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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...

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.

1,8-bis-(dimethylamino)-naphthalene, the first ever reported proton sponge, has been snatching much attention with its spectacular proton affinity (PA) for decades. This manuscript discusses the affinities of DMAN towards s-block metal ions Li+, Na+, K+, Be++, Mg++ and Ca++ and compare with PA. We report that the affinity of DMAN towards Be++ is higher than PA. It was observed that increasing methylation at the peri-nitrogen atoms increases the beryllium ion affinity like PA. In light of all these discussions, this manuscript discusses if DMAN can better be termed as a beryllium ion sponge.

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.

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