In silico development of an inflammation-triggered β-cyclodextrin carrier for a redox-active vanadium–INAP–tryptophan complex

Coumestrol is an estrogenic isoflavonoid which belongs to the class of phytochemicals known as coumestans, with interesting therapeutic applications such as antioxidant and anticancer properties. Coumestrol is widely spread in leguminous plants, alfalfa, ladino clover, strawberry, soya bean, sprouts, pea silage, and beans. The structure of coumestrol is closely resembles to the (E)-4,4’-dihydroxystilbene derivatives, which have promising pharmacological activity, and is responsible for the estrogenic activity of coumestrol. The present work, deals with the computational investigation of the structural analysis of coumestrol, by using M06 as level of theory and 6–31++G (d, p) as basis set in Gaussian 09 software package. The stable conformer of coumestrol has been identified through the potential energy scan (PES) and the lowest energy conformer is selected for further investigation. Before going to the deep knowledge of bioactivities shown by the title compound, one must have in-depth knowledge about the molecular structure of the compound. The most robust computational tool, density functional theory (DFT) has been 42enhanced to a great extent, especially for the structural analysis of organic compounds, a computational exploration into the structural analysis of the title compound is particularly relevant. Detailed structural analysis has been done using H1 and C13 NMR as well as UV-visible spectroscopy. Moreover, the reports showing the detailed structural characterization of coumestrol is found to be rare and the reported papers are mostly focused on its bioactivities. In this scenario, the present work aims to explore a detailed computational approach towards the structural characterization of coumestrol. The work clearly explains the molecular structure, spectral characterizations, and frontier molecular orbital analysis. In addition, the global reactive and Fukui indices of the title compound have also been explained. The work can be extended to detailed bioactivity analysis, molecular docking analysis, QSAR/QSPR studies, etc.

In the present work 4,6-bis(4-fluorophenyl)-5,6-dihydropyrimidin-2(1H)-one was synthesized by condensation of (2E)-1,3-bis(4-fluorophenyl)prop-2-en-1-one with urea in basic medium. The synthesized compound was characterized by using FT-IR and 1H NMR spectroscopic techniques. To determine the molecular structure of synthesized molecule some quantum chemical calculations were carried out by density functional theory (DFT) with employing B3LYP level at 6-311++G(d,p) basis set in gas phase, water and CCl4 solvents by using Gaussian-03 package. The optimized geometrical parameters, thermochemical parameters and global reactivity descriptors have been computed. The frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analysis also performed to explore the reactivity of title molecule at same level of theory. The vibrational frequencies of title molecule were analysed and compared with the corresponding experimental data. The results show fair correlation between the calculated frequencies in gas phase and experimental frequencies. The effect of water and CCl4 solvents on vibrational frequencies and global chemical reactivity descriptors were also examined. Obtained results show that polar solvent water decreased the carbonyl stretching frequency largely while other frequencies in water and CCl4 are slightly different than gas phase. There is no significant change by solvents were observed on energy gap (∆E) and global reactivity descriptors of studied molecule.

The biological activity of steroidal compounds such as dexamethasone (DX) and hydrocortisone (HC) is closely linked to subtle variations in their molecular structure and electronic properties. This study provides a comparative quantum chemical analysis of DX and HC to clarify how these differences influence hydrogen bonding strength, reactivity, and their potential interactions with the glucocorticoid receptor (GR). Optimized geometries, natural bond orbital (NBO) analyses, frontier molecular orbitals (FMO), global reactivity descriptors, and average local ionization energy (ALIE) calculations demonstrate that DX exhibits greater polarity and electrophilic character compared to HC. These differences help explain the stronger receptor binding affinity observed for DX. Indeed, notably, despite the inherent limitations of gas-phase DFT calculations compared to experimental X-ray data, the theoretical results exhibit good agreement with experimental observations, suggesting the reliability of the computational approach in predicting molecular interactions within the GR active site. All quantum chemical calculations were performed using density functional theory (DFT) with the B3LYP functional and 6-311++G(d,p) basis set. Structural optimization, FMO analysis, global reactivity descriptors, and dipole moment evaluations were carried out in Gaussian 09. NBO analysis was performed with NBO 5.0. Average local ionization energy (ALIE) surfaces were generated using Multiwfn 3.8, and molecular visualizations were produced with GaussView 5.0.

Herein, based on density functional theory (DFT) simulations, the static and dynamic hyperpolarizabilities of the superalkalides based on Janus molecules have been explored. The designed superalkalides M2F(F)-DDFP-M2F(H) contain Janus based Dodecafluorophenylene (DDFP) molecule doped with superalkalis on both sides acting as both electron acceptors and donors. Thermodynamic stabilities are evident from the negative values of interaction energies, which are observed in the range of −2.96 eV to −3.63 eV. The maximum interaction energy (Eint) obtained is −3.63 eV for Li2F(F)-DDFP-Li2F(H) complex. The NBO (natural bond orbital) and FMO (frontier molecular orbital) analyses confirm the true superalkalide nature of the designed complexes. FMO analysis further reveals the reduction in energy gap E(H-L) from 10.43 eV (for bare DDFP) to 3.17 eV for the designed superalkalis. Furthermore, NLO response of the studied complexes reveals that the maximum values of polarizability (617 au) and hyperpolarizability are seen for Na2F(F)-DDFP-K2F(H) (4.25 × 104 au) complex, which confirms the remarkable NLO response of newly designed superalkalides. Moreover, frequency dependent analysis indicates that the maximum values of simple harmonic generation (SHG), electro-optical pockel effect (EOPE) and hyper Rayleigh scattering are 7.79 × 106, 2.75 × 106 and 4.45 × 106 au, respectively. The EOKE and EFISHG values are 6.79 × 107 and 7.68 × 1010 at 1339 nm suggesting significant increase in the NLO response of the reported complexes. These results manifest that our designed complexes might provide new paths towards the exceptionally high performance NLO materials. Moreover, we expect that the present work will provide guidance for designing and synthesis of superalkali based NLO materials in future.

Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses

The structural and geometry parameters of 3‐phenyl coumarins were studied utilizing DFT/BL3YP/6‐311++G(d,p) approach. The frontier molecular orbital (FMO) analysis was implemented to understand the nature of intramolecular charge transfer (ICT) within the molecules. The analysis also computes the global descriptors to account for their electronic and optical properties. The electrostatic potential surfaces (ESP) and Mulliken charges on their optimized geometries reveal charge distribution across the molecular framework. UV–Visible absorption spectra of molecules were obtained from TDDFT computations to identify the different peaks and corresponding electronic transitions. IR spectra have been elucidated to examine the vibrational frequencies of different bonds. Hirshfeld surface (HS) analysis and 2D fingerprint plots investigated the type of interactions in the molecule and interpret H⋯H interactions as the prominent one. The ESP maps confirmed O 2 atom and hydrogen atom of coumarins as electrophilic and nucleophilic centers, respectively. The global descriptors ( η , χ , μ p , and ω ) calculated from FMO analysis labeled molecules as strong electrophiles with high chemical reactivity and stability. The results validated the computed molecular properties relationship with the chemical substitutions. The present analysis fortifies the stability of 3‐phenyl coumarins and reflects amplified ICT in polar solvents proposing their suitability in various energy‐modulated applications.

The absorption and fluorescence characteristics of coumarin derivative 4-(4-Nitro-phenoxymethyl)-benzo[h]chromen-2-one (NM2BC) are studied at room temperature in pure organic solvents to understand the nature of its electronic transitions and solvent interactions. The study aims to investigate the solvent-dependent photophysical behavior of NM2BC and estimate the electric dipole moments in both the ground and excited states using solvatochromic methods. Additionally, the work seeks to explore the intramolecular charge transfer (ICT) nature in the excited state and assess the chemical reactivity and stability of NM2BC. The effects of solvents on spectral characteristics were examined using solvatochromic techniques, and Density Functional Theory (DFT) at the CAM-B3LYP/6-311 + + G (d, p) level was utilized in conjunction with quantum chemistry calculations and the solvatochromic shift to estimate electric dipole moments in both the ground and excited states. The electronic structure was analyzed using Frontier Molecular Orbital (FMO) analysis. To evaluate reactivity and stability, Global Reactivity Descriptors were calculated using FMOs. To determine the preferred electrophilic and nucleophilic attack sites, Molecular Electrostatic Potential (MEP) analysis was performed. Strong interactions and intramolecular charge delocalization were investigated using Natural Bond Orbital (NBO) analysis.

Integrated insights into the structure, spectroscopy, and reactivity of a novel Brucinium Tetraphenylborate: A comprehensive computational and experimental study

Molecular structure simulation of (E)-2-(butan-2-ylidene) hydrazinecarbothioamide using the DFT approach, and antioxidant potential assessment of its complexes

Peptoids are peptidomimetics in which the side chain is attached to the nitrogen of the amide group rather than the α-carbon. This alteration in the backbone structure is highly valued because it endows beneficial properties, including enhanced resistance to proteolysis, greater immunogenicity, improved biostability, and superior bioavailability. In this current study, we focused on the Ugi-4CR-based one-pot synthesis of peptoids using 1,4-dithiane-2,5-diol as the carbonyl component together with amine, carboxylic acid, and isocyanides. Four new peptoids-5a, 5b, 5c, and 5d-were designed and efficiently prepared in good chemical yields and were subjected to DFT investigations for their electronic behavior. These compounds have free OH, SH, and terminal triple bonds for further chemistry. In a computational analysis, the spectral data of compounds 5a-5d were juxtaposed with calculated spectral values derived from the B3LYP/6-311G(d,p) level. The electronic excitation and orbital contributions of 5a-5d were predicted using TD-DFT calculations. A natural bond order (NBO) analysis was utilized to investigate the electronic transition of newly synthesized peptoids, focusing on their charge distribution patterns. Furthermore, MEP and NPA analyses were conducted to predict charge distribution in these compounds. The reactivity and stability of the targeted peptoids were evaluated by global reactivity descriptors, which were determined with frontier molecular orbital analysis. The DFT results revealed that compound 5c displayed marginally higher reactivity compared to 5a, 5b, and 5d, possibly due to its extended conjugation.

Indole-based hydrazone derivatives are a valuable group of molecules owing to their adjustable electronic structures, strong donor–acceptor properties, and broad biological applications in antioxidants, antibacterials, and optoelectronics. In the current work, indole 3-butyric acid (IBH) derivatives of hydrazones (DHIBH, PIBH, NIBH, MBIBH, 4-MBIBH, ICIBH, 4-PCIBH, and TCIBH) were prepared using a multi-step method with aldehydes or ketones substituted to form the hydrazide group. Melting point analysis and FTIR, UV-visible and NMR spectroscopy confirmed the structures of the hydrazine derivatives. The evaluation of biological activity showed trends in activity. DHIBH outperformed all other compounds synthesized in terms of antibacterial screening against Escherichia coli and Staphylococcus aureus, with maximum zones of inhibition of 18.3 mm and 19.3 mm, respectively, and an MIC of 2.5 mg mL−1. Meanwhile, ICIBH and 4-PCIBH exhibited selective performance against the Gram-positive strain at a dosage of 2.5 mg mL−1, while the antioxidant activity was observed using the DPPH assay, with DHIBH being the most effective radical scavenger with an IC50 of 44.51 ± 7.46 µL mL−1. The findings of the experiment were justified by extensive DFT computations. There was good agreement between the experimental vibrational frequencies and the calculated vibrational frequencies, which verified the structural stability and functional group integrity of the structure using comparative IR analysis. Frontier molecular orbital analysis has shown that the HOMO–LUMO energy gaps are substituent-dependent, which shows variable chemical reactivity and charge-transfer capacity. UV-vis analysis favors the predominant π → π and n → π transitions with the bathochromic effects of extended conjugation and electron-withdrawing substituents, respectively. Nonlinear optical (NLO) computations proved an increase in the dipole moment, polarizability, and first hyperpolarizability of a few derivatives, which denoted their multifunctional behavior. Molecular electrostatic potential, global reactivity descriptors, and NBO analyses were further used to provide greater insights into and confirm the presence of efficient intramolecular charge transfer. A strong correlation between molecular docking with DNA gyrase B (PDB ID: 6F86) and antioxidant-related protein (PDB ID: 1HD2) was observed against experimental antibacterial and antioxidant data, especially with DHIBH and NIBH. The ADMET results confirmed the favorable drug-like and pharmacokinetic properties of all the compounds. In general, these findings indicate that indole-based hydrazones are promising lead structures that should be further optimized structurally and biologically prior to the determination of their therapeutic potential.

Synthesis, spectroscopic, chemical reactivity, molecular docking, DFT calculations and in-vitro anticancer activity studies of a novel ionic liquid; Metforminium ibuprofenate

Elucidation of the structure, spectroscopic techniques and quantum chemical investigations on nonlinear optical material 2‑hydroxy-5-methylbenzaldehyde

Structural preferences and multiple bonding interactions in hetero-closo-dodecaborates of group-14 elements - A theoretical study.

The ligand o-phenylenediamine (opda) and its oxidized form, o-benzoquinonediimine (bqdi), act as a fascinating candidate coordinating toward transition metal ions leading to the photochemical hydrogen production in absence of photosensitizers. Herein, we report the systematic study of the interaction between the oxidized form bqdi ligand, tris-(o-benzoquinonediimine) with divalent first-row transition metal series using DFT calculations. The lowest energy structures, bond length, binding energies, frontier molecular orbital analysis, natural bond orbitals, and global reactivity descriptor were calculated using B3LYP/6-311G(d,P) level of theory. The time dependent-DFT at the CAM-B3LYP/6-311+G(d,p) level of theory was applied to determine the electronic structures and the optical spectra. The theoretical binding trend of the divalent first-row transition metal series is decreasing as follows: Cu >Ti > V > Co > Ni > Fe > Cr > Zn >Mn. Among them, the binding potency of iron (II) by the bqdi ligand was not predominantly sturdy as compared to other first-row divalent transition metal ions. The origin of strong coordination with Fe(II) is attributed to its extra capability to induce covalent coordination of bqdi ligands. The complex exhibited two strong peaks at 370 nm and 452 nm, due to the HOMO-3 to LUMO+1 and HOMO-1 to LUMO transitions, respectively. Natural bond orbital analysis showed that the major interaction happens between the N lone pair electrons of the ligand with an anti-bonding orbital of metal ions, in which Ti showed the highest interaction energy than other metal ions. The present systemic DFT study of bqdi ligands with the first-row transition metals strongly encourages the future establishment of photochemical hydrogen production in absence of photosensitizers.