Molecular Electrostatic Potential Analysis Research Articles

Gold(I) Catalysis in Alkyne-Alkene Reactions: A Systematic Exploration through Molecular Electrostatic Potential Analysis.

Gold catalysis enables selective chemical transformations with catalytic activity tunable through ligand selection. This study uses the density functional theory (DFT) to explore the impact of phosphine ligands (PR3) on gold(I)-catalyzed alkyne-alkene cyclobutene formation. We analyze the following key steps: (i) PR3-Au+ complexation, (ii) alkyne binding, (iii) alkene binding, (iv) C-C coupling transition state, (v) cyclobutene formation transition state, and (vi) cyclobutene dissociation. Molecular electrostatic potential (MESP) analysis provided a deeper understanding of electronic effects and revealed a strong correlation between the change in MESP at the gold nucleus (ΔNVAu+) upon complex formation with various ligands and the corresponding complexation energy, as well as between the change in MESP at the alkyne carbon (ΔVC) and the C-C coupling step activation barrier. This establishes MESP as a powerful tool for understanding ligand influence on catalysis. Our findings suggest that electron-donating phosphine ligands, combined with electron-withdrawing alkyne substituents, enhance catalyst turnover, promote cyclobutene product dissociation from the gold(I) complex, and facilitate catalyst regeneration. Solvent effects also play a crucial role. Bulky XPhos, JohnPhos, and CyJohnPhos ligands enhance gold(I) catalysis via steric protection, electron donation, and catalyst regeneration efficiency. In conclusion, this study provides insights into ligand effects in gold(I)-catalyzed cyclobutene formation, guiding future catalyst design.

Co incorporated pentagraphene as an efficient single-atom catalyst for reduction of CO2: First-principles investigations

Hydrogenation of carbon dioxide (CO2) to formic acid is explored through density functional theory calculations over Co decorated penta-graphene (Co@PG) as single atom catalyst (SAC). Co is successfully stabilized over pentagraphene due to strong overlapping of Co-3d and C-2p states of pentagonal ring of pentagraphene near fermi level. The higher diffusion barrier for Co over pentagraphene evince that the clustering of Co atom is restricted. This suggests that Co@PG can be used as a catalyst for reducing CO2. Moreover, the Hirshfeld charge density, molecular electrostatic potential and spin density analysis indicates that the Co site is the highly active site for CO2 hydrogenation reaction. Both CO2 and H2 show strong interaction with Co@PG. In co-adsorbed state, the interactions are even larger due to greater mutual polarization of reactants and localization of positive charge on Co with adsorption energy of -2.57 eV. The hydrogenation can proceed at ambient temperature due to a small energy barrier of 0.29 eV, the competitive reaction i.e. CO hydrogenation with CO2 hydrogenations almost impossible over the catalyst surface due to larger energy barriers i.e. 1.98 eV. Thus, this work shows that Co@PG can be used as an efficient and promising catalyst for CO2 hydrogenation at room temperature.

A mechanism – based perspective on the interplay of new drug candidate with biomolecules

This research deals with the synthesis and analysis of a novel Pd(II) compound, [Pd(dach)(SA)], featuring 1,2-diaminocyclohexane (dach) and salicylic acid (SA). The compound's structure was refined and its electronic properties including HOMO-LUMO energies, molecular electrostatic potential and natural bond analysis were calculated using B3LYP functional of DFT. Biologically, the compound demonstrated significant antitumor efficacy against the K562 leukemia cell line (IC50 = 37 μM). In-silico methods predicted the favorable characteristics and low risks of new compound. Interactions with DNA and serum albumin were explored using both experimental and computational techniques, revealing that the compound binds through hydrogen bonds and van der Waals forces having Kb,DNA = 1.7 × 105, ΔG°DNA = - 7.32 kcal/mol, Kb,BSA = 1.25 × 106 and ΔG°BSA = - 8.36 kcal/mol, as indicated by fluorescence spectroscopy. UV–Vis spectroscopy showed a reduction in the absorption spectra of both DNA and BSA upon interaction. DNA binding affinity was confirmed via gel electrophoresis and viscosity measurements. Molecular docking suggested the groove binding with DNA, and site I of BSA, primarily through hydrogen binding. The stability and conformational changes of these interactions over the time were affirmed by molecular dynamics simulations and QM/MM calculations. These comprehensive studies underscore the potential of [Pd(dach)(SA)] complex as a candidate for cancer therapy, highlighting its strong binding interactions with crucial biomolecules.

Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C17H19F3N3O3·C4H5O6·2(H2O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL.

Neutral Adducts of Molybdenum Hexafluoride: Structure and Bonding in MoF6(NC5H5) and MoF6(NC5H5)2.

The first Lewis acid base adducts of MoF6 and an organic base have been synthesized, i. e., MoF6(NC5H5) and MoF6(NC5H5)2. These adducts are structurally characterized with X-ray crystallography, showing that both adducts adopt capped trigonal prismatic structures. The MoF6(NC5H5) and MoF6(NC5H5)2 adducts are fluxional on the NMR time scale at room temperature. Two different fluorine environments could be resolved by 19F NMR spectroscopy at -80 °C for the 1 : 2 adduct, MoF6(NC5H5)2, whereas MoF6(NC5H5) remains fluxional at that temperature. Density functional theory (DFT) calculations aide the assignment of the infrared and Raman spectra. Natural Bond Order and Molecular Electrostatic Potential analyses elucidate the structures and properties of the MoF6 pyridine adducts. Regions of significantly higher molecular electrostatic potential, i. e., σ-holes, in trigonal prismatic compared to octahedral MoF6 rationalize the capped trigonal prismatic geometry of the adducts. Whereas MoF6(NC5H5) is stable at room temperature under exclusion of moisture, MoF6(NC5H5)2 decomposes at 60 °C in pyridine solvent, and the solid slowly decomposes at room temperature after 24 h.

Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

Design, synthesis, and characterization of a novel pH-responsive azo dye incorporating a 1,3,4-thiadiazole ring for advanced textile applications

This study presents the synthesis and comprehensive characterization of a novel azo dye derived from 2-(5-amino-1,3,4-thiadiazol-2-yl) phenol (1a). The synthesis was initiated by reacting salicylic acid with thiosemicarbazide in the presence of phosphorus oxychloride (POCl3), yielding an 89 % conversion to compound 1a. The subsequent diazotization and coupling of 1a under alkaline conditions led to the formation of the azo dye (1b). Structural elucidation was confirmed through Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The incorporation of the 1,3,4-thiadiazole ring is significant due to its known influence on enhancing dye stability, reactivity, and potential biological activities, while the salicylic acid moiety contributes to the dye's pH responsiveness. A notable pH-dependent color transition from yellow (pH < 6.0) to red (pH > 8.0) was observed, driven by protonation-induced resonance changes. Computational studies, including Frontier Molecular Orbital (FMO) analysis, revealed a Highest Occupied Molecular Orbital (HOMO)-Lowest Unoccupied Molecular Orbital (LUMO) gap of 1.94 eV, indicating efficient electronic transitions critical for its color properties. Molecular Electrostatic Potential (MEP) and Fukui function analyses provided further insights into the dye's reactivity and potential applications. The dyeing properties were rigorously assessed through K/S values, CIELAB color space, and fastness properties on cotton fabric, demonstrating varied color depths and hues influenced by different mordants, with copper and manganese significantly enhancing color intensity. Colorfastness tests revealed good to fair durability, with untreated fabrics showing optimal performance. This thorough characterization underscores the promising potential of this newly synthesized azo dye for applications in pH-responsive textiles and functional materials, highlighting its relevance for advanced textile and material science applications.

2D hydrogen bonded organic framework (2D-HOF) in benzodioxane-coupled-pyridine as a charge carrier: Synthesis, structural, quantum computational investigation

This research presents a comprehensive investigation into the synthesis, structural features, and charge carrier properties of a novel 2D Hydrogen-Bonded Organic Framework (2D-HOF) formed by Benzodioxane-Coupled-Pyridine. The synthesis involves the reaction of 2,3-dihydrobenzo[b][1,4]dioxin-6-carbaldehyde with pyridine-2-carbohydrazide in the presence of acetic acid and ethanol solvent, leading to the formation of (E)-2-(2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)hydrazinyl)pyridine (DDMP). Single crystal X-ray diffraction analysis reveals the monoclinic crystal system with the P21/n space group, showcasing a non-planar structure due to a distinctive twisting motion in the dioxane ring. The crystal packing is governed by a complex network of intermolecular interactions, including hydrogen bonds, short contacts, and π-stacking, ultimately forming a stable 2D-HOF. Hirshfeld Surface (HS) analysis provides insights into key interactions, emphasizing the significance of hydrogen bonding, short contacts, and stacking interactions in molecular packing. The 2D fingerprint (FP) plots quantitatively highlight crucial interatomic contacts, with hydrogen bonding, CH…H, and O…H interactions dominating. Molecular Electrostatic Potential (MEP) analysis reveals potential sites for electrophilic and nucleophilic attacks, aiding in predicting reactive sites and charge carrier behavior. Energy framework analysis sheds light on the pairwise interaction energies within the crystal structure, emphasizing the role of dispersive forces in stabilizing the crystal lattice. Density functional theory calculations indicate the molecule's charge transfer capabilities, suggesting its suitability for applications such as batteries, supercapacitors, and solar cells. Additionally, global reactivity parameters suggest that the 2D HOF material has electron and proton conduction capabilities, making it versatile for various applications. Atoms-in-molecules (AIM) topology analysis, particularly non-covalent interaction (NCI) analysis, provides a detailed understanding of intra and intermolecular interactions, highlighting hydrogen bonding and π…π interactions. H-bond binding energy analysis confirms the non-covalent nature of identified interactions, emphasizing their strength and significance.

Novel benzoyl and acetyl pyrazine-2-carbohydrazonamide hybrid derivatives: Experimental and theoretical insights

A series of novel benzoyl and acetyl pyrazine-2-carbohydrazonamide hybrid derivatives, namely N’-benzoylpyrazine-2-carbohydrazonamide (1), N’-(4-methylbenzoyl)pyrazine-2-carbohydrazonamide (2), N’-(2-phenylacetyl)pyrazine-2-carbohydrazonamide (3) and N’-(2-(1H-indol-3-yl)acetyl)pyrazine-2-carbohydrazonamide (4), were readily obtained using a metallic Na-assisted interaction of 2-cyanopyrazine with benzohydrazide, 4-methylbenzohydrazide, 2-phenylacetohydrazide or 2-(1H-indol-3-yl)acetohydrazide in dry MeOH. Compounds 1–4 were studied by a set of physical measurements, including FTIR, 1H NMR and UV–vis spectroscopy, while their crystal structures were elucidated by single crystal X-ray diffraction and the corresponding crystal packing was further studied in detail using the Hirshfeld surface analysis. Compounds 3 and 4 were found to adopt both the E- and Z-isomeric forms in DMSO‑d6. Molecules of the title compounds are linked via NH⋯O and NH⋯N hydrogen bonds and π⋯π interactions, yielding supramolecular aggregates. As it was found by the Hirshfeld surface analysis, molecules of 1–4 mainly interact through the H⋯X (X = H, C, N and O) and C⋯X (X = C and N) contacts. The molecular interactions were quantified and compared using DFT calculations, molecular electrostatic potential (MEP) analysis and quantum theory of atoms in molecules (QTAIM) analysis, highlighting the dominant role of hydrogen bonding interactions in governing the crystal packing.

Development of pivalic acid conjugated Nafion modified glassy carbon electrode for sensitive detection of Cu(II) by electrochemical approach

In this work, pivalic acid (pivH) molecule is employed for an electrochemical sensing of copper cations in an aqueous medium. For sensitive as well as selective potential sensor application, pivH was fabricated onto a glassy carbon electrode (GCE) facilitated by adhesive conducting binder, nafion, so as make it selective and effective electrochemical probe (pivH/Nafion/GCE) towards specific heavy metal cations. This newly fabricated pivH/Nafion/GCE reveals enhance electrochemical activity toward copper ions in the presence of other interfering heavy metal cations in phosphate buffer solution (PBS) of pH=7. The calibration plot was linear (r2 = 0.9879) across broad linear dynamic range (LDR) spanning Cu2+ concentration from 0.1 nM to 0.01 M. The sensitivity and detection limit was found to be 0.0212 × 10−2 µAµM−1cm−2 and 0.014 nM, respectively. So, this newly fabricated GCE as selective electrochemical probe offers a sensitive as well as selective detection of Cu2+ cations in real environmental samples using a novel electrochemical, current–potential (I-V), approach, for the first time. Further, we explored pivalic acid for the preparation of new di-nuclear copper complex, [Cu2(piv)4(pivH)2] (where piv = pivalate; pivH=pivalic acid) and characterized by Fourier transform infrared spectroscopy (FTIR) spectroscopy, elemental analysis and single crystal X-ray diffractometry. Density functional theory (DFT) calculations were carried out to confirm the interactions and these calculations well-support to experimental data. In case of deprotonated form of pivH, Molecular Electrostatic Potential (MEP) analysis exhibits electrostatic potential equals to −148.4 kcal/mol which suggest about the strong interaction of –COOH with copper centers. Similarly, interaction energies, the quantum theory of atoms in molecules (QTAIM) study and Natural Bond Orbital (NBO) analysis also favor to experimental work. Thus, this novel study demonstrates an excellent approach for highly selective and sensitive detection of Cu2+ cations in short response time with low detection limit and good reproducibility by using I-V method based on newly designed pivH/Nafion/GCE as selective Cu2+ cationic electrochemical sensor. The experimental data was compactable with theoretical calculations.

Zn(II) and Cd(II) complexes of dithiocarbamate ligands: synthesis, characterization, anticancer, and theoretical studies

ABSTRACT A potassium 4-(ethoxycarbonyl)phenyldithiocarbamate, (4-etphdtc), and 6-ethoxybenzothiazol)-dithiocarbamate, (6-etbedtc), ligands have been isolated and four metal dithiocarbamate complexes of the type [M(4-etphdtc)2] and [M(6-etbedtc)2] (M = Zn, Cd;) were synthesized and characterized by elemental analysis and spectroscopic techniques (FT-IR,1H and13C{1H}-NMR, HRMS, UV–vis). Thermogravimetric studies of all four complexes were performed and the final product of the thermal decomposition was metal sulfides. The theoretical study with density functional theory (DFT) has been utilized to optimize the structures of the complexes for HOMO–LUMO energy calculation. Non-bonding orbitals (NBO) analysis was performed to determine the numerous hyper-conjugative interactions responsible for the stability of the compound. In addition, Molecular Electrostatic Potential (MEP) analysis was conducted to identify the compounds’ electron-rich, electron-poor, reactive sites, and bonding characteristics. The Electron Localization Function (ELF), and AIM Charges are also calculated. In vitro cytotoxicity, the complexes were examined against cervical cancer cells (HeLa) to assess their reactivity. Molecular docking studies were conducted to confirm the biological activity by simulating the binding orientation and affinity of the ligands and their complexes against VEGFR-2 kinase, The investigated ligands interact with the binding site as; hydrophilic (Lys868, Glu885, His1026, Cys1045, and Asp1046) and hydrophobic (Val889 and Leu889) for 4-etphdtc; hydrophilic (Lys868, Glu885, Cys1045, and Asp1046) and hydrophobic (Val889, Leu889, Leu1035, and Phe1047) for 6-etphdtc. The calculated binding free energy values for Zn(4-etphdtc)2 and Zn(6-etphdtc)2complexes are – 9.700 kcal/mol, – 10.003 kcal/mol, respectively.

Menadione sodium bisulfite as an efficient anti-corrosion additive for mild steel in acid corrosion: Electrochemical, surface morphological and theoretical studies

The corrosion inhibition behavior of Menadione Sodium Bisulfite (MSB) in 1.0 M HCl medium was evaluated using weight loss, electrochemical techniques (Tafel polarisation and Electrochemical impedance spectra), surface analysis (SEM and EDX), Density Functional Theory (DFT), Noncovalent interaction- Reduced Density Gradient (NCI-RDG) and Monte Carlo (MC) simulation techniques. Weight loss measurement showed that as inhibitor concentration increased, the corrosion rate decreased which means that a protective film formed on the metal surface. At 300 ppm, the inhibitor showed a maximum inhibition efficiency of 89.7 %. Tafel polarisation studies indicate that the inhibitor is mixed-type in nature. The inhibitor adsorption on the mild steel is the best fit for the Langmuir isotherm model. As the weak interaction of sodium and oxygen in the inhibitor molecules, the inhibitor exhibits two distinct equilibrium behaviors. (i) inhibitor with sodium (solid-state) and inhibitor without sodium (in liquid-state). These two behaviors were theoretically investigated using DFT and MD simulation studies. The inhibitor and metal interaction is further supported using these theoretical studies. The electron population of the inhibitor was analyzed using molecular electrostatic potential, NCI-RDG, Fukui function, and natural bond orbital analysis. These studies further give an understating of the inhibitor and metal interactions.

Preparation, structure and optical properties of TCNB-based charge-transfer cocrystals

Organic charge transfer cocrystals exhibit interesting properties due to their multi-components synergistic and collective effect. Herein, using 1,2,4,5-tetracyanobenzene (TCNB) as electron acceptor, carbazole (CARB), dibenzothiophene (DBZP) and dibenzofuran (DBZF) as electron donors, three charge transfer cocrystals of CARB-TCNB, DBZP-TCNB and DBZF-TCNB were synthesized by solvent evaporation method and solvent-assisted grinding method. These cocrystals were constructed based on the π–π stacking interactions and CH…N hydrogen bonds and confirmed by the SXRD analysis. The stacking modes are consistent with the model that predicted by molecular electrostatic potential analysis (ESP). The IGM and AIM analyses suggested that the π-π stacking and CH…N hydrogen bonds are weak in nature. The purity and homogeneity of cocrystals and grinding products were verified by PXRD analysis. In addition, the IR, UV–vis absorption and luminescent properties were investigated, and the cocrystals and grinding products exhibited different behaviors from that of their precures. In short, this work not only reports the CT complexes synthesized by liquid- and solid- strategies, but also provides an in-depth understanding of the spectral changes caused by the CT interactions.

Phenytoin from antiepileptic to covid-19: Synthesis, crystal structure, DFT, HSA, MEP and green biological study of phenytoin derivative as potential covid-19 drug candidates

That's an interesting point! Phenytoin's potential in reducing cognitive deficits during COVID-19 is indeed intriguing. Its established status as an approved antiepileptic medication could lend credibility to exploring its effects on cognitive function in COVID-19 patients. This dual functionality could provide a unique angle for research and potential therapeutic interventions. This study reports the synthesis, characterization and importance of a new phenytoin derivative PD, C23H24N4O5. A biological molecular modelling study using a computer-aided tool, which is a clean technique of PD compared to the approved Phenytoin anti-COVID-19 drugs, was achieved. Docking the three compounds into 7JQ0 of COVID-19 Mpro showed the potential capability of PD compared to Phenytoin and the inhibitor. Binding affinity, for example, was -7.3, -6.9 and -6.6 kcal/mol, respectively. Noticeably, PD interacted with 75 % of the essential functional Mpro amino acids, such as G143 and H164, M49, C145, M165 and E166, comparable to the standards used. Further interesting findings that predicted compound toxicity and drug-likeness also found that PD was less toxic and bio-available as a drug than Phenytoin and the inhibitor. Superposition of our ligand PD against Phenytoin and the Inhibitor docked into7JQ0 using the same parameters showed similar interactions in the amino acid cavity, enhancing the possibility of PD being an anti-COVID-19 drug. The free computer-aided methods were used to significantly speed up the initial stages of drug discovery by narrowing down potential candidates for further laboratory testing.This compound adopts an L-shaped conformation. The lone pairs on the ring nitrogen atoms participate in π bonding in the ring. In the crystal, a layer structure was generated by NH···N, NH···O and CH···O hydrogen bonds plus CH···π(ring) interactions. Theoretical studies of the compound were calculated using the density functional theory (DFT) method with a B3LYP 6–311++G(d,p) basis set. The geometrical parameters after optimization were compared with the experimental values. Molecular Electrostatic Potential (MEP) and Hirshfeld Surface Analysis (HSA) were studied to investigate intermolecular interactions. Frontier Molecular Orbitals (FMOs), which were Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), were created, and the energy gap between these orbitals was calculated to understand the chemical stability of the molecule.

Exploration of supramolecular interactions, Hirshfeld surface, FMO, molecular electrostatic potential (MEP) analyses of pyrazole based Zn(II) complex

The supramolecular interactions of title compound [Zn(HL2)](ClO4)2(MeOH)2] (1) where, HL2=((Z)-N’-(5-methyl-1H-pyrazole-3-carbonyl)pyrazine-2-carbohydrazonamide) are explored in detail. With a detailed scrutiny of visualizing of title compound 1, the crystal packing is mainly directed by strong hydrogen bonding interactions observed N–H⋯N and N–H⋯O but, in addition, weak interactions such as C–H⋯π, π⋯π are also sighted to stabilize the crystal self-assembly. Electronic structure of the complex is determined using DFT calculations at B3LYP level with mixed basis set. Theoretically calculated structural parameters are in good match with the experimentally obtained parameters from XRD. TDDFT calculation is performed to simulate the UV–Vis absorption spectra of the complex. Molecular reactivity and stability of the complex has been assessed through frontier molecular orbital analysis and also through evaluation of molecular electrostatic potential (MEP). Hirshfeld surface analysis, which uses molecular surface contours and 2D fingerprint plots to visually analyze intermolecular interactions in crystal structures, has been used to examine molecular morphologies. The Hirshfeld surface and fingerprint plots are accompanied by crystal structure analysis allowed for the discovery of the important intermolecular interactions.

Pyrimidine-based sulfonamides and acetamides as potent antimicrobial Agents: Synthesis, Computational Studies, and biological assessment

A series of novel sulfonamide and acetamide derivatives of pyrimidine were synthesized and their antimicrobial activities were assessed. Based on the Microbroth dilution method, the minimum inhibitory concentration (MIC) of the synthesized compounds demonstrated moderate to good levels of antifungal and antibacterial activity. Structure-activity relationship analysis suggested that the presence of electron-withdrawing groups, such as halogens, nitrile, and nitro groups, on the pyrimidine ring contributed to the enhanced antimicrobial potency, while electron-donating substituents led to a decrease in activity. Computational studies, including density functional theory (DFT), frontier molecular orbitals (FMO), and molecular electrostatic potential (MEP) analysis, provided insights into the electronic properties and charge distribution of the compounds. Drug-likeness evaluation using ADME/Tox analysis indicated that the synthesized compounds possess favorable physicochemical properties and could be potential drug candidates. Molecular docking against the Mycobacterium TB protein tyrosine phosphatase B (MtbPtpB) revealed that the synthesized compounds exhibited strong binding affinities (−46 kcal/mol to − 61 kcal/mol) and formed stable protein–ligand complexes through hydrogen bonding and π-π stacking interactions with key residues in the active site. The observed interactions from the docking simulations were consistent with the predicted interaction sites identified in the FMO and MEP analyses. These findings suggest that the synthesized pyrimidine derivatives could serve as promising antimicrobial agents and warrant further investigation for drug development.

Microwave-assisted click synthesis, characterisation, and In silico studies of novel 2H-chromene-1,2,3-triazolyl glycoconjugates as potent anticancer and antibacterial agents

A series of novel 2H-chromene-1,2,3-triazolyl glycoconjugates 10a-w were synthesized, well characterized and evaluated for their in vitro antimicrobial and anticancer activities. Among the tested compounds, 10a, 10b, 10u, 10v, and 10w exhibited the most excellent potency against both gram-positive (S. aureus) and gram-negative (E. coli) bacterial strains relative to the standard drug, Gentamicin. The anticancer results showed that in MCF-7 cell line all the tested compounds exhibited better activity as compared to other two cancer cell lines (MDA-MB-231 and A549). Compounds 10t, 10u, 10v, and 10w showed significant cytotoxicity against MCF-7 cell line. The molecular docking studies suggested that all the four potent compounds exhibited a greater affinity for the selected receptors. Experimentally and computationally observed structure-activity relationships indicates, -OCH3 group at R2 position in benzopyran ring with tosyl-protected sugar containing compound 10b and benzyl-protected sugar containing compound 10t enhanced the antibacterial and anticancer activity respectively. Frontier molecular orbital analysis of compounds using the global reactivity parameters indicated that benzyl-protected sugar and acetyl-protected sugar containing compounds are stable and exhibits low reactivity. Moreover, molecular electrostatic potential analysis plots clearly showed that the compounds have strong electrophonic reaction potential. Moreover, the assessment of ADMET predictions revealed favourable pharmacokinetic properties of the investigated compounds. Collectively, it was observed that compounds 10u, 10v, and 10w could be considered as promising dual anticancer antibiotic inhibitors.

Adsorption and dissociation of NO on gold–palladium alloy clusters: A density functional theory study

Alloy nanoclusters often exhibit distinctive and exceptional performance, making them especially appealing as catalysts. In this study, the adsorption and dissociation of NO on AumPdn (m + n = 8) clusters was studied using density functional theory (DFT). The most stable structures of AumPdn (m + n = 8) clusters were reported by the CALYPSO search screening program and DFT geometric optimization. The binding energy and bond critical point (BCP) analysis show that alloying could lead to a more compact structure and relatively stronger stability. Molecular electrostatic potential (MESP) analysis revealed that the optimal site for the adsorption of the NO molecule on AumPdn (m + n = 8) clusters was at the top site, with Pd atoms being the preferred choice. Projected density of states (PDOS) calculations demonstrate that the d-band center of the Au5Pd3 cluster was closest to the Fermi level, enhancing the interaction between the cluster surface and adsorbed molecules. The activation energy of NO dissociation on the Au5Pd3 surface is the lowest at 0.48 eV. These findings indicate that the Au5Pd3 nano-alloy cluster shows promise as an effective catalyst in the direct transformation of NO into non-toxic substances.

Quantum Chemical Computational Studies on the Structural Aspects, Spectroscopic Properties, Hirshfeld Surfaces, Donor-Acceptor Interactions and Molecular Docking of Clascosterone: A Promising Antitumor Agent

In the present investigation, computations based on density functional theory (DFT) were employed to scrutinize the molecular configurations of clascosterone. Optimization was achieved using the DFT/B3LYP method with the 6-31G (d,p) basis set to thoroughly explore its structural and spectroscopic features. Additionally, molecular electrostatic potential (MEP) and Mulliken population analyses were conducted to comprehend the bonding characteristics and reactive sites. The Hirshfeld surface highlighted predominant H•••H interactions (71.5%), followed by O•••H interactions (25.5%). The stability of the compound was confirmed through the determination of hyperconjugative interactions using Natural Bond Orbital (NBO) analysis. Furthermore, molecular docking assessed the potential biological significance of clascosterone as an antitumor agent, targeting SMAD proteins like SMAD3 and SMAD4, resulting in binding energies of -8.22 and -8.57 kcal/mol, respectively.

Theoretical study the photophysical mechanism of fluorescent probe on detecting mitochondria-targeted hydrogen peroxide

The photophysical mechanism and dynamics behaviors of (E)-4-(2-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)vinyl)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)pyridin-1-ium (Compound 1) on detecting hydrogen peroxide (H2O2) has been theoretically studied. The boron ester in Compound 1 is cleaved when H2O2 is added to the solution, resulting in the formation of (E)-7-(diethylamino)-3-(2-(pyridin-4-yl)vinyl)-2H-chromen-2-one (Compound 2). Theoretical calculations show that the fluorescence spectra of the compounds exhibit a significant blue shift from 616 nm of Compound 1 to 542 nm of Compound 2 before and after the reaction, which are in good agreement with the experimental results (640 nm → 535 nm). The calculated electron–hole transfer distance of Compound 1 (5.986 Å) is larger than that of Compound 2 (3.544 Å), and Compound 1 is demonstrated to be charge transfer excitation while the Compound 2 is localized excitation, which results in a blue shift of the fluorescence spectra. The analysis of molecular electrostatic potential demonstrates that compound 1 has the highest electrostatic potential (4.60 eV) at the pyridine position and the lowest (−0.30 eV) at the oxygen atom of the coumarin moiety, suggesting that compound 1 undergoes fragmentation at this position. This study provides a theoretical explanation for the reaction mechanism of molecular probes.