-IR, UV–Vis, and FT-NMR, etc., followed by detailed electronic structure studies using different theoretical models. Detailed vibrational and electronic spectral explanations are reported using experimental spectra and theoretically simulated spectra. The electronic spectra were generated using TD-DFT and same basis sets. Schiff base from cytosine was found to show good light-harvesting properties (61.98%). Physical and chemical properties, active sites, biological activities, stabilities, light-harvesting efficiency, light-polarization properties, occupancies of electrons in nature of bonding orbitals, weak, and strong hydrogen bonds, steric force of interactions, delocalization of electrons, and reactive sites for nucleophilic, electrophilic attacks, and drug likeness property were determined and reported. PASS and subsequent docking studies indicate that the first Schiff base show anti-eczematic and second Schiff base shows acrocylindropepsin inhibitor properties.

Artesunate and its derivatives belong to a family of compounds that are highly effective against Malaria. This drug is active against several other conditions like neurodegerative diseases and cancer. The compound forms a metabolite dihydroartemisinine, which contain an endoperoxide bridge that is stimulated by heme iron leading to oxidative stress, protein and nucleic acid synthesis inhibition, morphologic changes and reduced growth and survival of parasites. This manuscript examines the structure and conformational preferences of the compound and investigates the energy and reactivity descriptors using computational simulations. Studies indicates that the compound forms stable self-assemblies with graphene quantum dots and modified graphene quantum dots, where the more stable complex was formed with the modified system. This self-assembly formation leads to enhancement in Raman activity of the compound after complex formation, hence can be used an analytical tool for the detection of the compound in a mixture. Natural bond orbital analysis examines the various intramolecular electron delocalisations. This drug is found to be a nonlinear optically active compound with respect to standards materials like urea and paranitroacetanilide. We also report the non covalent interactions present in the molecule, reduced density gradient, Lapalcian electron density and local information entropy of the molecule.

Ozanimod is a newly formulated drug used to manage relapsing multiple sclerosis. Here, we use computational chemistry tools to study the structure and various physio-chemical properties of the molecule. We applied the dispersion corrected ωB97XD functional with DGDZVP as a basis set and DEF2SV as a fitting set to determine the geometry of the molecule. Potential energy scan predicts that the most stable conformer is stable by 8.15 kcal/mol with respect to the eclipsed conformation. Time dependent density functional theory (TD-DFT) with CAM-B3LYP and the same basis sets were used to study the electronic spectra in methanol solvent. Non covalent interactions, average local ionization energy, and energy descriptors helped in predicting the reactivity and stability of the molecule. The compound also had excellent non-linear optical properties when compared to the standard material urea. Screening for biological activity followed by molecular docking studies suggested that ozanimod interacts with three proteins responsible for autoimmune disorders.

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., Graphical abstract Unlabelled Image

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., Highlights • Structure of Ripretinib used for advanced stromal gastrointestinal tumor was carefully examined. • Quantum mechanical properties studied. • Compound is highly NLO active. • Docking studies show excellent activity against SARS-COVID-2 proteins.

Avapritinib is a complex molecule with many heterocyclic rings developed for the treatment of advanced PDGFRA D842V-mutant gastrointestinal stromal tumours. The manuscripts presents the study of the structure, ground state and excited state reactivity and stability indices in different solvent atmosphere using density functional theory in B3LYP/aug-cc-pVDZ level. Different molecular properties like reactivity surface, average local ionization energy, nuclear and electronic electrostatic potential, reduced density gradient assay, and localized molecular orbital analysis are studied in detail. The various intramolecular electron delocalisations were studied using natural orbital formalism and intermolecular interactions analysed by evaluating the extended of non-covalent interactions. Another interesting study is the enhancement in Raman activity of the compound when it forms a self-assembly with graphene quantum dots leading to SERS/GERS, which is studied by incorporating Grimme's dispersion into the previous functional. The electronic spectrum was studied in detail using time dependent density functional theory using long range corrected CAM-B3LYP functionals. The compound showed good light harvesting efficiency also. The local information entropy study provides uncertainty of electrons in spatial distribution.

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., Highlights • Detailed quantum mechanical studies of the sleep regulating hormone melatonin • Analysed the intramolecular stabilisation and nonlinear properties • Excited state properties using TD-DFT formalism • Compound active binds to three known novel coronavirus 2019 proteins.