Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Enhancing catalytic activity of Cr2O3 in CO2-assisted propane dehydrogenation with effective dopant engineering: a DFT-based microkinetic simulation.

Using CO2 as a mild oxidizing agent in propane dehydrogenation (PDH) presents an attractive pathway for the generation of propene while maintaining high selectivity. Cr2O3 is one of the most important catalysts used for the CO2-assisted PDH process. In this study, the doping of Cr2O3 with single atoms such as Ge, Ir, Ni, Sn, Zn, and Zr was used for the PDH process. The introduction of dopants significantly modifies the electronic structure of pristine Cr2O3, leading to substantial alterations in its catalytic capabilities. The dehydrogenation reactions were explored both in the absence and presence of CO2. The addition of CO2 introduces two distinct pathways for PDH. On physisorbed CO2 surfaces, Ge and Ni-Cr2O3 enhance dehydrogenation. On the dissociated surface, the CO* and O* species actively participate in the reaction. All doped surfaces exhibit low energy barriers for dehydrogenation, except undoped Cr2O3 on dissociated CO2 surfaces. The Ni-Cr2O3 surface emerges as the most active surface for dehydrogenation of propane in all scenarios. Additionally, the catalytic surface is re-oxidized through H2 release, and doped surfaces facilitate coke removal via the reverse Boudouard reaction more efficiently than undoped Cr2O3. Microkinetics simulations identify the removal of the first H-atom as the rate-determining step. CO2 reduces the apparent activation energy, directly impacting C3H8 conversion and C3H6 formation. This study offers a decisive description of Cr2O3 modification for the CO2-assisted PDH process.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment.

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Novel benzimidazole derivatives as effective inhibitors of prolyl oligopeptidase: synthesis, in vitro and in silico analysis.

Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61 ± 0.15 to 43.72 ± 1.18 µM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzyme offers promising prospects for future research in the field of neuropharmacology.

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation.

Background: Novel α-amylase inhibitors play a crucial role in managing diabetes and obesity, contributing to improved public health by addressing these challenging and prevalent conditions. Moreover, the synthesis of anti-oxidant agents is essential due to their potential in combating oxidative stress-related diseases and promoting overall health. Objective: Synthesis of thoisemicarbazone derivatives of 2,4-dichlorophenyl acetic acid and to screened them for their biological activities. Method: Thiosemicarbazone derivatives (4-13) were synthesized by refluxing 2,4-dichlorophenyl acetic acid with sulfuric acid in ethanol to get the ester (2), which was further refluxed with thiosemicarbazide to get compound (3). Finally, different aromatic aldehydes were refluxed with compound (3) in ethanol in catalytic amount of acetic acid to obtained the final products (4-13). Using modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR, the structures of the created derivatives were confirmed. Results: The synthesized derivatives showed excellent to good inhibitory activity in the range of IC50 values of 4.95 ± 0.44 to 69.71 ± 0.05 µM against α-amylase enzyme when compared to standard drug acarbose (IC50 = 21.55 ± 1.31 µM). In case of iron chelating activity, these products showed potent activity better than standard EDTA (IC50 = 66.43 ± 1.07 µM) in the range of IC50 values of 22.43 ± 2.09 to 61.21 ± 2.83 µM. However, the obtained products also show excellent to good activity in the range of IC50 values of 28.30 ± 1.17 to 64.66 ± 2.43 µM against hydroxyl radical scavenging activity when compared with standard vitamin C (IC50 = 60.51 ± 1.02 µM). DFT used to calculate different reactivity factors including ionization potential, electronegativity, electron affinity, chemical softness, and chemical hardness were calculated using frontier molecular orbital (FMO) computations. The molecular docking studies for the synthesized derivatives with α-amylase were carried out using the AutoDock Vina to understand the binding affinities with active sites of the protein.

Efficient Screening of Metal Promoters of Pt Catalysts for C-H Bond Activation in Propane Dehydrogenation from a Combined First-Principles Calculations and Machine-Learning Study.

Platinum-based materials are the most widely used catalysts in propane direct dehydrogenation, which could achieve a balanced activity between both propane conversion and propene formation. One of the core issues of Pt catalysts is how to efficiently activate the strong C-H bond. It has been suggested that adding second metal promoters could greatly solve this problem. In the current work, first-principles calculations combined with machine learning are performed in order to obtain the most promising metal promoters and identify key descriptors for control performance. The combination of three different modes of adding metal promoters and two ratios between promoters and platinum sufficiently describes the system under investigation. The activity of propane activation and the formation of propene are reflected by the increase or decrease of the adsorption energy and C-H bond activation of propane and propene after the addition of promoters. The data of adsorption energy and kinetic barriers from first-principles calculations are streamed into five machine-learning methods including gradient boosting regressor (GBR), K neighbors regressor (KNR), random forest regressor (RFR), and AdaBoost regressor (ABR) together with the sure independence screening and sparsifying operator (SISSO). The metrics (RMSE and R2) from different methods indicated that GBR and SISSO have the most optimal performance. Furthermore, it is found that some descriptors derived from the intrinsic properties of metal promoters can determine their properties. In the end, Pt3Mo is identified as the most active catalyst. The present work not only provides a solid foundation for optimizing Pt catalysts but also provides a clear roadmap to screen metal alloy catalysts.

Metal-Free Electrocatalysts for the Selective 2 e- Oxygen Reduction Reaction: A Never-Ending Story?

Hydrogen peroxide (H2 O2 ) electrosynthesis via the 2e- Oxygen Reduction Reaction (ORR) represents a highly challenging, environmentally friendly and cost-effective alternative to the current anthraquinone-based technology. Various lightweight element hetero-doped carbon nanostructures are promising and cheap metal-free electrocatalysts for H2 O2 synthesis, particularly those containing O-functionalities. The exact role of O-containing functional groups as electroactive sites for the process remains debated if not highly controversial. Herein, we have reported on the covalent exohedral functionalization of the outer surface of extra-pure multi-walled carbon nanotubes (MWCNTs) with discrete O-functional groups as a unique approach to prepare selective electrocatalysts for the process. This kind of decoration has added fundamental tiles to the puzzling structure/reactivity relationship of O-containing carbon-based catalysts for ORR, clearing doubts on the controversial role of hydroxyl/phenol groups as key functionalities for the design of more performing 2e- ORR electrocatalysts.

Computational insights of excited state intramolecular proton transfer (ESIPT) based fluorescent detection and imaging of γ-glutamytranspeptidase activity.

γ-Glutamytranspeptidase (GGT) is an important tumor biomarker that widely appears in the tumor cells. Therefore, accurate imaging and detection of GGT activity in live cells, serum and pathological cells grasp great importance for the diagnosis, management, and treatment of cancer. Herein, 2-(2-hydroxyl-phenyl)-6-chloro-4-(3H)-quinazolinone (HPQ) is considered as the fluorophore probe for the detection of GGT activity, which is known for the typical mechanism of excited-state intramolecular proton transfer (ESIPT). All the simulations adopted to evaluate the sensing mechanism were carried out via DFT and TDDFT calculations at CAM-B3LYP/TZVP level of theory. The emission properties of HPQ and HPQ-TD are thoroughly studied to understand the photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) process. The results reveal that the fluorescence quenching of HPQ (enol form) is assigned to the PET process, whereas the large Stokes shift in fluorescence emission of HPQ (keto form) is related with ESIPT mechanism. The obtained results are further cross validated by frontier molecular orbital (FMO) analysis, geometric analysis, and potential energy curve (PEC) scanning. Our calculations provide powerful evidence for the ESIPT based sensing mechanism of HPQ (keto-enol form) for GGT activity.

Engineering the catalytic properties of CeO2 catalyst in HCl-assisted propane dehydrogenation by effective doping: A first-principles-based microkinetic simulation.

HCl-assisted propane dehydrogenation (PDH) is an attractive route for propene production with good selectivity. In this study, the doping of CeO2 with different transition metals, including V, Mn, Fe, Co, Ni, Pd, Pt, and Cu, in the presence of HCl was investigated for PDH. The dopants have a pronounced effect on the electronic structure of pristine ceria that significantly alters the catalytic capabilities. The calculations indicate the spontaneous dissociation of HCl on all surfaces with a facile abstraction of the first hydrogen atom except on V- and Mn-doped surfaces. The lowest energy barrier of 0.50 and 0.51eV was found for Pd- and Ni-doped CeO2 surfaces. The surface oxygen is responsible for hydrogen abstraction, and its activity is described by the p-band center. Microkinetics simulation is performed on all doped surfaces. The increase in the turnover frequency (TOF) is directly linked with the partial pressure of propane. The adsorption energy of reactants aligned with the observed performance. The reaction follows first-order kinetics to C3H8. Furthermore, on all surfaces, the formation of C3H7 is found as the rate-determining step confirmed by the degree of rate control (DRC) analysis. This study provides a decisive description of catalyst modification for HCl-assisted PDH.

Pulmonary Nocardiosis In A Patient With Diabetes Mellitus.

Nocardiosis is considered as one of the rare systemic infections. It is usually prevalent in immunocompromised individuals though few cases have been reported in immunocompetent individuals as well. With the advent of new microbiological classifications and increasing progress in laboratory technology this infection is being diagnosed more frequently. Hence it is important to diagnose and treat this disease timely in order to reduce its associated morbidity and mortality. Nocardiosis is a rare condition and is often overlooked. Hence this case is presented.