Chemical Reactivity Parameters Research Articles

Studies on New Imidazo[2,1-b][1,3,4]thiadiazole Derivatives: Molecular Structure, Quantum Chemical Computational, and In silico Study of Inhibitory Activity Against Pim-1 Protein by using Molecular Modelling Methods and ADMET Profiling

Imidazothiadiazole derivatives (KITD4 and KITD10) have been synthesized and characterized by NMR (1H&13C) spectra and single-crystal X-ray diffraction techniques. Density functional theory (DFT) calculations were performed to investigate the effect of substituents on the structures and intramolecular charge transfer (ICT) using natural bond orbital (NBO) analysis. Furthermore, DFT studies were extended to investigate the reactive sites of the title compounds through the molecular electrostatic potential (MEP) and frontier molecular orbitals (FMOs), including HOMO-LUMO, energy gap, and other chemical reactivity parameters. Hirshfeld surface and energy frameworks evaluated the different intermolecular interactions and energies based on the anisotropy of the topology. SwissADME drug design server predicted the oral bioavailability in the physicochemical space and showed good pharmacokinetic properties based on the boiled egg model. In addition, in silico molecular docking studies were executed to predict the biological activity of the molecules, as anticancer, against Pim-1 protein (homo sapiens PDB id: 3A99) and revealed prominent interactions with the active site of both the ligands showing reasonable conformity with the reported cocrystal ligand interactions. Besides, molecular dynamics simulations of holoprotein confirmed the structural constancy and stability of the protein-ligand complexes with minimal deviation showing faithful convergence throughout the entire trajectory of simulations. Both the simulations justify the hydrogen bond formations of the compounds with the vital amino acid LYS67, which is very much crucial for the inhibition of Pim-1 protein and shows similar conformity of hydrophobic residues interactions.

Novel substituted isoindolinones derived from lawsone: synthesis, characterization, theoretical, biological activity and docking studies

An efficient Mannich type multicomponent reaction approach was developed for the synthesis of a series of novel substituted isoindolinones derived from Lawsone, 2-formyl benzoic acid, and various primary amines. This protocol features direct construction of C-N and C-C bonds via metal-free method at room temperature using an environment-friendly solvent. The synthesized isoindolinone compounds 4a-4m were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and ESI-MS. Computational studies were carried out by the DFT method using B3LYP/6-31G (d,p) basic set as a tool to analyse the chemical reactivity parameters and comprehend the molecular interaction. The molecular electrostatic potential (MEP), dipole moment, chemical reactivity, and stability features of investigated isoindolinones revealed that 4i, 4j, 4l, and 4m could be promising candidates for further biological activity. The cytotoxic activity of selected compounds was evaluated using MTT assay against HepG2 cell lines (Human liver cancer cell line). The data revealed that screened compounds displayed excellent to moderate activity. The docking examination was executed on a promising liver cancer-associated Alpha fetoprotein (AFP). It showed a positive outcome with minimum binding energy and hydrogen bond interaction. Furthermore, In vivo studies ascertained that synthesized isoindolinone derivatives can lead to enhanced cancer cell death and prevention of tumor growth by restoring serum SGOT and SGPT levels near to normal. It further restores matrix metallopeptidase (MMP-2 and MMP-9 levels) near to control confirms the effectiveness of the compound.

Molecular Iodine-Catalyzed Synthesis of Imidazo[1,2-a]Pyridines: Screening of Their In Silico Selectivity, Binding Affinity to Biological Targets, and Density Functional Theory Studies Insight.

The present paper discloses an ultrasonication strategy assisted by molecular iodine as an environmentally benign catalyst leading to the synthesis of pharmacologically significant imidazo[1,2-a]pyridine scaffolds. The molecular-iodine-catalyzed approach for the synthesis of biologically active synthetic equivalents was achieved through three-component coupling embracing 2-aminopyridine derivatives, pertinent acetophenones, and dimedone in water medium under aerobic conditions. The higher product yield (up to 96%) with a miniature reaction time and modest catalyst loading as demonstrated by higher ecological compatibility and sustainability factors are fascinating features of this protocol. The structures of synthesized compounds were accomplished through FT-IR, 1H NMR,13C NMR, mass, and elemental analysis data. The virtual screening of synthetic moieties was performed to ascertain the in silico selectivity and binding affinities against several biological targets. Lipinski’s rules of five, ADMET, and TOPKAT descriptors were used to evaluate the drug-likeness assets. Furthermore, a quantum computational study was computed at the B3LYP/6-311G++(d,p) level of theory to investigate the density functional theory-based chemical reactivity parameters and HOMO–LUMO energy gap of the synthesized derivatives. The present studies open the way for in vitro and in vivo testing of synthesized derivatives as potent inhibitors with an improved pharmacological profile against farnesyl diphosphate synthase, phosphodiesterase III, CXCR4, and GABAa receptor agonists.

Free energies of 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium chlorides monohydrates and arylsulfonates formation at β-aminopropioamidoximes arylsulfochlorination

We have previously obtained new spiropyrazolinium compounds by arylsulfochlorination of β-aminopropioamidoximes. But it was found that under certain conditions, the main or by-product of β-(thiomorpholine-1-yl)propioamidoxime tosylation was 2-amino-8-thia-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride monohydrate. In the case of other β-aminopropioamidoximes, only 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium arylsulfonates were isolated. The aim of the work is to perform a theoretical comparison of reactions of tosylation, para- and ortho-nitrobenzenesulfochlorination of β-aminopropioamidoximes and evaluate the propability of 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium chlorides monohydrates formation. Methodology. The calculations were performed using Gaussian 09 package by DFT/B3LYP/6-31G++(d,p) method. Results and discussion. Thermodynamically preferred products were identified by comparing the Gibbs free energies of reactions. Chemical stability and reactivity parameters for 2-amino-8-thia-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride monohydrate, tosylate, para-nitrophenylsulphonate and ortho-nitrophenylsulphonate were predicted based on calculated HOMO and LUMO energies. In most cases arylsulfonates are thermodynamically favorable, except when the initial substrate is β-(thiomorpholine-1-yl)propioamidoxime. Conclusion. 2-Amino-8-thia-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride monohydrate is more preferred compared to the corresponding arylsulphonates.

Rapid Computational Approach Towards Designing Singlet-Fission Chromophores by Tuning the Diradical Character of Heteroatom-Doped Polycyclic Aromatic Hydrocarbons Using the Atom-Specific Fukui Function.

Singlet fission (SF) is proposed as a promising method to circumvent the Shockley-Queisser threshold of single junction photovoltaics. Progress towards realizing efficient SF-based devices has been impeded by the fact that only a handful of molecules and their derivatives practically exhibit efficient SF. In the present work, we demonstrate a TDDFT-based rapid and cost-effective computational approach for designing SF chromophores by doping various atomic sites (substituting carbon atoms) of polycyclic aromatic hydrocarbons with nitrogen, phosphorus, and silicon. We establish a hitherto unexplored, direct correlation between the atom-specific chemical reactivity parameter─Fukui function─of these molecules with their frontier molecular orbital energies, diradical characters, and vertical singlet and triplet excitation energies. These quantitative correlations show exactly opposite trends for nitrogen-doped molecules and phosphorus- or silicon-doped molecules. The doped derivatives that have the Fukui function falling in a range of 0.03-0.14 possess the required intermediate diradical character and suitable singlet-triplet energies to qualify for SF candidature. Our findings enable one, at reasonable computational times and cost, to easily assess the doping criteria and to develop design rules for SF molecules in particular and for diradicaloids in general.

A Competition between Hydrogen, Stacking, and Halogen Bonding in N-(4-((3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)selanyl)phenyl)acetamide: Structure, Hirshfeld Surface Analysis, 3D Energy Framework Approach, and DFT Calculation.

N-(4-((3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)selanyl)phenyl)acetamide (5), C19H15NO3Se, was prepared in two steps from 4,4′-diselanediyldianiline (3) via reduction and subsequent nucleophilic reaction with 2-methyl-3-bromo-1,4-naphthalenedione, followed by acetylation with acetic anhydride. The cytotoxicity was estimated against 158N and 158JP oligodendrocytes and the redox profile was also evaluated using different in vitro assays. The technique of single-crystal X-ray diffraction is used to confirm the structure of compound 5. The enantiopure 5 crystallizes in space group P21 with Flack parameter 0.017 (8), exhibiting a chiral layered absolute structure. Molecular structural studies showed that the crystal structure is foremost stabilized by N-H···O and relatively weak C-H···O contacts between molecules, and additionally stabilized by weak C-H···π and Se···N interactions. Hirshfeld surface analysis is used to quantitatively investigate the noncovalent interactions that stabilize crystal packing. Framework energy diagrams were used to graphically represent the stabilizing interaction energies for crystal packing. The analysis of the energy framework shows that the interactions energies of and C-H···π and C-O···π are primarily dispersive and are the crystal’s main important forces. Density functional theory (DFT) calculations were used to determine the compound’s stability, chemical reactivity, and other parameters by determining the HOMO-LUMO energy differences. The determination of its optimized surface of the molecular electrostatic potential (MEP) was also carried out. This study was conducted to demonstrate both the electron-rich and electron-poor sites.

The sensing mechanism of HCHO gas sensor based on transition metal doped graphene: Insights from DFT study

Formaldehyde (HCHO), as primary chemical feedstock, is widely used in various fields. Unfortunately, it can cause harmful impacts on human health due to its high toxicity. Therefore, effective monitoring and detection of HCHO is significant. HCHO gas sensor based on doped graphene was extensively investigated in recent years. However, the relationship between gas-sensing performance and electronegativity of doped atoms has not been clarified. In this research, Ni, Pd and Pt are used as dopants, and the adsorption behaviors, energies, electronic and optical properties of HCHO molecule on doped graphene were systematically investigated by density functional theory (DFT) method to explore the effect of electronegativity of doped atoms on the sensing property. The calculated results show that graphene doped with higher electronegativity atoms is beneficial to cause a recordable electric signal due to larger change of energy gap. The adsorption energy increases steadily with an enhancement in the electronegativity of doped atoms. It is clear that there is an obvious linear relationship between gas-sensing performance and electronegativity of doped atoms. In other words, specific sensitivities (e.g., adsorption energy, electrical conductivity, recovery time, chemical reactivity parameters and so on) of gas sensor can be adjusted by embedding different electronegativity atoms in graphene, which provide meaningful information to design highly sensitive graphene-based gas sensors. Besides, the adsorption and desorption performance of HCHO can be controlled by applying positive or negative electric field.

DFT study of 2D graphitic carbon nitride based preferential targeted delivery of levosimendan, a cardiovascular drug

2D nanocarriers particularly graphitic carbon nitride (g-C3N4) have shown its momentum in nanomedicine to augment the efficacy and safety of pharmaceutical drugs owing to its excellent compatibility and nontoxic nature. In current study, DFT/TD-DFT evaluation is performed for a cardiovascular drug levosimendan, g-C3N4 carrier and their complex g-C3N4-levosimendan at CAMB3LYP/6-31G (++) ** with a high precision of 0.1 eV in charge transfer. To study the nature of the complex different parameters such as non-covalent interaction analysis, density of states, charge decomposition analysis, natural bonding orbital analysis, electrostatic potential and UV–Visible spectra are investigated. The BSSE corrected adsorption energy of complex has confirmed an exothermic reaction indicating successful adsorption of levosimendan on g-C3N4 while solvation energy has described a good solubility index and stability for the complex. All the chemical reactivity parameters indicate a favorable complex having a potential of preferential targeting to the heart tissue. Dipole moment shows a significant increase for complex indicating its high solubility in water while NBO studies has signified the more pronounced interactions where the E value is larger for levosimendan and g-C3N4 which is further supported by ELF and ESP plots. Moreover, less distortion of bonds has been seen with +1 and −1 charges on the surface of g-C3N4-levosimendan-complex. PET based on electron-hole theory specifies g-C3N4 as a chelator while levosimendan as a fluorophore in the g-C3N4-levosimendan complex (also confirmed by UV–Visible results). All the results are in a good support of the complex which signify that g-C3N4 offers an excellent route of administration for levosimendan and has a potential to spark active research in nanomedicine particularly in targeted drug delivery systems.

Molecular Modeling and Antimicrobial Screening Studies on Some 3-Aminopyridine Transition Metal Complexes

Seven transition metal complexes of Mn2+, Ni2+, Co2+, Cu2+ and Zn2+ with 3-aminopyridine (3-APy) as ligand have been synthesized, characterized by different techniques and their antibacterial activities were studied. Molecular modeling calculations were performed using DMOL3 program in materials studio package which is designed for the realization of large scale density functional theory calculation (DFT). The quantum mechanical and chemical reactivity parameters such as chemical hardness, chemical potential, electronegativity, electrophilicity index and Homo-Lumo energy gap were obtained theoretically and were used to understand the biological activity of the prepared compounds. Some complexes were tested for their in-vitro cytotoxic activity in human lung cancer cell lines (A-549 cell line), and structureactivity relationships were established. In general, the coordination to Co2+ increased the cytotoxicity while the Ni2+ complexes show reduced cytotoxic activity compared to the metal-free 3-aminopyridine.

Reinvigorate the synthesis, spectroscopic findings, SEM morphology investigation, and antimicrobial silhouette of contemporary Salen ligands: A comprehensive DFT landscape

This article has serendipitously synthesized three trendy Salen ligands (H2L1/H2L2/H2L3) prepared from Salicylaldehyde/ortho-vanillin and the corresponding diamines backbone. The synthesized compounds were characterized vividly by different spectroscopic techniques. Further, the SEM examined the morphology of the ligands. B3LYP, HF, and M062X methods with 6–31++g (d, p) basis sets optimized the molecular geometry. The divergent DFT-based analysis considered the chemical and biological activities of the studied molecules. The global chemical reactivity parameters, HOMO-LUMO energy gap, and ESP ensure the same. However, it is seen that the activity of the H2L3 molecule is higher than the other molecules to the ΔE energy gap value. The cardinal information about the NLO properties of the molecules has been studied where the nonlinear hyperpolarizability (β) of the three studied molecules was fortunately compared. The numerical values of H2L1 and H2L2 were very close, but the value of H2L3 was 1.5 times. Beyond the bounds, the first two molecules had lower dipole moments than H2L3. Theoretical IR/NMR calculations explore important assignments. Molecular docking (MD) examines the activities of molecules against biological materials that are breast cancer protein (PDB ID: 1A52), liver cancer protein (PDB ID: 2JW2), and prostate cancer protein (PDB ID: 3A99). The theoretical drug properties have been investigated in-depth so they can be used as drugs by ADME/T analysis. The prepared compounds were screened in vitro against two grams + ve and two-gram −ve bacterial strains using the agar well diffusion method. MIC determines the good antibacterial activity of the compounds. The MIC values ​​for H2L1 range from 15.62 to 125 g/mL, while for H2L2, 31.25–500 g/mL, and for H2L3, 31.25–500 g/mL. Based on the MIC values, the tested compounds' potency order was H2L1 > H2L3 > H2L2. Eventually, the time-kill kinetics study led to promising bactericidal activities.

Synthesis, growth, DFT, and HOMO-LUMO studies on pyrazolemethoxy benzaldehyde single crystals

Pyrazolemethoxy benzaldehyde (PMB) was synthesized and crystals were grown by slow evaporation solution growth method. PMB was crystallized in a monoclinic crystal system with a centrosymmetric C2/c space group, according to single-crystal X-ray diffraction analysis. The crystalline planes were identified using powder X-ray diffraction analysis. FTIR - FT-Raman spectroscopic techniques were performed to determine the vibrational modes of functional groups for the grown crystal. UV-visible spectral analysis and photoluminescence studies were taken to investigate the linear optical properties of the grown crystal. Thermogravimetric and differential thermal analysis (TG/DTA) were used to determine the thermal stability of the PMB crystal. In addition to this density functional theory (DFT) calculations such as frontier molecular orbital's (FMOs), global chemical reactivity parameters, hyperpolarizability, natural bond orbital (NBO) analysis, Mullikan atomic charge distribution, and molecular electrostatic potential map analysis were carried out in gaseous phase using B3LYP/6-311G* basis set.

Synthesis, structural and spectroscopic analysis, and antiproliferative activity of chalcone derivate (E)-1-(4-aminophenyl)-3-(benzo[b]thiophen-2-yl)prop‑2-en-1-one in Trypanosoma cruzi

There is an urgent need for new inhibitors against T. cruzi, a protozoal infection that affects about 8 million people annually around the world. In this study, we describe the synthesis, characterization, and the inhibitory effects of the chalcone (E)-1-(4-aminophenyl)-3-(benzo[b]thiophen-2-yl)prop‑2-en-1-one (BNZTHP) against T. cruzi Y strain forms. The molecular structure of this compound was characterized by spectroscopic techniques, and its potential against T. cruzi was evaluated by in vitro assays and in silico analysis. The structural data analyses allowed drawing the molecular structure of the BNZTHP chalcone. Computational quantum chemical calculations provided the normal modes of vibrations, the global chemical reactivity parameters, the most probable regions for electrophilic and nucleophilic reactive attacks, and the singlet states for BNZTHP chalcone. Regarding the activity against T. cruzi the compound exhibited more active on trypomastigote than epimastigote forms with lower toxic on LLC-MK2 host cells. Furthermore, it presented a more powerful inhibitory effect than benznidazole. From the molecular docking studies showed that trypomastigote forms were able to interact with the cruzain, trypanothione reductase, and TcGAPDH enzymes, indicating good affinity toward the active pocket. These results bring attention to the BNZTHP chalcone as candidate for the development of new option for the treatment of Chagas disease.

Synthesis, crystal structure, Hirshfeld surface, DFT and docking studies of 4-[(5‑hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)(phenyl)methyl]-5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one

In the present work, 4-[(5‑hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)(phenyl)methyl]-5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (BPZ) was synthesized by one pot multicomponent reaction of ethylacetoacetate, phenylhydrazine and benzaldehyde in the presence of Ce-MCM-48 catalyst. The title compound was characterized by FT-IR, 1H NMR, and 13C NMR spectral studies and single crystal XRD technique. The intermolecular contacts of the title compound were studied by Hirshfeld surface (dnorm surfaces and 2D fingerprint plots) analysis whereas an intra-molecular hydrogen bonding interaction was examined through NCI-RDG plot. The geometry of the molecular structure was optimized by using the density functional theory (DFT) at B3LYP/6–311 g(d,p) level. Molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, nonlinear optical properties (NLO) and global chemical reactivity parameters (GCRP) were described through computational method. Further, the molecular docking study was done for title compound with COVID-19 caused protein structure (6LU7, nCoV-SARS-2 Mpro). The study revealed that the significant conventional hydrogen bonding and other interactions were observed between the active amino acid residue of SARS-nCoV-2 Mpro and BPZ ligand.

Theoretical and electrochemical analysis on inhibition effects of benzotriazole derivatives (un- and methyl) on copper surface

The corrosion inhibition effects of benzotriazole (BTA) and its derivative-methylbenzotriazole (M-BTA) at molecular level were studied using quantum chemical method. The adsorption mechanism of inhibitors on copper surface was evaluated by Density Functional Theory (DFT) at BLYP/3.5DNP level and Monte Carlo simulation. The inhibition effects of BTA and M-BTA were investigated by chemical reactivity parameters. Both inhibitors have a considerable excess of negative charges around the nitrogen atoms N7 and N8, indicating that they are the coordination sites of the inhibitors. Under the circumstance of gaseous and aqueous phases molecules, the BTA adsorption and M-BTA adsorption on Cu (111) surface was further simulated by Monte Carlo simulations. In addition, the interaction energy between inhibitors and copper was calculated. The electrochemical measurement results confirm that the inhibition effect of 15mM M-BTA is greater than that of BTA, and the inhibition efficiency is up to 96.05%, which is helpful for further study of corrosion system.

Synthesis, spectra (FT-IR, NMR) investigations, DFT study, in silico ADMET and Molecular docking analysis of 2-amino-4-(4-aminophenyl)thiophene-3-carbonitrile as a potential anti-tubercular agent

• Synthesis the studied compound. • Spectral (FT-IR and NMR) characterization. • Frontier Molecular Orbital. • NBO second perturbation energy investigations. • Population (ADCH and NBO) analysis. • Nonlinear optical (NLO) studies. • Pharmacological investigation. • Molecular docking studies against antitubacular agent. The title compound 2-amino-4-(4-aminophenyl)thiophene-3-carbonitrile ( AI3 ), was synthesized and characterized experimentally by FT-IR, NMR and theoretically by quantum chemical calculations. The results were compared and the analysis of the results showed mutual agreement between the experimental and theoretical data. The theoretical calculations were performed using Density Functional Theory (DFT) method, Becke-3-Parameter-Lee-Yang-Parr (B3LYP) in 6–311++ G (d,p) basis set. The Non Linear Optics (NLO), Natural Bond Orbital (NBO) including chemical reactivity parameters; Fukui function, Mulliken Population Analysis (MPA), Atomic Dipole Moment Corrected Hirshfeld (ADCH) population methods and the Natural Population Analysis were evaluated using the same level of theory. The results of the 3 population methods, MPA, NPA and ADCH were compared to examine charge distribution in the molecule. The Frontier Molecular Orbital indicated high bioactivity and NLO effects of the compound with a reduced value of the energy gap (-4.608103 eV) of the HOMO/LUMO which is also relatively comparable to its counterparts in the +1/-1 and +2/-2 states. The entire chemical reactivity analysis revealed C4 and N21 among the high donor atoms, then, S5 and C1 among the best acceptor atoms and this correlates with the location of the HOMO and LUMO in the studied compound. In addition, the antitubercular activities of the title compound against 3 (three) Mycobacterium tuberculosis proteins; 1P44, 1P45 and 4TZK were investigated using molecular docking simulations and the results were compared to those of Isoniazid (a standard anti-tubercular drug). AI3 showed greater binding affinities (-6.0, -3.9 and - 7.2 kcal/mol) in comparison to the Isoniazid drug (-5.5, -3.8 and -5.6 kcal/mol) for each target protein. Furthermore, an in silico study was performed to predict absorption, distribution, metabolism, excretion and toxicity profiles (ADMET) of the studied compound. The results reveal good to moderate anti-tubercular activity of the studied compound.

Synthesis, molecular structure, DFT studies, in silico docking and molecular dynamics simulations of 2,6 dimethoxychalcone derivatives as BRD4 inhibitors

Methoxyphenyl chalcone derivatives (MAHB1 and MAHB3) have been synthesized and characterised by NMR (1H&13C) spectra and single crystal X-ray diffraction techniques. The crystal structures revealed the crystallization of the both compounds in the monoclinic systems and P2(1)/c space groups. Supramolecular architecture unveiled the stability of compounds and build of crystal packings upon short contacts and weak interactions. Density functional theory (DFT) with B3LYP functional under 6–311++G(d,p) basis set have been adopted to calculate the geometry and investigate intramolecular charge transfer (ICT) using natural bond orbital analysis (NBO) as well as the frontier molecular orbitals (FMOs), hardness, softness, energy gap and other chemical reactivity parameters. Hirshfeld surface and energy frameworks were adopted to evaluate the different intermolecular interaction and energies based on the anisotropy of the topology. The inhibitory activity of the compounds against the first bromodomain of human BRD4 protein have been assessed by using in silico molecular docking and molecular dynamics simulations against 5H21 protein (homo sapiens), which revealed prominent interactions of both the ligands at the active site of BRD4 protein showing with a reasonable conformity as similar with the co-crystal ligand interactions. Furthermore, apo and holo states in the molecular dynamic simulations confirmed the stability and structural constancy of the protein-ligand complexes with minimal deviation based on RMSD and RMSF plots. Both the simulation results confirmed the hydrogen bonds of the compounds with the vital amino acid ASN140 which is necessary for the inhibition of BRD4 as well as exhibiting similar hydrophobic residues interactions. Furthermore, the newly synthesized compounds were screened against human leukemia MV4–11 cells based on MTT and apoptosis assays system. These compounds exhibited anti-proliferation activity and induced the apoptotic effect. This study indicated that the MAHB1 is a promising compound against leukaemia with IC50 value of 79.10 μM and exhibited better apoptogenic effect. Furthermore, the expression of BRD4 in MV4–11 cell line was measured by western blotting, while the protein thermal shift assay was conducted to determine the impact of MAHB1 compound against the thermal stability of BRD4.

Visualizing Non-Covalent interactions between Propylamine and 2-Chlorobenzyl alcohol in Benzene: Theoretical and Dielectric relaxation studies

The non-covalent interactions of propylamine (pa) with 2-chlorobenzyl alcohol (2cbOH) in benzene have been studied by theoretical and dielectric relaxation studies. In the theoretical method, the optimized structure of pa2cbOH is achieved by the DFT method in B3LYP/6-311++G (d,p) basis set at ground level d,p orbitals. The Vibrational energy distribution analysis is adopted to find the vibrational assignment of pa2cbOH, as well as it compared with the experimental observations. Stability, electronic effects are determined through the chemical reactivity parameters with the help of FMO analysis. The hydrogen bonding and Vander Waals interactions of pa2cbOH are confirmed with reduced density gradient (RDG) isosurface. In Dielectric relaxation analysis, various dielectric parameters like ε′, ε″, ε0 and ε∞ were determined for five different mole ratios of pa2cbOH. Higasi’s single frequency equation and Gopalakrishna’s single frequency concentration variation methods are validated by measuring the multiple relaxation time τ1 and relaxation time τ2 for group rotation of pa2cbOH. The strength of hydrogen bonding and other weak interactions were determined using the values τ1 and τ2.

Conceptual DFT based electronic structure principles in a dynamical context

Within the context of quantum fluid density functional theory diverse processes simulating a chemical reaction like interaction of an atom or a molecule with an externally applied electric or magnetic field or its collision with a proton have been analyzed in a dynamical situation. The changes produced in the chemical reactivity parameters namely chemical potential, hardness, polarizability during such processes have been identified and discussed. In addition, confinement is also introduced to observe the necessary variation in the different reactivity parameters.

Epigallocatechin Gallate (EGCG) – A Novel Covalent NF- κB Inhibitor: Structural and Molecular Characterization

Tea contains antioxidant catechins thought to exert health-promoting protective effects against conditions involving chronic inflammation, such as cardiovascular diseases. The most abundant catechin in tea is Epigallocatechin Gallate (EGCG), thought to be a key contributor to tea’s health-promoting actions. EGCG exerts protective cardiovascular effects via its antioxidant, antiinflammatory, hypolipidemic, anti-thrombogenic, and anti-hypertensive actions. Because EGCG inhibits the strong proinflammatory gene-inducing transcription factor NF-κB, we analyzed the chemical and molecular details of the mechanism by which EGCG mediates NF-κB inhibition. We quantified and mapped key parameters of its chemical reactivity including its electrophilic Fukui ƒ+ function, in silico covalent binding, and identified its frontier Molecular Orbitals (MOs) and nucleophilic susceptibility. These physical and chemical reactivity parameters revealed that the bond-forming MOs are distributed on the B ring of the EGCG oxidized state with nucleophilic susceptibility, and that this B ring has properties that favor participating in a Cys-alkylating 1,4-addition reaction. Molecular modeling and docking analysis further revealed that EGCG bonds covalently with Cys-38 of NF-κB-p65, and thereby inhibits its DNA binding ability. We also generated a model pharmacophore based on the EGCG-NF-κB complex. We conclude that EGCG covalently binds to NF-κB-p65 and inhibits it by abolishing its DNA binding, by chemical mechanisms that may inform design of EGCG derivatives as novel anti-inflammatory agents.

Structural, Spectroscopic (UV-Vis and IR), Electronic and Chemical Reactivity Studies of (3,5-Diphenyl-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone

The (3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone (DPPPM) were synthesized by using rapid and recyclable reaction media polyethylene glycol-400 (PEG-400) and catalytic amount of acetic acid. This method gives remarkable advantages such as simple workup and a greener method by avoiding hazardous and toxic solvents. The computational calculations for title compound have been carried out by using DFT method with B3LYP hybrid functional and 6-311++G (d, p) basis set. The structural parameters like bond lengths, bond angle, and dihedral angles were obtained from the optimized molecular geometry and discussed. This structural analysis shows, the DPPPM molecule has non-planar structure and possess C1 point group symmetry. The infrared vibrational spectral bands assignments were made by correlating experimental findings with the computed data and results shows good agreement. The electronic spectral properties were explored using the time-dependent density functional theory (TD-DFT) in the gas phase and two different polarity solvents. This obtained theoretical UV-Visible absorption results are in acceptable concurrence with the UV-Visible absorption experimental results. The solvent effect on wavelength of absorption also been reported. The frontier molecular orbital, MESP and global chemical reactivity parameters for the title molecule in the gas phase were reported and discussed. Theses result shows molecule possesses good strength and stability.