课程文献中心 更多>>

关键词： Cocrystal   Spectroscopic analysis   DSC   DFT   Molecular docking   Breast cancer  

摘要： A cocrystal composed of 5-fluoro-1,2,3,4-tetrahydropyrimidine-2,4-dione and 4-hydroxy-3,5-dimethoxybenzoic acid (5FUDMBA) was produced through neat-grinding synthesis and characterized using PXRD, FT-IR, NMR (¹H and ¹³C), Mass spectrometry, DSC and UV–Visible analysis. The above said studies, PXRD, NMR, Mass spectrometry and DSC confirmed the formation of cocrystal. Density Functional Theory calculations (DFT/B3LYP, 6-311++ G(d,p)) were used to optimize the molecular geometry, which closely matched the reported X-ray crystal structure. The stability of the cocrystal is governed by intermolecular O–H···O and N–H···O hydrogen-bond networks. Vibrational features were interpreted by correlating experimental spectra with theoretically calculated frequencies supported by PED analysis. Comprehensive electronic-structure analysis—including HOMO/LUMO energies (ΔE = 4.65 eV), global reactivity indices, molecular electrostatic potential, thermodynamic characteristics, Mulliken charges, and nonlinear optical responses was performed. Reactive regions were identified using Fukui index calculations and average local ionization energy mapped onto the electron-density surface. Further insight into intramolecular and intermolecular interactions was obtained through ELF, LOL, and NCI topological analyses. Docking simulations showed that 5FUDMBA interacts strongly with the AKT1 protein, with a binding affinity of -9.5 kcal/mol, while MTT cytotoxicity experiments confirmed enhanced activity of 5FUDMBA compared to free 5FU against MDA-MB-231 breast cancer cells. Collectively, these findings indicate that 5FUDMBA displays robust physicochemical properties and anticancer potential, making it as one of the promising molecules for therapeutic development.

关键词： 22-hydroxy-23,24-bisnorchol-4-ene-3-one (HBC)   3-ketosteroid Δ(1)-dehydrogenase (KstD)   Biotransformation   CRISPR   M. neoaurum  

摘要： Mycobacterium neoaurum can convert phytosterols (PS) into steroidal intermediates such as HBC (22-hydroxy-23,24-bisnorchol-4-ene-3-one). However, 3-ketosteroid Δ¹-dehydrogenase (KstD) can catalyze the dehydrogenation at the C1 position of the steroid nucleus, which leads to the accumulation of byproducts such as 22-hydroxy-23,24-bisnorchol-1,4-diene-3-one (1,4-HBC). This is further accompanied by 9-hydroxylation of the steroid framework, resulting in spontaneous degradation of the B ring. Using the known KstD1–3 sequences as probes, bioinformatic analysis identified two novel 3-ketosteroid Δ¹-dehydrogenases (KstD4 and KstD5) in M. neoaurum WIII. Recombinant E. coli BL21 strains expressing kstD4 and kstD5 exhibited 1-position dehydrogenation activity toward HBC and androstenedione (AD). Purified enzyme assays revealed that KstD5 preferentially catalyzes the C-19 steroid intermediate such as AD, whereas KstD4 favors the incomplete side-chain degradation intermediate HBC. These findings suggest that KstD4 and KstD5 have different physiological function but both contribute to steroid nucleus degradation and byproduct accumulation during PS transformation. Inactivation of KstD4 and KstD5 in M. neoaurum reduced the 1,4-HBC byproduct concentration from 0.27 g/L to 0.12 g/L and increased the HBC yield from 32.85 g/L to 34.20 g/L. Moreover, the mutant strain showed improved performance under industrially relevant conditions, including in a system with reduced cyclodextrin ratio and simulated autolyzed cells.

关键词： Dirichlet problem   Gaussian noise   Maximal Lp-regularity   Nonlocal equations   Stochastic partial differential equations  

摘要： This paper provides a comprehensive Sobolev regularity theory for the Dirichlet problem of stochastic partial differential equations in $C^{1,\sigma }$ open sets. We consider substantially large classes of nonlocal operators and generalized Gaussian noise. Our main results include the existence and uniqueness of strong solutions in weighted Sobolev spaces, along with maximal $L_p$-regularity estimates for the solutions.

关键词： 2-methylpropane-1,2-diy1jbis(diphenylphosphine oxide   DFT-calculation   Synthesis   U(VD)   Np(VD)   Structures  

摘要： The crystal structure of (2-methylpropane-1,2-diyl)bis(diphenylphosphine oxide) (L) has been determined for the first time. The complexes [UO₂(NO₃)₂(L)]∙CH₃CN and [NpO₂(NO₃)₂(L)] were isolated in crystalline form characterized by single-crystal X-ray diffraction, FTIR and electronic absorption spectroscopy. The [UO₂(NO₃)₂(L)]∙CH₃CN complex was further characterized by PXRD and NMR methods. The complex of L with PuO₂²⁺ was characterized by FTIR and electronic absorption spectroscopy. The effect of introducing one or two methyl groups into the ethylene bridge on the spatial arrangement of the coordinating phosphoryl oxygen atoms in dioxides of ethylene diphosphines 1, 2 and L was investigated using quantum-chemical calculations in the framework of the electron density-functional theory (DFT). The synthesis of L has been conducted under thermal and microwave heating conditions.

关键词： AChE inhibition   Biosynthetic pathway   Enantiomeric   Enzyme kinetics   Molecular dynamics   Norsesquiterpenoids   Pharmacokinetic predictions  

摘要： Chemical investigation of the soft coral Sclerophytum humesi led to the discovery of (±)-norsclerohumin A (1), a pair of enantiomeric norsesquiterpenoids possessing an unprecedented oxatricyclo[7.***.1.0^1,9]dodecane scaffold with a rare C5-O-C8 intramolecular ether-bridge. Their structures were elucidated by comprehensive spectroscopic analysis, including NMR, HRESIMS, ECD, and DP4+ analysis. A plausible biosynthetic pathway is proposed to account for the formation of the unique ether-bridged oxatricyclic framework and the generation of the enantiomeric pair (±)-norsclerohumin A. In addition, the absolute configuration of sinunorcaryophyllenol (2) was fully determined for the first time. Mechanistic studies revealed pronounced stereoselective inhibition of acetylcholinesterase (AChE), in which (−)-1b was far more potent than its antipode (+)-1a, with IC₅₀ values of 10.08 ± 0.48 μM and 149.8 ± 1.02 μM, respectively. Enzyme kinetics showed that (−)-1b is a mixed-type AChE inhibitor (K_i = 6.61 μM), binding both the free enzyme and enzyme-substrate complex. Molecular docking indicated that its ether-bridged oxatricyclic skeleton fits optimally in the AChE active site, stabilizing key interactions within both the catalytic and peripheral binding regions. Importantly, (−)-1b displayed selective AChE inhibition without detectable cytotoxicity toward normal cells (IC₅₀ > 256 μM), underscoring its favorable safety profile. Furthermore, pharmacokinetic predictions and quantum chemical parameters further suggest favorable drug-like properties, including high gastrointestinal absorption, blood-brain barrier permeability, and low risk of P-glycoprotein/cytochrome P450 interactions. These findings highlight the oxatricyclo[7.***.1.0^1,9]dodecane scaffold as a promising lead for neurotherapeutic development.

关键词： Algae inactivation   Bi-Cl covalent bonding   Photocatalyst   TC degradation  

摘要： The occurrence of antibiotics and the proliferation of harmful algal blooms in aquatic environments raise significant concerns regarding their potential risks to aquatic ecosystems and human health. Here, a novel Z-scheme heterojunction photocatalyst, BiOCl_1-xI_x/CAU-17 (CAUB-x), was successfully constructed using a combined solvothermal and in situ growth strategy. An intimate interfacial contact between CAU-17 and BiOCl_1-xI_x was achieved via Bi–Cl covalent bonds, which establishes a direct Z-scheme charge transfer pathway. The optimized CAUB-0.3 sample achieved a high tetracycline (TC) degradation rate of 90.87 ± 2.24 % within 90 min under UV light, demonstrating its excellent photocatalytic activity. Additionally, CAUB-0.3 acts by inducing oxidative stress through generated reactive oxygen species (ROS), effectively disrupting both the cellular structure and antioxidant system of Microcystis aeruginosa, resulting in its inactivation. This work provides a novel strategy for developing dual-purpose photocatalysts that are both efficient and stable for concurrently degrading antibiotics and controlling algal blooms.

关键词： Symmetrical azine (5BEH)   Single-crystal XRD   Hirshfeld surface analysis   HOMO-LUMO   NBO   Molecular docking   ADMET  

摘要： A new symmetrical azine, 1,2-bis(1-(5-bromothiophen-2-yl)ethylidene)hydrazine (5BEH), was synthesized via a simple ionic-liquid-assisted protocol and fully characterized using FT-IR, NMR, and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic P2₁/c space group, and Hirshfeld surface analysis revealed that the Br⋯H/H⋯Br and S⋯H/H⋯S interactions dominated the supramolecular packing, supported by additional dispersion-driven H⋯H contacts. Density functional theory (DFT) calculations at the B3LYP/6-311++G(d,p) level reproduced the experimental geometry and vibrational features with high accuracy. Frontier molecular orbital and NBO analyses showed a moderately narrow HOMO–LUMO gap (3.58 eV), strong π→π* and LP→π* charge-transfer pathways, and a bipolar electrostatic profile with electrophilic N–N/C=N regions and nucleophilic Br/S sites. Docking studies against meningitis-associated targets (4CVD and 4UMB) indicated that 5BEH binds more favourably than ceftriaxone, although with a weak absolute inhibitory affinity. ADME predictions further demonstrated good intestinal absorption, BBB penetration, low toxicity, and no hERG or carcinogenic risk, with CYP2D6 inhibition being a noted metabolic consideration. Overall, the structural, electronic, and in silico findings identify 5BEH as a stable, electronically versatile azine scaffold with in silico indicative potential for medicinal and materials-oriented applications.

关键词： Paclitaxel derivatives   Site-selective synthesis   Antitumor activity   Tubulin binding  

摘要： Starting from readily available 1-deoxybaccatin VI, we developed a site-selective carbonate installation strategy that enables the selective introduction of carbonate groups at C-7 and C-9, obtaining paclitaxel derivatives bearing a carbonate group at the C-7 and C-9 positions. This positional selectivity was consistent across the series and streamlined access to a diversified set of analogs. In vitro, these derivatives showed stronger and broader activity than paclitaxel derivatives bearing carbonate groups at their C-9 and C-10 positions. Notably, Compound 16 was approximately 28 times more potent than paclitaxel against resistant lung carcinoma epithelial cells (the A549/T line) and maintained comparable or superior activity in human breast cancer and human hepatocellular carcinoma cells (the MDA-MB-231 and HepG2 cell lines, respectively). Molecular docking and molecular dynamics revealed a stable interaction network at the taxane site of tubulin. Calculations demonstrated that Compound 16 preserves its high tubulin affinity on L215H and L215F mutants. Compound 16 emerges as a promising solution to tubulin mutation–associated multidrug resistance and can potentially enhance the efficacy of next generation taxane therapies.

关键词： Cu3Pd atomic cluster   Hydrogen adsorption energy   Interfacial water structure   Lattice-matched heterointerface   α-MoC1-x support  

摘要： Activating the dissociation of H₂O molecules and optimizing the adsorption energy of active hydrogen (H*) to achieve efficient alkaline hydrogen evolution are crucial and challenging. Herein, a Cu₃Pd@α-MoC_1-x/C composite electrocatalyst is developed via an impregnation-pyrolysis strategy, in which Cu₃Pd atomic clusters are conformally anchored on the surface of α-MoC_1-x nanoparticles confined in porous hollow carbon octahedral matrices. Advanced atomic-resolution techniques confirm that the formation of abundant lattice-matched interfaces, which promotes electron transfer from Cu₃Pd to α-MoC_1-x. Operando electrochemical impedance spectroscopy and surface-enhanced Raman spectroscopy reveal enhanced interfacial K⁺·H₂O surface coverage on α-MoC_1-x, substantially lowering the H₂O dissociation barrier. Theoretical calculations further reveal that the strong electronic interactions at the Cu₃Pd@α-MoC_1-x interface downshift the Pd d‐band center, achieving a thermoneutrality H* adsorption energy. Consequently, Cu₃Pd@α-MoC_1-x/C delivers a remarkable mass activity of 591 mA mg_Pd⁻¹ at 200 mV overpotential (4.3-fold higher than commercial Pd/C) with a low Tafel slope of 55 mV dec⁻¹, alongside superior durability. This work provides a lattice-matched heterointerface engineering strategy to achieve atomic-level construction of dual sites in composite catalysts to simultaneously accelerate water dissociation and optimize H* adsorption energy.

关键词： 1,2,4-Triazole thioethers   15-LOX inhibition   DNA docking studies   In silico studies   MCF-7 cell line   MD simulations  

摘要： 15-Lipoxygenase (15-LOX) has emerged as a strategic target for therapeutic intervention in inflammatory diseases and the advancement of malignancy owing to its involvement in arachidonic acid metabolism. In this regard, in the pursuit of new 15-LOX inhibitors, a new series of alkyl/aralkyl derivatives (6a-h) of 4-phenyl-5-p-tolyloxymethyl-4H-1,2,4-triazole was designed and synthesized and then screened against the target enzyme. The synthesis started by the conversion of 2-p-tolyloxyacetic acid (a) into its corresponding ester (1), hydrazide (2), thiosemicarbazide (3) and 4-phenyl-5-p-tolyloxymethyl-4H-1,2,4-triazole-3-thiol (4). The target compounds 6a-h were achieved by the reaction of alkyl/aralkyl halides (5a-h) with 4 in the presence of alcoholic KOH. The intermediates and the products were characterized using advanced spectroscopic and spectrometric techniques. The screening data for compounds 6a-h showed them as potent inhibitors (IC₅₀ from 0.53±0.11 to 3.67±0.28 μM). Structure-activity relationship (SAR) studies revealed that the compounds with greater lipophilic character demonstrated greater activity than those with less lipophilic assembly. The compounds were not toxic towards blood mononuclear cells. Compounds 6g displayed an IC₅₀ value of 5.32 μM when tested against the MCF-7 breast cancer cell line, followed by 6f, 6d and 6b compared with that of quercetin. Pharmacodynamic studies revealed good druggability profiles. In silico studies supported the in vitro data. DNA docking studies revealed major groove binding. Docking studies of the analogues with the components of the NF-κB signalling pathway (ID:4KIK and 1VKX) exhibited excellent binding affinities