Physical Chemistry Research
Volume:11 Issue: 3, Summer 2023

A virtual screening protocol, by combining on 3D-QSAR model with molecular docking procedure and prediction of physico-chemical properties, was applied to find novel inhibitors of Enoyl ACP reductase against M. tuberculosis. Initially, a series of thirty two isoniazid analogues was collected from literature and was investigated against tuberculosis target (PDB Id: 2IE0) using molecular docking. The docking studies were used to position the inhibitors into the active site of Enoly ACP reductase to derive a receptor based 3D-QSAR model. 3D-QSAR model was built and showed to be statistically significant and with a high predictive ability for the training (R2= 0.97) and test set (Q2= 0.73). Contour cubes analysis of the 3D-QSAR model revealed the chemical features necessary for the enoyl ACP reductase enzyme inhibition. The model was then used for virtual screening with the aim of identifying new inhibitors of Enoyl ACP reductase and predicts their potential activity. The outcome of the above studies, ten new molecules are proposed as Enoyl ACP reductase inhibitors with high binding affinity, activity prediction and favorable ADME properties.

Modulation of photophysical properties and entrapping of fluorescence drug molecules in microhetrogeneous systems are embracing potential applications in therapeutic pursuit. The present contribution describes the fascinating photobehaviour of ananticancer drug Doxorubicin (DOX) in micellar solutions of cationic cetyl trimethylammonium bromide (CTAB), anionic sodium dodecyl sulfate (SDS) and non-ionic p-tert-octylphenoxy polyoxyethanol (TX-100) surfactants by means of steady state, time resolved emission and emission anisotropy procedures. Drug resides at the micelle-water interface in all these micellar systems as revealed by the fluorometric studies. Steady-state anisotropy and rotational relaxation time enhance in the micellar environment compared to it in pure aqueous solution reveal that the drug presents in a motionally constrained environment.

Uricase is widely used to treat hyperuricemia and gout. Its clinical use is complicated by patients severe allergy, hypersensitivity and anaphylactic reactions. Uricase from Arthrobacter globiformis (Ag) and Bacillus fastidious (Bf) was chosen to improve enzyme binding energy by reducing the deleterious effects in treatment. Reducing the adverse effects of uricase was achieved by in silico mutagenesis. Pymol altered the active site amino acids of uricase from both sources.The ligand uric acid was docked to mutated uricase by Autodock 4.0, which helps in improving uricase binding energy. It has been found that mutation of Val64 with Alanine in Ag uricase and Gly42 with Isoleucine in Bf uricase improved the binding energy ability of enzyme by 50%. The binding affinity of Ag uricase docked with uric acid was found to be -8.414 Kcal/mole while for the mutated protein it was found to be -8.570 Kcal/mole. Binding energies for Bf uricase were found to be -5.221, and 5.389 Kcal/mole for native and mutated protein. We infer that our In silico model with improved uricase binding energy can assist to make a potent drug by the help of protein mutagenesis which leads to develop a drug with minimum adverse effects to treat hyperuricemia.

With the aim of eliminating toluene as volatile organic compound, a collection of Pt-(Sn/Re)-HZSM-5/HMS catalysts with different weight percent of Sn/Re have been synthesized. Also, the catalytic performances of the prepared catalysts were compared to obtain the best activity and CO2 and CO selectivity versus various catalyst weight percent, temperature (200-500 °C) and time on stream (1-65 h). The results show that incorporation of Sn and Re into Pt-HZSM-5/HMS structure promotes catalyst activity in which the high amount of 99.8% conversion obtained with PRSZH at T=500 °C. Increasing temperature has an adverse effect on CO selectivity in all catalysts. The best CO2 selectivity (100%) was observed at 500 ○C and Pt(0.3 wt%)‐Sn(0.3 wt%))-HZSM-5/HMS. The proper kinetics study leads to suitable decisions about catalytic performance. Employing two models, it was possible to provide good information about the kinetic behavior of the prepared catalysts. Although both modeling methods exhibit outstanding performances, however, kinetics data reveal that Mars-van Krevelen model has better performances compared to the Power law model.

The motive of the present work is to study the structural, optical properties of Cadmium Strontium Phosphate nanopowder (CSP) prepared by Solid State Reaction(SSR)method, a well-known commercial and conventional synthesis technology to produce nanopowders. To study the nature of the prepared samples various characterization techniques like P-XRD-Powder X-Ray Diffraction studies, SEM-Scanning Electron Microscopy with EDS-Energy-Dispersive X-ray Spectroscopy, DRS-Diffuse Reflectance Spectroscopy, FT-IR-Fourier Transform Infrared Spectroscopy and PL-Photo Luminescence studies were adapted. From P-XRD, the average crystallite size is found in the order of 15 nm. SEM micrographs reveal non-uniform biscuit shaped flakes for the prepared sample. From DRS study, the estimated band gap value of the prepared nanopowder is 5.3 eV. FT-IR study confirms the presence of ions related to phosphate group in the prepared nanopowder. From PL studies the prepared sample exhibits intense emission at 596 nm for an excitation wavelength of 401 nm. The values of CP-Color Purity, CRI-Color Rendering Index and CCT- Color Correlated Temperature are also calculated.

During this work, we studied the reactivity of 4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one with Dibromine and with Sulfuryl Chloride by the DFT method at the level of base 6-311 G(d,p), using a descriptor of regio-selectivity called fukui indices. We noted from this study that the attack of Dibromine and Sulfuryl Chloride is carried out preferentially at the level of the C2=C3 bond of 4-isothiazoline-3-one and 2-methyl-4-isothiazoline-3-one. We also noticed that the 4-isothiazolin-3-one/SO2Cl2 and 2-methyl-4-isothiazolin-3-one/SO2Cl2 reactions are more favored kinetically than the 4-isothiazolin-3-one/Br2 and 2-methyl- 4-isothiazolin-3-one/Br2. The differences in electrophilic Δω between {Br2, SO2Cl2} and 4-isothiazolin-3-one and also between {Br2, SO2Cl2} and 2-methyl-4-isothiazolin-3-one vary from 3.430649 eV to 3.611297 eV. This shows that all the reactions studied have a polar character (Δω >1).

In this study, the molecular and atomic adsorption energies, and total density of states (DOS) of the hydrogen on the on-top, bridge, and hollow positions of FCC (100), and FCC (111) surfaces of the metallic platinum were investigated using the DFT calculations. The total DOS result shows higher interaction between hydrogen molecule and metallic surface for the FCC (111) than the FCC (100) surface. Also, the intensity of the anti-bonding orbital for the bridge position is higher than two other positions on the FCC (100) surface, which shows that the hydrogen molecule in this position is ready to be dissociated into hydrogen atoms. In addition, the intensity of the anti-bonding orbital for hollow and bridge positions are higher than the on-top position on FCC (111) surface, which shows the hydrogen molecule in these positions are dissociated into hydrogen atoms. The results show that the comparison between the activation barrier energy (ΔEads) calculated from Lennard-Jones potential curves, and molecular adsorption energy determines whether the hydrogen molecule is dissociated on the surface. If the activation barrier energy (ΔEads) is higher than molecular adsorption energy, the probability that the hydrogen molecule will dissociate on the surface is very low.

Quantum mechanical study on the interaction between carcinogens and DNA nucleobase is an exciting and significant aspect in cancer research. Common aromatic carcinogens like; β-napthylamine, α-benzopyrone, phthalazine, quinoline, α-naphthol and β-naphthol; comfortably interact with DNA nucleobases (i.e., A, T, G, C, AT & GC) and it happens due to the effective π-π stacking interactions. In general, such type of interaction occurs through intercalation mechanism which takes place via π-stacking and results in very strong interaction with DNA nucleobases. In our case, all the carcinogen-DNA base pair stacked models have been investigated using density functional theory (DFT) method; as it theoretically helps to predict the proper molecular interaction and selectivity of carcinogens with DNA base pairs. Herein, computational calculations have been carried out to analyse the carcinogenicity of some common polycyclic aromatic hydrocarbons (PAH); and study reveals that β-naphthylamine (BNA) is highly GC-specific than that of other aromatic carcinogens. Hence, BNA shows higher carcinogenic or toxic effect on the DNA nucleobase than other selected carcinogens. On the other hand, carcinogens like quinoline (QUN) and phthalazine (PHZ) result in the least carcinogenic effect towards AT and GC base pairs of DNA nucleobases.

Polyelectrolyte complexes (PECs) based on oppositely charged polyelectrolytes-surfactants have gained great attention for their potential range of applications, such as membranes for filtration or in fuel cells and flocculants for water purification. In this current paper, the complex formed between carboxymethylcellulose sodium salt polyelectrolyte and cocamidopropyl betaine surfactant was reported. Conductimetry, potentiometry, viscometry and FTIR methods were used to study the structure and properties of this complex. The result shows that the complex is formed by ionic binding and hydrophobic aggregates. The measurements confirmed the interactions between the different functions in both components. Also, the characteristic concentrations of the complex NaCMC-CAPB such as critical aggregation concentration (CAC) and saturation concentration (X2) were calculated using the conductivity plots. The presence of charges in the complex explains water solubility in a wide range of polyelectrolyte and surfactant concentrations. Additionally, the effect of surfactant on reduced viscosity of polyelectrolyte solutions will be discussed.

Undoped and Sr-doped -MnO2 nanowires were synthesized through hydrothermal method to be used as catalyst and photocatalyst for the degradation of Methylene Blue (MB) dye. The Sr concentrations were 2, 4, 6 and 8 wt%. X-ray diffraction demonstrated the synthesis of the -MnO2 tetragonal phase with large tunnels along c-axis in which Sr dopant is incorporated. FT-IR and Raman spectroscopy confirmed the synthesis of -MnO2. The SEM microscopy showed that -MnO2 crystallites have nanowire morphology with length up to 5.91 µm. Optical investigation demonstrated that the -MnO2 nanowires have a band gap which slightly decreases with increasing Sr concentration and photoluminescence exhibits emission bands in visible region. The evaluation of catalytic and photocatalytic activity of -MnO2 nanowires was conducted against Sr concentration, the results demonstrated a high efficiency in the catalytic degradation of MB which reached in only 2 min 49.93% for undoped sample and is almost total 99.63% for the highly doped sample. Under UV irradiation (=365 nm), the photocatalytic degradation by undoped sample is more important and reached 97.74% in 60 min. The effect of UV irradiation, size, morphology and Sr doping of -MnO2 nanowires greatly improved the degradation of MB and led to its mineralization.

The synthesis and characterization of ZnS dandelion-like nanoparticles (NPs) via simple and template-free sonochemical method are reported. The elimination of an organic dye methylene blue (MB) as an organic pollutant from an aqueous solution is carried out via photodegradation procedure by the ZnS NPs as a photocatalyst under ultraviolet (UV) irradiation. The ZnS NPs are investigated by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), diffuse reflectance spectroscopy (DRS), energy dispersive x-ray spectroscopy (EDS), ultraviolet-visible (UV-Vis) spectroscopy and N2 physisorption analysis. The DRS result reveals that the optical band gap energy of ZnS NPs is 3.55 eV. The FE-SEM and TEM show the average size of dandelion-like NPs is 60 nm. The Brunauer-Emmet-Teller (BET) and Burret-Joyner-Halenda (BJH) techniques are used to determine the porosity properties, including pore volume, special surface area and mean pore diameterwith the values of 57.72 m^3/g, 9.76 m^2/g and 16.5 nm, respectively.

Medicinal plants belonging to Cameroon flora, could be a source for the discovery of potential inhibitors of SARS-CoV-2. These two proteins play a pivotal role in mediating viral replication and transcription, making them the attractive targets of drug designing against SARS-CoV-2. The aim of this in silico study is to evaluate the behavior of the isolated secondary metabolites from Cameroonian medicinal plant species towards SARS-CoV-2 Mpro and spike proteins. In the present study, six plant species are selected among the frequently used plants to treat COVID19 and related symptoms in Cameroon. To highlight the interactions of studied secondary metabolites with SARS-CoV-2 Mpro and spike proteins a molecular docking analysis is used. Among the 125 screened compounds, 35 showed high binding affinity against the two targeted proteins. Furthermore, molecular dynamics simulations were performed to support the docking results. Additional investigations, including physicochemical properties, pharmacokinetics and toxicological profile show that only 11 compounds bind tightly to Mpro and spike proteins and could be considered as promising drug candidates of SARS-CoV-2. The selected twelve compounds are evaluated for their acute and chronic toxicity, possible mutagenic, tumorigenic, irritant, and reproductive effectiveness.

Recent works in green solvents research trend towards ternary deep eutectic solvents (DESs) as a breakthrough which enhanced the performance of biomass dissolution and tunability of DESs for varying applications. In this context, water is extremely facile in such purpose as it is both a hydrogen bond acceptor and a donor with limited studies reported on modulating the properties of DES. ChCl/Malic acid 1:1 (CCMA) and ChCl/Lactic acid 1:18 (CCLA) DESs with varying water content were synthesized and characterized. Fourier transform infrared spectroscopy (FTIR) spectra with broadened OH stretching, diminished choline chloride characteristic peak associated with its OH group as well as bathochromic shift of the C=O stretch associated with carboxylic acids demonstrated the formation of hydrogen bond. The addition of water also caused the density of CCMA and CCLA reduced by 2.8 % and 3.6 %, respectively with 50 wt% of water content due to the lowered free volume of DESs. CCLA showed the highest lignin solubility at 6.32 wt% and further addition of water resulted in weakened structure with degradation in dissolution performance. Both CCMA and CCLA water content tailored green solvents which hindered self-degradation from esterification reaction demonstrated great potential to be applied in biomass pretreatment.

In the present study, undecan-1-ol was used as an extractant to remove caproic acid from aqueous phase. Experimental tie-line data of the ternary system (water + caproic acid + undecan-1-ol) were measured at T = 298.2 K and atmospheric pressure. Acid-base and Karl Fisher titrations were applied to determine the mass fractions of the acid and water, respectively. Solvent compositions were computed using mass balance equation. Obtained tie-line data were then correlated by UNQUAC and NRTL thermodynamic models. The values of root mean square deviations (up to 0.4 %) proved that the correlated results of both the models are in great accordance with experimental points. Distribution coefficients of caproic acid (23.2 to 49.4) and separation factors (678 to 904) were calculated over the biphasic region. Both partition factors have high values and confirm high ability of undecan-1-ol for purification of caproic acid. Efficiency of extraction was also calculated for each tie-line and the results were better than 96 %.

Selected monoclonal antibody molecules were conducted using the antibody–antigen docking mode, as well as the antibody-antigen docking approach.Objective of the study was to check effects of CetuximabCOVID-19 proteins (Nsp15 and 3CLpro) by using antibody–antigen docking mode, as well as the antibody-antigen docking approach.The results of molecular docking revealed that Cetuximab, a cancer-fighting antibody, ranks first among antibodies to both COVID-19 proteins (Nsp15 and 3CLpro).In cetuximab–3CLpro and cetuximab–Nsp15 complexes, the antigen interacts with both antibody chains, H and L.According to the findings, Cetuximab can be added to the COVID-19 treatment protocol, which may have the desired effect of inhibiting viral replication and decreasing mortality by targetingCOVID-19 proteins (Nsp15 and 3CLpro).Validation of these computational findings will require additional in vitro and in vivo research, which can be considered as a contribution in the field of biotechnology

Cooling enhancement by mixed convection in a tilted enclosure heated on one wall and vented by injecting or sucking an imposed flow by Alumina-water nanofluid has been analyzed. The inclination angle, 0°    90°, the nanoparticles volume fraction, 0    0.05, and the mode of the external flow are the control parameters for this study. The combined effects of the above controlling parameters on heat transfer and fluid flow are examined. The results indicate that adding nanoparticles driving to an increase of the average temperature and heat transfer rate in the cavity. Moreover, an enhancement in heat transfer rate is also achieved by varying the tilt of the cavity. More specifically, the better cooling is achieved at higher inclination angles (  70°). Finally, higher heat transfer performance and better cooling effectiveness are reached by the suction mode. Quantitatively, for  = 0.05 and  = 0°, a decrease of about 17 % of the fluid mean temperature is achieved by altering the mode of injection with the suction.

DFT calculations was applied for modelling ascorbic acid in three homologous sulfoxides solvents including methyl, ethyl, and propyl groups using 6-31++G** basis sets in B3LYP level. NBO analysis was performed to evaluate Mulliken charge, electron donor and acceptor in AA/DRSO system. Vibrational analysis was evaluated by Gaussview package for the normal modes and hydrogen bonds between hydroxyl groups of AA and sulfoxide group in the solvent. Our calculation showed that DFT/B3LYP method with 6-31++G** basis set is good candidate for quantum calculation of AA/DRSO systems. It was found that the most changes of the bond length were obtained in the interaction region between AA and the solvent, especially hydrogen bonds between oxygen of S=O group of sulfoxide and hydroxyl groups located on lactan ring. Charge analysis indicated that the positive charge of sulphur decreases by increase of alkyl group. Charge transfer (q) and polarity of S=O bond in DESO were higher than the other solvents. Vibrational analysis showed that the strongest hydrogen bond is formed in AA/DESO system.

To assess the effect of missense variants and the degree of pathogenicity of each nsSNP on the function, structure, and stability of the glucokinase protein (GCK), several algorithms were utilized including PHD-SNP, PROVEAN, SNPs&GO, PolyPhen 2.0, SIFT, MutPred, I-Mutant, MUpro, Consurf, and STRING. We have evaluated the flexibility levels of the residues in GCK protein using PredFlexy server and then we used the DynOmics server to study the molecular dynamics and understand the correlated communications between the residues.Towards the end, TM-align and the PyMol program were used to analyze the topology and structural similarity between the native model and the generated mutants.In total, seven out of eight nsSNPs were fund to be the most damaging variants and to exhibit a deleterious effect on the structure of the GCK protein, and probably on its function. This in silico study gives information on functional polymorphisms that impact the structure, stability, and function of the GCK protein, and consequently susceptibility to Gestational Diabetes.

In this study, the shake-flask method was used to determine the solubility of lamotrigine (LTG) in non-aqueous mixtures of polyethylene glycol 400 (PEG 400) and 2-propanol at temperatures of 293.15 to 313.15 K. Five main mathematical models were used to correlate the experimental data. The overall mean relative deviations for these models were less than 18.7 %. In addition, the apparent thermodynamic properties of LTG dissolution were computed. It is found that the LTG dissolution in PEG 400-rich mixtures is more favorable and proceeds entropically. Both experimental and mathematical methods were used to determine the density of LTG-saturated solutions. The results showed that the Jouyban–Acree model could be used to predict the density of LTG saturated solutions in mixtures with a very good approximation (back-calculated MRD% of 0.4).

Uricase is a therapeutic enzyme that has application in adjuvant chemotherapy and management of treatment-resistance hyperuricemia. It constitutes a key element in gout treatment, a type of arthritis affecting humans due to increased serum uric acid levels. Available two formulations of uricase from the bacterial source are characterized by their high immunogenicity, resulting in the drug's inactivation and hypersensitivity reactions in many patients. Identifying and modifying epitopic areas of uricase from Aspergillus flavus and Candida utilis by in silico approach to lower protein immunogenicity. Both Uricase B-cell epitopes were predicted using Emini surface accessibility and Parker hydrophilicity. Mutations were made to the hot-spot residues to diminish the epitope's antigenicity. Finally, molecular docking was used to examine the effect of mutagenesis on uricase catalytic activity and structural stability. We performed the prediction of immunogenic and allergenic epitopes in the structure of uricase by using the relative frequency of immunogenic peptides. This study showed no significant differences in the level of immunogenicity between both enzymes. However, from a structural point of view, in our knowledge, this is the first research describing the structural antigenic determinants that contribute to the hypersensitivity response to this treatment.