Computational peptidology approach to the study of the chemical reactivity and bioactivity properties of Aspergillipeptide D, a cyclopentapeptide of marine origin

Aspergillipeptide D is a cyclic pentapeptide isolated from the marine gorgonian Melitodes squamata-derived fungus Aspergillus sp. SCSIO 41501 that it has been shown to present moderate activity against herpes virus simplex type 1 (HSV-1). Thus, this paper presents the results of a computational study of this cyclopentapeptide’s chemical reactivity and bioactivity properties using a CDFT-based computational peptidology (CDFT-CP) methodology, which is derived from combining chemical reactivity descriptors derived from Conceptual Density Functional Theory (CDFT) and some Cheminformatics tools which may be used. This results in an improvement of the virtual screening procedure by a similarity search allowing the identification and validation of the known ability of the peptide to act as a possible useful drug. This was followed by an examination of the drug’s bioactivity and pharmacokinetics indices in relation to the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. The findings provide further evidence of the MN12SX density functional’s superiority in proving the Janak and Ionization Energy theorems using the proposed KID approach. This has proven to be beneficial in accurately predicting CDFT reactivity characteristics, which aid in the understanding of chemical reactivity. The Computational Pharmacokinetics study revealed the potential ability of Aspergillipeptide D as a therapeutic drug through the interaction with different target receptors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

Synthesis of Functionalized Thiophene Based Pyrazole Amides via Various Catalytic Approaches: Structural Features through Computational Applications and Nonlinear Optical Properties

In the present study, pyrazole-thiophene-based amide derivatives were synthesized by different methodologies. Here, 5-Bromothiophene carboxylic acid (2) was reacted with substituted, unsubstituted, and protected pyrazole to synthesize the amide. It was observed that unsubstituted amide (5-bromo-N-(5-methyl-1H-pyrazol-3-yl)thiophene-2-carboxamide (7) was obtained at a good yield of about 68 percent. The unsubstituted amide (7) was arylated through Pd (0)-catalyzed Suzuki–Miyaura cross-coupling, in the presence of tripotassium phosphate (K3PO4) as a base, and with 1,4-dioxane as a solvent. Moderate to good yields (66–81%) of newly synthesized derivatives were obtained. The geometry of the synthesized compounds (9a–9h) and other physical properties, like non-linear optical (NLO) properties, nuclear magnetic resonance (NMR), and other chemical reactivity descriptors, including the chemical hardness, electronic chemical potential, ionization potential, electron affinity, and electrophilicity index have also been calculated for the synthesized compounds. In this study, DFT calculations have been used to investigate the electronic structure of the synthesized compounds and to compute their NMR data. It was also observed that the computed NMR data manifested significant agreement with the experimental NMR results. Furthermore, compound (9f) exhibits a better non-linear optical response compared to all other compounds in the series. Based on frontier molecular orbital (FMO) analysis and the reactivity descriptors, compounds (9c) and (9h) were predicted to be the most chemically reactive, while (9d) was estimated to be the most stable among the examined series of compounds.

Experimental and Theoretical Study For Removal of Trimethoprim (TMP) From Wastewater Using Organically Modified Silica With Pyrazole-3-Carbaldehyde Bridged To Copper Ions

BackgroundHuman and veterinary antibiotics are typically discharged as parent chemicals in urine or feces and are known to be released into the environment via wastewater treatment plants (WWTPs). Several research investigations have recently been conducted on the removal and bioremediation of pharmaceutical and personal care products (PPCPs) disposed in wastewater. ResultsSiNP-Cu, a chelating matrix, was produced by delaying and slowing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel from functionalized with 3-aminopropyltrimethoxysilane. The prepared sorbent material was characterized using several techniques including BET surface area, FT-IR spectroscopy, Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), and nitrogen adsorption-desorption isotherm. The pseudo-second-order model provided the best correlation due to the big match between the experimental and theoretical of different adsorption coefficients. The Langmuir and Freundlich adsorption models were used and the study showed better match with Fruendlich model. The removal capacity was depending on pH and increased by increasing pH The adsorbent demonstrated a high percentage removal of TMP, reaching more than 94 %. The sample was simply regenerated by soaking it for a few minutes in 1N HCl and drying it. The sorbent was repeated five times with no discernible decrease in removal capacity. Thermodynamic study also showed endothermic, increasing randomness and not spontaneous in nature. The findings of the DFT B3LYP/6-31+g (d,p) local reactivity descriptors revealed that nitrogen atoms and p-electrons of the benzene and pyrimidine rings in the TMP are responsible for the adsorption process with the SiNP surface. The negative values of the adsorption energies obtained by molecular dynamic simulation indicated the spontaneity of the adsorption process. ConclusionThe global reactivity indics prove that TMP is stable and it can be removed from wastewater using SiNP surface. The results of the local reactivity indices concluded that the active centers for the adsorption process are the nitrogen atoms and the p-electrons of the pyrimidine and benzene rings. Furthermore, the positive value of the maximum charge transfer number (DN) proves that TMP has a great tendency to donate electrons to SiNP surface during the process of adsorption.

Carbonyl Composition and Electrophilicity in Vaping Emissions of Flavored and Unflavored E-Liquids

It has been demonstrated that propylene glycol (PG), vegetable glycerin (VG), and flavoring chemicals can thermally degrade to form carbonyls during vaping, but less is known about carbonyl emissions produced by transformation of flavoring chemicals and the interactive effects among e-liquid constituents. This study characterized carbonyl composition and levels in vaping emissions of PG-VG (e-liquid base solvents) and four e-liquid formulations flavored with trans-2-hexenol, benzyl alcohol, l-(-)-menthol, or linalool. Utilizing gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS) methods, 14 carbonyls were identified and quantified. PG-VG emitted highest levels of formaldehyde, acetaldehyde, and acrolein. However, flavored e-liquids contributed to the production of a wider variety of carbonyls, with some carbonyls directly corresponding to the oxidation of alcohol moieties in flavoring compounds (e.g., trans-2-hexenol and benzyl alcohol transformed into trans-2-hexenal and benzaldehyde, respectively). Detections of formaldehyde-GSH and trans-2-hexenal-GSH adducts signify interactions of carbonyls with biological nucleophiles. The global reactivity descriptors (I, A, μ, η, and ω) and condensed Fukui parameters (fk0, fk−, fk+, and dual-descriptor) were computed to elucidate site reactivities of selected simple and α,β-unsaturated carbonyls found in vaping emissions. Overall, this study highlights carbonyl emissions and reactivities and their potential health risk effects associated with vaping.

New Insights to Understand the CoMFA Analysis within the Density Functional Theory Framework

The Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) models now have a wide range of applications; however, new methodologies are required due to the complexity in understanding their results. This research presents a generalized version of quantum similarity field and chemical reactivity descriptors within the density functional theory framework. By taking reference compounds, this generalized methodology can be used to understand the biological activity of a molecular set. In this sense, this methodology allows to study of the CoMFA in quantum similarity and chemical reactivity. It is feasible to investigate steric and electrostatic effects on local substitutions using this method. They were considering that how these methodologies could be used when the receptor is known or unknown.

Therortical Studies and Investagting of Selected Potnet CDK2 Inhibitors as Anticancer Agents

In this study eight selected of the most potent cyclin dependent kinase 2 inhibitors in which targeting adenosine triphosphate -pocket site theoretically investigated to support literature information of frontier molecular orbitals, molecular electrostatic maps, and global chemical reactivity descriptors such as chemical hardness, chemical softness, chemical potential, electronegativity and electrophilicity of cyclin dependent kinase 2 inhibitors. Calculation and three-dimensional plotting were achieved through Gaussian 09W and Gausview 6 software’s utilizing density functional theory quantum modeling applying both hybrids extended and not extended basis set. Crystal structure of CDK2 with inhibitors was obtained from protein data bank and visualized through PyMol Schrödinger software to assign polar and non-polar interactions of inhibitors with enzyme. A promising conclusion trend obtained in this research regarding to molecules that could have an inhibition activity toward the cyclin dependent kinase 2 enzymes. Our theoretical investigation emphasizes that, the anti-cancer activity has directly relationship with value of chemical hardness and chemical softness, where the most potent compounds was the pyrazolopyrimidine and imidazole pyrimidine and they have higher chemical hardness value and at the same time lower value of chemical softness compared with the rest of compounds.

Aromatic Clusters as Potential Hydrogen Storage Materials

The scientific community is engrossed in the thought of a probable solution to the future energy crisis keeping in mind a better environment-friendly alternative. Although there are many such alternatives, the green hydrogen energy has occupied most of the brilliant minds due to its abundance and numerous production resources. For the advancement of hydrogen economy, Government agencies are funding pertinent research projects. There is an avalanche of molecular systems which are studied by several chemists for storing atomic and molecular hydrogens. The present review on molecular hydrogen storage focuses on all-metal and nonmetal aromatic clusters. In addition to the effect of aromaticity on hydrogen trapping potential of different molecular moieties, the importance of using the conceptual density functional theory based reactivity descriptors is also highlighted. Investigations from our group have been revealing the fact that several aromatic metal clusters, metal doped nonmetal clusters as well as pure nonmetal clusters can serve as potential molecular hydrogen trapping agents. Reported systems include N4Li2, N6Ca2 clusters, Mgn, and Can (n = 8–10) cage-like moieties, B12N12 clathrate, transition metal doped ethylene complexes, M3+ (M = Li, Na) ions, E3-M2 (E = Be, Mg, Al; M = Li, Na, K) clusters, Li3Al4− ions, Li decorated star-like molecules, BxLiy (x = 3–6; y = 1, 2), Li-doped annular forms, Li-doped borazine derivatives, C12N12 clusters (N4C3H)6Li6 and associated 3-D functional material, cucurbiturils, lithium–phosphorus double-helices. Ni bound C12N12 moieties are also reported recently.

Chemical Reactivity Descriptors and Molecular Docking Studies of Octyl 6-O-hexanoyl-β-D-glucopyranosides

The present study describes different chemical reactivity predictions of 6-O-hexanoylation of octyl β-D-glucopyranosides prepared from octyl β-D-glucopyranoside (OBG). Also, molecular docking of the OBGs was conducted against SARS-CoV-2 main protease (6LU7), urate oxidase (Aspergillus flavus; 1R51) and glucoamylase (Aspergillus niger; 1KUL). DFT optimization indicated that glucoside 1 and its ester derivatives 2-7 exist in 4C1 conformation with C1 symmetry. Interestingly, the addition of ester group(s) decreased the HOMO-LUMO gap (Δԑ) of glucosides indicating their good chemical reactivities, whereas the other chemical reactivity descriptors indicated their moderate reactive nature. This fact of moderate reactivity was confirmed by their molecular docking with 6LU7, 1R51 and 1KUL. All the esters showed a moderate binding affinity with these three proteins. More importantly, incorporation of the ester group(s) increased binding affinity with 6LU7 and 1R51, whereas decreased with 1KUL as compared to non-ester OBG 1.