Frontier Molecular Orbital Analysis Research Articles

Justicia adhatoda L. vasicin and vasicinone as bioactive phytochemical compounds: Isolation, characterization, and computational studies

Justicia adhatoda L. has wide applications in traditional and modern medicine. Its major potency is due to the presence of two alkaloids viz. Vasicine and Vasicinone. In industry, the demand for both marker compounds as well as quality Justicia adhatoda L. material is very high. The isolation of bioactive phytochemical compounds for the development of an in-house phytochemical reference standard library to verify quality control is of prime demand for an analytical chemist. For these reasons, the objective of the present study was to isolate two members of the alkaloids Vasicine and Vasicinone marker compounds from Justicia adhatoda L. Extraction was carried out by using a cold percolation method in a successive manner by increasing the order of polarity of the solvents from petroleum-ether to ethanol. Isolation was achieved for the above said two maker compounds by using separation, purification though column chromatography on silica-gel using mobile phase chloroform, and ethanol. Characterization of the isolated compounds was carried out by UV–VIS, IR, 1H NMR, 13C NMR and mass spectroscopy techniques. The isolated and purified solid compounds were confirmed as Vasicine and Vasicinone by comparison and co-relating with observed spectroscopy data and literature data. The compounds had a good to high amount of yield (0.4 % to 0.63 %) with high purity (98–100 %) through HPL. Lastly, frontier molecular orbital analysis (HOMO and LUMO), and global descriptive parameters (such as chemical potential, electronegativity, hardness, softness, etc.) were analyzed using computational approaches. Results revealed a good correlation with experimental data except for a few alternations in 1H NMR data.

Hirshfeld Surface Analysis and Density Functional Theory Calculations of 2-Benzyloxy-1,2,4-triazolo[1,5-a] quinazolin-5(4H)-one: A Comprehensive Study on Crystal Structure, Intermolecular Interactions, and Electronic Properties

This study employs a comprehensive computational analysis of the 2-benzyloxy-1,2,4-triazolo[1,5-a] quinazolin-5(4H)-one (ID code: CCDC 834498) to explore its intermolecular interactions, surface characteristics, and crystal structure. Utilizing the Hirshfeld surface technique and Crystal Explorer 17.5, the study maps the Hirshfeld surfaces for a detailed understanding of atom pair close contacts and interaction types. The study also investigates the compound’s electronic and optical characteristics using Frontier Molecular Orbital (FMO) analysis and Global Reactivity Parameters (GRPs). The compound is identified as electron-rich with strong electron-donating and accepting potential, indicating its reactivity and stability. Its band gap suggests Nonlinear Optical (NLO) attributes. The Molecular Electrostatic Potential (MEP) map reveals charge distribution across the compound’s surface. The computational methods’ reliability is validated by the low Mean Absolute Error (MAE) and Mean Squared Error (MSE) in the comparison of experimental and theoretical bond lengths and angles.

QSAR, DFT studies, docking molecular and simulation dynamic molecular of 2-styrylquinoline derivatives through their anticancer activity

In this study, a 2D-QSAR (quantitative structure–activity relationship) was performed on 54 new 2-Styrylquinoline derivatives as anticancer substances capable of inhibiting the p53 protein in the cell HCT116++. The 54 2-Styrylquinoline derivatives was calculated applying DFT 6-31G basis to calculate Quantum descriptors, using MM2 for: Topological, Physico-chemical, Geometrical and Constitutional. The study was carried out by performing multiple linear regression (R2 = 0.90), the QSAR model achieved was tested by artificial neural networks method, which is showed high predictability (R2ANN = 0.89). A DFT study was performed to determine the reactivity of the 2-Styrylquinoline derivatives using frontier molecular orbital analysis and analysis of the molecular electrostatic potential (MEP). Derivatives of 2–4 Styrylquinoline are studied for their synthetic accessibility and their similarity to drug. The obtained results show that all the evaluated compounds have similar properties to drug and are accessible to synthesize.A molecular docking analysis was performed for three compounds: 14, 34, and 54, having various reactivities against the p53 HCT116++ protein (identified by PDB ID: 2GEQ). The results showed strong interactions between the three ligands and the 2GEQ protein, the amino acids HIS 176, SER A180, PRO A188 and ARG A178 are the most active sites of the 2GEQ protein, and based on these result we performed a molecular dynamics simulation to evaluate the stability of our complexes. The MD demonstrates the thermodynamic stability of select compounds during 40 and 100 ns, with all three complexes showing a high level of structural stability.

Theoretical investigations on structural, spectral, NBO, NLO and topology exploration (AIM, ELF, LOL, RDG) of piperazine-2,5-dione oxalic acid monohydrate

The present work investigates the structural stability and nonlinear optical (NLO) activity of piperazine-2,5‑dione oxalic acid monohydrate (PDOAH) using quantum chemical computational techniques. The optimized molecular structure and vibrational wavenumbers of the PDOAH molecule are determined by density functional theory (DFT) with B3LYP/6–311G(d,p) basis set. The vibrational wavenumbers, IR intensities, Raman activities and their corresponding PED values are obtained and analysed. Natural bond orbital (NBO) analysis is carried out to determine inter and intramolecular charge transfer interaction, intermolecular hydrogen bonding and hyperconjugative interactions that stabilize the structure. The charge transfer interaction, electrophilic, nucleophilic and chemical reactivity sites are identified with the aid of molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis. The TD-DFT method is utilized in UV–Vis spectral analysis for the molecule in the water solvent. RDG and IRI analysis is performed to spot the van der Waals interaction and steric effect within the molecule. The Hirshfeld surface analysis is carried out to scrutinize the intermolecular interactions. The nonlinear optical (NLO) parameters of PDOAH are evaluated through DFT calculation and compared with that of urea.

Investigational, computational explorations on betanin, lycopene, cyanidin, and peonidin organic photo sensitizers for green energy harvesting

In keeping green energy harvesting as a prime priority and lowering the cost per watt, three potential red-colored organic photosensitizers were separated and employed for proficient titanium dioxide (TiO2) photoanodes. In a prime attempt, Rivina Humilis fruit extract (Betanin) was used for natural dye-sensitized solar cells (NDSSCs). The Prunus cerasus fruits and Solanum lycopersicum fruits (Lycopene) extracts were also successfully employed to fabricate NDSSCs. Cyanidin, Peonidin, and Lycopene are the prominent colorants existent in Prunus cerasus, and their optimized molecular structure was premeditated via Density functional theory. Their thermochemistry and associated physical parameters, Frontier molecular orbitals (FMOs) analyses, theoretical ultraviolet (UV) – visible exploration, and molecular electrostatic potential reactivity analysis were studied. Microwave-assisted sol–gel practice has yielded pure anatase TiO2 nanoparticles (NPs). The pure, red dye-sensitized TiO2 NPs endured needed studies. Environment-friendly, cost-per-watt effective NDSSCs were accomplished by expanding three red-colored organic photoanodes. Among three photosensitizers, Rivina Humilis fruits showed 1.35%, followed by Prunus cerasus at 1.27 % and slightest by Solanum lycopersicum at 0.82%. And, owing to the above performances, these NDSSCs have the potential to be employed in low-power indoor energy harvesting.

Spectroscopic, quantum chemical investigation and molecular docking studies on N-(2-benzoylamino) phenyl benzamide: A novel SARS-CoV-2 drug.

The present work describes the structural and spectral properties of N-(2-benzoylamino) phenyl benzamide (NBPB). The geometrical parameters of NBPB molecule such as bond lengths, bond angles and dihedral angles are calculated and compared with experimental values. The assigned vibrational wave numbers are in good agreement with the experimental FTIR and FT Raman spectra. The vibrational frequency of C=O stretching was downshifted to a lower wave number (red shift) due to mesomeric effect. The UV-Vis spectrum of the title compound was simulated and validated experimentally. The energy gap and charge transfer interaction of the title molecule were studied using frontier molecular orbital analysis. The electrophilic and nucleophilic reactivity sites of NBPB were investigated through the analysis of the molecular electrostatic potential surface and the Fukui function. An assessment of the intramolecular stabilization interactions of the molecule was performed using natural bond orbital analysis. The drug-likeness parameter was calculated. To investigate the inhibitory potential of the molecule, molecular docking analysis was conducted against SARS-CoV-2 proteins, revealing its capability to serve as a novel inhibitor against SARS-CoV-2. The high binding affinity of NBPB molecule was due to the presence of hydrogen bonds along with different hydrophobic interactions between the drug and the SARS-CoV-2 protein receptor. Hence, the title molecule is identified to be a potential candidate for SARS-CoV-2.

Rational design of co-ordination compounds in combination of bipyridine type of ligands and group 7 metal (M = Mn, Re) for photoCORM: a DFT study.

A large number of manganese and rhenium tricarbonyl complexes are known in literature along with various applications in different fields. CO-releasing molecules (CORMs) got recent research attention because CO can act as a prodrug for different diseases. CORMs offer the promising prospect of a safe and controllable amount of CO release. In this research work, we have explored the electronic properties of compounds such as bipyridine-related [Mn(CO)3] and [Re(CO)3] and we have compared the electronic properties of both manganese and rhenium tricarbonyl complexes in the light of carbon monoxide releasing tendency. The chosen Mn and Re metals have enough possibility to vary or play with ligands and design a new and novel CORM molecule. In this context, we have taken a range of 4,4'-disubstituted 2,2' bipyridyl ligands (Rbpy, where R = NH2, tBu, OCH3, H, CF3, CN, NO2) to investigate CO's liberation ability to identify and study such molecules. The calculated absorbance of designed complexes (1-14) shows visible/near-IR region (350-850 nm). The HOMO-LUMO energy gap of 7 (ΔE=2.40 eV) complex and for complex 14 (ΔE=2.28 eV) which is lesser in all complexes but the MLCT percentage is greater in Mn tricarbonyl complexes in comparison to Re tricarbonyl complexes. The calculated results of the FMO approach revealed that complex 7 and 14 have the lowest energy gap which is also in good agreement with DOSs and TDM results. The theoretically calculated results revealed that the both Mn and Re tricarbonyl complexes have a tendency for labialization of CO, but Mn tricarbonyl complexes are more prone to CO release because they have higher MLCT percentage. In this research work, we have performed density functional theory (DFT) calculations to explore the physical properties of compounds such as bipyridine-related [Mn(CO)3] and [Re(CO)3] and we have compared the physical properties of both manganese and rhenium tricarbonyl complexes in the light of carbon monoxide releasing tendency. DFT-based calculations were performed by using B3LYP/LANL2DZ basis set followed by acetonitrile solvent using the conductor-like polarizable continuum model (CPCM) for different calculations. Various geometrical calculations were performed using the Gaussian16 suite of programs and the output results obtained from Gaussian16 were visualized using GaussView 5.0.16. The same level of theory was used for various calculations, including frontier molecular orbital (FMO) analysis, metal to ligand charge transfer (MLCT), density of state (DOS) calculations, and transition density of matrix (TDM) calculations. For specific calculations, GaussSum 2.2 software package was used to calculate the density of states, and the Multiwfn 3.8 program was used to analyze the transition density matrix, which is presented using heat maps for both electrons and holes.

Fine-Tuning of the Electronic and Optical Properties of Dodecabenzocoronene through Boron and Nitrogen Doping: A DFT Insight

Nanographene provides a wide range of possibilities in graphene engineering for future applications due to the higher degrees of configurational freedom with the electronic parameters that may also be continuous or discrete, depending on the intended application. Therefore, the optical and electronic properties of nanographene are of substantial technological interest. Moreover, doping of graphene with heteroatoms (B, P, N, and S, etc.) alters their chemical and electronic characteristics which are suitable for the economical construction of optoelectronic devices. Herein, geometric, electronic, and optical properties of nanographene are evaluated as a function of the nature and position of dopant. Three different nanographene including coronene, hexabenzocoronene (HBC), and dodecabenzocoronene (DBC) are considered for doping (N and B as dopants) in this study with the key focus on DBC-doped systems. For any dopant number, all possible dopant sites are studied except edge position in order to avoid the edge effect. Frontier molecular orbital (FMO) analysis is performed to evaluate the perturbations in electronic characteristics of doped nanographene. A decrease in energy gap is seen for all doped systems. Natural bond orbital (NBO) analysis indicates that doping of boron (B) and nitrogen (N) results in variation in distribution of charges over the nanographene surfaces. The density of states (DOS) analysis reveals that Fermi level ([Formula: see text] is shifted for all B- and N-doped systems. The UV-visible (UV-Vis) absorption spectra are computed to evaluate the changes in the intensity and maximum adsorption wavelength ([Formula: see text] in all doped DBC. Various chemical reactivity descriptors are also evaluated which reveal the degree of stability and chemical reactivity of doped systems. The results indicate that multiple B and N atoms doping offers a new possibility for fine-tuning of electronic and optical properties of nanographene at atomic level, thus providing guidance in development of future advanced optoelectronic devices.

Influence of azacycle donor moieties on the photovoltaic properties of benzo[c][1,2,5]thiadiazole based organic systems: a DFT study

Fullerene free organic chromophores are widely utilized to improve the efficacy of photovoltaic materials. Herein, we designed D-π-A-π-D form chromophores (TAZD1-TAZD5) via end-capped redistribution of donor moieties by keeping the same π-bridge and central acceptor unit for organic solar cells (OSCs). To analyze the photovoltaic characteristics of these derivatives, DFT estimations were accomplished at B3LYP/6–311 G (d,p) functional. Different investigations like frontier molecular orbital (FMO), absorption spectra (UV–Vis), density of states (DOS), binding energy (Eb), open circuit voltage (Voc), and transition density matrix (TDMs) were performed to examine the optical, photophysical and electronic characteristics of afore-mentioned chromophores. A suitable band gap (∆E = 2.723–2.659 eV) with larger bathochromic shift (λmax = 554.218–543.261 nm in acetonitrile) was seen in TAZD1-TAZD5. An effective charge transference from donor to acceptor via spacer was observed by FMO analysis which further supported by DOS and TDM. Further, lower binding energy values also supported the higher exciton dissociation and greater CT in TAZD1-TAZD5. Among all the designed chromophores, TAZD5 exhibited the narrowest Egap (2.659 eV) and maximum red-shifted absorption in solvent as well as gas phase i.e. 554.218 nm and 533.219 nm, respectively which perhaps as a result of the phenothiazine-based donor group (MPT). In a nutshell, all the tailored chromophores can be considered as efficient compounds for promising OSCs with a good Voc response, interestingly, TAZD5 is found to be excellent chromophores as compared to all these designed compounds.

Comparison of the binding energies of approved mpox drugs and phytochemicals through molecular docking, molecular dynamics simulation, and ADMET studies: An in silico approach

The mpox (previously monkeypox) outbreak in more than 100 non-endemic countries in 2022 posed a serious global health concern. Mpox is emerging as a global public health threat from a seemingly neglected disease. A42R profilin-like protein from mpox virus (PDB ID: 4QWO) could be a preferred target lead. The binding affinity of commonly used drugs/mAbs (tecovirimat, brincidofovir, cidofovir) for A42R profilin-like protein was examined in silico through molecular docking. Further, the results were compared with those of the phytochemicals curcumin, rutin, and theaflavin. Tecovirimat (−7.31 kcal/mol, IC50 = 4.39 µM) and theaflavin (−6.99 kcal/mol, IC50 = 7.54 µM) had the highest affinities. Molecular dynamics simulation of the theaflavin–4QWO complex was performed to ascertain the stability of ligand–protein interactions in natural charge, molecular electrostatic potential, and frontier molecular orbital analyses. The predicted QSAR and pharmacokinetic properties of all compounds were evaluated to find a suitable candidate for designing and developing new drugs. The evaluated log P values for brincidofovir and tecovirimat were higher than those of the other drugs in the QSAR study. Theaflavin had an impressive log P of 4.77, which hints at its high biological activity. The findings recommend further in vitro experimental validation to develop potential low-cost mpox therapies.

Structural analysis, reactivity descriptors (HOMO-LUMO, ELF, NBO), effect of polar (DMSO, EtOH, H2O) solvation, and libido-enhancing potential of resveratrol by molecular docking

The profound impact of health challenges related to libido, encompassing sexual dysfunction, hormonal imbalances, relationship difficulties, stress, anxiety, depression, and the effects of certain medical conditions or medications, calls for urgent mitigative measures. As a result, this study meticulously explores the compound Resveratrol (Res) to uncover its substantial properties concerning libido enhancement. The compound was optimized using the DFT/ωB97XD/6–311G++(d, p) basis set in different solvents, namely DMSO (dimethyl sulfoxide), ethanol, and water. Notably, the geometry investigation reveals that the structural bond variations can be attributed to factors such as solvent polarity, screening effects, hydrogen bonding, solvation energy, and conformational preferences. Substantially, the Frontier Molecular Orbital (FMO) analysis explored the HOMO values of the compound in different solvents, resulting in 7.59198 eV, 7.5514 eV, and 7.59687 eV for RES_DMSO, RES_EtOH, and RES_H2O, respectively. Correspondingly, their LUMO values were found to be 7.5955 eV, 7.5648 eV, and 7.5982 eV, leading to respective band gaps of 0.0035 eV, 0.0133 eV, and 0.0014eV Remarkably, RES_H2O displayed the smallest energy gap (0.0014 eV) among the interacting compounds, indicating increased conductivity and sensitivity. Furthermore, the natural bond orbital analysis revealed that RES_H2O had the highest permutation energy among the three complexes (376.5 kcal/mol for RES_DMSO, 371.79 kcal/mol for RES_EtOH, and 378.77 kcal/mol for RES_H2O), indicating a stronger interaction between the donor and acceptor orbitals. Finally, the molecular docking studies unveiled a notable difference in binding affinity, with RES exhibiting a greater affinity for 1UDT at -8.1 kcal/mol compared to 1UDU, which demonstrated a binding affinity of -6.6 kcal/mol. Thus, RES has the potential to reverse erectile dysfunction and improve libido by inhibiting the activities of phosphodiesterase (1UDT and 1UDU), ultimately promoting vasodilatory signals from cGMP to the smooth muscles of the penis, leading to enhanced erection. These groundbreaking findings offer promising prospects for the development of new and effective drugs to combat various medical conditions.

Role of Delocalization, Asymmetric Distribution of π-Electrons and Elongated Conjugation System for Enhancement of NLO Response of Open Form of Spiropyran-Based Thermochromes.

Switchable nonlinear optical (NLO) materials have widespread applications in electronics and optoelectronics. Thermo-switches generate many times higher NLO responses as compared to photo-switches. Herein, we have investigated the geometric, electronic, and nonlinear optical properties of spiropyranes thermochromes via DFT methods. The stabilities of close and open isomers of selected spiropyranes are investigated through relative energies. Electronic properties are studied through frontier molecular orbitals (FMOs) analysis. The lower HOMO-LUMO energy gap and lower excitation energy are observed for open isomers of spiropyranes, which imparts the large first hyperpolarizability value. The delocalization of π-electrons, asymmetric distribution and elongated conjugation system are dominant factors for high hyperpolarizability values of open isomers. For deep understanding, we also analyzed the frequency-dependent hyperpolarizability and refractive index of considered thermochromes. The NLO response increased significantly with increasing frequency. Among all those compounds, the highest refractive index value is observed for the open isomer of the spiropyran 1 (1.99 × 10-17 cm2/W). Molecular absorption analysis confirmed the electronic excitation in the open isomers compared to closed isomers. The results show that reversible thermochromic compounds act as excellent NLO molecular switches and can be used to design advanced electronics.

Predicting benzodithiophene based donor materials with enhanced 19.09% PCE, open-circuit voltage and optoelectronic attributes for solar cell applications: Photochemical insights from DFT

Seven benzo[1,2-b:4,5-b′]dithiophene (BDT) based novel donor (D1-D7) molecules with A-π-D-π-A configuration are investigated by DFT and TD-DFT methods and a power conversion efficiency (PCE) of 19.09% is predicted for organic solar cells (OSCs). The fundamental core of these novel compounds is the BDT molecule (R), with other significant acceptors substituted on the outer borders. To study the geometrical, photovoltaic, and optoelectronic properties of the newly designed sensitizers (D1-D7), the CAM-B3LYP/6-31G(d,p) method was employed for computational analysis and comparison with BDT (R) Evaluations were conducted on open circuit voltage (Voc), power conversion efficiency (PCE), fill factor (FF), absorption spectra, the distribution pattern of electron density, charge mobility, electron, and hole reorganizational energy, the density of state (DOS), frontier molecular orbital (FMO), and transition density matrices (TDM)of the investigated compounds. In comparison to the reference compound (R), D2, D3, and D4 have better optical and chemical characteristics. The DOS plots and the FMOs analysis showed that the addition of acceptor groups finely improved the charge distribution in the molecules under study. The optoelectronic characteristics of the proposed structure D2 in chloroform solvent were the most improved, with a lower band gap (3.87 eV), higher maximum absorbance (533 nm), and lower binding energy (1.55 eV) than others investigated. The TDM graphs revealed the reliability of the charge transfer capability. In several molecules, the mobilities of charge transfer in designed compounds were equivalent to the reference R while the D2 was the lowest among all implying that the charge carriers would be more maneuverable. For all donors, the Voc was calculated with PC71BM. Voc is high for D2, D3, and D4, compared to R. All investigated compounds were predicted to have remarkable PCEs with high FF values. Especially, D2 has the higher Voc (2.422 V) and FF (94.12), which leads to the highest PCE of 19.09%. Hence, all calculated characteristics are very favorable to the potential of our designed molecules in photovoltaic applications.

Microwave assisted green synthesis, Single crystal XRD, DFT, Hirshfeld surface analysis, Antibiofilm, Anti-inflammatory activity and Molecular docking study of 4-(4-Fluorophenyl)-5-methyl-1,3-thiazole-2-amine

The title compound 4-(4-Fluorophenyl)-5-methyl-1,3-thiazole-2-amine was synthesized by the green microwave irradiation method and the structure was confirmed by spectroscopic techniques. Single crystal X-ray diffraction study was performed to investigate the crystal structure of the title compound. Further, the molecular structure was optimized by density functional theory (DFT) calculations using the B3LYP/6-311G++ (d, p) basic set and compared with X-ray diffraction data. DFT optimized structure, geometrical parameters and IR spectra of the title compound showed excellent correlations with the experimental results. The chemical reactivity and stability of the title compound were studied by molecular electrostatic potential (MEP) and Frontier molecular orbitals (FMOs) analysis. Intermolecular interactions of the title compound were analyzed by Hirschfeld surfaces and 2D-fingerprint plots. In vitro, antibiofilm activity against C. albicans, suggests a potential biofilm inhibitor (MIC 12.5 μg/ml). A molecular docking study of the title compound with the active sights of the target protein (PDB:5TZ1) justifies the results of the antibiofilm activity whereas a drug-likeness pharmacokinetic study is used to analyze the safety and efficiency of the drug. Furthermore, the Anti-inflammatory activity study of the title compound indicates significant (82.63%) inhibition of protein denaturation.

Probing the catalytic activity of first-row transition metal doped C20 fullerene as remarkable HER electrocatalysts: A DFT study

Hydrogen evolution reaction (HER) has captivated the interest of researchers due to ever increasing demand for future sources of energy. With the advancement in renewable energy resources, electrocatalytic production of hydrogen has been considered as the most suitable way for hydrogen production for fuel cells and combustion engines. Herein, we studied HER activity of transition metal doped C20 fullerene (M@C20) by means of adsorption energy, Gibbs free energy and electronic density calculations. Ni@C20 and Cu@C20 complexes provide the best HER activity with Gibbs free energy of −0.09 eV for each. Furthermore, electronic properties such as the density of states (DOS) and frontier molecular orbital analyses are performed which indicate that transition metal doping significantly alters the electronic properties of studied M@C20 complexes. Whereas the adsorption of hydrogen does not affect the electronic parameters much. The basic understanding of hydrogen adsorption mechanism together with analyses of electronic parameters is crucial for the synthesis of highly efficient electrocatalysts for hydrogen energy applications. The critical findings of this study declares that both Ni@C20 and Cu@C20 complexes can act as promising electrocatalysts for hydrogen evolution reaction with low overpotential.

Shedding light into the biological activity of aminopterin, via molecular structural, docking, and molecular dynamics analyses

In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the experimental values. The vibrational assignments were performed based on the computed potential energy distribution (PED) of the vibrational modes. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were carried out for the optimized structure and the chemical reactivity has been scrutinized. To enlighten the biological activity of aminopterin as anticancer and anti-COVID-19 agents, aminopterin was docked into DNA, αIIBβ3 and α5β1integrins, human dihydrofolate reductase, main protease (Mpro) of SARS-CoV-2 and SARS-CoV-2/ACE2 complex receptor. The binding mechanisms of aminopterin with the receptors were clarified. The molecular docking results revealed the strong interaction of the aminopterin with DNA (−8.2 kcal/mol), αIIBβ3 and α5β1 integrins (−9.0 and −10.8 kcal/mol, respectively), human dihydrofolate reductase (−9.7 kcal/mol), Mpro of SARS-CoV-2 (−6.7 kcal/mol), and SARS-CoV-2/ACE2 complex receptor (−8.1 kcal/mol). Moreover, after molecular docking calculations, top-scoring ligand-receptor complexes of the aminopterin with SARS-CoV-2 enzymes (6M03 and 6M0J) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail, and to determine the binding free energies accurately. The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown. Communicated by Ramaswamy H. Sarma

Synthesis and characterization of tetradentate benzophenone derivative Schiff base and properties in different lyotropic media

A new Schiff base ligand of 6,6′-(1Z,1′Z)-(butane-1,4-diylbis(azanylyidene))bis (phenylmethanylylidene))bis(3-octyloxy) phenol) was synthesized and characterized using XRD and different spectroscopic analyses (FTIR, 1H NMR, 13C NMR, and UV–Vis.) DFT/B3LYP/6-31G(d,p) level of theory was applied successfully to the present compound. Theoretically calculated parameters of the synthesized compound were compared with the experimentally obtained results. The optimized structure has been investigated using the same level of theory for various studies, including frontier molecular orbital analysis, molecular electrostatic potential, chemical reactivity indexes, natural bond orbital analysis, electrostatic potential, and the electrophilicity-based charge transfer with DNA bases.

Single Crystal XRD, Hirshfeld Surface, Quantum Chemical and Molecular Docking Studies on Diethyl1-(4-Nitrobenzyl)-4-(4-Nitrophenyl)-2,2-Dioxooctahydro-2-Pyrrolo[2,1-c]1,2Thiazine-1,3-Dicarboxylate: a Novel HIV-1Inhibitor

The single crystal of the title compound Diethyl 1-(4-nitrobenzyl)-4-(4-nitrophenyl)-2,2-dioxooctahydro-2-pyrrolo[2,1-c]1,4thiazine-1,3-dicarboxylate was grown and characterized by single crystal X-ray diffraction technique. Further, Hirshfeld surface, quantum chemical, and molecular docking analyses of the compound were carried out. The title compound was crystallized in a triclinic crystal system with a centrosymmetric space group of P-1 and has one molecule in the asymmetric unit. The stability of the grown crystal structure was confirmed by the C-H…O and π…π interactions. The hydrogen bonding features were analyzed and the prominent intermolecular interactions present in the structure were investigated using Hirshfeld surface analysis. The interaction energy between pairs of the molecule was obtained from Energy Framework analysis. The molecular structure of the title compound was optimized using density functional theory calculation in the ground state and the calculated structural parameters of the compound were compared with the experimental XRD data. Mulliken atomic charge distribution and frontier molecular orbitals analyses were also carried out to validate the reactivity of the title molecule. Molecular docking studies confirm that the title compound has potent inhibitory nature against the human mutant HIV-1 reverse transcriptase protein. Thus, the present study paves the way for the development of a novel HIV-1 drug.

Influence of anionic species on the molecular structure, nature of bonding, reactivity, and stability of ionic liquids-based on 1-butyl-3-methylimidazolium

The unique physicochemical properties of ionic liquids (ILs) have positioned them as a significant class of solvents, making them a subject of considerable interest. In this investigation, the experimental analysis involved solvothermal reflux techniques, while theoretical approaches utilized density functional theory (DFT) with the def2-SVP/ωB97XD computational approach to explore the electronic properties, reactivity, stability, and structural aspects of ILs based on the combinations of [BMIM]+ cation with [MeSO3]-, [BF4]-, [PF6]-, and [C2H3O2]- anions. The experimental and theoretical data exhibited good agreement, demonstrating that the choice of cation and anion greatly influences the stability of ILs. By employing Frontier molecular orbital analysis, the reactivity and stability of the studied ionic species were observed to follow the order of [BMIM]+[MeSO3]- > [BMIM]+[BF4]- > BMIM > [BMIM]+[PF6]- > [BMIM]+[C2H3O2]-, with corresponding energy gaps of 4.8474 > 3.1971 > 2.013 > 1.8830 and 1.3276 eV, respectively. The Natural Bond Orbital (NBO) analysis, encompassing second-order perturbation energy, revealed the strength of interactions within the investigated systems in the following order: [BMIM]+[PF6]- < [BMIM]+[MeSO3]- < [BMIM]+[BF4]- < [BMIM]+[C2H3O2]-. Topology analysis indicated a higher electron density (ρ(r)) value of 0.8966 a.u., indicating a denser distribution of electrons. Furthermore, the nature of bonding in the studied ion pairs displayed the following order: [BMIM]+[MeSO3]- > [BMIM]+[BF4]- > [BMIM]+[PF6]- > [BMIM]+[C2H3O2]-, signifying that [BMIM]+[MeSO3]- exhibited stronger interactions compared to the other combinations. The vibrational spectra and UV–vis results of the investigated ILs underscored the sensitivity of characteristic peaks in frequency and intensity to the specific cation–anion combination. These findings have the potential to guide experimental researchers in exploring the applications of the studied ionic species in diverse areas such as energy storage and catalysis.

Novel Zn- and Cd-Schiff base complexes as the potent anticancer agents: Synthesis, spectral characterization and theoretical study

A novel unsymmetrical bidentate Schiff base ligand and its complexes, with the common formula of MLX2 (M(II) = Zn(II) and Cd(II); X− = Cl−, Br− and I−), using a reaction between 1,2-diaminobenzene and (E)-3-(4-(Dimethylamino) phenyl) acrylaldehyde were successfully synthesized. The structure of all the as-made compounds was identified by techniques including 1H NMR,13C NMR, ESI-mass, FT-IR, UV–Vis, melting point and molar conductivity. The analytical and spectral data confirmed the metal to ligand ratio of 1:1 in the Zn(II) and Cd(II) complexes. The anticancer activity of the compounds on cancer cells was investigated on HCT116 cell line, where the MTT method was used to screen cytotoxicity effects. The flow cytometry method also was used to determine the mechanism of cell death. Our data reveal that CdLCl2 can block the cell cycle and induction apoptosis. In addition, using Gaussian 16 program, the structure of the samples was optimized, and some important properties such as enthalpy change, entropy change and total energy were extracted. The molecular electrostatic potential, nonlinear optical properties, natural bond orbital and frontier molecular orbitals analysis were calculated for all compounds. Further, the electrophilic and nucleophilic sites, energy gap, ionization potential, electron affinity, natural population analysis and natural atomic orbitals were studied.