Kcal Mol Research Articles

Leveraging Limited Experimental Data with Machine Learning: Differentiating a Methyl from an Ethyl Group in the Corey-Bakshi-Shibata Reduction.

We present a case study on how to improve an existing metal-free catalyst for a particularly difficult reaction, namely, the Corey-Bakshi-Shibata (CBS) reduction of butanone, which constitutes the classic and prototypical challenge of being able to differentiate a methyl from an ethyl group. As there are no known strategies on how to address this challenge, we leveraged the power of machine learning by constructing a realistic (for a typical laboratory) small, albeit high-quality, data set of about 100 reactions (run in triplicate) that we used to train a model in combination with a key-intermediate graph (of substrate and catalyst) to predict the differences in Gibbs activation energies ΔΔG‡ of the enantiomeric reaction paths. With the help of this model, we were able to select and subsequently screen a small selection of catalysts and increase the selectivity for the CBS reduction of butanone to 80% enantiomeric excess (ee), the highest possible value achieved to date for this substrate with a metal-free catalyst, thereby also exceeding the best available enzymatic systems (64% ee) and the selectivity with Corey's original catalyst (60% ee). This translates into a >50% improvement in relative ΔG‡ from 0.9 to 1.4 kcal mol-1. We underscore the transformative potential of machine learning in accelerating catalyst design because we rely on a manageable small data set and a key-intermediate graph representing a combination of catalyst and substrate graphs in lieu of a transition-state model. Our results highlight the synergy of synthetic chemistry and data-centric approaches and provide a blueprint for future catalyst optimization.

Experimental and Computational Study of Pyrogenic Carbonaceous Matter Facilitated Hydrolysis of 2,4-Dinitroanisole (DNAN).

This study investigated the reaction pathway of 2,4-dinitroanisole (DNAN) on the pyrogenic carbonaceous matter (PCM) to assess the scope and mechanism of PCM-facilitated surface hydrolysis. DNAN degradation was observed at pH 11.5 and 25 °C with a model PCM, graphite, whereas no significant decay occurred without graphite. Experiments were performed at pH 11.5 due to the lack of DNAN decay at pH below 11.0, which was consistent with previous studies. Graphite exhibited a 1.78-fold enhancement toward DNAN decay at 65 °C and pH 11.5 relative to homogeneous solution by lowering the activation energy for DNAN hydrolysis by 54.3 ± 3.9%. This is supported by our results from the computational modeling using Car-Parrinello simulations by ab initio molecular dynamics/molecular mechanics (AIMD/MM) and DFT free energy simulations, which suggest that PCM effectively lowered the reaction barriers by approximately 8 kcal mol-1 compared to a homogeneous solution. Quaternary ammonium (QA)-modified activated carbon performed the best among several PCMs by reducing DNAN half-life from 185 to 2.5 days at pH 11.5 and 25 °C while maintaining its reactivity over 10 consecutive additions of DNAN. We propose that PCM can affect the thermodynamics and kinetics of hydrolysis reactions by confining the reaction species near PCM surfaces, thus making them less accessible to solvent molecules and creating an environment with a weaker dielectric constant that favors nucleophilic substitution reactions. Nitrite formation during DNAN decay confirmed a denitration pathway, whereas demethylation, the preferred pathway in homogeneous solution, produces 2,4-dinitrophenol (DNP). Denitration catalyzed by PCM is advantageous to demethylation because nitrite is less toxic than DNAN and DNP. These findings provide critical insights for reactive adsorbent design that has broad implications for catalyst design and pollutant abatement.

Screening Stability, Thermochemistry, and Chemical Kinetics of 3-Hydroxybutanoic Acid as a Bifunctional Biodiesel Additive.

The thermo-kinetic aspects of 3-hydroxybutyric acid (3-HBA) pyrolysis in the gas phase were investigated using density functional theory (DFT), specifically the M06-2X theoretical level in conjunction with the cc-pVTZ basis set. The obtained data were compared with benchmark CBS-QB3 results. The degradation mechanism was divided into 16 pathways, comprising 6 complex fissions and 10 barrierless reactions. Energy profiles were calculated and supplemented with computations of rate coefficients and branching ratios over the temperature range of 600-1700 K at a pressure of 1 bar using transition state theory (TST) and Rice-Ramsperger-Kassel-Marcus (RRKM) methods. Thermodynamics results indicated the presence of six stable conformers within a 4 kcal mol-1 energy range. The estimated chemical kinetics results suggested that TST and RRKM approaches are comparable, providing confidence in our calculations. The branching ratio analysis reveals that the dehydration reaction pathway leading to the formation of H2O and CH3CH═CHCO2H dominates entirely at T ≤ 650 K. At these temperatures, there is a minor contribution from the simple homolytic bond fission reaction, yielding related radicals [CH3•CHOH + •CH2CO2H]. However, at T ≥ 700 K, this reaction becomes the primary decomposition route. At T = 1700 K, there is a minor involvement of a reaction pathway resulting in the formation of CH3CH(OH)•CH2 + •CHO(OH) with an approximate contribution of 16%, and a reaction leading to [•CH3 + •CH2OHCH2CO2H] with around 9%.

Investigation of cyclopentene + OH and cyclopentene thermal decomposition reactions

This study presents the first high-temperature measurements of cyclopentene+OH→k1Products reaction over 856 – 1258 K and 1.03 – 4.33 bar. The determined rate coefficients of k1 exhibited Arrhenius temperature dependence with an activation energy ∼ 3.3 kcal mol−1 and negligible pressure dependence. Rate coefficients of OH + cyclopentene are faster than OH + 1-pentene but comparable to OH + 2-pentene, highlighting the significance of allylic CH bonds in these reactions. At 1258 K, our rate coefficient is ∼ 30 % slower than the average room-temperature measurement, indicating the role of OH-addition pathways at low temperatures. Site-specific rate coefficients and branching ratios are determined, with H-abstraction at the allylic CH site accounting for ∼68 % of the reaction and alkylic CH bond contributing ∼22 %. Our measured k1 may be given as (unit: cm3molecule−1s−1):k1=1.64×10−10e(−1660T)Cyclopentene decomposition reaction (cyclopentene→k2cyclopentadiene+H2) is studied over 1186–1472 K and 1.17 – 1.38 bar. Time-resolved yields of the product, cyclopentadiene, are monitored using a sensitive UV laser diagnostic near 220 nm. Absorption cross-sections of cyclopentadiene, measured in two separate mixtures, showed weak positive temperature dependence (8.7 – 9.8 × 10−18 cm2molecule−1) over 961 – 1326 K. Our rate coefficients of k2 exhibited a positive Arrhenius temperature dependence with an activation energy of ∼ 54.7 kcal mol−1. At 1300 K, the decomposition of cyclopentene proceeds 5.5 and 28 times faster than that of cyclopentadiene and cyclopentane, respectively. Our measured k2 may be expressed as (unit: s−1):k2=2.55×1012e(−27,527.6T)The pentagonal structure of cyclopentene influences its H-abstraction and decomposition reactions distinctively. While H-abstraction by OH follows a mechanism akin to cyclohexene and linear alkenes, with comparable rate coefficients at allylic CH bonds, the penta-ring structure significantly impacts the decomposition mechanism. Cyclopentene decomposition predominantly produces cyclopentadiene and H2 in a ring-conserving manner, differing from the cleavage of allylic-alkylic CC bonds in the decompositions of 1-alkenes and cyclohexene.

Understanding the stability of a plastic-degrading Rieske iron oxidoreductase system.

Rieske oxygenases (ROs) are a diverse metalloenzyme class with growing potential in bioconversion and synthetic applications. We postulated that ROs are nonetheless underutilized because they are unstable. Terephthalate dioxygenase (TPADO PDB ID 7Q05)is a structurally characterized heterohexameric α3β3 RO that, with its cognate reductase (TPARED), catalyzes the first intracellular step of bacterial polyethylene terephthalate plastic bioconversion. Here, we showed that the heterologously expressed TPADO/TPARED system exhibits only ~300 total turnovers at its optimal pH and temperature. We investigated the thermal stability of the system and the unfolding pathway of TPADO through a combination of biochemical and biophysical approaches. The system's activity is thermally limited by a melting temperature (Tm) of 39.9°C for the monomeric TPARED, while the independent Tm of TPADO is 50.8°C. Differential scanning calorimetry revealed a two-step thermal decomposition pathway for TPADO with Tm values of 47.6 and 58.0°C (ΔH = 210 and 509 kcal mol-1, respectively) for each step. Temperature-dependent small-angle x-ray scattering and dynamic light scattering both detected heat-induced dissociation of TPADO subunits at 53.8°C, followed by higher-temperature loss of tertiary structure that coincided with protein aggregation. The computed enthalpies of dissociation for the monomer interfaces were most congruent with a decomposition pathway initiated by β-β interface dissociation, a pattern predicted to be widespread in ROs. As a strategy for enhancing TPADO stability, we propose prioritizing the re-engineering of the β subunit interfaces, with subsequent targeted improvements of the subunits.

Nonalternant Nanographenes Containing N-Centered Cyclopenta[ef]heptalene and Aza[7]Helicene Units.

Introducing helical subunits into negatively curved π-systems has a significant effect on both the molecular geometry and photophysical properties; however, the synthesis of these helical π-systems embedded with nonbenzenoid subunits remains challenging due to the high strain deriving from both the curvature and helix. Here, we report a family of nonalternant nanographenes containing a nitrogen (N)-doped cyclopenta[ef]heptalene unit. Among them, CPH-2 and CPH-3 can be viewed as hybrids of benzoannulated cyclopenta[ef]heptalene and aza[7]helicene. The crystal structures revealed a saddle geometry for CPH-1, a saddle-helix hybrid for CPH-2, and a twist-helix hybrid for CPH-3. Experimental measurements and theoretical calculations indicate that the saddle moieties in CPHs undergo flexible conformational changes at room temperature, while the aza[7]helicene subunit exhibits a dramatically increased racemization energy barrier (78.2 kcal mol-1 for CPH-2, 143.2 kcal mol-1 for CPH-3). The combination of the nitrogen lone electron pairs of the N-doped cyclopenta[ef]heptalene unit with the twisted helix fragments results in rich photophysics with distinctive fluorescence and phosphorescence in CPH-1 and CPH-2 and the similar energy fluorescence and phosphorescence in CPH-3. Both enantiopure CPH-2 and CPH-3 display distinct circular dichroism (CD) signals in the UV-vis range. Notably, compared to the reported fully π-extended helical nanographenes, CPH-3 exhibits excellent chiroptical properties with a |gabs| value of 1.0 × 10-2 and a |glum| value of 7.0 × 10-3; these values are among the highest for helical nanographenes.

Effect of metal doping (M = Sc, V, Ti, Fe and Mn) on the sensing performance of the Si12C12 nanocage towards the penicillamine drug molecule: a DFT study

In this work, we have investigated the electronic properties of the pristine and metal(M)-doped Si12C12 (M = Sc, V, Ti, Fe and Mn) nanocages and their sensing performances towards the penicillamine (PCE) molecule using DFT calculations at the B3LYP/LanL2DZ/6-311G(d,p) method. The results reveal that the doping of the Si12C12 nanocage with a metal atom significantly improves its reactivity, therefore their interaction with the nucleophilic centres of the PCE molecule becomes easy. The most stable complexes were obtained when the PCE molecule was chemisorbed onto the MSi12C12 nanocages through its oxygen atom with adsorption energies which vary from –18.0 to –40.2 kcal mol−1. The results also demonstrate that the MSi12C12 possess high sensitivity towards the PCE molecule. The presence of solvent sharply reduces the adsorption energy of the PCE molecule over the clusters surface, resulting in a substantial decrease in the recovery time. A comparative study between the values of the sensitivity of the studied clusters in liquid phase suggests that the FeSi12C12 and MnSi12C12 clusters present high sensing performances compared with the other clusters, so they are regarded as the best sensors to detect the PCE drug molecule.

Characterization and molecular docking of sustainable wine lees and gelatin-based emulsions: innovative fat substitution.

The present study aimed to determine how various amounts (0.00, 0.58, 1.52 and 4.50 g 100 g-1) of wine lees (WL), which contains numerous essential components, impact the emulsifying properties of fish gelatin (FG) at a low concentration (0.5 g 100 g-1) in the high-fat phase (65 g 100 g-1). This study conducted rheology, physicochemical technical and characterization analyses on the emulsions to provide sustainable and innovative approaches for spreadable oils. The addition of WL to FG emulsions improved oxidative stability, emulsion stability and bioactive compounds. The zeta potential (-101 ± 5.62 mV) of 0.58 g 100 g-1 WL-containing emulsion (PE1) was found to be high, whereas particle size (347.6 ± 5.25 nm) and polydispersity index (0.50) were statistically low. It was also found that the addition of WL improved the intermolecular interactions, crystallinity and microstructural properties of the emulsions. All these results were supported by simulating the molecular configuration between FG and WL. The compounds gallic acid, caffeic acid, myricetin, quercetin and resveratrol showed a strong affinity to FG, with free binding energies of -5.50, -5.88, -6.53, -6.68 and -6.66 kcal mol-1, respectively. As a result, WL-supported FG has the potential to be used as an alternative to egg proteins to develop sustainable low-cost spreadable emulsions. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Computational study of charge transfer iso-surface in first three excited states, electron-hole transition effects, chemical nature and bond order analysis investigations of chrysogine

This work presents the theoretical DFT (Density Functional Theory) studies and the biological application of chrysogine, a marine alkaloid. Energy minimisation and additional DFT evaluations were performed for vacuum and solvent media. It has been observed that solvation with polar solvents has resulted in a slight variation in the molecule’s properties. The Multiwfn software was employed to carry out various topological analyses. Among these, the charge transfer studies show that the second and third excited states are the most significant. From the reactivity analysis, the least energy gap (4.9624 eV) is obtained in water, indicating that chrysogine is most reactive in aqueous media. Theoretical UV studies show that the trends in λmax values correspond to n -->π* and n -->σ* electronic transitions within the molecule. An increase in medium polarity has demonstrated in the MEP (Molecular Electrostatic Potential) maps an increase in the potential range from −6.619 × 10−2 a.u. to 6.619 × 10−2 a.u. in the gas phase, to a sharp rise to −8.036 × 10−2 a.u. to 8.036 × 10−2 a.u. in ethanol, −8.098 × 10−2 a.u. to 8.098 × 10−2 a.u. in methanol, −8.130 × 10−2 a.u. to 8.130 × 10−2 a.u. in DMSO, and −8.127 × 10-2 a.u. to 8.127 × 10−2 a.u. in water. The most significant transition contributing to molecular stability from NBO (Natural Bond Orbital) analysis is: (O2-C9) π* → π* (C7-C8) with the energy of 258.13 kcal mol−1. The ADMET profile for the molecule was assimilated with the help of online servers. The molecule was docked against lung cancer target proteins (PDB ID: 1NTK, 3QFB) using software such as AutoDock Tools and PyMOL. The respective illustrations and data were visualised using Discovery Studio Visualizer. Good binding affinities (−5.69 kcal mol−1 for 1NTK and −6.64 kcal mol−1 for 3QFB proteins) and interactions were achieved with the selected targets.

Bis(dimethylpyrazolyl)-aniline-s-triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies.

4,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-1,3,5-triazin-2-amine (PTA-1), N-(4-bromophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine (PTA-2) and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine (PTA-3) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H2SO4 was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that s-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor PTA-2 and PTA-3 bearing -Br and -OCH3 groups on aniline, respectively. While PTA-1 without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant K°ads and free energy change ΔG°ads revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement dE ads/dN i, for both forms of PTA-2 and PTA-3 with electron donating groups (-439.73 and -436.62 kcal mol-1) is higher than that of PTA-1 molecule (-428.73 kcal mol-1). This aligned with experimental inhibition efficiency results.

Hemisynthesis of Pentacyclic Triterpenoids from Diospyros foxworthyi with In vitro and In silico Anti-malarial Evaluation

Abstract: A total of twelve pentacyclic triterpenoid derivatives based on betulin (1) and lupeol (2) scaffolds isolated from Diospyros foxworthyi were hemisynthesized by acylation or acetylation reactions with appropriate acid chloride or acetic anhydride. The structures of the hemisynthesised compounds were characterised by means of FT-IR, 1D- and 2D-NMR, as well as HRMS analysis. These compounds were assayed for in vitro anti-malarial studies by inhibition of β-hematin formation assay with chloroquine as a positive control. Compounds 1d and 2f showed the strongest potential as β-hematin formation inhibitors with IC50 values of 6.66 ± 1.36 and 11.89 ± 0.15 μM, respectively, compared with the positive control (chloroquine; IC50 = 37.50 ± 0.60 μM). In silico molecular docking simulations were performed using AutoDock Vina for compounds 1d and 2f to investigate the binding interactions and free energy of binding (FEB) with the hemozoin supercell crystal structure (CCDC number: XETXUP01). The findings revealed several hydrophobic interaction modes between the 1d, 2f and hemozoin, with calculated FEBs of -8.4 ± 0.2 and -8.9 ± 0.0 kcal mol-1, indicating strong and favourable interactions.

Anharmonic rotational and vibrational spectroscopic constants of NH2CH2OH

The recent experimental identification of aminomethanol (NH2CH2OH) and its synthesis under simulated interstellar conditions suggests that it may be formed, and thus observable, in the interstellar medium. To aid in its possible detection, this work presents high-level theoretical, anharmonic vibrational and rotational spectroscopic data for the three lowest-energy conformers of NH2CH2OH. All three conformers fall within 0.80 kcal mol−1 of each other at the CCSD(T)-F12b/cc-pCVTZ-F12 level, with an anharmonic zero-point vibrational energy correction. Additionally, all three conformers are shown to have multiple vibrational frequencies with intensities greater than 100 km mol−1. The most notable of these are the symmetric O-C-N stretch of the lower-energy C1 conformer at 976.4 cm−1, the C-O stretch of the Cs conformer at 964.9 cm−1, and the antisymmetric O-C-N stretch of the higher-energy C1 conformer at 1099.0 cm−1. While much of the vibrational spectra of the three overlap, these features should help to separate them. Finally, all three conformers have non-zero dipole moments on the order of 1 D, suggesting that they may be observable by rotational spectroscopy, as well. In all cases, the computational data provided herein will help to facilitate future experimental and observational studies on this key molecule in the formation of extraterrestrial amino acids.

Electrochemical Investigations and Molecular Docking Analysis to Evaluate the Molnupiravir-Calf Thymus dsDNA Interaction

Molnupiravir (MLP) is an important antiviral drug recommended for the treatment of COVID-19. In order to design new pharmaceuticals, exploring drug and DNA interaction is crucial. This study aimed to determine the interaction of MLP with calf thymus double-stranded DNA (ct-dsDNA) by electrochemical methods. Investigation of these interactions was carried out using the differential pulse voltammetry technique (DPV) on the biosensor surface and in-solution studies. Changes in ct-dsDNA between deoxyguanosine (dGuo) and deoxyadenosine (dAdo) oxidation signals were examined before and after the interaction. It was found that MLP interacts significantly with bases of ct-dsDNA dAdo. Limits of detection and quantification for MLP-ct-dsDNA interaction were calculated as 2.93 and 9.67 μM in the linear range of 10–200 μM, respectively, based on dAdo’s decreasing peak current. To calculate the binding constant of MLP and ct-dsDNA, cyclic voltammetry was used, and it was found to be 8.6 × 104 M. As for molecular docking techniques, the binding energy of MLP with DNA is −8.1 kcal mol−1, and this binding occurred by a combination of strong conventional hydrogen bonding to both adenine and guanine base pair edges, which indicates the interaction of MLP with DNA.

Solution-processable polymers of intrinsic microporosity for selective silver removal from aqueous solution and subsequent disinfection by silver-laden coatings

Silver ions (Ag+) in waterways pose a growing threat to the environment and living organisms. Achieving an effective and green process for Ag+ removal requires an adsorbent with excellent specificity for silver ions and easy recoverability after fouling or blocking. However, this remains a major challenge. To address this concern, we developed a high-performance adsorbent by grafting polymers of intrinsic microporosity (PIM) with thioamide groups. This thioamide-modified PIM (TPIM-1) adsorbent exhibited an exceptional adsorption capacity of 656 mg g−1 and high selectivity (distribution coefficient of 833.3 mL g−1, selectivity coefficient of 346 over Cd2+) for aqueous Ag+ removal. TPIM-1 also features good solubility in selected solvents, allowing regeneration through a dissolution separation precipitation (DSP) procedure once fouling or blocking occurs. Over 80 % of the adsorption capacity was recovered after nine continuous regeneration cycles, showcasing potential cost-effective reusability. Density Functional Theory (DFT) results reveal that the grafted thioamide groups play a critical role in selective Ag+ adsorption, with a binding energy of 54 kcal mol−1. In addition, the Ag+-loaded PIM-coated glass surface showed excellent antibacterial ability, inhibiting the growth of Bacillus subtilis and E. coli. This study provides a viable strategy for the development of a low-carbon footprint silver removing adsorbent from wastewater.

Chemical Repair of Radical Damage to the GC Base Pair by DNA-Bound Bisbenzimidazoles.

The migration of an electron-loss center (hole) in calf thymus DNA to bisbenzimidazole ligands bound in the minor groove is followed by pulse radiolysis combined with time-resolved spectrophotometry. The initially observed absorption spectrum upon oxidation of DNA by the selenite radical is consistent with spin on cytosine (C), as the GC• pair neutral radical, followed by the spectra of oxidized ligands. The rate of oxidation of bound ligands increased with an increase in the ratio (r) ligands per base pair from 0.005 to 0.04. Both the rate of ligand oxidation and the estimated range of hole transfer (up to 30 DNA base pairs) decrease with the decrease in one-electron reduction potential between the GC• pair neutral radical of ca. 1.54 V and that of the ligand radicals (E0', 0.90-0.99 V). Linear plots of log of the rate of hole transfer versus r give a common intercept at r = 0 and a free energy change of 12.2 ± 0.3 kcal mol-1, ascribed to the GC• pair neutral radical undergoing a structural change, which is in competition to the observed hole transfer along DNA. The rate of hole transfer to the ligands at distance, R, from the GC• pair radical, k2, is described by the relationship k2 = k0 exp(constant/R), where k0 includes the rate constant for surmounting a small barrier.

Integrated spectroscopic and computational analyses unravel the molecular interaction of pesticide azinphos-methyl with bovine beta-lactoglobulin.

Organophosphorus are typically hazardous chemicals used in the pharmaceutical, agricultural, and other industries. They pose a serious risk to human life and can be fatal upon direct exposure. Hence, studying the interaction between such compounds with proteins is crucial for environmental, health, and food safety. In this study, we investigated the interaction mechanism between azinphos-methyl (AZM) and β-lactoglobulin (BLG) at pH 7.4 using a combination of biophysical techniques. Intrinsic fluorescence investigations revealed that BLG fluorescence was quenched in the presence of increasing AZM concentrations. The quenching mechanism was identified as static, as evidenced by a decrease in the fluorescence quenching constant (1.25 × 104, 1.18 × 104, and 0.86 × 104 M-1) with an increase in temperatures. Thermodynamic calculations (ΔH > 0; ΔS > 0) affirmed the formation of a complex between AZM and BLG through hydrophobic interactions. The BLG's secondary structure was found to be increased due to AZM interaction. Ultraviolet -visible spectroscopy data showed alterations in BLG conformation in the presence of AZM. Molecular docking highlighted the significant role of hydrophobic interactions involving residues such as Val43, Ile56, Ile71, Val92, Phe105, and Met107 in the binding between BLG and AZM. A docking energy of -6.9 kcal mol-1, and binding affinity of 1.15 × 105 M-1 suggest spontaneous interaction between AZM and BLG with moderate to high affinity. These findings underscore the potential health risks associated with the entry of AZM into the food chain, emphasizing the need for further consideration of its impact on human health.

Tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C-H Bonds.

The tert-butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~ 100 kcal mol-1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert-butyl C-H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro-tert-butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese-oxo species that effectively oxidizes tert-butyl C-H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site-selective and product chemoselective hydroxylation of the tert-butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late-stage hydroxylation at tert-butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert-butyl as a potential functional group in strategic synthetic planning for complex molecular architectures.

MOLECULAR DOCKING AND ADMET BASED MINING OF NATURAL COMPOUNDS FROM PTEROCARPUS MARSUPIUM AGAINST PRIME TARGETS OF DIABETES MELLITUS

In the Ayurvedic system of medicine, Pterocarpus marsupium Linn bark extract is used for the treatment of diabetes. It has a rich profile of chemical constituents. However, phytochemicals with antidiabetic activity are not reported yet. To comprehend more about this plant’s antidiabetic mechanism of action, 26 reported phytochemicals, namely, pterostilbene, marsupsin/ carpusin, 7-O-α-L-rhamnopyranosyloxy4′-methoxy-5-hydroxy isoflavone, (-)-epicatechin, pterosupin, liquiritigenin, vijayoside, pteroside, propterol-b, beta-eudesmol, pseudobaptigenin, isoliquiritigenin, garbanzol, 5-de-oxykaempferol, catechol, gallic acid, 3,4-dihydroxybenzoic acid, naringetol, 4-hydroxybenzaldehyde, trans-stilbene, 3,7,4’-trihydroxyflavone, 7,4’-dihydroxyflavone, (2S)-7-hydroxyflavanone, oleanolic acid, lupeol and marsupol/ebanol, were subjected to molecular docking studies using six targets of diabetes, namely, C and N-terminal subunits of human maltase-glucoamylase, glucagon like peptide-1, N-terminal sucraseisomaltase, human peroxisome proliferator-activated receptor –α and ϒ. The docking studies were carried out using PyRx and AutoDock Vina 1.1.2 software. Compounds with optimum binding affinity were subjected to evaluate drug likeliness and toxicity using SwissADME and admetSAR web tools. Vijayoside was found to have maximum affinity (-8.5 Kcal mol-1) with N-terminal subunit of human maltaseglucoamylase. The binding energies of O-α-L-rhamnopyranosyloxy-4'-methoxy-5-hydroxy isoflavone was found to be maximum with C-terminal (-10.0 Kcal mol-1). Danugliprion, a standard, was found to have maximum binding affinity (-11.4 Kcal mol-1) with glucagon-like peptide-1. Pteroside was found to bind favorably (-7.5 Kcal mol-1) with N-terminal sucrase-isomaltase.7-O-α-L-rhamnopyranosyloxy4′-methoxy-5-hydroxy isoflavone has exhibited stable interactions with other receptors (-10.2 and -8.2 Kcal mol-1 for human peroxisome proliferator-activated receptor–α and ϒ). These three phytochemicals also exhibited druggability properties. Further in vitro and in vivo studies may fully validate the results.

Deoxygenation reactions of nitrous oxide assisted by oriented external electric field

AbstractDue largely to the high stability and the potential ozone‐depleting, the transformation of greenhouse gas nitrous oxide has gained much attentions. In present paper, a new insight into the deoxygenation of nitrous oxide with silane was reported by using oriented external electric field (OEEF) as a catalytic strategy. When the OEEF was employed, the reaction barrier of deoxygenation was marvelously decreased as it was oriented along the positive NO/OSi bond‐axis. Especially the field strength is 300 × 10−4 a.u., the differences are up to 22.4/18.3 kcal mol−1 as compared with that of nonfield. In addition, once the H atom in SiH4 was replaced by methyl, two reaction modes were obtained, in which the deoxygenation process was easier when the N2O captured the H atom attached to the Si atom, not attached to the C atom. Further, the solvent effects of deoxygenation reaction were also considered, but with a weak influence were obtained.

Evaluation of novel pyridoxal isonicotinoyl hydrazone (PIH) derivatives as potential anti‐tuberculosis agents: An in silico investigation

AbstractThis investigation employed computational methodologies to assess the therapeutic potential of derivatives (1–16) of pyridoxal isonicotinoyl hydrazone (PIH) as potential treatments for tuberculosis. Various computational techniques, including molecular dynamics simulation, molecular docking, density functional theory, and global chemical descriptors, were employed to analyze the interactions between the ligands and target proteins. Docking results indicated that ligands 6, 7, 8, and rifampin exhibited binding affinities of −8.4, −7.4, −9.2, and − 7.2 kcal mol−1, respectively, against mycobacterium tuberculosis enoyl acyl carrier protein reductase (INHA), with ligand 8 demonstrating superior inhibition. Molecular dynamics (MD) simulations were utilized to assess the stability of protein‐ligand interactions. Remarkably, the Root Mean Square Deviation (RMSD) of the INHA‐ligand 8 complex remained minimal, with peak values at .40, .56, .37, and .50 nm at temperatures of 300, 305, 310, and 320 K, respectively. This suggests superior stability compared to the reference drug rifampin and INHA complex, which exhibited an RMSD range of .2 to .8 nm at 300 K. Furthermore, analysis using Frontier Molecular Orbital (FMO) revealed that the Egap value of ligand 8 (4.407 eV) is lower than all the reference drugs except rifampin. This comprehensive theoretical analysis positions ligand 8 as a promising candidate for anti‐tuberculosis drug development, underscoring the need for further exploration through in vitro and in vivo studies.