Molecular Surface Analysis Research Articles

The solid–liquid equilibrium behavior of ε-CL-20 in 10 pure solvents and its molecular mechanism

The solubility performance of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane has been investigated by the combination of experimental measurement, solvent parameter analysis, and molecular simulation methods. The solubility in 10 pure solvents at 293.15 K to 343.15 K was determined. It was found that the solubility in nine solvents increased with temperature, except for isoamyl propionate. However, it has the largest solubility in isoamyl propionate (4.36 × 10−2 ∼ 5.39 × 10−2). Additionally, a correlation analysis was performed using four equations, which showed that the NRTL equation provided the best fit (overall average relative deviation = 3.74 %, overall coefficient of determination = 0.991). Moreover, the solvent effect was analyzed by Hansen solubility parameters, predicting good solubility in solvents with Ra(V) ≤ 12.47 MPa0.5 or Δδt ≤ 7.77 MPa0.5, indicating weak polarity of solvent and weak solvent–solvent intermolecular hydrogen bonds enhance dissolution. Furthermore, molecular electrostatic potential surface and radial distribution function analyses provided that weak hydrogen bonding C-H···O promotes dissolution.

The facile preparation of polydopamine-modified sepiolite and its adsorption properties and microscopic mechanism for cadmium ion

Natural sepiolite (SEP) has the characteristics of cation exchange, abundant reserves, low cost, and environmental friendliness, but its adsorption capacity for heavy metal pollutants is limited. Because polydopamine (PDA) molecules contain rich functional groups such as phenolic and amino groups, in the present work, dopamine and natural sepiolite were utilized as raw materials to prepare polydopamine-modified sepiolite composite (SEP/PDA) by simple co-precipitation method. According to Langmuir isotherm model, the maximum adsorption capacity of SEP/PDA for Cd2+ can reach 203.21 mg/g at 298 K. At the initial concentration of 100 mg/L, the adsorption capacity was 2.9 times that of natural sepiolite. The composite material has good reusability and anti-cationic interference performance and has 100 % removal ability of low concentration Cd2+ in actual electroplating wastewater. Density Functional Theory (DFT) calculations were performed to obtain the electronic structure information. To elucidate the microscopic mechanism, molecular surface analyses, Interaction Region Indicator (IRI), Atom In Molecules (AIM) theory, Bond Order Density (BOD), and Electron Localization Function (ELF) were conducted. These analyses revealed that the amino nitrogen and phenolic oxygen atoms in the dopamine molecules donate lone pair electrons to coordinate with cadmium ions. Polydopamine, which possesses multiple oxidation states, contains catechol, quinone, and indole or a lesser extend pyrrole groups that can complex with cadmium ions, resulting in the formation of a surface complex. This coordination significantly enhances the adsorption properties of the SEP/PDA composite.

Structural analysis and theoretical studies of 2-(2-chlorobenzylidene) malononitrile (CS) “a riot controlling agent”

In solvent methanol, malononitrile and 2-chlorobenzaldehyde were stirred in the presence of base piperidine to synthesise the target chemical 2-(2-chlorobenzylidene) malononitrile (CS). The crystal structure of the target compound C10H5ClN2 has been elucidated through X-ray crystallographic analysis. It crystallises in the monoclinic crystal system within the P21 space group, containing four molecules per asymmetric unit. The unit cell dimensions are a = 3.8825(3) Å, b = 21.0202(18) Å, c = 21.3481(18) Å, and β = 95.096(4)°. The phenyl and malononitrile groups, which make up the molecular components, are each planar but slanted towards one another at a dihedral angle of 12.7° (4). Besides this, target molecule is also stabilized by hydrogen bonding, halogen bonding and π stacking interactions. Solid-state structure has been analysed through Hirshfeld surface analysis, including the evaluation of the different energy frameworks, indicating that the molecular sheets are primarily formed by hydrogen bonds and halogen bonds and the stabilization is dominated via the electrostatic energy contribution. Fingerprint plots were carried out to study the relative contribution of noncovalent interactions in the target compound CS. Further, the density functional theory calculations were employed using B3LYP hybrid functional with 6-311++G level basic set to optimize the structural coordinates in gas phase and in different solvents (chloroform, water, and methanol). The chemically active regions of the target compound were identified by the analysis of molecular electrostatic potential surface. Further, from PASS analysis and literature reports, molecular docking of title compounds was carried out with human transient receptor potential ankyrin 1 ion channel (hTRPA1) (PDB-ID 6PQO). ΔGb (docking energy) and inhibition constant was calculated to be −7.53 kcal/mol and 3.33 μM respectively, with the target ion channel.

Unveiling the adsorption mechanism of propanehydrazine derivatives on magnesium oxide surface: Insights from computational approach

The use of green and effective inhibitors for preventing metal oxide (MgO) corrosion in industrial applications is highly significant in promoting environmental protection and sustainable development. This study delves into the adsorption behavior and interfacial mechanism of environmentally friendly inhibitor derived from propane hydrazine (PH) on MgO surface. Specifically, PH1, PH2, PH3, and PH4 were explored for their effectiveness in preventing corrosion by using advanced theoretical simulations-based density functional theory (DFT) for assessing the reactivity and adsorption characteristics. The study considered a detailed exploration of local and global reactivity descriptors, providing insights into the inhibitors’ reactivity and adsorption abilities in both isolated and adsorbed states. These findings focus more in the mechanisms underlying organic-inorganic interactions and present promising prospects for further development and application. Using first-principles DFT calculations alongside quantitative molecular surface analyses, we examined the adsorption patterns of PHs on the MgO(100) surface. These investigations are boosted by the application of independent gradient model (IGM) framework, providing robust verification of PHs' adsorption behavior on MgO(100) surface. Our calculations reveal a substantial decrease in the energy gap following complex formation, suggesting that charge density changes occur upon interaction with MgO surfaces, thereby facilitating direct electron transfer in all the studied systems. Noreover, the results highlight the crucial role of intermolecular interactions in boosting the interaction between PHs and the [Mg(H2O)6]2+ cation. First-principles DFT calculations show that all PH molecules consistently display parallel adsorption on the MgO surface, where the oxygen atoms form bonds with adjacent magnesium atoms. The bond lengths vary from 2.18 to 2.35 Å when PHs bind to the Mg atoms in parallel orientations through the oxygen atom, suggesting a stable parallel arrangement for PH molecules on the MgO surface. The calculated adsorption energy (Eads) varies in the following order: MgO-PH3 (−815.14 Kcal mol−1) > MgO-PH2 (−803.85 Kcal mol−1)) > MgO-PH4 (−695.38 Kcal mol−1) > MgO-PH1 (−125.77 Kcal mol−1). This trend indicates that parallel interactions enhance the adsorption behavior and binding of PH compounds through inter- and intra-molecular interactions, resulting in the PHs being centered at specific sites on the MgO surface. The potential enhancement in electrochemical properties is believed to stem from the synergistic interaction between the PHs and the MgO surface, which theoretically allows for a precise adjustment of their adsorption and interaction within the composite structure. This understanding provides a fundamental framework for examining the complex interfacial dynamics between inhibitor structures and elucidating how these molecular interactions influence the selection of corrosion inhibitors and their adsorption behaviors on the corrosion layer's surface, rather than on metallic Mg.

Anticancer activity, DFT calculation, ADMET study and molecular docking of synthetic Chalcone (2E)-1-(4-Aminophenyl)-3-(3,4,5-trimethoxyphenyl)-2- propen-1-one in breast cancer cell line (MCF-7)

The (2E)-1-(4-Aminophenyl)-3-(3,4,5-trimethoxyphenyl)-2-propen-1-one was prepared by the reaction between 4-aminoacetophenone and 3,4,5, trimethoxy benzaldehyde in ethanolic NaOH. Then in vitro anticancer activity was evaluated against the MCF-7 breast cell line. The molecular properties like bond length, bond angle, molecular electrostatic potential surface (MEPs), Mullikan charge, HOMO-LUMO, and NBO analysis data obtained by DFT/B3LYP method using 6- 31+G(d,p) basis set to get electronic states and molecular parameters of the title molecule. Because of their advantageous pharmacokinetic properties, the synthesized compound was shown to have moderate anticancer activity and could advance to a higher level of the drug development process. Molecular docking studies were utilized to foresee the binding interactions of the title compound with the EGFR tyrosine kinase domain (PDB ID: 1M17). In silico ADME study is also performed to predict the pharmacokinetic profile which expressed good oral drug-like behavior.

Novel Trifunctional Intramolecular Frustrated Lewis Pair Derived From Aminoboronic Acid for Converting CO2 Into Valuable Chemicals

ABSTRACTThe conversion of CO2 into valuable chemicals remains a significant challenge for achieving environmental sustainability, primarily due to the stability of the CO2 molecule. This necessitates the development of efficient and ecofriendly catalysts. In recent years, frustrated Lewis pairs (FLPs) have shown promise for CO2 utilization. In this study, we introduce α‐aminodiboronic acid (DBA), a novel trifunctional aminoboronic acid, as an intramolecular FLP for converting CO2 into cyclic carbonate and formic acid. Using density functional theory (DFT) calculations, we explored the reaction mechanism and investigated DBA's electronic structure through molecular electrostatic potential surface (MESP) and natural bond orbital (NBO) analyses. Our results reveal that one −B (OH)2 group induces an unusual state of frustration in the molecule due to charge transfer from the nitrogen atom's lone pair to the π* orbitals, enhancing catalytic performance. The additional −B (OH)2 group serves as an anchoring site for reactive species. The epoxide activation energy is reduced by approximately 27 kcal/mol compared to the uncatalyzed reaction, and the reduction of CO2 occurs with a requirement of 26 kcal/mol. The additional −B (OH)2 plays a crucial role in the catalytic mechanism and minimizes the energies of various structures observed in the reaction path. The reaction energetics align with structural analysis observations, marking this study as the first report on single‐molecule trifunctional FLPs for transforming CO2 into valuable chemicals.

Solubility behavior and solvation effect of a photomechanical molecular crystal trans-4-chlorocinnamic acid in twelve neat solvents at temperatures from 283.15 to 323.15 K

Solubility of trans-4-chlorocinnamic acid as a photomechanical molecular crystal material in twelve pure solvents (water, ethanol, methanol, n-propanol, isopropanol, n-butanol, isobutanol, acetonitrile, 1,4-dioxane, acetone, methyl acetate and ethyl acetate) were measured from 283.15 to 325.15 K at 101.2 kPa. The results showed that the trans-4-chlorocinnamic acid solubility increased with the temperature, the order is: 1,4-dioxane > acetone > n-butanol > ethanol > n-propanol > isopropanol > isobutanol > methanol > methyl acetate > ethyl acetate > acetonitrile > water. Powder X-ray diffraction pattern (PXRD) and differential scanning calorimetry (DSC) were used to identify and characterize the equilibrated solid phase samples. The solubility behavior and the solute–solvent interaction of trans-4-chlorocinnamic acid in each selected mono-solvent were explored by the empirical solvents polarity parameter (ET(30)), hydrogen bonding, cohesive energy density, molecular structure, and Hansen solubility parameters (HSPs). In addition, the experimental solubility data were correlated by the modified Apelblat model and Yaws model, and the fitting results of this models were all satisfactory. The intermolecular forces were determined through molecular simulations, including Hirshfeld surface (HS) and Molecular Electrostatic Potential Surface (MEPS) analysis. The results showed that hydrogen bond can be formed between trans-4-chlorocinnamic acid and the selected solvents, which can help to further explain the dissolution behavior of trans-4-chlorocinnamic acid in the solvents.

Single crystal, conformational, quantum reactivity, hirshfeld surface, molecular interactions, ADMET, and molecular docking investigations on HIV-1 site of 3-isopropyldiphenyl-1-(2-(thiophen-2yl)acetyl)piperidin-4-one

The 3-isopropyl-2,6-diphenyl-1-(2-(thiophen-2yl)acetyl)piperidin-4-one (IPTP) single crystals were grown by slow evaporation method and the structure is confirmed through FT-IR, 1H NMR, and 13C NMR spectral analyses. Single crystal X-ray diffraction revealed that the title compound having chair conformation of the piperidine ring, with an axial orientation of phenyl rings at C-2 and C-6 positions and an isopropyl group at C-3. Hirshfeld surface analysis was employed to examine intermolecular contacts and strong and weak attractive, repulsive, and van der Waals interactions in the molecule were determined using the reduced density gradient method (RDG). The geometrical parameters obtained through Density Functional Theory are compared with experimental values and also conducted to optimize structural parameters, frontier molecular orbitals (FMOs), and molecular electrostatic potential surface analysis (MEPS). NBO calculations were employed to investigate intermolecular and intramolecular charge movement, as well as the molecule's stability. Vibrational Energy Distribution Analysis (VEDA) software facilitated potential energy decomposition (PED) analysis using FT-IR wave numbers. The title compound molecular docking data were compared with the markedly available FDA-approved anti-HIV drug of Nelfinavir and their results were discussed, ADME analysis studies were discussed concerning FDA-approved anti-HIV drugs, including Nelfinavir, Betulinic Acid, Haloperidol, and Donepezil.

Dissolution behavior and thermodynamic study of N-ethyl-2,2-diisopropylbutylamide in fourteen mono solvents by experiments and molecular simulation

N-ethyl-2,2-diisopropylbutylamide (WS-27) is a new cooling agent with a soothing, long-lasting cooling effect, widely used in personal care and cosmetic products. The dissolution behavior of WS-27 in fourteen mono solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, n-pentanol, methyl acetate, ethyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dichloromethane, cyclohexanone, and acetone) was measured using a dynamic laser monitoring method from 263.15 K to 298.15 K under 101.6 ± 1.2 kPa. In these selected solvents, the solubility of WS-27 increased with increasing temperature. The van't Hoff equation, λh equation, modified Apelblat equation, Wilson model, and NRTL (non-random two-liquid) model were applied to correlate the experimental solubility data of WS-27, and the modified Apelblat equation showed the best-fitting results. In addition, the intermolecular interactions and solvent effect were analyzed using the Hirshfeld surface analysis, molecular electrostatic potential surface analysis, and KAT-LSER model analysis to understand the dissolution behavior of WS-27. The results indicate that the solubility of WS-27 is influenced by multiple factors, and there can be other factors as well. These fundamental data can provide essential information for the crystallization and purification process of WS-27.

Highly selective and sensitive immunoassays for flurogestone acetate analysis in goat milk: From rational hapten design and antibody production to assay development

The preparation of high specificity and affinity antibodies is challenging due to limited information on characteristic groups of haptens in traditional design strategy. In this study, we first predicted characteristic groups of flurogestone acetate (FGA) using quantitative analysis of molecular surface combined with atomic charge distribution. Subsequently, FGA haptens were rationally designed to expose these identified characteristic groups fully. As a result, seven monoclonal antibodies were obtained with satisfactory performance, exhibiting IC50 values from 0.17 to 0.45 μg/L and negligible cross-reactivities below 1% to other 18 hormones. The antibody recognition mechanism further confirmed hydrogen bonds and hydrophobic interactions involving predicted FGA characteristic groups and specific amino acids in the antibodies contributed to their high specificity and affinity. Finally, one selective and sensitive ic-ELISA was developed for FGA determination with a detection limit as low as 0.12 μg/L, providing an efficient tool for timely monitoring of FGA in goat milk samples.

Investigations on the growth and antibacterial behaviour of bioactive creatininium hydrogen bromide (CRBr) single crystal

The major aim is to synthesize a creatininium hydrogen bromide (CRBr) single crystal through a slow evaporation technique, and its antibacterial activity. According to Single Crystal X-ray Diffraction (SXRD) analysis, the generated crystal belongs to monoclinic structure and centrosymmetric space group P21/n. The optimized structural parameters explain the structural stability with NH…O, CH…O, and OH…O interactions. To verify the existence of intermolecular interactions, Hirshfeld surface analysis of a grown-up single crystal was carried out and that shows the stable nature of the molecule. Intermolecular and intramolecular hydrogen bonding, intermolecular charge transfer and delocalization of electron density can all be studied effectively by Natural Bond Orbital (NBO) analysis. In addition to examining the functional groups, the vibrational analysis gives the absorption peaks and bands associated with the formed crystal. The generated crystal has thermal stability up to 200 °C according to TG/DTA analysis. The material's electronic transition was determined by analyzing the UV–visible absorbance spectrum, showing an optical band gap of 4.2 eV and a lower cut-off wavelength of 265 nm. The charge transfer within the molecule has been elucidated using frontier molecular orbital analysis that shows its antibacterial properties. Molecular electrostatic surface analysis shows that excellent ICT interactions exist in the crystal lattice, where the positive potential is scattered throughout the creatinine portion and the negative region is dispersed on the bromine atom. Molecular docking has been used to examine the compound's antibacterial properties. In addition, the generated compound is tested for its in vitro antibacterial activity against several bacterial strains, including Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Bacillus cereus, and Staphylococcus aureus. The above findings demonstrated the remarkable antibacterial effectiveness of the compound under study.

Spectroscopic characterization, quantum chemical and molecular docking investigations on methyl indole-3-carboxylate: A potent cervical cancer drug

Bioactive indole derivatives had great importance in recent years due to their numerous biological and pharmaceutical applications. In the present work, the vibrational, electronic, physicochemical, and inhibitory properties of the Methyl Indole-3-Carboxylate (MIC) molecule were predicted and analyzed. Initially, the molecular structure of the title molecule was optimized and its structural parameters were calculated, which were highly correlated with the previous reports. The simulated infrared and Raman spectra of the molecule were in good agreement with the FT-IR and FT-Raman spectra that were observed via the experiment. The observed UV–Visible spectrum validates the MIC molecule's π→π* electronic transition, which was also well matched with the simulated UV–Visible spectrum. The investigation of frontier molecular orbitals highlights intramolecular charge transfer across the molecule, establishing the bioactivity of the MIC molecule. The electron transport from the methyl group hydrogen atom H22 to the oxygen atom O11 is confirmed by Mulliken atomic charge distribution analysis and molecular electrostatic potential surface analysis. The calculated Fukui functions values validated the FMOs and Mulliken atomic charge distribution results. The natural bond orbital study further confirms the MIC molecule's intramolecular charge transfer and bioactivity. Molecular docking investigation results that the MIC molecule hinders the function of an enzyme known as Mitogen-activated protein kinase 14, which has been linked to cervical cancer. As a result, the present study provides the possibility towards the development of innovative to treat cervical cancer.

DFT and Molecular Docking Studies of Two Heterocyclic Chalcone Derivatives

AbstractThe newly synthesized heterocyclic chalcone derivatives 3‐(5‐methyl furan‐2‐yl)‐1‐phenyl prop‐2‐en‐1‐one (MFPP) and 1‐(4‐chlorophenyl)‐3‐(5‐methylfuran‐2‐yl) prop‐2‐en‐1‐one (CPMFP) are recently being recognized for their cytotoxicity and anti‐plant pathogenic fungi activities. The quantum chemical calculations for the above‐mentioned compounds have been performed using B3LYP/6‐311++G (d,p) level of theory to get perceptive information about the molecules. After verifying the drug‐likeness of the title compounds, chemical reactivity has been analyzed through frontier molecular orbital analysis. The quantitative and qualitative description of activity at various sites has been investigated through conceptual DFT approach and molecular electrostatic potential surface analyses, respectively. In‐silico bioactivity studies of these compounds with the main protease (6LU7) present in SARS‐CoV‐2 causing COVID‐19, human breast cancer cell line (6VJ3), plant pathogenic fungi R. Solani (4G9N), and G. Zeae (2L2F) have exposed a reasonable binding affinity and inhibition constant with all these targets.

Novel Pharmaceutical Cocrystals of Tegafur: Synthesis, Performance, and Theoretical Studies.

Tegafur (TF) is one of the most important clinical antitumor drugs with poor water solubility, severely reducing its bioavailability. This work develops new cocrystals to improve the solubility of TF and systematically investigates the intermolecular interactions to provide new insights into the formation of cocrystal and changes in physicochemical properties. In this paper, two new 1:1 cocrystals of TF with 2,4 dihydroxybenzoic acid (2,4HBA) and p-nitrophenol (PNP) were synthesized. The cocrystal products were identified and characterized by various solid state analysis techniques. And the high performance liquid chromatography (HPLC) was conducted to determine the solubility and dissolution rate of TF and cocrystals. Moreover, the quantum chemistry calculations of crystal structure provided theoretical support for the results. Compared with pure TF, the solubility and dissolution rate of TF-2,4HBA is significantly increased in a pH 6.8 buffer at 37°C. Under accelerated storage conditions (40°C, 75% RH), all cocrystal exhibits excellent stability over 8weeks. Hirshfeld surface (HS) analysis, atoms in molecules (AIM) analysis, interaction region indicator (IRI) analysis, molecular electrostatic potential surface (MEPS) analysis and frontier molecular orbital (HOMO-LUMO) analysis were integrated to understand the hydrogen bonding interaction more comprehensively. The simulation results are in good agreement with the experimental data. The results show that the analysis of physical and chemical properties of TF-PNP cocrystal and TF crystal by quantum chemistry method is reliable at molecular level. These results are helpful to provide guiding methods in the cocrystal development and theoretical study of tegafur.

Synthesis, structure, growth, characterization and quantum chemical studies on 2-amino-5-bromopyridinium trichloroacetate: A novel phasematchable organic NLO single crystal

Organic crystals have become excellent candidates towards nonlinear optical (NLO) applications as they possess superior second and third order optical nonlinearities and high electro-optic coefficients when compared with their inorganic counterparts. In this direction, 2-Amino-5-bromopyridinium trichloroacetate (2A5BPT), a new organic second-order nonlinear optical compound is synthesized and optical grade single crystals are formed utilizing a slow evaporation solution growth approach at room temperature while using methanol as the solvent. Single crystal X-ray diffraction study shows that the title compound is assigned to monoclinic crystal system having non-centrosymmetric space group Cc. The crystal is transparent ( ̴ 85%) throughout the whole visible spectrum, according to the Ultraviolet-Visble (UV–Vis) spectra, with a cutoff wavelength of 367 nm and an optical energy band gap Eg of 3.32 eV. The crystal possesses good thermal stability. The compound has a 1.6 times greater powder second harmonic generation (SHG) efficiency than potassium dihydrogen phosphate (KDP). The phase matchability of the 2A5BPT is studied through particle size dependence of SHG. The intermolecular connection demonstrated by numerous inter contacts has been shown by a molecular Hirshfeld surface analysis of the crystal structure, and the related 2-dimensional finger print analysis further evaluates the individual contribution from each atom. In order to examine the first order hyperpolarizability, molecular electrostatic potential, and Highest occupied molecular orbital-Lowest unoccupied molecular orbital (HOMO-LUMO) energies, the quantum chemical calculations for the title molecule (2A5BPT) were carried out by density functional theory (DFT) utilizing the B3LYP/6–311++G(d,p) basis set. According to these results, the 2A5BPT crystal could be suitable for optoelectronic applications.

Understanding the adsorption performance of hetero-nanocages (C12-B6N6, C12-Al6N6, and B6N6-Al6N6) towards hydroxyurea anticancer drug: a comprehensive study using DFT.

Cancer is a paramount health challenge to global health, which forms tumors that can invade nearby tissues and spread to neighboring cells. Recently, nanotechnology has been used to control the growth of cancer, in which anticancer drugs are delivered to cancerous cells via nanoparticles without damaging healthy tissues. In this study, DFT investigations were carried out to examine the adsorption behavior of C24, B12N12, and Al12N12 nanocages as well as their heterostructures C12-B6N6, C12-Al6N6, and B6N6-Al6N6 towards the hydroxyurea (HU) anticancer drug. In this regard, adsorption energy, interaction distance between the drug and nanocages, charge transfer, energy gap, dipole moment, quantum molecular descriptors, work function, and COSMO surface analysis were analyzed to understand their adsorption performance. Findings demonstrate that the adsorption energies of two hetero-nanocages on their hexagonal (SH) and tetragonal (ST) sites are favorable for the drug delivery process. The computed adsorption energy of B6N6-Al6N6 of the ST/AlN site is 183.59 kJ mol-1, which is higher than that of the C12-Al6N6 nanocage, including minimum adsorption distances. Negative adsorption energy with low adsorption distances implies an attractive interaction between the drug and nanocages. During the interaction, a significant amount of charge is transferred between the drug and nanocages. Furthermore, for both complexes, larger dipole moments were observed in water media compared to gas media. From DOS spectra, prominent peaks were found in the Fermi level after adsorption of HU on the nanocages, implying the reduction of the energy gap. Noticeable overlaps between the PDOS spectra of the nanocages and HU's close contact atom demonstrate the formation of chemical bonds between two specific atoms. Therefore, it can be concluded that among the nanocages, C12-Al6N6 and B6N6-Al6N6 may be suitable carriers for HU drug.

Boiling, critical, and freezing temperatures in light of molecular descriptors: correlation and causation.

In the pursuit of tracking some physicochemical properties of fluids down to the molecular level, ab initio molecular surface analyses were performed on 169 molecules. This included electrostatic potential (EP), average local ionization energy (ALIE), and electron localization function (ELF) mapped onto an electron density isosurface value of 0.001 au. Using stepwise linear regression (SLR) analysis, it was found that besides the well-studied EP, ALIE and ELF played important roles in determining the normal boiling and freezing points and critical temperatures of fluids. Apparently, the ALIE and ELF were relevant to the attractive polarization forces and repulsive Pauli forces, respectively, between molecules. To further demonstrate and rationalize this assumption, a localized molecular orbital energy decomposition analysis (LMO-EDA) was carried out. In the LMO-EDA analysis, the complexes of the helium atom, He, and ClCl, ClBr, ClI, OCO, OCS, OCSe, and CO/OC molecules were investigated, where the helium atom faced different molecular sites in each molecule. Fortunately, the results showed that lower the ALIE value on a molecular site, the stronger (i.e., more attractive) the polarization interaction energy. The results also indicated that higher the ELF value on a molecular site, the stronger (i.e., more repulsive) the Pauli interaction. The work is aimed to present novel molecular-based rationales to physical chemists, chemical engineers, and materials scientists.

In-Silico Aided Screening and Characterization Results in Stability Enhanced Novel Roxadustat Co-Crystal

Roxadustat (RXD) is an approved drug substances for the treatment of renal anemia. It has poor aqueous solubility and photochemical stability. This study employs a comprehensive approach to enhance the stability and physicochemical properties RXD through coformer selection and characterization. The investigation integrates delta pKa analysis, molecular complementary assessment, molecular electrostatic potential surface analysis, and machine learning techniques to predict potential co-crystal formation and binding interactions between drug molecules and coformers. The co-crystal screening which lead to in a novel RXD-nicotinamide co-crystal (RXD-NA). Experimental characterization underscores the physical and chemical stability of the co-crystals. To elucidate the supramolecular synthons and understand the intermolecular interactions in the RXD-NA co-crystal, Hirshfeld surfaces analysis, quantum theory of atoms in molecules (QTAIM) analysis and non-covalent interaction (NCI) analysis were performed. Computational analysis of photo-isomer formation aligns with experimental observations, further enhancing our understanding of RXD-coformer interactions. RXD-NA co-crystal was found photo-chemically stable as compared to free base API drug substance. This integrated methodology provides a systematic framework for informed co-crystal design, holding promise for optimizing RXD formulations based on molecular interactions and stability considerations. Consequently, this study contributes valuable insights to the field of rational drug design and formulation optimization.

Nonlinear optical response of silver trimer adsorbed para-aminobenzoic acid: A DFT study

The reported study is motivated by our previously done experimental demonstration of the optical limiting behavior of para-aminobenzoic acid and enhanced nonlinear optical responses of compounds with Ag3 nanoparticle complex. The present study is a theoretical insight into the nonlinear optical responses of para-aminobenzoic acid adsorbed with Ag3 trimer. The enhancement in the optical nonlinearity of the para-aminobenzoic acid after the adsorption of the silver trimer (Ag3) was accounted in the present study. The density functional theory was used to establish the occurrence of the intra and intermolecular charge transfer between the donor and acceptor moieties of the para-aminobenzoic acid and Ag3 trimer. The molecular electrostatic potential surface and inter-fragment charge transfer analysis were used to establish the donor nature of the Ag3 trimer, amino group, and acceptor of the carboxyl group. The absorption spectra and Fourier-transform infrared spectra were used to account for the electronic and vibrational modes. The value of first-order hyperpolarizability of para-aminobenzoic acid and Ag3 complex was observed to increase by six times that of para-aminobenzoic acid. The high value of first-order hyperpolarizability shows the potential nonlinear optical activity of para-aminobenzoic acid adsorbed with Ag3 trimer. The presented study forms a strong base for experimental demonstration of the nonlinear optical activity of the PABA and the silver nanoparticles and the experimental work will be done in the near future for the NLO responses and optical limiting activity of PABA combined with silver nanoparticles.

Prediction of cosolvent effect on solvation free energies and analysis of intermolecular forces of tizanidine hydrochloride in ethyl acetate + methanol / ethanol mixtures

The solubility of small molecule drug in solvents can be dramatically affected by addition of a suitable cosolvent, which makes the screening of the best-suited cosolvent an important task for the purification and preparation. The present work aims to improve the fundamental understanding of tizanidine hydrochloride (TIZ HC) solvation by cosolvent. Solubility experimental data from TIZ HCl in mixtures of ethyl acetate + alcohols were obtained at different temperatures with the method of isothermal equilibrium. In the system of ethyl acetate + methanol, the solubility data increased firstly and then decreased with an increase in ethyl acetate content, however, the strictly monotonic decreasing of solubility in ethyl acetate + ethanol mixtures was observed. The solubility correlation fitting was performed with the Jouyban-Acree model and CNIBS/R-K model. The solvent effect analysis indicates that the hydrogen bond acidity, the polarity / polarizability and the cohesive forces of the solvent have a greater influence on the solubility, which was further validated by the local quantitative molecular surface analysis results of electrostatic potential (ESP). The dissolution process of TIZ HCl in systems with different solvent compositions was analyzed in the form of preferential solvation parameters, it was found that methanol is the preferred solvent in the solvation shell of TIZ HCl in methanol-rich and ethyl acetate-rich mixtures but the ethanol is preferred in intermediate compositions and ethyl acetate-rich mixtures. Moreover, the types of intermolecular solute–solvent interactions were discussed on the basis of the structural characteristics of TIZ HCl. The solvation free energy is a key parameter describing solvent effects, which is extremely important for understanding solution chemistry. For this part, with the aid of density functional theory (DFT) and molecular dynamics (MD) simulations, it was found that the cosolvent effect is consistent with the prediction trend of solvation free energy of TIZ HCl in each systems. The effect of the cavity formed by the solvent molecules and dipole moment of solute was calculated accordingly by the solvation model based on density (SMD) for explaining the former behavior.