The molecule of 2-Biphenyl Carboxylic Acid (2BCA), which contains peculiar features, was explored making use of density functional theory (DFT) and experimental approaches in the area of quantum computational research. The optimised structure, atomic charges, vibrational frequencies, electrical properties, electrostatic potential surface (ESP), natural bond orbital analysis and potential energy surface (PES) were obtained applying the B3LYP approach with the 6-311++ G (d,p) basis set.. The 2BCA molecule was examined for possible conformers using a PES scan. The methods applied for spectral analyses included FT-IR, FT-RAMAN, NMR, and UV-Vis results. Vibrational frequencies for all typical modes of vibration were found using the Potential Energy Distribution (PED) data. The UV-Vis spectrum was simulated using the TD-DFT technique, which is also seen empirically. The Gauge-Invariant Atomic Orbital (GIAO) approach was employed to model and study the 13C and 1H NMR spectra of the 2BCA molecule in a CDCL3 solution. The spectra were then exploited experimentally to establish their chemical shifts. To predict the donor and acceptor interaction, the NBO analysis was used. The electrostatic potential surface was employed to anticipate the locations of nucleophilic and electrophilic sites. Hirshfeld surfaces and their related fingerprint plots are exploited for the investigation of intermolecular interactions. Reduced Density Gradient (RDG) helps to measure and illustrate electron correlation effects, offering precise insights into chemical bonding, reactivity, and the electronic structure of 2BCA. According to Lipinski and Veber's drug similarity criteria, 2BCA exhibits the typical physicochemical and pharmacokinetic properties that make it a potential oral pharmaceutical candidate. According to the findings of a molecular docking study, the 2BCA molecule has promise as a treatment agent for the Nipah virus (PDB ID: 6 EB9), which causes severe respiratory and neurological symptoms in humans.

Amorphous solid dispersions (ASDs) are a prevalent method for increasing the bioavailability and apparent solubility of poorly soluble drugs. Consequently, extensive research, encompassing both experimental and computational approaches, has been dedicated to developing methods for assessing the key factors influencing their stability, notably drug-polymer interactions. A common computational approach to rank the compatibility of a drug with a set of solvents or polymers is to compare thermodynamic observables, such as solvation free energies at infinite dilution. However, the impact of the molecular weight of the polymer excipient on these interactions remains underexplored. This study delves into this impact through atomistic simulations of Indomethacin in PVP(-VA) and HPMC, and through simulations using a coarse-grained model, emphasizing its critical importance. First, we demonstrate that the molecular weight of the polymer plays a pivotal role in determining the solvation free energy of the drug, at times exerting a more significant influence than the specific chemical identity of the polymer. Additionally, our simulations suggest that higher molecular weight polymers lead to lower solvation free energies and, thus, suggest better compatibility with the drug. Yet, the lower free energy of solvation of the drug in longer polymers does not translate into a higher solubility. This work highlights the subtle role polymer molecular weight plays when measuring thermodynamic observables in amorphous solid dispersions, a role which must be considered when optimizing pharmaceutical formulations.

In this study, three imidazole derivatives : 2,4,5-triphenyl-1-(4-(phenyldiazenyl)phenyl)-1 H-imidazole (N1), 2-(4-chlorophenyl)-4,5-diphenyl-1-(4-(phenyldiazenyl)phenyl)-1 H-imidazole (N2), and 2-(2,4-dichlorophenyl)-4,5-diphenyl-1-(4-(phenyldiazenyl)phenyl)phenyl)-1 H-imidazole (N3), which were prepared using N-methyl-2-pyrrolidone hydrogen sulfate ionic liquid as a catalyst, were selected for detailed evaluation. The antimicrobial activities of these compounds were assessed against a panel of pathogenic microorganisms, including Gram-positive bacteria (Staphylococcus aureus, Bacillus anthracoides), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae), and the fungal strain Candida albicans. The Density Functional Theory (DFT) results showed that the N3 molecule exhibited the highest stability with the largest ΔEgap (2.9546 eV) and chemical hardness, while N1 showed the highest reactivity. Frontier molecular orbital (FMO) and electrostatic potential (ESP) analyses revealed that the HOMO orbitals are delocalized over the imidazole ring and neighboring aromatic fragments, and the LUMO orbitals are spread over the phenyldiazenyl phenyl fragments. A comparative analysis suggests that while N3 is the most chemically stable, N2 demonstrates the highest potential for biological activity, consistent with experimental antimicrobial results. Both in-vitro and in-silico results revealed that the N2 molecule exhibits superior biological activity compared to N1 and N3. Molecular docking studies of N2 were performed with its target protein to explore its binding interactions with several amino acid residues, elucidating its potential antioxidant mechanism. Docking results revealed that all ligands exhibit strong binding affinities, with N1 showing the highest MolDock score and N2 demonstrating strong specificity through key hydrogen bonding and π-interactions. Molecular dynamics simulations, including RMSD, RMSF, radius of gyration (Rg), solvent-accessible surface area (SASA), and principal component analysis (PCA), further confirmed the structural stability and dynamic behavior of the protein-ligand complexes. MMPBSA binding free energy calculations indicated that N2@1AI9 forms the most stable complex, primarily driven by favorable van der Waals and electrostatic interactions. In silico ADMET analysis suggests all compounds, particularly the lead compound N2, face challenges with high lipophilicity, low solubility, and predicted drug-drug interaction risk (CYP2C19 inhibition for all; CYP3A4 and P-gp substrate for N2), yet their lack of BBB permeation supports their further development, especially for topical or intravenous use. Overall, the results suggest that N2 is a promising candidate for further development as a potential antimicrobial anti-fungal agent targeting the ergosterol biosynthesis pathway in Candida albicans.

In this study, it is attempted to scrutinize the noncovalent interaction and two mechanisms of covalent between Flutamide anti-cancer drug (FLU) and functionalized carbon nanotubes (f-CNT) employing density functional theory (DFT) calculations regarding their geometries, binding energies and topological features of the electron density in the water solution. For designed noncovalent interactions, binding energies, natural bond orbital (NBO), atom in molecule (AIM) and quantum molecular descriptors analyses were applied for further understanding of the adsorption process. The computed theoretical results confirmed that binding of Flutamide molecule with functionalized CNT is thermodynamically suitable and among two considered systems containing COOH functionalized CNT (NTCOOH) and COCl functionalized CNT (NTCOCl), the NTCOOH revealed more binding energy value which suggests it as a favorable system as a drug delivery within biological and chemical systems (noncovalent). NTCOOH and NTCOCl can bond to the NH group of flutamide through OH (COOH mechanism) and Cl (COCl mechanism) groups, respectively. Finally, to obtain the values of activation energies, the activation enthalpies and the activation Gibbs free energies of two considered pathways different calculations were performed and the results have been compared with each other. Numerical studies for calculating activation parameters related to the COOH mechanism show higher values than those related to the COCl mechanism and

Heterocyclic compounds, including pyrimidine derivatives, exhibit a broad variety of biological and pharmacological activities. In this paper, a previously synthesized novel pyrimidine molecule is proposed, and its pharmaceutical properties are investigated. Computational techniques such as the density functional theory, ADMET evaluation, and molecular docking were applied to elucidate the chemical nature, drug likeness and antibacterial function of molecule. The viewpoint of quantum chemical computations revealed that the molecule was relatively stable and has a high electrophilic nature. The contour maps of HOMO-LUMO and molecular electrostatic potential were analyzed to illustrate the charge density distributions that could be associated with the biological activity. Natural bond orbital (NBO) analysis revealed details about the interaction between donor and acceptor within the bond. Drug likeness and ADMET analysis showed that the molecule possesses the agents of safety and the effective combination therapy as pharmaceutical drug. The antimicrobial activity was investigated using molecular docking. The investigated molecule demonstrated a high affinity for binding within the active sites of antibacterial and antimalarial proteins. The high affinity of the antibacterial protein was proved by its low binding energy (−7.97 kcal/mol) and a low inhibition constant value (1.43 µM). The formation of four conventional hydrogen bonds in ligand–protein interactions confirmed the hi

In this paper, the possible interactions between 5-fluorouracil (5FU) as an anticancer drug and gallium nitride (Ga12N12) nanocage (NC) in aqueous solution have been investigated using DFT/CPCM/B3LYP-D/6-31G(d,p) level of theory. Eleven different orientations were used to mimic the 5FU adsorbed on Ga12N12 (5FU@GaNNC). To investigate the interaction mechanism between the two components, the adsorption energies and thermodynamic parameters, the electronic properties such as the energies and orbitals distribution of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), the HOMO-LUMO energy gaps (Eg), the density of states (DOS), partial DOS (PDOS), and the molecular electrostatic potential (MEP) have been calculated and compared. The natural bond orbitals (NBOs) and the quantum theory of atoms in molecules (QTAIM) calculations have been applied for understanding chemical interactions and chemical bonding. Additionally, some quantum molecular descriptors were calculated for the understanding of molecular reactivity. Main results revealed that (1) the key factor that leads to stabilization of the formed complex/s is the relocation of one of the H atoms that originally belonging to one of the N atoms in 5FU to one of the nearest Ga atoms in GaNNC and (2) the adsorption energies for the eleven adsorbed systems are relatively larger compared with reported similar systems indicating from a theoretical point of view, a probable chemisorption typ

We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753-8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large-scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design.

BackgroundHigh-risk HPV infection initiates cervical cancer through E6-mediated degradation of the p53 tumor suppressor protein via the ubiquitin-proteasome system, leading to apoptotic failure and genomic instability. No FDA-approved therapies currently target HPV E6, representing a significant unmet clinical need. This study aimed to identify repurposable compounds predicted to engage the p53 interface disrupted by E6-mediated proteasomal degradation, as a starting point for future p53-stabilisation studies.MethodsAn integrated computational and experimental repurposing strategy was applied, encompassing network pharmacology, molecular docking, density functional theory (DFT), in silico ADMET profiling, and 500 ns molecular dynamics simulations. Network analysis was used to identify the primary hub protein targeted by HPV E6. Candidate compounds were screened for binding affinity against p53 chains C and D within the HPV16-associated degradation complex (PDB: 4XR8). In vitro validation was conducted by antioxidant, anti-inflammatory, anti-angiogenic, and cytotoxicity assay was assessed in SiHa (HPV16-positive) cells.ResultsNetwork analysis confirmed TP53 as the principal hub disrupted by the HPV E6 protein. Among all screened compounds, adenosine demonstrated the highest binding affinities against p53 chains C and D (−6.318 kcal/mol and −7.104 kcal/mol, respectively), suggesting a stabilizing interaction at the p53 interface. DFT calculations revealed moderate electronic st

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

sets for ab initio molecular orbital calculations and inter- molecular interactions. In: Lipkowitz KP … devoted to methods for the computation of molecular structure: molecular mechanics, semiempirical methods, wave … Gasteiger Molecular Electrostatic Potentials Peter Politzer and Jane S. Murray Nonbonded Interactions Steve

Technol. 3, 378 (1973). L. B. Kier, Molecular Orbital Theory in Drug Research, Academic Press, New York … AND APPLICATIONS OF MOLECULAR SIMILARITY CONCEPTS AND APPLICATIONS OF MOLECULAR SIMILARITY Edited by … application of molecular similarity that emphasizes current research trends and highlights molecular similarity