Synthesis, Reactivity Properties, Experimental and Computational Analysis of Sulfathiazole-4-Nitrobenzoic Acid: An Antimicrobial Agent

The structure of sulfathiazole-4-nitrobenzoic acid (STZBA) was characterized by X-ray diffraction (XRD). The crystal was stabilized by C–H…O, N–H…O, and S–O…S intermolecular interaction along with C–H…π and π…π interactions. The experimental FT-IR, FT-Raman, and UV-Vis spectra of STZBA were recorded and the results were compared with quantum chemical computation using the DFT method. Molecular electron density, topology, and natural bond orbital (NBO) analysis were used to explain the strength of the interaction. The molecular electrostatic potential and Fukui function of STZBA was determined to give a visual representation of charge distribution and provide information about the electrophilic and nucleophilic site of the molecule. Hirshfeld surface analysis was carried out to analyze the stability of the crystal structure. The antimicrobial activity of STZBA was determined against anticancer, bacterial strain E. coli and fungal stain Candida albicans and Sars-cov. Molecular docking analysis was performed with antimicrobial proteins to confirm the bioactivity of the molecule and drug likeness factors were calculated to comprehend the biological assets of STZBA. The molecular dynamic (MD) simulation result explains the protein stability, ligand properties, and protein-ligand interactions. The compounds were assessed for their structural, physic-chemical, pharmacokinetic, and toxicological properties. [ FROM AUTHOR] Copyright of Polycyclic Aromatic Compounds is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A DFT study of vibrational spectra of 5-chlorouracil with molecular structure, HOMO-LUMO, MEPs/ESPs and thermodynamic properties.

The density functional theory calculation has been carried out for the analysis of 5-chlorouracil using DFT/Gaussian 09 with GAR2PED. Recorded experimental spectra for Raman and IR of 5-chlorouracil have been analyzed all fundamental vibrational modes using the outcome results of DFT at 6-311++G** of Gaussian 09 calculations and the GaussView 5.09. To help the analysis of vibrational modes, GAR2PED program has been used in the calculation of PEDs. The charge transfer properties of 5-chlorouracil have been analyzed using HOMO and LUMO level energy analysis. HOMO and LUMO energy gap study supports the charge transfer possibility in molecule. These have been made to study for reactivity and stability of heterocyclic molecules for the analysis of antiviral drugs against the new corona virus: COVID-19. Here, the smaller energy gap of 5-chlorouracil is more responsible for charge transfer interaction in the heterocyclic drug molecules and a reason of more bioactivity. The electron density mapping within molecular electrostatic potential plot and electrostatic potential plotting within iso-surface plot have been evaluated the charge distribution concept in the molecule as the nucleophilic reactions and electrophilic sites. These computations have been used to produce the molecular charges, structure and thermodynamic functions of biomolecule. This study has been made to all internal modes of chloro group substituent at pyrimidine ring of C5 atom. The splitting of frequencies has arisen in the two species for the normal distribution modes.

Computational study of some potential inhibitors of COVID-19: A DFT analysis

Background: There is an urgent demand of drug or therapy to control the COVID-19. Until July 22, 2021 the worldwide total number of cases reported is more than 192 million and the total number of deaths reported is more than 4.12 million. Several countries have given emergency permission for use of repurposed drugs for the treatment of COVID-19 patients. This report presents a computational analysis on repurposing drugs-tenofovir, bepotastine, epirubicin, epoprostenol, tirazavirin, aprepitant and valrubicin, which can be potential inhibitors of the COVID-19.Method: Density functional theory (DFT) technique is applied for computation of these repurposed drug. For geometry optimization, functional B3LYP/6-311G (d, p) is selected within DFT framework.Results: DFT based descriptors-highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, molecular hardness, softness, electronegativity, electrophilicity index, nucleophilicity index and dipole moment of these species are computed. IR and Raman activities are also analysed and studied. The result shows that the HOMO-LUMO gap of these species varies from 1.061 eV to 5.327 eV. Compound aprepitant with a HOMO-LUMO gap of 1.419 eV shows the maximum intensity of IR (786.176 km mol-1) and Raman spectra (15036.702 a.u.).Conclusion: Some potential inhibitors of COVID-19 are studied by using DFT technique. This study shows that epirubicin is the most reactive compound whereas tenofovir is found to be the most stable. Further analysis and clinical trials of these compounds will provide more insight.

A computational study of potential therapeutics for COVID-19 invoking conceptual density functional theory.

The pandemic, COVID-19, has caused social and economic disruption at a larger pace all over the world. Identification of an effective drug for the deadliest disease is still an exigency. One of the most promising approaches to combat the lethal disease is use of repurposed drugs. This study provides insights into some of the potential repurposed drugs viz. camostat mesylate, hydroxychloroquine, nitazoxanide, and oseltamivir in terms of the computational quantum chemical method. Properties of these compounds have been elucidated in terms of Conceptual Density Functional Theory (CDFT)-based descriptors, IR spectra, and thermochemical properties. Computed results specify that hydroxychloroquine is the most reactive drug among them. Thermochemical data reveals that camostat mesylate has the utmost heat capacity, entropy, and thermal energy. Our findings indicate that camostat mesylate and hydroxychloroquine may be investigated further as potential COVID-19 therapeutics. We anticipate that the current study will aid the scientific community to design and develop viable therapeutics against COVID-19.

Structural, spectral, bioactivity, antioxidant and molecular docking (with SARS-CoV-2) analyses on a new synthesized thiosemicarbazide derivative

Spectroscopic characterization of the N'-(4-nitrophenylcarbonothioyl) nicotinohydrazide molecule has been studied using both experimental (X-ray diffraction and IR spectroscopy) and quantum mechanical methods. The tautomeric energetic analysis, structural optimization parameters (bond lengths and angles), vibrational wave numbers, UV-Vis. parameters, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) analyses and Molecular Electrostatic Potential (MEP) surface have been calculated by using DFT/B3LYP method with 6-311++G(2d,2p) level of theory to compare with the experimental results. The radical scavenging activity of the synthesized new compound has been evaluated using three different test methods. For this purpose, 2,2'-azino-bis-(3- ethylbenzothiazoline-6-sulfonate) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests has been done. The pharmacokinetic, physicochemical, and toxicity properties have been defined by using drug-likeness and in silico ADMET studies. The interaction characterization with SARS-CoV-2 main protease (Mpro) of the title compound has been investigated via the help of a molecular docking study.

Molecular Structure, Spectroscopic, Quantum Computational, and Molecular Docking Investigations on Propyl Gallate

Propyl gallate was characterized by utilizing quantum computational investigations using the DFT technique and B3LYP/6-311++G (d, p) basis set using GAUSSIAN 16 W software. The FT-IR, FT-RAMAN, UV-Vis, and NMR chemical shifts of propyl gallate were studied theoretically and experimentally. The estimated vibrational wavenumbers were scaled using a suitable scaling factor after the optimized geometrical parameters were determined. FMO and the HOMO-LUMO energy gap were calculated using the TD-DFT method. NBO and NLO properties were also calculated. The reactive sites were predicted using MEP, ELF, LOL, and RDG. Propyl gallate follows Lipinski's rule and has good drug-likeness, according to the bioactivity evaluation. Molecular docking was performed and the protein-ligand binding properties were discussed and compared to pharmaceuticals already in use against COVID-19, which showed good suppression of SARS-CoV-2. Propyl gallate assay studies were used to predict antibacterial and anti-inflammatory properties. These discoveries could help researchers figure out how to employ the title compound to prevent and cure SARS-CoV-2. [ FROM AUTHOR] Copyright of Polycyclic Aromatic Compounds is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Probing the biomolecular (DNA/BSA) interaction by new Pd(II) complex via in-depth experimental and computational perspectives: synthesis, characterization, cytotoxicity, and DFT approach

Scientists should not forget that the rate of death as a result of cancer is far more than that of other diseases like influenza or coronavirus (COVID-19), so the research in this field is of cardinal significance. Therefore, a new and hydrophilic palladium(II) complex of the general formula [Pd(bpy)(proli-dtc)]NO3, in which bpy and proli-dtc are 2,2'-bipyridine and pyrroline dithiocarbamate ligands, respectively, was synthesized and characterized utilizing spectral and analytical procedures. Density functional theory (DFT) calculation was also performed with B3LYP method in the gas phase. The DFT and spectral analysis specified that the Pd(II) atom is found in a square-planar geometry. HOMO/LUMO analysis, quantum chemical parameters and MEP surface of the complex were investigated to acquire an intuition about the nature of the compound. Partition coefficient and water solubility determination showed that both lipophilicity and hydrophilicity of the compound are more than cisplatin. The 50% inhibition concentration (IC50) value was evaluated against K562 cancer cells, the obtained result has revealed a promising cytotoxic effect. DNA and BSA binding of the complex were explored through multi-spectroscopic (UV–Vis, fluorescence, FRET, and CD) and non-spectroscopic (gel electrophoresis, viscosity and docking simulation) techniques. The obtained findings demonstrated that the complex strongly interacts with CT-DNA by hydrophobic interactions and possesses medium interaction with BSA via hydrogen bond and van der Waals forces, thus BSA could efficiently carry out complex transportation. Furthermore, the results of docking simulation agree well with the experimental findings. In conclusion, the new Pd(II) complex has cytotoxic activity and could interact with DNA and BSA effectively. Graphical : [Figure not available: see fulltext.] © 2022, Iranian Chemical Society.

Synthesis, Spectral, Crystal structure, Hirshfeld surface, Computational analysis, and Antimicrobial studies of Ethyl-(E)-4-(2-(2arylidenehydrazinyl)-2-oxoethyl)piperazine-1-carboxylat es

A new series of ethyl-(E)-4-(2-(2-arylidenehydrazinyl)-2-oxoethyl)piperazine-1-carboxylates (hydrazones) 4a-4e and 5a-5c were designed and synthesized from 1-ethoxycarbonylpiperazine. The hydrazones structure interpretations were achieved by spectroscopic analysis using FT-IR, 1D and 2D NMR and mass. Among the aforementioned hydrazones 4a-4e and 5a-5c, single crystal XRD structure was reported for hydrazone 4a. Both NMR and single crystal XRD analysis are clearly indicated the existence of E configuration of the azomethine group (-C=N-) and cis conformation of the amide group. Hirshfeld surface analysis and 2D fingerprint plot were employed to get a better understanding of non-covalent interactions (NCIs), which showed that the N-H center dot center dot center dot O and C-H center dot center dot center dot O intermolecular hydrogen bonding interactions are the key contributor to stabilize the molecular solids. Density functional theory (DFT) study was carried out to explore the geometrical parameters and electronic properties of frontiers molecular orbitals (FMO), global chemical reactivity descriptor parameter (GCRD), natural bond orbital (NBO), and non-linear optical (NLO) properties for 4a at B3LYP/6-311G(d,p) level. The molecular docking study was performed for hydrazone 4a with nCoV-SARS-2 main protease for COVID-19. Finally, the hydrazones in this synthetic series were screened for their antibacterial and antifungal activities using selected strains. Antimicrobial studies revealed that 4a and 5b against A. niger, 4c and 5c against K. pneumonia, 4e against B. subtilis, 5a, 5b, and 5c against A. flavus, A.niger and C. neoformans, respectively exhibits remarkable antibacterial and antifungal activity at a minimum concentration of 6.25 mu g/mL. (C) 2021 Elsevier B.V. All rights reserved.

Synthesis of novel 2,5-bis(substituted thio)-1,3,4-thiadiazoles by acid catalyzed intermolecular cyclization reactions of substituted dithiocarbazates as a possible 2019-nCoV main protease inhibitor

A convenient and facile synthesis of a privileged pharmaceutical scaffolds, 2,5-bis(substituted thio)-1,3,4-thiadiazoles is accomplished. The reaction of hydrazine hydrate with carbon disulfide and substituted alkyl/aryl chloride in basic medium yielded S-substituted alkyl/aryl dithiocarbazates in high yield. These dithiocarbazates on reaction with tetrafluoro acetic acid underwent a unique acid catalyzed intermolecular cyclization reaction to afford a novel 2,5-bis(substituted thio)-1,3,4-thiadiazoles. A simple procedure and high yields are the characteristic features of these reactions. These compounds are characterized on the basis of physico-chemical and spectral (FT-IR, ESI Mass, 1H, 13C and DEPT 135° 13C {1H} NMR) studies. Compound 2b crystallizes in orthorhombic system with point group P bca. Using the DFT/B3LYP/6–311 G (d,p) level of theory, HOMO-LUMO energy gap and molecular electrostatic potential (MEP) analyses were carried out. The HOMO-LUMO energy gap allowed the calculation of chemical hardness, chemical inertness, electronegativity and the electrophilicity index of the molecule, which depicted their potential kinetic stability and reactivity. The molecular docking studies of 2b-2e with 2019-nCoV main protease(7BRO) revealed binding free energies of (ΔGb) = -6.22, -5.38, -4.43 and -4.25 kcal mol−1 respectively. Docking study revealed that the aromatic congeners exhibit appreciable therapeutic efficiency to be used as 2019-nCoV main protease inhibitors. © 2021 Elsevier B.V.

Synthesis, spectroscopic, and computational studies on molecular charge-transfer complex of 2-((2-hydroxybenzylidene) amino)-2-(hydroxymethyl) propane-1, 3-diol with chloranilic acid: Potential antiviral activity simulation of CT-complex against SARS-CoV-2.

An innovative charge-transfer complex between the Schiff base 2-((2-hydroxybenzylidene) amino)-2-(hydroxymethyl) propane-1,3-diol [SAL-THAM] and the π-acceptor, chloranilic acid (CLA) within the mole ratio (1:1) was synthesized and characterized aiming to investigate its electronic transition spectra in acetonitrile (ACN), methanol (MeOH) and ethanol (EtOH) solutions. Applying Job`s method in the three solvents supported the 1:1 (CLA: SAL-THAM) mole ratio complex formation. The formation of stable CT- complex was shown by the highest values of charge-transfer complex formation constants, KCT, calculated using minimum-maximum absorbance method, with the sequence, acetonitrile > ethanol > methanol DFT study on the synthesized CT complex was applied based on the B3LYP method to evaluate the optimized structure and extract geometrical and reactivity parameters. Based on TD-DFT theory, the electronic properties, 1H and 13C NMR, IR, and UV-Vis spectra of the studied system in different solvents showing good agreement with the experimental studies. MEP map described the possibility of hydrogen bonding and charge transfer in the studied system. Finally, a computational approach for screening the antiviral activity of CT - complex towards SARS-CoV-2 coronavirus protease via molecular docking simulation was conducted and confirmed with molecular dynamic (MD) simulation.

Dietary polyphenols mitigate SARS-CoV-2 main protease (Mpro)-Molecular dynamics, molecular mechanics, and density functional theory investigations.

The recent evolution of the SARS-like Coronavirus has ravaged the world. The deadly virus has claimed over millions of lives across the world and hence highlights the need to develop effective therapeutic drugs to contain the disease posed by this parasite. In this study, the inhibitory potential of fifty (50) dietary polyphenols against Coronavirus (SARS-CoV-2) main protease (Mpro) was conducted using the Autodock Vina Molecular docking tool. In the virtual screening process, the binding affinity of Remdesivir (-7.7 kcal/mol) currently used to treat COVID-19 patients was set as the cut-off value to screen out less probable inhibitors. Ellagic acid, Kievitone, and Punicalin were the only promising ligands with binding affinities (-8.9 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol respectively) lower than the set cut-off value. Furthermore, we validated Ellagic acid and Kievitone efficacy by subjecting them to molecular dynamics simulation and further stability was assessed at the molecular mechanics and quantum levels. The overall analysis indicates both compounds demonstrate higher stability and inhibitory potential to bind to the crucial His41 and Cys145 catalytic dyad of Mpro than the standard drug. However, further analysis of punicalin after evaluating its docking score was not conducted as the ligand pharmacokinetics properties suggests it could pose serious adverse effect to the health of participants in clinical trials. Hence, we employed a more safe approach by filtering out the compound during this study. Conclusively, while Ellagic acid and kievitone polyphenolic compounds have been demonstrated to be promising under this in silico research, further studies are needed to substantiate their clinical relevance.

Pharmacophore-Based Virtual Screening, Quantum Mechanics Calculations, and Molecular Dynamics Simulation Approaches Identified Potential Natural Antiviral Drug Candidates against MERS-CoV S1-NTD.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >-9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.

Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: Molecular docking and DFT calculations.

Structure-activity relationships for hydroxychloroquine compound and its derivatives resulted in a potent antiviral activity. Where hydroxychloroquine derivatives showed an apparent efficacy against coronavirus related pneumonia. For this reason, the current study is focused on the structural properties of hydroxychloroquine and hydroxychloroquine sulfate. Optimized structures of these molecules have been reported by using DFT method at B3LYP/6-31G* level of theory. The geometric were determined and compared with the experimental crystal structure. The intra and intermolecular interactions which exist within these compounds are analyzed by different methods namely the topological analysis AIM, ELF and the reduced gradient of the density. These approaches make it possible in particular to study the properties of hydrogen bonds. The highest occupied molecular orbital and the lowest unoccupied molecular orbital energy levels are constructed and the corresponding frontier energy gaps are determined to realize the charge transfer within the molecule. The densities of state diagrams were determined to calculate contributions to the molecular orbitals. The molecular electrostatic potential surfaces are determined to give a visual representation of charge distribution of these ligands and to provide information linked to electrophilic and nucleophilic sites localization. Finally, these derivatives were evaluated for the inhibition of COVID-19 activity by using the molecular docking method.