Pub Date : 2025-12-29DOI: 10.1016/j.molstruc.2025.145191
David Oliveros Garavito , Andrea Pastrana-Dávila , Javier Ellena , Pedro H.O. Santiago , Oscar Rojas , Dominik Pentlehner , Luis A. Illicachi , Richard D’Vries
This work presents the synthesis, spectroscopic characterization, and structural analysis of N'-((1Z,2E)-1,3-diphenylallylidene)-2-hydroxybenzohydrazide (DAHH). Comprehensive spectroscopic characterization was performed using ¹H and ¹³C NMR, MS, FT-IR, and optical spectroscopy. Single crystal X-ray diffraction analysis shows that the new benzohydrazide derivative crystallizes in the monoclinic space group P21/c with one molecule per asymmetric unit and general formula C22H18N2O2. The structural data enabled supramolecular analysis, showing that crystalline packing is formed by N-H···O and O-H···O hydrogen interactions. It also features weak T-shape C-H···π (edge-to-face) and C=C···π interactions. These results were corroborated and quantified using Hirshfeld surface and fingerprint plot analysis. The most abundant interaction is H···H dispersion (50.2%), followed by C···H (28%) and O···H (10.1%). Lattice energies and energy frameworks for the DAHH compound were also calculated. Finally, the luminescence properties of DAHH were studied.
{"title":"Structural, supramolecular analysis, and photoluminescence properties of a new hydroxybenzohydrazide Schiff base","authors":"David Oliveros Garavito , Andrea Pastrana-Dávila , Javier Ellena , Pedro H.O. Santiago , Oscar Rojas , Dominik Pentlehner , Luis A. Illicachi , Richard D’Vries","doi":"10.1016/j.molstruc.2025.145191","DOIUrl":"10.1016/j.molstruc.2025.145191","url":null,"abstract":"<div><div>This work presents the synthesis, spectroscopic characterization, and structural analysis of <em>N</em>'-((1<em>Z</em>,2<em>E</em>)-1,3-diphenylallylidene)-2-hydroxybenzohydrazide (<strong>DAHH</strong>). Comprehensive spectroscopic characterization was performed using ¹H and ¹³C NMR, MS, FT-IR, and optical spectroscopy. Single crystal X-ray diffraction analysis shows that the new benzohydrazide derivative crystallizes in the monoclinic space group <em>P2<sub>1</sub>/c</em> with one molecule per asymmetric unit and general formula C<sub>22</sub>H<sub>18</sub>N<sub>2</sub>O<sub>2</sub>. The structural data enabled supramolecular analysis, showing that crystalline packing is formed by N-H···O and O-H···O hydrogen interactions. It also features weak T-shape C-H···π (edge-to-face) and C=C···π interactions. These results were corroborated and quantified using Hirshfeld surface and fingerprint plot analysis. The most abundant interaction is H···H dispersion (50.2%), followed by C···H (28%) and O···H (10.1%). Lattice energies and energy frameworks for the <strong>DAHH</strong> compound were also calculated. Finally, the luminescence properties of <strong>DAHH</strong> were studied.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145191"},"PeriodicalIF":4.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.molstruc.2025.145196
Zubair Ahmed , Nurul. I Azmi , Kong W. Tan , Nobuto Yoshinari , Mohd. R. Razali
This paper presents the formation of silver(I) and copper(II) complexes of Diels-Alder derivatives ligand, l-. The ligand which constitutes an aromatic scaffold shows an excellent characteristic toward metal ions. The formation of square planar silver(I) complex of l- in the presence of co-ligands 4,4′-bipyridine represent a rare example, as only 2 % of such geometry are reported to date, primarily dominated by tetrahedral geometry. However, the photoluminescence study on this complex reveals that the characteristics are similar to that of tetrahedral geometry due to the similar orbital overlapping of the ligand and metal ions. This unusual combination of geometry and photophysical behaviour provides valuable insight into how ligand design can influence excited-state properties. The results further suggest that Diels–Alder-derived ligands may serve as promising candidates for tuning luminescent responses, particularly in silver(I) and copper(II) coordination complexes.
{"title":"Metal complexes of diels-alder derivatives: A rare example of square planar silver(I) complex and photoluminescence activity of d10 complexes","authors":"Zubair Ahmed , Nurul. I Azmi , Kong W. Tan , Nobuto Yoshinari , Mohd. R. Razali","doi":"10.1016/j.molstruc.2025.145196","DOIUrl":"10.1016/j.molstruc.2025.145196","url":null,"abstract":"<div><div>This paper presents the formation of silver(I) and copper(II) complexes of Diels-Alder derivatives ligand, <strong><span>l</span></strong><sup>-</sup>. The ligand which constitutes an aromatic scaffold shows an excellent characteristic toward metal ions. The formation of square planar silver(I) complex of <strong><span>l</span></strong><sup>-</sup> in the presence of co-ligands 4,4′-bipyridine represent a rare example, as only 2 % of such geometry are reported to date, primarily dominated by tetrahedral geometry. However, the photoluminescence study on this complex reveals that the characteristics are similar to that of tetrahedral geometry due to the similar orbital overlapping of the ligand and metal ions. This unusual combination of geometry and photophysical behaviour provides valuable insight into how ligand design can influence excited-state properties. The results further suggest that Diels–Alder-derived ligands may serve as promising candidates for tuning luminescent responses, particularly in silver(I) and copper(II) coordination complexes.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145196"},"PeriodicalIF":4.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-28DOI: 10.1016/j.molstruc.2025.145181
Li Yan , Ai-Juan Li , Ke Qiao , Lan Li , Tao Zhang , Zhan-Xin Zhang , Jing Li , Sheng-Li Huang
Three isostructural binuclear Cu2-metallacycles were synthesized using flexible (N^N)-(N^N) ligands with varied spacer lengths to precisely modulate the intramolecular Cu···Cu distance. These Cu2-metallacycles were assembled with a Ru(N^N)3-photosensitizer via phenyl–pentafluorophenyl interactions. The different Cu2-metallacycles displayed distinct photocatalytic CO2 reduction performances, demonstrating how microstructural modulation of otherwise isostructural architectures influences catalytic behavior. Notably, photocatalytic activity was greatly enhanced when a pentafluorophenyl-containing photosensitizer was employed, owing to improved charge-transfer capability. This work aims to provide reference and inspiration for exploring the impact of complex microstructure regulation on catalytic performance and for developing charge-transfer pathways in dual-catalyst systems.
{"title":"Photocatalytic CO2 reduction using (Cu2-Metallacycle) mediated by phenyl–pentafluorophenyl interaction","authors":"Li Yan , Ai-Juan Li , Ke Qiao , Lan Li , Tao Zhang , Zhan-Xin Zhang , Jing Li , Sheng-Li Huang","doi":"10.1016/j.molstruc.2025.145181","DOIUrl":"10.1016/j.molstruc.2025.145181","url":null,"abstract":"<div><div>Three isostructural binuclear Cu<sub>2</sub>-metallacycles were synthesized using flexible (N^N)-(N^N) ligands with varied spacer lengths to precisely modulate the intramolecular Cu···Cu distance. These Cu<sub>2</sub>-metallacycles were assembled with a Ru(N^N)<sub>3</sub>-photosensitizer via phenyl–pentafluorophenyl interactions. The different Cu<sub>2</sub>-metallacycles displayed distinct photocatalytic CO<sub>2</sub> reduction performances, demonstrating how microstructural modulation of otherwise isostructural architectures influences catalytic behavior. Notably, photocatalytic activity was greatly enhanced when a pentafluorophenyl-containing photosensitizer was employed, owing to improved charge-transfer capability. This work aims to provide reference and inspiration for exploring the impact of complex microstructure regulation on catalytic performance and for developing charge-transfer pathways in dual-catalyst systems.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145181"},"PeriodicalIF":4.7,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-28DOI: 10.1016/j.molstruc.2025.145184
Shaoqiang Feng , Chengan Wan , Xiaoqiang Liang , Feng Zhang , Lei Feng , Chen Wen
The development of metal‒organic frameworks (MOFs) for proton conduction has garnered significant interest due to their tunable structures and promising applications in fuel cells and other energy technologies. However, controlling the hydrophilicity of internal microenvironments remains challenging, hindering precise understanding of its role in proton transport. Herein, we report two new isoreticular MOFs, [CoII3CoIII(Ci)4(NH3)4(DMF)]NO3·5C2H5OH (Co-Ci-DMF, H2Ci = 1H-indazole-5-carboxylic acid, DMF = N,N'-dimethylformamide) and [CoII3(Ci)4][CoII(NH3)6]·2C2H5OH·7AC (Co-Ci-AC, AC = Acetone), which enable precise tuning of proton conductivity by varying the exposure of hydrophilic sites within the pores. As expected, the two MOFs exhibited different proton conductivities: Co-Ci-DMF showed a higher conductivity of 3.37 × 10−4 S cm−1, while Co-Ci-AC demonstrated a lower value of 1.52 × 10−4 S cm−1. Quantitative surface energy analysis reveals that the more exposed hydrophilic groups in Co-Ci-DMF result in a higher surface energy (19.13 mJ m−2) than in Co-Ci-AC (12.24 mJ m−2), thereby enhancing interfacial hydrophilicity and facilitating efficient proton migration. Moreover, water adsorption and temperature-dependent dielectric measurements indicated that the combined effects of additionally adsorbed water molecules and varying hydrogen bond contraction behavior contribute to the relatively small difference in activation energies between the two materials. This study establishes a clear correlation between hydrophilic microenvironments, surface energy, and proton conductivity, highlighting interfacial hydrophilicity as a decisive factor and offering a general design principle for the development of high-performance proton-conducting MOFs.
用于质子传导的金属有机框架（MOFs）由于其可调谐的结构和在燃料电池和其他能源技术中的应用前景而引起了人们的极大兴趣。然而，控制内部微环境的亲水性仍然具有挑战性，阻碍了对其在质子运输中的作用的精确理解。在此，我们报道了两种新的等孔mof， [CoII3CoIII(Ci)4(NH3)4(DMF)]NO3·5C2H5OH （Co-Ci-DMF, H2Ci = h -吲哚-5-羧酸，DMF = N，N'-二甲基甲酰胺）和[CoII3(Ci)4][CoII(NH3)6]·2C2H5OH·7AC （Co-Ci-AC, AC =丙酮），它们可以通过改变孔内亲水性位点的暴露来精确调节质子电导率。正如预期的那样，两种mof表现出不同的质子电导率：Co-Ci-DMF的电导率较高，为3.37 × 10−4 S cm−1，而Co-Ci-AC的电导率较低，为1.52 × 10−4 S cm−1。定量表面能分析表明，Co-Ci-DMF中暴露的亲水性基团越多，其表面能（19.13 mJ m−2）高于Co-Ci-AC (12.24 mJ m−2)，从而增强了界面亲水性，促进了质子的有效迁移。此外，水吸附和温度相关的介电测量表明，额外吸附的水分子和不同的氢键收缩行为的综合作用导致两种材料之间的活化能差异相对较小。本研究建立了亲水性微环境、表面能和质子电导率之间的明确相关性，强调了界面亲水性是一个决定性因素，并为开发高性能质子导电mof提供了一般设计原则。
{"title":"Tuning proton conductivity via hydrophilic group exposure in isoreticular metal‒organic frameworks: hydrogen bond length dynamics probed by dielectric spectroscopy","authors":"Shaoqiang Feng , Chengan Wan , Xiaoqiang Liang , Feng Zhang , Lei Feng , Chen Wen","doi":"10.1016/j.molstruc.2025.145184","DOIUrl":"10.1016/j.molstruc.2025.145184","url":null,"abstract":"<div><div>The development of metal‒organic frameworks (MOFs) for proton conduction has garnered significant interest due to their tunable structures and promising applications in fuel cells and other energy technologies. However, controlling the hydrophilicity of internal microenvironments remains challenging, hindering precise understanding of its role in proton transport. Herein, we report two new isoreticular MOFs, [Co<sup>II</sup><sub>3</sub>Co<sup>III</sup>(Ci)<sub>4</sub>(NH<sub>3</sub>)<sub>4</sub>(DMF)]NO<sub>3</sub>·5C<sub>2</sub>H<sub>5</sub>OH (Co-Ci-DMF, H<sub>2</sub>Ci = 1<em>H</em>-indazole-5-carboxylic acid, DMF = <em>N</em>,N<em>'</em>-dimethylformamide) and [Co<sup>II</sup><sub>3</sub>(Ci)<sub>4</sub>][Co<sup>II</sup>(NH<sub>3</sub>)<sub>6</sub>]·2C<sub>2</sub>H<sub>5</sub>OH·7AC (Co-Ci-AC, AC = Acetone), which enable precise tuning of proton conductivity by varying the exposure of hydrophilic sites within the pores. As expected, the two MOFs exhibited different proton conductivities: Co-Ci-DMF showed a higher conductivity of 3.37 × 10<sup>−4</sup> S cm<sup>−1</sup>, while Co-Ci-AC demonstrated a lower value of 1.52 × 10<sup>−4</sup> S cm<sup>−1</sup>. Quantitative surface energy analysis reveals that the more exposed hydrophilic groups in Co-Ci-DMF result in a higher surface energy (19.13 mJ m<sup>−2</sup>) than in Co-Ci-AC (12.24 mJ m<sup>−2</sup>), thereby enhancing interfacial hydrophilicity and facilitating efficient proton migration. Moreover, water adsorption and temperature-dependent dielectric measurements indicated that the combined effects of additionally adsorbed water molecules and varying hydrogen bond contraction behavior contribute to the relatively small difference in activation energies between the two materials. This study establishes a clear correlation between hydrophilic microenvironments, surface energy, and proton conductivity, highlighting interfacial hydrophilicity as a decisive factor and offering a general design principle for the development of high-performance proton-conducting MOFs.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1356 ","pages":"Article 145184"},"PeriodicalIF":4.7,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.molstruc.2025.145171
Eunice Cerqueira de Jesus , Larissa de Souza Ferreira , Feik Amil de Campos , Dione da Costa Oliveira , Taíse Matte Manhabosco , Thiago Cazati , Lorenzo Conti Serra , Ivan H. Bechtold , André Alexandre Vieira
New luminescent liquid-crystalline derivatives based on the 5‑chloro-4,7-bis(phenylethynyl)[2,1,3]benzothiadiazole (BTD-Cl) core were synthesized and characterized. The molecules bear alkoxy chains of varying lengths connected through acetylenic linkages. This study aimed to elucidate the influence of the chlorine atom directly bound to the BTD ring on the mesomorphic and photophysical behavior. Polarized optical microscopy and differential scanning calorimetry revealed liquid-crystalline properties for all alkylated derivatives, predominantly displaying nematic phases. Chlorine substitution lowered both the melting and clearing points, and suppressed smectic organization compared to unsubstituted BTDs. The BTD-Cl derivatives exhibited intense yellow fluorescence with emission maxima ranging from 498 to 543 nm and singlet excited-state lifetimes on the nanosecond timescale. High fluorescence quantum yields were observed both in solution and in the solid state (0.68–0.81), higher than those of unsubstituted BTDs. Fluorescence quenching experiments using the non-fullerene acceptor Y18 revealed efficient photoinduced electron transfer, underscoring the BTD-Cl:Y18 pair as a promising donor–acceptor system for photovoltaic applications. Numerical calculations revealed the nature of the photophysical properties and the mesophase organization.
{"title":"Influence of side‑chloro substitution on the thermal and photophysical properties of 2,1,3-benzothiadiazole-based liquid crystals","authors":"Eunice Cerqueira de Jesus , Larissa de Souza Ferreira , Feik Amil de Campos , Dione da Costa Oliveira , Taíse Matte Manhabosco , Thiago Cazati , Lorenzo Conti Serra , Ivan H. Bechtold , André Alexandre Vieira","doi":"10.1016/j.molstruc.2025.145171","DOIUrl":"10.1016/j.molstruc.2025.145171","url":null,"abstract":"<div><div>New luminescent liquid-crystalline derivatives based on the 5‑chloro-4,7-bis(phenylethynyl)[2,1,3]benzothiadiazole (BTD-Cl) core were synthesized and characterized. The molecules bear alkoxy chains of varying lengths connected through acetylenic linkages. This study aimed to elucidate the influence of the chlorine atom directly bound to the BTD ring on the mesomorphic and photophysical behavior. Polarized optical microscopy and differential scanning calorimetry revealed liquid-crystalline properties for all alkylated derivatives, predominantly displaying nematic phases. Chlorine substitution lowered both the melting and clearing points, and suppressed smectic organization compared to unsubstituted BTDs. The BTD-Cl derivatives exhibited intense yellow fluorescence with emission maxima ranging from 498 to 543 nm and singlet excited-state lifetimes on the nanosecond timescale. High fluorescence quantum yields were observed both in solution and in the solid state (0.68–0.81), higher than those of unsubstituted BTDs. Fluorescence quenching experiments using the non-fullerene acceptor Y18 revealed efficient photoinduced electron transfer, underscoring the BTD-Cl:Y18 pair as a promising donor–acceptor system for photovoltaic applications. Numerical calculations revealed the nature of the photophysical properties and the mesophase organization.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1356 ","pages":"Article 145171"},"PeriodicalIF":4.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.molstruc.2025.145175
Priyanka Kataria , Shiva Vairale , Chandrashekhar Mote , Kaustubh Joshi , Rakesh Joshi , Mahesh J. Kulkarni , Ashok P. Giri , Ravindar Kontham , Sachin B. Agawane
In this study, we present the design, synthesis, and evaluation of novel eugenol analogs aimed to overcome its limited bioavailability due to insolubility in aqueous media. Thus, we re-engineered eugenol using prodrug-inspired structural modifications to improve pharmacokinetic properties. First, we structurally modified eugenol and synthesized its natural amino acid conjugates as esters and carbamates. These were prepared in N-Boc protected, free amine, and HCl salt forms. These modifications are expected to improve the polarity and solubility of eugenol congeners in biological systems. They can also release the parent eugenol through enzymatic hydrolysis, enhancing its therapeutic potential. Next, we comprehensively screened for these derivatives through in silico studies followed by in vitro and in vivo assays. These include DPPH radical scavenging (IC50 range: 37.7 to 103.7 µM), inhibition of (i) α-amylase (IC50 23.1 to 67.3 µM), (ii) α-glucosidase (IC50 43.6 to 50.4 µM), (iii) glycation (IC50 31.9 to 110.3 µM) along with pharmacokinetic profiling and toxicity assessments. These experiments collectively demonstrated improved activity of eugenol analogs for several important parameters. Specifically, six analogs-epoxy eugenol (39), hydroxy eugenol (43), aspartate eugenol (26), isoleucinate eugenol (24), glutamate eugenol (37), and glutamate-salt eugenol (27) exhibited superior bioavailability, absorption, and distribution over to the parent compound eugenol. These analogs were found to be non-toxic and safe for oral administration. Overall, the study establishes a mechanistic and rational framework for modifying eugenol to overcome its inherent biopharmaceutical limitations, positioning them as promising candidates for treating diabetes and glycation-related conditions.
在这项研究中，我们提出了新的丁香酚类似物的设计、合成和评价，旨在克服其在水介质中不溶性造成的生物利用度限制。因此，我们使用前药物启发的结构修饰来重新设计丁香酚，以改善药代动力学特性。首先对丁香酚进行结构修饰，合成其天然氨基酸缀合物酯类和氨基甲酸酯类。它们以N-Boc保护、游离胺和HCl盐的形式制备。这些修饰有望改善丁香酚同系物在生物系统中的极性和溶解度。它们还可以通过酶水解释放母体丁香酚，增强其治疗潜力。接下来，我们通过计算机研究全面筛选这些衍生物，然后进行体外和体内分析。这些包括DPPH自由基清除（IC50范围：37.7至103.7µM），抑制(i) α-淀粉酶（IC50范围：23.1至67.3µM）， (ii) α-葡萄糖苷酶（IC50 43.6至50.4µM）， （iii）糖基化（IC50 31.9至110.3µM）以及药代动力学分析和毒性评估。这些实验共同证明了丁香酚类似物在几个重要参数上的活性有所提高。具体来说，六种类似物——环氧丁香酚（39）、羟基丁香酚（43）、天冬氨酸丁香酚（26）、异euceucinate丁香酚（24）、谷氨酸丁香酚（37）和谷氨酸盐丁香酚（27）表现出优于母体化合物丁香酚的生物利用度、吸收和分布。这些类似物被发现是无毒的，口服是安全的。总的来说，该研究建立了一个机制和合理的框架来修饰丁香酚，以克服其固有的生物制药局限性，将其定位为治疗糖尿病和糖化相关疾病的有希望的候选者。
{"title":"Novel prodrug-inspired eugenol derivatives with enhanced bioavailability, anti-diabetic and anti-glycation efficacies","authors":"Priyanka Kataria , Shiva Vairale , Chandrashekhar Mote , Kaustubh Joshi , Rakesh Joshi , Mahesh J. Kulkarni , Ashok P. Giri , Ravindar Kontham , Sachin B. Agawane","doi":"10.1016/j.molstruc.2025.145175","DOIUrl":"10.1016/j.molstruc.2025.145175","url":null,"abstract":"<div><div>In this study, we present the design, synthesis, and evaluation of novel eugenol analogs aimed to overcome its limited bioavailability due to insolubility in aqueous media. Thus, we re-engineered eugenol using prodrug-inspired structural modifications to improve pharmacokinetic properties. First, we structurally modified eugenol and synthesized its natural amino acid conjugates as esters and carbamates. These were prepared in <em>N</em>-Boc protected, free amine, and HCl salt forms. These modifications are expected to improve the polarity and solubility of eugenol congeners in biological systems. They can also release the parent eugenol through enzymatic hydrolysis, enhancing its therapeutic potential. Next, we comprehensively screened for these derivatives through <em>in silico</em> studies followed by in vitro and in vivo assays. These include DPPH radical scavenging (IC<sub>50</sub> range: 37.7 to 103.7 µM), inhibition of (i) α-amylase (IC<sub>50</sub> 23.1 to 67.3 µM), (ii) α-glucosidase (IC<sub>50</sub> 43.6 to 50.4 µM), (iii) glycation (IC<sub>50</sub> 31.9 to 110.3 µM) along with pharmacokinetic profiling and toxicity assessments. These experiments collectively demonstrated improved activity of eugenol analogs for several important parameters. Specifically, six analogs-epoxy eugenol (<strong>39</strong>), hydroxy eugenol (<strong>43</strong>), aspartate eugenol (<strong>26</strong>), isoleucinate eugenol (<strong>24</strong>), glutamate eugenol (<strong>37</strong>), and glutamate-salt eugenol (<strong>27</strong>) exhibited superior bioavailability, absorption, and distribution over to the parent compound eugenol. These analogs were found to be non-toxic and safe for oral administration. Overall, the study establishes a mechanistic and rational framework for modifying eugenol to overcome its inherent biopharmaceutical limitations, positioning them as promising candidates for treating diabetes and glycation-related conditions.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145175"},"PeriodicalIF":4.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, three thiosemicarbazones (2a-2c), three thiazole–Schiff base derivatives (3a-3c), and three thiazole-Schiff base thiosemicarbazones (4a-4c) were synthesized (Scheme 1) through three consecutive reactions. The structures of the compounds were confirmed using various spectral analyses, including IR, 1H NMR, 13C NMR, ES-MS, and HRMS. In vitro antimicrobial experiment revealed significantly higher antifungal activity of 4b against all fungal strains than the standard amphotericin B, and some moderate antibacterial activity. The most prominent activity of 4b against N. crassa (45.5 ± 0.2 mm), A. flavus (42.6 ± 0.6 mm), and T. harzianum (42.3±0.5 mm) was three to four times higher than the standard amphotericin B (15.3±0.5 mm, 11.3±0.4 mm, and 9.3±0.6 mm), respectively. The antioxidant activity of the synthesized analogues was assessed by DPPH free radical scavenging assays, in which 4b displayed higher antioxidant activity (IC50 = 35.73 ± 4.03 μg/mL) compared to the standard ascorbic acid (IC50 = 40.47 ± 1.11 μg/mL). Along with good wet lab activity, compound 4b displayed good drug-likeness and drug-score in silico ADMET properties, and all new derivatives follow Veber’s rule and Lipinski’s rule of five. Moreover, the molecular docking and dynamics studies indicated high binding affinities and stability of 4b inside the target protein receptors. The simple synthetic pathways and enhanced biological activities of the synthesized analogues reported in this study could be beneficial for future drug discovery.
{"title":"Synthesis of thiazole based thiosemicarbazones and in vitro and in silico evaluation of their antibacterial and antifungal activities","authors":"Md. Mizanur Rahman , Sumita Saznin Marufa , Md. Abdur Razzak , Joya Rani Debnath , Md. Shawon , Monika Das , Hiroshi Nishino , Mohammad Mostafizur Rahman , Md. Aminul Haque","doi":"10.1016/j.molstruc.2025.145173","DOIUrl":"10.1016/j.molstruc.2025.145173","url":null,"abstract":"<div><div>In this study, three thiosemicarbazones <strong>(2a-2c</strong>), three thiazole–Schiff base derivatives (<strong>3a-3c</strong>), and three thiazole-Schiff base thiosemicarbazones <strong>(4a-4c)</strong> were synthesized (Scheme 1) through three consecutive reactions. The structures of the compounds were confirmed using various spectral analyses, including IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, ES-MS, and HRMS. In vitro antimicrobial experiment revealed significantly higher antifungal activity of <strong>4b</strong> against all fungal strains than the standard amphotericin B, and some moderate antibacterial activity. The most prominent activity of <strong>4b</strong> against <em>N. crassa</em> (45.5 ± 0.2 mm), <em>A. flavus</em> (42.6 ± 0.6 mm), and <em>T. harzianum</em> (<em>42.3</em> <em>±</em> <em>0.5</em> mm) was three to four times higher than the standard amphotericin B (<em>15.3</em> <em>±</em> <em>0.5</em> mm, <em>11.3</em> <em>±</em> <em>0.4</em> mm, and <em>9.3</em> <em>±</em> <em>0.6</em> mm), <em>respectively. The</em> antioxidant activity <em>of the synthesized analogues</em> was assessed <em>by DPPH free radical scavenging assays,</em> in which <strong>4b</strong> displayed higher antioxidant activity (IC<sub>50</sub> = 35.73 ± 4.03 μg/mL) <em>compared to</em> the standard ascorbic acid (IC<sub>50</sub> = 40.47 ± 1.11 μg/mL). Along with good wet lab activity, compound <strong>4b</strong> displayed good drug-likeness and drug-score <em>in silico</em> ADMET properties, and all new derivatives follow Veber’s rule and Lipinski’s rule of five. Moreover, the molecular docking and dynamics studies indicated high binding affinities and stability of <strong>4b</strong> inside the target protein receptor<em>s.</em> The simple synthetic pathways and enhanced biological activities of the synthesized analogues reported in this study could be beneficial for future drug discovery.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1356 ","pages":"Article 145173"},"PeriodicalIF":4.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.molstruc.2025.145172
Mahmood Mohammed Ali , Ahmed Mishaal Mohammed , Yousif H. Khalaf
This study presents, for the first time, the eco-friendly synthesis of iron nanoparticles (FeNPs) using Annona muricata leaf phytochemicals and evaluates their dual antidiabetic and antioxidant effects in vivo. In this context, green nanotechnology offers a promising approach for producing nanoparticles with high biological activity and improved biocompatibility. In this study, iron nanoparticles (FeNPs) were synthesized biologically using Annona muricata (soursop) leaf extract and then thoroughly characterized using multiple techniques. HPLC analysis identified key plant compounds, including rutin, quercetin, luteolin, kaempferol, and gallic acid. In vivo experiments were conducted on 48 male Wistar rats randomly divided into eight groups. The study evaluated antidiabetic effects, antioxidant and α-amylase inhibitory properties. Oral administration of FeNPs (10 mg/kg and 20 mg/kg), Annona muricata extract (100 mg/kg), and metformin (100 mg/kg) for 21 days resulted in a significant reduction in fasting blood glucose levels, improved insulin and serum lipids, and restored liver and kidney functions compared to the diabetic group (p < 0.001). Pretreatment with FeNPs or the extract also provided significant protection against hyperglycemia and tissue damage, as confirmed by histological examinations showing intact pancreas, liver, and kidneys, with histological analysis showing significant tissue regeneration and reduced damage in pancreatic, liver, and kidney sections. In vitro tests and enzyme kinetic studies showed that FeNPs strongly inhibit α-amylase (IC₅₀ = 146.3 μg/mL) through a mixed inhibition mechanism, leading to decreased catalytic efficiency and an increased Km value, indicating reduced affinity for the enzyme substrate. FeNPs showed excellent colloidal stability during storage, with little aggregation over the first two weeks and maintaining optimal stability at 4 °C. However, exposure to high temperatures and freeze–thaw cycles caused a significant red-shift and particle clumping. Antioxidant assays also confirmed the activity of FeNPs in DPPH, ABTS, and FRAP tests. Overall, these findings indicate that A. muricata-derived FeNPs are a promising, cost-effective, and easily developed nanotherapeutic system that combines antidiabetic and antioxidant properties. This versatility is supported by diverse phytochemical, mineral, and enzyme-inhibition profiles, making them worthy of further research and development for potential clinical applications.
{"title":"Molecular and structural characterization of Annona muricata-derived iron nanoparticles exhibiting in vivo antidiabetic activity and mixed-type α-amylase inhibition","authors":"Mahmood Mohammed Ali , Ahmed Mishaal Mohammed , Yousif H. Khalaf","doi":"10.1016/j.molstruc.2025.145172","DOIUrl":"10.1016/j.molstruc.2025.145172","url":null,"abstract":"<div><div>This study presents, for the first time, the eco-friendly synthesis of iron nanoparticles (FeNPs) using Annona muricata leaf phytochemicals and evaluates their dual antidiabetic and antioxidant effects in vivo. In this context, green nanotechnology offers a promising approach for producing nanoparticles with high biological activity and improved biocompatibility. In this study, iron nanoparticles (FeNPs) were synthesized biologically using Annona muricata (soursop) leaf extract and then thoroughly characterized using multiple techniques. HPLC analysis identified key plant compounds, including rutin, quercetin, luteolin, kaempferol, and gallic acid. In vivo experiments were conducted on 48 male Wistar rats randomly divided into eight groups. The study evaluated antidiabetic effects, antioxidant and α-amylase inhibitory properties. Oral administration of FeNPs (10 mg/kg and 20 mg/kg), Annona muricata extract (100 mg/kg), and metformin (100 mg/kg) for 21 days resulted in a significant reduction in fasting blood glucose levels, improved insulin and serum lipids, and restored liver and kidney functions compared to the diabetic group (<em>p</em> < 0.001). Pretreatment with FeNPs or the extract also provided significant protection against hyperglycemia and tissue damage, as confirmed by histological examinations showing intact pancreas, liver, and kidneys, with histological analysis showing significant tissue regeneration and reduced damage in pancreatic, liver, and kidney sections. In vitro tests and enzyme kinetic studies showed that FeNPs strongly inhibit α-amylase (IC₅₀ = 146.3 μg/mL) through a mixed inhibition mechanism, leading to decreased catalytic efficiency and an increased Km value, indicating reduced affinity for the enzyme substrate. FeNPs showed excellent colloidal stability during storage, with little aggregation over the first two weeks and maintaining optimal stability at 4 °C. However, exposure to high temperatures and freeze–thaw cycles caused a significant red-shift and particle clumping. Antioxidant assays also confirmed the activity of FeNPs in DPPH, ABTS, and FRAP tests. Overall, these findings indicate that A. muricata-derived FeNPs are a promising, cost-effective, and easily developed nanotherapeutic system that combines antidiabetic and antioxidant properties. This versatility is supported by diverse phytochemical, mineral, and enzyme-inhibition profiles, making them worthy of further research and development for potential clinical applications.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1356 ","pages":"Article 145172"},"PeriodicalIF":4.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.molstruc.2025.145145
Ahmad Amiri , Mehdi Salehi , Mohammad Reza Binaeizadeh , Dorsa Jamali , Parnia Pishva , Farzaneh Fadaei-Tirani
Four new metal complexes, [Zn(HL)2] (1), [Ni(HL)2] (2), [Mn3(L)2(OAc)4(OH2)] (3) and [Co(L)(HL)] (4) were synthesized using a tridentate ONO-type Schiff base ligand (H2L), derived from the condensation of 2-amino-2-methyl-1-propanol and 5‑bromo salicylaldehyde. Single crystal X-ray diffraction revealed that the mononuclear Zn(II), Ni(II), and Co(III) complexes (1, 2 and 4) exhibit distorted octahedral geometries, whereas the mixed-valance Mn(III)/Mn(II) complex (3) crystallizes as a trinuclear specieswith acetate-bridged Mn centers.
Electrochemical investigations in DMF demonestrated irreversible redox processes for complexes 2–4, consistent with the expected electrochemical characteristics of Ni(II), Mn(III), and Co(III) centers in distorted octahedral environments.
The antibacterial activity of the complexes 1–4 was evaluated against Staphylococcus aureus, Bacillus subtili, Escherichia coli and Salmonella enterica using Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Among the series, complex 3 displayed the most antibacterial potency, with MIC values as low as 1.56 µg/mL against B. subtilis and 3.12 µg/mL against S. enterica. These findings demonstrate that the nature of the central metal ion and its coordination environment play a decisive role in tuning the redox behavior and antibacterial properties of Schiff base complexes, highlighting their potential for further functional and bioinorganic applications.
{"title":"X-ray structures, redox behavior, and antibacterial evaluation of Zn(II), Ni(II), Mn(III), and Co(III) complexes with a tridentate ONO Schiff base ligand","authors":"Ahmad Amiri , Mehdi Salehi , Mohammad Reza Binaeizadeh , Dorsa Jamali , Parnia Pishva , Farzaneh Fadaei-Tirani","doi":"10.1016/j.molstruc.2025.145145","DOIUrl":"10.1016/j.molstruc.2025.145145","url":null,"abstract":"<div><div>Four new metal complexes, [Zn(HL)<sub>2</sub>] (<strong>1</strong>), [Ni(HL)<sub>2</sub>] (<strong>2</strong>), [Mn<sub>3</sub>(L)<sub>2</sub>(OAc)<sub>4</sub>(OH<sub>2</sub>)] (<strong>3</strong>) and [Co(L)(HL)] (<strong>4</strong>) were synthesized using a tridentate ONO-type Schiff base ligand (H<sub>2</sub>L), derived from the condensation of 2-amino-2-methyl-1-propanol and 5‑bromo salicylaldehyde. Single crystal X-ray diffraction revealed that the mononuclear Zn(II), Ni(II), and Co(III) complexes (<strong>1, 2</strong> and <strong>4</strong>) exhibit distorted octahedral geometries, whereas the mixed-valance Mn(III)/Mn(II) complex (<strong>3</strong>) crystallizes as a trinuclear specieswith acetate-bridged Mn centers.</div><div>Electrochemical investigations in DMF demonestrated irreversible redox processes for complexes <strong>2–4</strong>, consistent with the expected electrochemical characteristics of Ni(II), Mn(III), and Co(III) centers in distorted octahedral environments.</div><div>The antibacterial activity of the complexes <strong>1–4</strong> was evaluated against <em>Staphylococcus aureus, Bacillus subtili, Escherichia coli</em> and <em>Salmonella enterica</em> using Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Among the series, complex <strong>3</strong> displayed the most antibacterial potency, with MIC values as low as 1.56 µg/mL against <em>B. subtilis</em> and 3.12 µg/mL against <em>S. enterica</em>. These findings demonstrate that the nature of the central metal ion and its coordination environment play a decisive role in tuning the redox behavior and antibacterial properties of Schiff base complexes, highlighting their potential for further functional and bioinorganic applications.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1356 ","pages":"Article 145145"},"PeriodicalIF":4.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-25DOI: 10.1016/j.molstruc.2025.145161
Kgaugelo C. Tapala , Mpho P. Ngoepe , Garland K. More , Hadley S. Clayton
This study investigates the synthesis of complexes 1, 2 and 3 and characterisation using the various methods such as vibrational (FTIR and Raman), NMR (1H, 13C, 19F, and 31P) spectroscopy, thermal analysis, elemental analysis, mass spectrometry, conductivity and the crystal structures of 2 and 3 are also reported. Introducing an aryl phosphine moiety increases the thermodynamic stability and the thermal stability of complexes 2 and 3. In complex 2, π-π interactions have been demonstrated to play a crucial role in stabilising the crystal packing. Hirshfeld surface analysis provides insight into the non-covalent interactions of complexes 2 and 3. Molecular docking studies provide insight into the interactions of the complexes with protein receptors associated with the cancer cell lines screened in the in vitro cytotoxicity studies. Osmium(II)-cymene complexes exhibit an interesting trend in in vitro cytotoxicity against cancer cell lines, MCF-7 and A549, as well as the healthy cell line HEK293. Complex 3 demonstrated relatively high inhibitory activity against the MCF-7 and A549 cells, with IC50 values of 2.9 ± 0.18 µM and 2.4 ± 0.19 µM, respectively. This was followed by complex 2, which had IC50 values of 2.7 ± 0.22 µM for MCF-7 cells and 3.4 ± 0.23 µM for A549 cells. In contrast, complexes 2 and 3 were less toxic to normal HEK293 cells, exhibiting IC50 values of 8.7 ± 0.06 µM and 10.80 ± 0.25 µM, respectively. Furthermore, molecular docking was conducted to validate the findings from the in vitro anticancer activities. Results show that PPh3 significantly enhances the in vitro cytotoxicity and antioxidant activities of complexes 2 and 3, suggesting that metal-PPh3 complexes are promising scaffolds for the rational design of multifunctional therapeutic agents with potential applications for future drug development strategies.
{"title":"Synthesis, characterization, structural analysis, DFT investigations, molecular docking, in vitro cytotoxicity and antioxidant activity of Os(II)-cymene complexes of the type [(η6-p-cymene)OsBr(CH3CN)n(PPh3)m]+BF4−","authors":"Kgaugelo C. Tapala , Mpho P. Ngoepe , Garland K. More , Hadley S. Clayton","doi":"10.1016/j.molstruc.2025.145161","DOIUrl":"10.1016/j.molstruc.2025.145161","url":null,"abstract":"<div><div>This study investigates the synthesis of complexes <strong>1, 2</strong> and <strong>3</strong> and characterisation using the various methods such as vibrational (FTIR and Raman), NMR (<sup>1</sup>H, <sup>13</sup>C, <sup>19</sup>F, and <sup>31</sup>P) spectroscopy, thermal analysis, elemental analysis, mass spectrometry, conductivity and the crystal structures of <strong>2</strong> and <strong>3</strong> are also reported. Introducing an aryl phosphine moiety increases the thermodynamic stability and the thermal stability of complexes <strong>2</strong> and <strong>3</strong>. In complex <strong>2</strong>, <em>π-π</em> interactions have been demonstrated to play a crucial role in stabilising the crystal packing. Hirshfeld surface analysis provides insight into the non-covalent interactions of complexes <strong>2</strong> and <strong>3</strong>. Molecular docking studies provide insight into the interactions of the complexes with protein receptors associated with the cancer cell lines screened in the <em>in vitro</em> cytotoxicity studies. Osmium(II)-cymene complexes exhibit an interesting trend in <em>in vitro</em> cytotoxicity against cancer cell lines, MCF-7 and A549, as well as the healthy cell line HEK293. Complex <strong>3</strong> demonstrated relatively high inhibitory activity against the MCF-7 and A549 cells, with IC<sub>50</sub> values of 2.9 ± 0.18 µM and 2.4 ± 0.19 µM, respectively. This was followed by complex <strong>2</strong>, which had IC<sub>50</sub> values of 2.7 ± 0.22 µM for MCF-7 cells and 3.4 ± 0.23 µM for A549 cells. In contrast, complexes <strong>2</strong> and <strong>3</strong> were less toxic to normal HEK293 cells, exhibiting IC<sub>50</sub> values of 8.7 ± 0.06 µM and 10.80 ± 0.25 µM, respectively. Furthermore, molecular docking was conducted to validate the findings from the <em>in vitro</em> anticancer activities. Results show that PPh<sub>3</sub> significantly enhances the <em>in vitro</em> cytotoxicity and antioxidant activities of complexes <strong>2</strong> and <strong>3</strong>, suggesting that metal-PPh<sub>3</sub> complexes are promising scaffolds for the rational design of multifunctional therapeutic agents with potential applications for future drug development strategies.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1356 ","pages":"Article 145161"},"PeriodicalIF":4.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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