Global Reactivity Descriptors Research Articles

Free radical scavenging activity of gallic acid toward various reactive oxygen, nitrogen, and sulfur species: a DFT approach

Gallic acid is a well-recognized naturally occurring compound possessing antioxidant activities. The free radical scavenging ability of gallic acid for fifty reactive species, such as oxygen, nitrogen, and sulfur-containing species, has been studied using the formal hydrogen atom transfer mechanism. The theoretical studies have been conducted in the gas phase and aqueous solution at M05-2X/6-311++G** level using the density functional theory (DFT) calculations. The relative damaging potential of all the reactive species has been compared by investigating their hydrogen atom and electron affinity. Furthermore, a comparison of their relative reactivity was made by evaluating several global chemical reactivity descriptors. Additionally, the feasibility of scavenging the species by gallic acid has been studied by computing the redox potentials and equilibrium constants for the overall process in the aqueous solution.

Electro‐Optical Properties of MBBA Liquid Crystal Surrounded by Acetonitrile Medium Enhanced under the Presence of Electric Field: An Ab Initio Study

AbstractThis study has used ab initio technique to investigate the electro‐optical and electronic properties of N‐(4‐methoxybenzylidene)‐4‐butylaniline (MBBA), a nematic liquid crystal between 21 and 48 °C, surrounded by gas and acetonitrile medium, in the presence and absence of electric field. The optimization and analysis of various electro‐optical and electronic parameters along with absorption spectrum have been performed using ωB97xD/6‐311+G(d,p) and M062X/6‐311+G(d,p) methods. Under the electric field, electro‐optical parameters of MBBA surrounded by acetonitrile are increased, indicating its suitability for display device development application. Global reactivity descriptors reveal that electronic properties of the MBBA LC also high in acetonitrile medium as compared to that of the gas. Furthermore, using second order perturbation theory and the multicentered‐multipole expansion technique, the mutual interactions between a pair of MBBA molecules are examined, revealing the nematic behavior of MBBA molecule.

Phytochemical components of Allium Jesdianum flower as effective corrosion-resistant materials for Fe(1 1 0), Al(1 1 1), and Cu(1 1 1): DFT study

As anticorrosive materials, natural products such as flower extracts are widely used. In lieu of using the whole product, it is better to apply the isolated phytochemical active component among all existing components in the flower as anticorrosive. Therefore, identifying the component or components responsible for anticorrosion paves the road for its experimental synthesis and effective application. In the present investigation, a comprehensive investigation of three phytochemicals present in Allium Jesdianum (AJ) flower, namely Methyl heptadecanoate (Palmitic acid), Ethyl (9Z,12Z)-octadeca-9,12-dienoate (a-Linolenic acid), and Icosan-1-ol (1-Ecosanol) was characterized using computational methods (DMol3, and Monti Carlo (MC) simulations) to determine the inhibition potentials for corrosion, chemical reactivities, and adsorption behaviors. Isolated forms were characterized by local and global reactivity descriptors such as the energies and distributions of the highest occupied molecular orbitals (HOMOs), Lowest unoccupied molecular orbitals (LUMOs), their gaps, hardness (h), global softness (s), global electronegativity (χ), chemical potential (μ), electrophilicity (ω), nucleophilicity (ε), electron-accepting power (ω-), electron-donating power (ω+), and net electrophilicity (Δω±). A further investigation has been made into the adsorption of three types of industrial metals, namely Fe(110), Al(111), and Cu(111). Based on the most stable adsorption configurations, the three phytochemicals adsorbed parallel to all surfaces. Adsorbate and surfaces interact primarily via chemisorption. In line with this result, the radial distribution function (RDF) has been analyzed. Computed parameters illustrated 1-Ecosanol's superiority over other phytochemicals and justified the reason behind its efficiency.

Experimental and theoretical studies of a thiourea derivative: 1-(4-chloro-benzoyl)-3-(2-trifluoromethyl-phenyl)thiourea

The 1-(4-chloro-benzoyl)-3-(2-trifluoromethyl-phenyl)thiourea compound was synthesized by a two-step reaction and a single crystal of it was obtained by recrystallization method. Its structure was elucidated by elemental analyzes, FT-IR, 1H NMR, and 13C NMR techniques, and its molecular and crystal structure was also determined by single-crystal X-ray diffraction analysis. The Hirshfeld surface analyzes of the crystal structure indicate that the most important contributions for crystal packing are from H···H (23.8%), H···S/S···H (14.5%), H···F/F···H (14.3%), C···H/H···C (14.2%), and Cl···F/F···Cl (9.0%). In addition, energy-framework calculations are used to analyze and visualize the three-dimensional topology of the crystal packing. The electrostatic energy framework is dominant over the dispersion energy framework. The density functional theory method with the basis set of B3LYP/6-311G(d,p) has been employed to obtain the optimized structural geometry, Mulliken charges, molecular electrostatic potential, frontier molecular orbitals, the total density of states, reduced density gradient analysis and natural bond orbitals. The experimental crystal structure parameters and optimized structure parameters are very similar. The HOMO–LUMO energy gap of the compound is 3.5307 eV. Different global chemical reactivity descriptor parameters were also calculated. Nonlinear optical properties such as anisotropy of polarizability, mean polarizability, static dipole moment, and first-order hyperpolarizability values were theoretically determined. The Fukui functions as electron density-based local reactivity descriptors were also calculated to explain the chemical selectivity or the reactivity site in the molecule. Molecular docking studies were also carried out to determine the inhibitory action of the title compound against the main protease (6LU7) of a new coronavirus (COVID-19).

Synthesis, spectroscopic characterization, DFT and molecular dynamics of quinoline-based peptoids

Peptoids mimic the functions of peptides which have a side chain appended to amidic nitrogen instead of α carbon. This structural change in their backbone gives them increased resistance from proteolysis, improved biostability, greater immunogenicity, and better bioavailability. Therefore, they are specifically designed for various biological activities, including antibacterial, antifungal, antioxidant, antifouling, and anticancer properties. The aim of the research is the one-pot synthesis of quinoline-based peptoids 5(a-b)via Ugi-4CR by the reaction of 1R-(-)-myrtenal 1, benzylamine 2, quinoline-based carboxylic acids 3(a-b), and cyclohexyl isocyanide 4. These peptoids were characterized by FT-IR, 1H NMR, 13C NMR, and HR ESI-MS. In computational studies, the spectral results of 5(a-b) were compared with the calculated spectral values computed at B3LYP/6-311G (d,p) level. TD-DFT method was used to predict electron excitation of 5(a-b) and the contribution of orbitals. The electronic transition of peptoids from charge distribution was computed using natural bond order (NBO) analysis. NPA and MEP analysis was calculated to predict charge distribution in 5(a-b). The FMOs analysis was executed to calculate the global reactivity descriptor to predict the reactivity and stability of peptoids. DFT analysis showed that 5b was slightly more reactive than 5a due to extended conjugation. The biological activities were also predicted using an in silico approach that involved molecular docking and molecular dynamic (MD) simulations. The antiulcer, antibacterial, and antifungal activities were predicted based on ligand–protein binding interactions, binding energy calculations, and dissociation constants. 5(a-b) were evaluated in-vitro for anticholinesterase activity, and they showed 71% inhibition. The umbrella sampling was performed to probe ligand–protein binding.

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy framework, docking and molecular dynamic simulations of (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one as anticancer agent

In this work, a novel crystal, (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (E-BSP) was synthesized via Knoevenagel condensation of benzaldehyde and (E)-6-(4-methoxystyryl)-4,5-dihydropyridazin-3(2H)-one. The molecular structure of E-BSP was confirmed by using FT-IR, 1H-NMR, 13C-NMR, UV-vis, ESI-MS, TGA/DTA thermal analyses and single crystal X-ray diffraction. The DFT/B3LYP methods with the 6-311++G(d,p) basis set were used to determine the vibrational modes over the optimized structure. Potential energy distribution (PED) and the VEDA 4 software were used to establish the theoretical mode assignments. The same approach was used to compute the energies of frontier molecular orbitals (HOMO-LUMO), global reactivity descriptors, and molecular electrostatic potential (MEP). Additionally, experimental and computed UV spectral parameters were determined in methanol and the obtained outputs were supported by FMO analysis. Molecular docking and molecular dynamics (MD) simulation analyses of the E-BSP against six proteins obtained from different cancer pathways were carried out. The proteins include; epidermal growth factor receptor (EGFR), Estrogen receptor (ERα), Mammalian target of rapamycin (mTOR), Progesterone receptor (PR) (Breast cancer), Human cyclin-dependent kinase 2 (CDK2) (Colorectal cancer), and Survivin (Squamous cell carcinoma/Non-small cell lung cancer). The results of the analyses showed that the compound had less binding energies ranging between −6.30 to −9.09 kcal/mol and formed stable complexes at the substrate-binding site of the proteins after the 50 ns MD simulation. Therefore, E-BSP was considered a potential inhibitor of different cancer pathways and should be used for the treatment of cancer after experimental validation and clinical trial. Communicated by Ramaswamy H. Sarma

Ab initio chemical kinetics of Isopropyl acetate oxidation with OH radicals

ABSTRACT Global reactivity descriptors of isopropyl acetate (IPA) and thermo-kinetic aspects of its oxidation via OH radicals have been studied. Transition state theory (TST) was utilized to estimate the bimolecular rate constants. Ten oxidation pathways have been investigated, and all of them are exothermic. The potential energy diagram has been sketched using different pre- and post-reactive complexes for all reaction pathways. Rate coefficient calculations were obtained directly by connecting the separated reactants with different transition states. The results indicate that the reaction of IPA with OH radicals occurs in the ground state rather than the excited state, and the rate constants obtained directly and from the effective approach are the same, which confirmed the accuracy of the estimated pre-reactive complexes and the reaction mechanism. Rate constants and branching ratios show that hydrogen atom abstraction from the iso C − H (C2 atom) bond is the most kinetically preferable route up to 1000 K, while at higher temperatures, H-atom abstraction from the out-of-plane CH3 group (C3 atom) became the most dominant route with high competition with that of the in-plane CH3 group (C4 atom).

A Theoretical Study of Tris-(<i>o</i>-benzoquinonediimine)-First-Row Divalent Transition Metal Complexes

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.

Synthesis, molecular structure, FMO, spectroscopic, antimicrobial and in-silico investigation of (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-aryl)prop-2-en-1-one derivative: Experimental and computational study

In the present investigation five (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-aryl)prop-2-en-1-one derivatives were prepared by Claisen Schmidt condensation. They are characterized by FT-IR, 1H NMR, 13C NMR, and HRMS spectroscopic methods. Theoretical investigation of these synthesized compounds was carried out by density functional theory (DFT) at the B3LYP/6–31+G(d,p) level of theory. The specifications for optimized geometries, frontier molecular orbitals, global reactivity descriptors, molecular electrostatic potential and harmonic vibrational wavenumber were calculated and addressed. All compounds were evaluated for in vitro antibacterial activities against Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96) and Streptococcus pyogenes (MTCC 442) strains, and in vitro antifungal activities against Candida albicans (MTCC 227), Aspergillus niger (MTCC 282) and Aspergillus clavatus (MTCC 1323) strains by using serial broth dilution method. Synthesized compounds show good antibacterial activity. In silico pharmacokinetics study is also carried out and study shows they have good ADME characteristics and might be used as antimicrobial agent.

Exploration of linear and third-order nonlinear optical properties for donor-π-linker-acceptor chromophores derived from ATT-2 based non-fullerene molecule.

In the current study, seven non-fullerene compounds abbreviated as ATTD2-ATTD8 were designed through structural tailoring and their nonlinear optical (NLO) properties were reported. The objective of this study was to explore the potential for newly configured D-π-A type non-fullerene-based compounds. Quantum chemical methods were adopted and revealed the molecules as highly efficient materials with favorable NLO characteristics for use in optoelectronic devices. The M06 functional along with the 6-311G(d,p) basis set in chloroform solvent were utilized for the natural bonding orbital (NBO) analysis, absorption spectra and computational assessments of frontier molecular orbitals (FMOs), global reactivity descriptors (GRPs), transition density matrix (TDM) and nonlinear optical properties (NLO) for ATTR1 and ATTD2-ATTD8. The HOMO-LUMO energy gap was significantly reduced in all the designed moieties compared to the reference compound in the following decreasing order: ATTR1 > ATTD8 > ATTD4 > ATTD5 > ATTD2 > ATTD7 > ATTD6 > ATTD3. All of the designed molecules (ATTD2-ATTD8) showed good NLO response. Global reactivity parameters were found to be closely associated with the band gap between the HOMO and LUMO orbitals, and the compound with the smallest energy gap, ATTD3, exhibited a lower hardness value of 1.754 eV and higher softness value of 0.570 eV with outstanding NLO response. For the reference compound and ATTD2-ATTD8 derivatives, attributes like dipole moment (μtot), average polarizability 〈α〉, first hyperpolarizability (βtot), and second hyperpolarizability γtot were calculated. Out of all the derivatives, ATTD3 revealed the highest amplitude with a βtot of 8.23 × 10-27 esu, which was consistent with the reduced band gap (1.754 eV) and suggested it was the best possibility for NLO materials in the future.

Investigating the New Schiff Base (E)-2-(((2-bromo-3-methylphenyl)imino)methyl)-4-methoxyphenol Using Synthesis, XRD, DFT, FTIR spectroscopy, Hirshfeld,

In this research, the title compound was synthesized and characterized using spectroscopic analyses like FTIR and XRD. The compoundand#39;s structure was optimized using Density Functional Theory (DFT) at B3LYP method with 6-311++G(d,p) basis set. The experimental parameters obtained by XRD were found to agree well with the theoretically calculated parameters. The title compound was studied using several methods, including FMOs, MEP, Hirshfeld surface analysis, 2D fingerprint plots, net charges, Electrophilicity-based Charge Transfer (ECT), Natural Bond Orbital analysis and global chemical reactivity descriptors.

Structural, electronic and nonlinear optical properties, reactivity and solubility of the drug dihydroartemisinin functionalized on the carbon nanotube

Density functional theory (DFT) calculations of the antimalarial drug dihydroartemisinin (DHA) functionalized on the carbon nanotube (CNT) were carried out in gas phase and in solution to investigate the role of fCNTs as a nanovector for the targeted delivery of the DHA drug and to predict their chemical descriptors and electronic and nonlinear optical (NLO) properties. The results of the geometric optimization indicate that the functionalization does not change the molecular structure of DHA. Based on our findings of binding and solvation energies, two energetically stable configurations were identified in 1st (fCNT1-2) and 2nd (2fCNT1-2) functionalization. For these stable configurations, the energy gap value goes from 1.52 eV for the (5,5) single wall pristine CNT to 1.27 eV for the 1st functionalization and to 1.06 eV for the 2nd functionalization regardless of the considered media; which gives these nanostructures excellent semiconductor properties. Findings from global reactivity descriptors show that the reactivity of the functionalized CNT is strongly improved in solvent media and that the stability of DHA decreases while its reactivity increases during the functionalization. Thus, the fundamental gap (Ef) in gas phase decreases from 3.65 eV for the virgin CNT to 3.30 eV for fCNT2 and to 3.02 eV for 2fCNT2. On the contrary, in water Ef goes from 1.20 eV for the virgin CNT to 0.95 eV for fCNT2 and to 0.74 eV for 2fCNT2; demonstrating an improvement in the reactivity of our fCNTs as nanovectors for targeted delivery of DHA drug. Finally, our findings show that these nanostructures may also have good NLO properties and can be promising materials for NLO applications.

Ab-initio and molecular dynamics simulation of a discotic liquid crystal in ionic solution

ABSTRACT The Physico-chemical, electro-optical and spectroscopic properties of 2,3,6,7,10,11-hexakispentyloxytriphenylene (HPTP) discotic liquid crystal (DLC) have been investigated in gas and NaCl solution using B3LYP/6-311++G(d,p) and M06-2X/6-311++G(d,p) methods. Both the computational techniques yield enhanced values of electro-optical and global reactivity descriptor parameters of HPTP LC molecule in NaCl solution. Neither of the techniques reveal a red or blue shift in the absorption spectra of the LC molecule. The electron localised function (ELF) and frontier molecular orbitals have been examined. Both in gas and solvation medium, electronic circular dichroism (ECD) spectra evidence significant optical activity of the discotic LC molecule. The range-separated hybrid functional such as LC-BLYP/LC-TDDFT formalism has also been used for estimating electronic property and excitation energy of the triphenylene LC molecule; and results obtained by LC-BLYP, B3LYP, and M06-2X computations have been juxtaposed for an extensive comparison. Furthermore, molecular dynamics simulation elucidates that stability and interaction ability of HPTP LC molecule are improved in the ionic (NaCl) solution. These findings provide a new framework for understanding the structural characteristics, and electro-optical, electronic, and dynamical behaviour of discotic triphenylene analogue in ionic solution.

Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids.

Lipophilicity is one of the basic properties of a potential drug determining its solubility in non-polar solvents and, consequently, its ability to passively penetrate the cell membrane, as well as the occurrence of various pharmacokinetic processes, including adsorption, distribution, metabolism, excretion, and toxicity (ADMET). Heterocyclic compounds containing a nitrogen atom play a significant role in the search for new drugs. In this study, lipophilicity as well as other physicochemical, pharmacokinetic and toxicity properties affecting the bioavailability of the quinolone-1,4-quinone hybrids are presented. Lipophilicity was determined experimentally as well as theoretically using various computer programs. The tested compounds showed low values of experimental lipophilicity and its relationship with the type of 1,4-quinone moiety. Introduction of the nitrogen atom reduced the lipophilicity depending on the position at the 5,8-quinolinedione moiety. The bioavailability of the tested compounds was determined in silico using the ADMET parameters. The obtained parameters showed that most of the hybrids can be used orally and do not exhibit neurotoxic effects. Similarity analysis was used to examine the relationship between the ADMET parameters and experimental lipophilicity. The ability of hybrids to interact with biological targets was characterized by global reactivity descriptors. The molecular docking study showed that the hybrids can inhibit the BCL-2 protein.

Computational studies on sulfonamide drug molecules by density functional theory

This paper reports the complete theoretical investigation of Sulfonamide drugs namely Sulfadiazine (SDZ), Sulfamerazine (SMZ) and Sulfamethazine (SMZ) using the Density functional theory (DFT) at B3LYP, CAM-B3LYP and B3PW91 level of theories with 6-311++G(d,P) basis set. The geometrical parameters namely bond lengths and bond angles are computed and compared with the literature values. The frontier molecular orbitals (FMO) have been computed. In addition, the global reactivity descriptors have been calculated using FMO to shine a light on the chemical reactivity and stability of titled molecules. The molecular electrostatic potential (MEP) study has been used to find out the preferred sites for electrophilic and nucleophilic attacks in the titled molecules. The Mulliken atomic charge distribution has been carried out at same level of theories and basis set. The NLO optical parameters have been computed for titled molecules to check their candidature for NLO applications. The assignment of FT-IR spectra of titled molecules has been carried out by potential energy distribution (PED) using the VEDA software. Natural bonding orbitals (NBO) are computed and used to identify the most possible intensive intermolecular interactions.

Synthesis, Structural Characterization and Theoretical NLO Activity of N-(4-Acetyl-5-(4-(Nitro) Phenyl)-4,5-Dihydro-1,3,4-Thiadiazol-2-yl)-N-Phenyl Acetamide

The special properties of organic compounds are due to the polyvalence of the carbon atom. In this research, the organic single crystal of N-(4-acetyl −5-(4-(nitro) phenyl) −4,5-dihydro-1,3,4-thiadiazol-2-yl) -N-phenylacetamide (NTDZ) was successfully synthesized and crystallized in isopropanol by using slow evaporation solution growth method. FT-IR, 1H and 13C NMR spectroscopic techniques were used to characterize the presence of various functional groups in the NTDZ molecular structure. Single crystal X-ray data have been collected and used for the structural determination of NTDZ. The title crystal crystallized in the monoclinic space group P21/c, according to X-ray analysis. Besides, quantum chemical studies were carried out using the density functional theory calculation method. The theoretical and experimental geometrical parameters were compared indicating a good accordance between them. Moreover, surface shapes were displayed using 3D-Hirshfeld surface analysis, and 2D-fingerprint graphs were used to quantify the contributions of C–H…O and C–H…N intermolecular interactions. Furthermore, the vibration spectrum of the NTDZ is calculated and compared with that obtained by FT-IR spectroscopy, and the predicted vibration assignments are made according to the potential energy distribution (PED). The chemical shifts of 1H and 13C-NMR were calculated using the GIAO approximation and compared to experimental values. Using the TD-DFT method, the theoretical UV-Vis absorption spectrum was calculated in chloroform solvent to obtain the most important electronic transitions. Frontier molecular orbitals (HOMO and LUMO) indicate the charge transfer within the molecule. The global chemical reactivity descriptors (GCRD) were calculated. In addition, the MEP was also computed showing the functional groups responsible for building interactions with other molecules. Finally, the nonlinear optical behavior was investigated by the determination of the dipole moment (μ), the polarizability (α), and the first and second hyperpolarizabilities using the same level of theory. All of these findings suggest that the NTDZ crystal may be a viable candidate for NLO applications. Highlights New 1,3,4-thiadiazol derivative was synthesized. X-ray geometry was determined and confirmed by theoretical calculation. Electronic behavior was investigated by DFT and TD-DFT. NLO properties of the compound were also computed.

Synthesis, characterization and biological evaluation of novel 2-aminopridinium nicotinate invitro antifungal, insilico ADME and molecular docking studies

Prospective anti-fungal compound 2-amino pyridinium nicotinate (2APNA) was synthesized and characterized using FT-IR, FT-Raman and UV-visible analysis. To validate the molecular structure, a single X-ray diffraction study was performed. The structure of the molecule was optimized and the structural parameters are determined by DFT method with B3LYP/6-31G(d,p) basis set. The presence of functional groups in 2APNA crystal is confirmed by FT-IR and FT-Raman spectral analysis. On contrary, FMO analysis, global chemical reactivity descriptors and natural charge analysis were studied. Molecular stability and bond strength have been probe by executing NBO analysis. The Fukui and electrostatic potential plot analysis can provide information about the molecules electrophilic and nucleophilic locations. UV–Vis spectrum was predicted by TD-DFT method in gaseous phase and compared with the experimental spectrum for displaying the intricate electronic transitions in the compound. The interactions within the 2APNA molecule was investigated via RDG analysis. To investigate the ligand-protein interaction, a molecular docking simulation was used, whereas drug likeness and ADMET analysis was used to determine the biological characteristics of the title molecule. Antifungal testing was performed to investigate the compound's efficacy against fungicidal strains.

Gallic acid-cholesterol conjugate: Synthesis spectroscopic characterization and quantum chemical calculations-an experimental and theoretical approach

Gallic acid is the major constituent in fruits Phyllanthusemblica (amla), of the family phyllanthaceae. Gallic acid was first methylated to 3,4,5 trimethoxygallic acid, which upon esterification using steglich method with cholesterol resulted in the product (3S,8S,10R,13R,17R) -10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro - 1H - cyclopenta[a]phenanthren-3-yl 3,4,5-trimethoxybenzoate. The synthesized compound has been characterized by 1H NMR, 13C NMR, UV, FT-IR and mass spectroscopy. Density functional theory (B3YLP) using a 6-31G (d,p) basis set has been used for quantum chemical calculations. The reactive site and reactivity within the molecule are rendered by global and local reactivity descriptors, whereas AIM (Atom in a molecule) approach illustrated weak molecular interactions within the molecule. The energies of HOMO and LUMO and frontier orbital energy gap are calculated by time dependent DFT approach using the IEFPCM model. A small value for the HOMO-LUMO energy gap indicates easier charge transfer within the synthesized compound. The nucleophilic and electrophilic reactivity is determined by MEP (molecular electrostatic potential) studies. The values calculated for polarizability, dipole moment, and first hyperpolarizability are used to depict the NLO (nonlinear optical) property of the synthesized compound.

Evaluation of nanoplastics toxicity to the human placenta in systems

Following the discovery of plastics in the human placenta, this study evaluated the toxicity of ten different nanoplastics (NPs) in the human placenta. Since the placenta performs metabolic and excretion functions by the enzymatic system, the NPs were docked on these human enzymes including soluble epoxide hydrolase, uracil phosphoribosyltransferase, beta 1,3-glucuronyltransferase I, sulfotransferase, N-acetyltransferase 2, and cytochrome P450 1A1at their active sites with toxicity (binding affinity) determined and compared to control compounds. Density functional theory analysis were conducted on the NPs to identify their global reactivity descriptors and Artificial Neural Networks to predict toxicity based on reactivity descriptors. Polycarbonate (PC), polyethylene terephthalate (PET) and polystyrene (PS) showed the highest toxicity to all enzymes and thus the most toxic polymers due to the presence of an electron-withdrawing group in their aromatic rings, which demonstrated an improved recognition of the enzyme active site by pi- and alkyl interactions. A 210–6 fractional factorial design approach was used in conjunction with a fixed effects model to assess the primary and secondary effects of NPs in a composite system on binding affinity to the placental enzymes. The simulation results suggest that NPs mixture may pose significant risks to the placenta through inhibition of its key enzymes.

A computational study of potent series of selective estrogen receptor degraders for breast cancer therapy

A detailed multistep framework combining quantitative structure-activity relationship, global reactivity, absorption, distribution, metabolism and elimination properties, molecular docking and molecular dynamics simulation (MD) on a series of Selective Estrogen Receptor Down-Regulators (SERDs) interacting with Estrogen Receptor α (ERα) has been performed. The partial least squares regression method derived an empirical model with better predictive capability. The results of global reactivity descriptors revealed that all the compounds are considered strong electrophiles, allowing them to participate in polar reactions more easily. The Brain Or IntestinaL EstimateD permeation diagram revealed that compounds 49 and 31 were predicted to be well absorbed by the human gastrointestinal tract and would not enter the brain. The elucidation of the binding mode between the most active compounds that comply with Lipinski’s and Veber’s rules from the dataset and ERα targets was explored by molecular docking. The MD simulations were performed for 100 ns on the best compounds, which indicated their stability state under dynamics simulations. These findings are expected to help predict the anticancer activities of the studied SERD compounds and better understand their binding mechanism with ERα targets. Communicated by Ramaswamy H. Sarma