Journal of Molecular Structure最新文献_第2页

Structure-guided design and synthesis of selective butyrylcholinesterase inhibitors 结构导向设计与合成选择性丁基胆碱酯酶抑制剂

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-09 DOI: 10.1016/j.molstruc.2026.145611

Christine Shing Wei Law , Zhe Ying Ha , Xavier Brazzolotto , Keng Yoon Yeong

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive and non-cognitive decline. Cholinesterase inhibitors remain among the few available treatments, acting by preventing the hydrolysis of acetylcholine to alleviate cholinergic deficits. As butyrylcholinesterase (BChE) activity progressively increases in advanced AD while acetylcholinesterase activity declines, selective BChE inhibition has emerged as a promising therapeutic approach. Benzimidazole is a versatile pharmacophore with diverse biological activities, including cholinesterase inhibition. This study aimed to develop more potent benzimidazole-based cholinesterase inhibitors by modifying the 1- and 2-positions of the benzimidazole core. Among the synthesized compounds, 5IIa exhibited the most potent selective BChE inhibition at a low micromolar level (IC₅₀ = 0.4 μM). Human BChE (hBChE) was co-crystallized with 5IIa to resolve the structure of the protein–ligand complex by X-ray crystallography. Owing to its labile nature, 5IIa was subsequently modified to yield a series of derivatives (5IIa1–7), which demonstrated potent and selective inhibition of equine BChE (eqBChE), with IC₅₀ values ranging from 1.07 to 7.86 μM. Lead compound 5IIa6 inhibited hBChE with an IC₅₀ of 5.9 μM and was identified as a mixed-mode inhibitor based on kinetic studies. 5IIa6 was also predicted to have high blood-brain barrier permeability in an in vitro model, while cell viability assay against neuroblastoma and microglial cells indicated no significant toxicity. Taken together, these findings identify 5IIa6 as a promising and selective BChE inhibitor that warrants further investigation as a potential therapeutic agent for AD.

阿尔茨海默病（AD）是一种以认知和非认知能力下降为特征的进行性神经退行性疾病。胆碱酯酶抑制剂仍然是少数可用的治疗方法之一，通过阻止乙酰胆碱的水解来减轻胆碱能缺陷。随着晚期AD患者丁胆碱酯酶（BChE）活性逐渐增加而乙酰胆碱酯酶活性下降，选择性抑制BChE已成为一种很有前景的治疗方法。苯并咪唑是一种多功能药效团，具有多种生物活性，包括抑制胆碱酯酶。本研究旨在通过修饰苯并咪唑核心的1位和2位来开发更有效的苯并咪唑基胆碱酯酶抑制剂。在所合成的化合物中，5IIa在低微摩尔水平（IC50 = 0.4 μM）下表现出最有效的选择性BChE抑制作用。将人BChE （hBChE）与5IIa共结晶，用x射线晶体学方法解析蛋白质-配体复合物的结构。由于其不稳定的性质，5IIa随后被修饰得到一系列衍生物（5IIa - 7），这些衍生物显示出对马BChE （eqBChE）的有效和选择性抑制，IC50值在1.07 ~ 7.86 μM之间。先导化合物5IIa6抑制hBChE的IC50值为5.9 μM，经动力学研究确定为混合模式抑制剂。5IIa6在体外模型中也被预测具有高血脑屏障通透性，而对神经母细胞瘤和小胶质细胞的细胞活力测定显示无明显毒性。综上所述，这些发现确定5IIa6是一种有前途的选择性BChE抑制剂，值得进一步研究作为AD的潜在治疗剂。

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引用次数: 0

Synthesis, biological evaluation, and molecular docking studies of novel 2′-aroyl-1′-(1,3-diaryl-1H-pyrazol-4-yl)-1′,2′,5′,6′,7′,7a'-hexahydro-2H-spiro[acenaphthylene-1,3′-pyrrolizin]-2-ones 新型2 '-芳基-1 '-（1,3-二烷基- 1h -吡唑-4-基）-1 ',2 ',5 ',6 ',7 ',7a'-六氢- 2h -螺[萘-1,3 '-吡咯啉]-2-酮的合成、生物学评价及分子对接研究

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-09 DOI: 10.1016/j.molstruc.2026.145610

Ayyanar Suguna Devi , Rajendran Aarthi , Chun-Wai Mai , Chennan Ramalingan

A series of novel molecular hybrids, 2′-aroyl-1′-(1,3-diaryl-1H-pyrazol-4-yl)-1′,2′,5′,6′,7′,7a'-hexahydro-2H-spiro[acenaphthylene-1,3′-pyrrolizin]-2-ones 34–43, was designed and synthesized via a synthetic strategy involving multi-steps. ¹H NMR, ¹³C NMR, DEPT, HSQC, COSY, and HMBC characteristics confirmed the structure of the synthesized hybrids. Of the molecular hybrids, the one possessing meta-nitrobenzoyl group integrated to pyrrolizine structural motif and para-nitrophenyl / para-bromophenyl unit tethered at pyrazole scaffold (36 / 37, respectively) exhibited appreciable radical scavenging potency (∼75 % / 71 %) as evinced from DPPH method. Cytotoxicity assessment through cell viability assay (CellTiter-Glo luminescent) reflects that all the molecular hybrids except 40 and 43 displayed potent efficacies against the cancer cell SW1990 (IC₅₀ < 55 µM), and amongst, the efficacy of the hybrid 36 was found to be the highest one (IC₅₀ ∼07 µM). Additionally, the most effective hybrid 36 showed a noteworthy binding affinity with the protein B-cell lymphoma 2 and human pancreatic secretory protein ZG16B as evidenced from molecular docking, a largely adopted method of computation in the drug design.

通过多步合成策略，设计并合成了一系列新型分子杂化物2 '-芳基-1 '-（1,3-二烷基- 1h -吡唑-4-基）-1 ',2 ',5 ',6 ',7 ',7a'-六氢- 2h -螺[苊-1,3 '-吡咯啉]-2- 1 34-43。1H NMR、13C NMR、DEPT、HSQC、COSY和HMBC表征证实了合成的杂化物的结构。DPPH方法表明，具有整合吡咯啉结构基序的间硝基苯甲酰基团和连接在吡唑支架上的对硝基苯基/对溴苯基单元的分子杂种（分别为36 / 37）具有明显的自由基清除能力（约75% / 71%）。通过细胞活力测定（CellTiter-Glo luminescence）进行的细胞毒性评估显示，除40和43外，所有分子杂交种对癌细胞SW1990都有较强的抑制作用（IC50 < 55µM），其中，杂交36的抑制作用最高（IC50 ~ 07µM）。此外，最有效的杂交36显示出与蛋白质b细胞淋巴瘤2和人胰腺分泌蛋白ZG16B的显著结合亲和力，这是药物设计中广泛采用的一种计算方法。

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引用次数: 0

Coordination architectures and substituent-dependent photophysical behavior of Zn(II) complexes with tridentate ONO Schiff base ligands 三齿ONO席夫碱配体Zn（II）配合物的配位结构和取代基依赖的光物理行为

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-08 DOI: 10.1016/j.molstruc.2026.145613

Ali Pazoki , Aria Tajally , Sudabeh Shokrollahi , Ahmad Amiri , Farzaneh Fadaei-Tirani , Zahra Emadi

Three Zn(II) complexes, [Zn(L_B)(N₃)]_n (1), [Zn(L_N)₂] (2), and [Zn(L_N)(C₂H₄N₄)]_n (3) were synthesized using two tridentate O,N,O-donor Schiff base ligands: H₂L_B (4‑bromo-2-(((1‑hydroxy-2-methylpropan-2-yl)imino)methyl)phenol) and H₂L_N (2-(((1‑hydroxy-2-methylpropan-2-yl)imino)methyl)-4-nitrophenol). The structures of the complexes were elucidated by FT-IR and UV–Vis spectroscopy, as well as single crystal X-ray diffraction analysis. Two tridentate O,N,O-donor Schiff base ligands, H₂L_B (4‑bromo derivative) and H₂L_N (4-nitro derivative), were designed to explore the substituent-dependent structural and photophysical behavior of Zn(II) complexes. Three new complexes ([Zn(L_B)(N₃)]ₙ (1), [Zn(L_N)₂] (2), and [Zn(LN)(C₂H₄N₄)]_n (3)) were synthesized and structurally characterized by FT-IR, UV–Vis spectroscopy, and single-crystal X-ray diffraction. Complex 1 forms a one-dimensional azide-bridged coordination polymer with a distorted trigonal-bipyramidal geometry, whereas 2 and 3 exhibit octahedral and square-pyramidal geometries, respectively. Photophysical investigations revealed a strong substituent effect: the bromo‑substituted complex 1 shows intense ligand-centered emission (λ_em = 448 nm) attributed to a chelation-enhanced fluorescence (CHEF) mechanism, while the nitro-substituted complexes 2 and 3 undergo pronounced fluorescence quenching via intramolecular charge transfer. TD-DFT analyses supported experimental observations, indicating that electron-withdrawing substituents localize the LUMO on the NO₂ group, favoring non-radiative relaxation. These findings demonstrate a clear structure-property relationship in Zn(II) Schiff base systems and highlight their potential as tunable platforms for designing photoluminescent coordination materials.

以两种三羧基希夫碱配体H2LB（4 -溴-2-（（1 -羟基-2-甲基丙烷-2-基）亚氨基）甲基）苯酚和H2LN（2-（（1 -羟基-2-甲基丙烷-2-基）亚氨基）甲基）-4-硝基苯酚为原料合成了[Zn(LB)(N3)]n (1), [Zn(LN)2] (2)]n (3)] Zn(LN)(C2H4N4)]n(3)。通过红外光谱、紫外-可见光谱和单晶x射线衍射分析对配合物的结构进行了表征。设计了两种三齿O，N，O给体希夫碱配体H2LB（4-溴衍生物）和H2LN（4-硝基衍生物），以探索Zn（II）配合物的取代基依赖结构和光物理行为。合成了三个新的配合物[Zn(LB)(N3)] n(1)、[Zn(LN)2](2)和[Zn(LN)(C2H4N4)]n(3)，并用红外光谱、紫外可见光谱和单晶x射线衍射对其进行了结构表征。配合物1形成一维叠氮化物桥接配位聚合物，具有扭曲的三角-双锥体几何形状，而配合物2和3分别具有八面体和方锥体几何形状。光物理研究发现了强取代基效应：溴取代配合物1表现出强烈的配体中心发射（λem = 448 nm），这是由于螯合增强荧光（CHEF）机制，而氮取代配合物2和3则通过分子内电荷转移发生了明显的荧光猝灭。TD-DFT分析支持实验观察，表明吸电子取代基将LUMO定位在NO2基团上，有利于非辐射弛豫。这些发现证明了Zn（II）希夫碱体系中明确的结构-性能关系，并突出了它们作为设计光致发光配位材料的可调平台的潜力。

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引用次数: 0

Ruthenium (II)-arene complexes with N,N-donor ligands containing pharmacophore groups: Evaluation of anticancer, antibacterial, and catalytic properties 钌(II)-芳烃配合物与含有药效团的N，N供体配体：抗癌，抗菌和催化性能的评价

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-07 DOI: 10.1016/j.molstruc.2026.145600

Venugopalsamy J. Tamilpriyai , Premnath Dhanaraj , Rajagopal Swaathy , Savarimuthu Philip Anthony , Dohyun Moon , Vedichi Madhu

Arene ruthenium(II) complexes , L1-Ru, L2-Ru, and L3-Ru were synthesized using N,N-donor ligands with pharmacophore functionalities such as morpholine, piperazine, and piperidine and evaluated their biological (anticancer and antibacterial) and catalytic properties. L1-Ru, L2-Ru, and L3-Ru complexes were structurally characterized using FT-IR, NMR, mass spectrometry, and single crystal X-ray crystallography. Solid-state structural analysis revealed the formation of typical "three-leg piano-stool" coordination geometry. The heterocyclic ring variation in the ligand significantly influenced on the molecular packing and supramolecular interactions. In-vitro studies against HeLa cells indicated strong anti-leukemic activity for L2-Ru and L3-Ru, with IC₅₀ values of 0.805 μM and 10.897 μM, respectively. Antibacterial tests against both gram-positive and gram-negative bacterial strains indicated that L3-Ru performed better than the other complexes. In catalytic studies, L3-Ru complex displayed superior efficiency in the hydrogenation of nitroaromatics into aniline using sodium borohydride. Thus, the present work explored the structure-activity relationships of Ru(II)-arene complexes in biological and catalytic properties.

利用具有药效团功能的N，N供体配体（如啉、哌嗪和哌啶）合成了芳烃钌（II）配合物L1-Ru、L2-Ru和L3-Ru，并评价了它们的生物学（抗癌、抗菌）和催化性能。L1-Ru、L2-Ru和L3-Ru配合物通过FT-IR、NMR、质谱和单晶x射线晶体学进行了结构表征。固态结构分析揭示了典型的“三脚琴凳”协调几何形态的形成。配体中杂环的变化对分子填充和超分子相互作用有显著影响。体外抗HeLa细胞实验表明，L2-Ru和L3-Ru具有较强的抗白血病活性，IC50值分别为0.805 μM和10.897 μM。对革兰氏阳性和革兰氏阴性菌株的抑菌试验表明，L3-Ru的抑菌效果优于其他配合物。在催化研究中，L3-Ru配合物在硼氢化钠催化硝基芳烃加氢制苯胺方面表现出优异的效率。因此，本工作探讨了Ru(II)-芳烃配合物在生物和催化性能方面的构效关系。

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引用次数: 0

Diastereoselective synthesis of dispiro[acenaphthylene-1,3′-pyrrolo[2,1-a] isoquinoline-1′,3′'-indole] derivatives via addition reaction of azomethine ylides with (Z)-3-benzylidene- scaffolds 偶氮亚甲基酰基与(Z)-3-苄基支架加成反应合成二苯基萘-1,3′-吡咯[2,1-a]异喹啉-1′，3′-吲哚]衍生物

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-07 DOI: 10.1016/j.molstruc.2026.145609

Goutam Sinha , Supratim Das , Supriyo Halder , Chhanda Mukhopadhyay

A series of new dispiro[acenaphthylene-1,3′-pyrrolo[2,1-a]isoquinoline-1′,3′'-indole]-2,2′'(1′'H)-dione derivatives have been synthesized using acenapthaquinone, (Z)-3-benzylidene-1-phenyl-3,5,6,7-tetrahydro-1H-indole-2,4-dione derivative and 1,2,3,4-tetrahydroisoquinoline (THIQ) derivatives. The diastereoselective synthesis of this spiropyrrolo[2,1-a]isoquinoline-oxindole skeleton consist of two steps. First step is the simple Knoevenegal condensation between 3,5,6,7-tetrahydro-1H-indole-2,4-dione and aromatic aldehyde followed by the second step being the addition of (Z)-3-benzylidene-1-phenyl-3,5,6,7-tetrahydro-1H-indole-2,4-dione with azomethine ylide to produce the final product. ¹H and ¹³C NMR spectroscopy and single-crystal analysis demonstrated the diastereoselective synthesis of spiropyrrolo[2,1-a]isoquinoline-oxindole skeleton.

以阿塞萘醌、(Z)-3-苄基-1-苯基-3,5,6,7-四氢- 1h -吲哚-2,4-四氢异喹啉衍生物和1,2,3,4-四氢异喹啉（THIQ）衍生物为原料，合成了一系列新的醌类[苊-1,3 '-吡咯[2,1- A]异喹啉-1 ',3 ' '-吲哚]-2,2 '(1 'H)-二酮衍生物。该螺旋吡咯[2,1-a]异喹啉-氧吲哚骨架的非对映选择性合成包括两个步骤。第一步是3,5,6,7-四氢- 1h -吲哚-2,4-二酮与芳醛之间的简单Knoevenegal缩合反应，第二步是(Z)-3-苄基-1-苯基-3,5,6,7-四氢- 1h -吲哚-2,4-二酮与亚甲酰基的加成反应生成最终产物。1H和13C核磁共振波谱和单晶分析证实了螺吡咯[2,1-a]异喹啉-氧吲哚骨架的非对映选择性合成。

引用次数: 0

Rb4Sb4S8 and Rb2Sb4S7·H2O: Solvothermal synthesis, characterization, and oxygen evolution reaction performance investigation Rb4Sb4S8和Rb2Sb4S7·H2O：溶剂热合成、表征及析氧性能研究

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-07 DOI: 10.1016/j.molstruc.2026.145606

Wei Zhu , Xin Liu , Menghe Baiyin

Two ternary sulfides Rb₄Sb₄S₈ (1) and Rb₂Sb₄S₇·H₂O (2) were synthesized under solvothermal conditions. Compound 1 was a zero-dimensional(0-D) clustered structure and compound 2 was a two-dimensional(2-D) layered structure. Compounds 1, 2 were studied for photoelectric properties and suggested that they had higher photocurrent densities and good reproducibility. The band gaps for compounds 1 and 2, derived from UV–visible diffuse reflectance measurements, were determined to be 2.15 and 1.98 eV, respectively. It indicated that they have semiconductor properties. Experimentally measured bandgap values are consistent with the theoretically calculated values. The electrochemical performance test results showed that compounds had good oxygen evolution reaction (OER) electrocatalytic properties. This study provided a new idea for the synthesis of new sulfides.

在溶剂热条件下合成了两种三元硫化物Rb4Sb4S8(1)和Rb2Sb4S7·H2O(2)。化合物1为零维（0-D）簇状结构，化合物2为二维（2- d）层状结构。对化合物1、2的光电性质进行了研究，发现它们具有较高的光电流密度和良好的重现性。化合物1和2的带隙分别为2.15 eV和1.98 eV，由紫外可见漫反射测量得到。这表明它们具有半导体性质。实验测量的带隙值与理论计算值一致。电化学性能测试结果表明，化合物具有良好的析氧反应（OER）电催化性能。该研究为新型硫化物的合成提供了新的思路。

引用次数: 0

Recent advances in Copper(II) Schiff base complexes: A comparative review of ligand core influence on biomedical applications 铜（II）希夫碱配合物的最新进展：配体核对生物医学应用影响的比较综述

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-07 DOI: 10.1016/j.molstruc.2026.145599

Shrikant Mali , Shubham D. Vatagude , Masaki Horitani , Prabhuodeyara M. Gurubasavaraj

Copper(II) Schiff base complexes are versatile redox-active systems with growing relevance in biomedical research; however, mechanistic understanding of how ligand architecture governs biological performance remains fragmented. This review critically analyses recent advances (2018–2025) in Cu(II) Schiff base complexes using a comparative structure–activity relationship (SAR) framework, focusing on four dominant ligand cores: salen, aminopyridine, hydrazone/hydrazide, and benzimidazole scaffolds. Across multiple independent studies, rigid and planar ligand architectures consistently exhibit superior antioxidant, antimicrobial, DNA-binding, and anticancer activities compared with more flexible systems. Frontier molecular orbital analyses demonstrate that reduced HOMO–LUMO gaps, enhanced metal–ligand orbital overlap, and limited steric shielding facilitate efficient Cu(II)/Cu(I) redox cycling and reactive oxygen species (ROS) generation. These redox processes promote oxidative DNA cleavage, mitochondrial dysfunction, and apoptosis, providing a unified redox-driven mechanistic rationale for observed bioactivity trends. Comparative evaluation indicates that salen and benzimidazole frameworks outperform aminopyridine and hydrazone/hydrazide systems due to their rigid N₂O₂ donor sets, extended π-conjugation, and favourable electronic distributions. Importantly, most biological evidence remains limited to in vitro or in silico, highlighting the need for in vivo validation and toxicity profiling. The SAR trends presented here define rational ligand-design principles for next-generation copper-based pharmacophores with improved selectivity, potency, and translational potential.

铜（II）希夫碱配合物是一种多用途的氧化还原活性体系，在生物医学研究中具有越来越重要的意义；然而，对配体结构如何支配生物性能的机制理解仍然是碎片化的。本文使用比较构效关系（SAR）框架批判性地分析了Cu（II）希夫碱配合物的最新进展（2018-2025），重点研究了四种主要配体核心：salen、氨基吡啶、腙/肼和苯并咪唑支架。在多个独立研究中，与更灵活的系统相比，刚性和平面配体结构始终表现出优越的抗氧化、抗菌、dna结合和抗癌活性。前沿分子轨道分析表明，减少HOMO-LUMO间隙、增强金属-配体轨道重叠以及有限的空间屏蔽有助于高效的Cu(II)/Cu(I)氧化还原循环和活性氧（ROS）的生成。这些氧化还原过程促进氧化DNA切割、线粒体功能障碍和细胞凋亡，为观察到的生物活性趋势提供了一个统一的氧化还原驱动的机制基础。对比评价表明，salen和苯并咪唑框架由于其刚性的N2O2给体集、扩展的π共轭和良好的电子分布，优于氨基吡啶和腙/肼体系。重要的是，大多数生物学证据仍然局限于体外或计算机，强调需要在体内验证和毒性分析。本文提出的SAR趋势定义了下一代铜基药物载体的合理配体设计原则，具有更高的选择性、效力和转化潜力。

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引用次数: 0

A novel macroplanarized triazine derivative with enhanced interfacial bonding for corrosion inhibition of carbon steel in strong acidic medium 一种具有增强界面结合的新型大平面化三嗪衍生物在强酸性介质中对碳钢的缓蚀作用

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-07 DOI: 10.1016/j.molstruc.2026.145608

Zhuohui Li, Yan Zhang, Weixing Ming, Kun Zhang, Ge Xu

In this work, a novel 4,6-bis((4-methoxyphenyl)amino)-1,3,5-triazin-2-piperidine-4-carboxylate (ZBZ) inhibitor was synthesized by a two-step acid-amine condensation under precise temperature control. This product uses cyanuric chloride as the raw material and p-aminophenol and isonicotinic acid is introduced into in sequential, aiming to enhance the interfacial bonding via the synergistic effect of adsorption and multi-site complexation in large planar layer. The structure of the product was systematically characterized by Fourier-transform infrared (FT-IR), proton nuclear magnetic resonance (¹H NMR), and mass spectrometry (MS), with results fully consistent with the target molecular structure. Electrochemical measurements reveal that 0.78 mmol/L ZBZ achieves up to inhibition efficiency of 98.65% for Q235 carbon steel in 1mol/L sulfuric acid, higher than 96.09% of disubstituted 2,4-bis(4-methoxyphenylamino)-6‑chloro-1,3,5-triazine (ZAZ) at 0.98 mmol/L. X-ray photoelectron spectroscopy (XPS) analysis further confirmed the formation of Fe–N/Fe–O coordination bonds between nitrogen and oxygen atoms in the ZBZ molecule and the carbon steel surface. Combined with interfacial characteristic changes such as the increase in contact angle (indicating enhanced hydrophobicity), these results demonstrate that ZBZ inhibits corrosion through a synergistic mechanism involving both chemical adsorption and physical coverage. Furthermore, density functional theory (DFT) calculations and molecular dynamics simulations reveal that the ZBZ molecule achieves excellent coverage on the Fe (110) surface through a parallel adsorption configuration, while its multi-site complexation enhance the interfacial bonding strength. The conjugated plane of p-anisidine in ZBZ molecule provides planar support for molecular adsorption, while the nitrogen and oxygen atoms provided by the isonicotinic acid group of the molecule effectively increase the density of coordination sites. A molecular design strategy featuring macroplanarized configuration and multiple coordination sites was proposed to improve the performance of corrosion inhibition in strong acidic medium.

在精确控制温度的条件下，采用酸胺两步缩合法合成了一种新型的4,6-二（（4-甲氧基苯基）氨基）-1,3,5-三嗪-2-哌啶-4-羧酸盐（ZBZ）抑制剂。本产品以三聚氰尿酸为原料，先后加入对氨基酚和异烟酸，旨在通过大平面层的吸附和多位点络合的协同作用，增强界面键合。通过傅里叶变换红外（FT-IR）、质子核磁共振（1H NMR）、质谱（MS）等手段对产物的结构进行了系统表征，结果与目标分子结构完全一致。电化学测试结果表明，0.78 mmol/L ZBZ在1mol/L硫酸中对Q235碳钢的缓蚀率高达98.65%，高于二取代2,4-二（4-甲氧基苯胺）-6 -氯-1,3,5-三嗪（ZAZ）在0.98 mmol/L时的96.09%。x射线光电子能谱（XPS）分析进一步证实了ZBZ分子与碳钢表面氮、氧原子之间形成Fe-N / Fe-O配位键。结合界面特征的变化，如接触角的增加（表明疏水性增强），这些结果表明ZBZ通过化学吸附和物理覆盖的协同机制抑制腐蚀。此外，密度泛函理论（DFT）计算和分子动力学模拟表明，ZBZ分子通过平行吸附结构在Fe（110）表面获得了良好的覆盖，其多位点络合作用增强了界面结合强度。ZBZ分子中对茴香胺的共轭平面为分子吸附提供了平面支撑，而分子的异烟酸基团所提供的氮原子和氧原子有效地增加了配位位点的密度。提出了一种具有大平面结构和多配位位点的分子设计策略，以提高其在强酸性介质中的缓蚀性能。

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引用次数: 0

Solid-state structure and physicochemical characterization of the hydrocortisone–β-cyclodextrin inclusion complex 氢化可的松- β-环糊精包合物的固态结构及理化性质

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-07 DOI: 10.1016/j.molstruc.2026.145607

Aleksandra Kowalska , Łukasz Szeleszczuk , Kostas Bethanis , Elias Christoforides , Marta K. Dudek , Monika Zielińska-Pisklak , Dariusz Maciej Pisklak

The inclusion complex formed between hydrocortisone and β-cyclodextrin was successfully obtained and structurally characterized in the solid state. Single-crystal X-ray diffraction provided direct evidence of hydrocortisone encapsulation within the β-cyclodextrin cavity, revealing a 2:1 host–guest stoichiometry and positional disorder of the guest molecules accommodated within head-to-head β-cyclodextrin dimers. The crystal packing adopts a channel-type arrangement stabilized by intermolecular hydrogen bonding and hydration networks. Complementary solid-state techniques, including PXRD, DSC–TGA, FT-IR spectroscopy, cryo-SEM, and ¹³C CP/MAS NMR, confirmed the formation of a distinct solid phase with reduced crystallinity and altered physicochemical properties compared with the parent compounds and their physical mixture. Periodic density functional theory calculations supported the experimental structure, demonstrating that the two crystallographically observed guest orientations represent energetically accessible configurations. Together, these results provide a comprehensive structural description of the hydrocortisone–β-cyclodextrin inclusion complex and clarify the molecular basis of its solid-state organization.

成功地获得了氢化可的松与β-环糊精之间形成的包合物，并在固态下进行了结构表征。单晶x射线衍射提供了氢化可的松包封在β-环糊精腔内的直接证据，揭示了在头对头的β-环糊精二聚体中容纳的客体分子的2:1的主客体化学计量和位置紊乱。晶体填料采用通道型排列，由分子间氢键和水化网络稳定。互补的固态技术，包括PXRD、DSC-TGA、FT-IR光谱、cro - sem和13C CP/MAS NMR，证实了与母化合物及其物理混合物相比，形成了独特的固相，结晶度降低，物理化学性质改变。周期密度泛函理论计算支持实验结构，证明两个晶体学上观察到的客体取向代表能量可达的构型。总之，这些结果提供了氢化可的松- β-环糊精包合物的全面结构描述，并阐明了其固态组织的分子基础。

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引用次数: 0

Adamantane tethered pyrazole carboxamides as antibacterial candidates: Synthesis, structural analysis and computational studies 金刚烷系链吡唑羧胺作为抗菌候选物：合成、结构分析和计算研究

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure

Pub Date : 2026-02-06 DOI: 10.1016/j.molstruc.2026.145598

Chandan Mallikarjuna , Udaya Kumar AH , Karthik Kumara , Pradeep M Uppar , Raghavendra Mylarappa , Neratur Krishnappagowda Lokanath , Kariyappa Ajay Kumar

A new series of nine adamantane-based pyrazole carboxamides (5a-i) was synthesized via a concise two-step protocol, affording good yields (72–87%). The novelty of this work lies in the strategic integration of a rigid lipophilic adamantane core, a biologically versatile pyrazole ring, and a terminal carboxamide functionality within a single molecular framework to enhance antibacterial potential. Structural elucidation was achieved using ¹H NMR, ¹³C NMR and ESI-MS, while the molecular and supramolecular architecture of compound 5c was unambiguously established by single-crystal X-ray diffraction. Hirshfeld surface and energy-framework analyses revealed that dispersion forces, supported by hydrogen-bonding and halogen-mediated interactions, dominate crystal stabilization. Density functional theory (DFT) calculations showed excellent agreement with experimental geometry (bond-length correlation R = 0.9963) and a large HOMO-LUMO energy gap (5.35 eV), indicating high electronic stability. Molecular docking studies demonstrated strong binding affinity of 5c toward antibacterial targets 1C1X and 3FY8 (−9.6 and −8.9 kcal mol⁻¹), outperforming ciprofloxacin. Antibacterial screening against Staphylococcus aureus and Escherichia coliusing the agar well diffusion method revealed inhibition zones ranging from 12 to 22 mm, with compound 5c exhibiting the highest activity (22 mm), comparable to ciprofloxacin. Overall, these results identify adamantane-pyrazole carboxamides, particularly 5c, as promising scaffolds for further antibacterial development.

采用简洁的两步法合成了9个金刚烷酮基吡唑羧酰胺（5a-i），收率为72-87%。这项工作的新颖之处在于在单一分子框架内战略性地整合了刚性亲脂金刚烷核心、生物学上通用的吡唑环和末端的羧酰胺功能，以增强抗菌潜力。通过1H NMR、13C NMR和ESI-MS对化合物5c进行了结构解析，通过单晶x射线衍射明确了化合物5c的分子结构和超分子结构。Hirshfeld表面和能量框架分析表明，由氢键和卤素介导的相互作用支持的色散力主导了晶体的稳定。密度泛函理论（DFT）计算结果与实验几何结构吻合良好（键长相关R = 0.9963），且HOMO-LUMO能隙大（5.35 eV），具有较高的电子稳定性。分子对接研究表明，5c对抗菌靶点1C1X和3FY8有很强的结合亲和力（- 9.6和- 8.9 kcal mol⁻），优于环丙沙星。琼脂孔扩散法对金黄色葡萄球菌和大肠杆菌进行抑菌筛选，抑菌区范围为12 ~ 22 mm，其中化合物5c的抑菌活性最高（22 mm），与环丙沙星相当。总的来说，这些结果确定金刚烷-吡唑羧酰胺，特别是5c，是进一步抗菌开发的有前途的支架。

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