Pub Date : 2026-01-30DOI: 10.1016/j.molstruc.2026.145529
C. Raksha , Jayasree G. Elambalassery , Akhil Sivan
The present work reports the design and synthesis of two benzimidazole-thiazolidine fused spiroheterocycles, STCH and STCP, developed through a combined computational and experimental approach. Density Functional Theory (DFT) calculations, including geometry optimisation and frequency analysis, confirmed their stability, while Natural Bond Orbital (NBO) analysis provided insights into their electronic characteristics. The compounds were synthesised via a multicomponent reaction and purified using column chromatography, with structures fully characterised by FT-IR, NMR, HRMS, and single-crystal X-ray diffraction (XRD). Topological analyses, including Electron Localisation Function (ELF), Localised Orbital Locator (LOL), Reduced Density Gradient (RDG), and Quantum Theory of Atoms in Molecules (QTAIM), revealed bonding and non-bonding interactions, intramolecular hydrogen bonding, and weak stabilising forces, further supported by Hirshfeld surface analysis. Drug-likeness and safety evaluations, based on ADME and toxicity predictions, suggested favourable pharmacokinetic properties. Molecular docking studies against α-glucosidase and α-amylase inhibitors highlighted strong binding affinities of both compounds, underscoring their potential as antidiabetic agents. Collectively, these integrative computational and experimental findings establish STCH and STCP as promising molecular scaffolds for further therapeutic development.
{"title":"Integrated spectroscopic, DFT, and topological analysis of benzimidazole-thiazolidine spiro heterocycles with promising antidiabetic potential","authors":"C. Raksha , Jayasree G. Elambalassery , Akhil Sivan","doi":"10.1016/j.molstruc.2026.145529","DOIUrl":"10.1016/j.molstruc.2026.145529","url":null,"abstract":"<div><div>The present work reports the design and synthesis of two benzimidazole-thiazolidine fused spiroheterocycles, <strong>STCH</strong> and <strong>STCP</strong>, developed through a combined computational and experimental approach. Density Functional Theory (DFT) calculations, including geometry optimisation and frequency analysis, confirmed their stability, while Natural Bond Orbital (NBO) analysis provided insights into their electronic characteristics. The compounds were synthesised <em>via</em> a multicomponent reaction and purified using column chromatography, with structures fully characterised by FT-IR, NMR, HRMS, and single-crystal X-ray diffraction (XRD). Topological analyses, including Electron Localisation Function (ELF), Localised Orbital Locator (LOL), Reduced Density Gradient (RDG), and Quantum Theory of Atoms in Molecules (QTAIM), revealed bonding and non-bonding interactions, intramolecular hydrogen bonding, and weak stabilising forces, further supported by Hirshfeld surface analysis. Drug-likeness and safety evaluations, based on ADME and toxicity predictions, suggested favourable pharmacokinetic properties. Molecular docking studies against α-glucosidase and α-amylase inhibitors highlighted strong binding affinities of both compounds, underscoring their potential as antidiabetic agents. Collectively, these integrative computational and experimental findings establish <strong>STCH</strong> and <strong>STCP</strong> as promising molecular scaffolds for further therapeutic development.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145529"},"PeriodicalIF":4.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171085","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 : 2026-01-30DOI: 10.1016/j.molstruc.2026.145518
Chen Li, Guo Xu, Yang Zhao, Jing Liang, Xiao-Peng Zhang
Herein, several neutral difluoro-substituted cyclometalated Pt(II) complexes incorporating halide/isocyanide ligands, [Pt(κ2-N^C)(CNXyl)X] (N^C = (−)-3-(4-fluoro-3-(3-fluoropyridin-2-yl)phenyl)-7,7-dimethyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline; CNXyl = 2,6-dimethylphenyl isocyanide; X = Cl (−)-1, Br (−)-2, or I (−)-3), were isolated from the reaction between [Pt(κ3-N^C^N′)(CNXyl)]OTf and n-Bu4NX. The preparation and photoluminescence properties of ionic [Pt(κ3-N^C^N′)(CNXyl)]OTf precursor and (−)-1 have been previously reported, and new complexes in this report are the -Br ((−)-2) and -I ((−)-3) derivatives. Single-crystal X-ray diffraction on (−)-2 and (−)-3 revealed a slightly distorted square-planar geometry in a trans-NC^N,CNR configuration. All κ2-N^C-coordinated Pt(II) complexes were weakly emissive in CH2Cl2 or THF but emitted bright luminescence with emission quantum yields of up to 77% in rigid media (solid state and PMMA films). A distinct aggregation-induced emission behavior was observed in mixed THF/H2O solution. Crystallites of the [Pt(κ2-N^C)(CNXyl)X] complexes demonstrated irreversible luminescence thermochromism with a luminescence change from green to red.
{"title":"Thermochromism and luminescent properties of κ2-N^C-coordinated cyclometalated Pt(II) complexes incorporating halide/isocyanide","authors":"Chen Li, Guo Xu, Yang Zhao, Jing Liang, Xiao-Peng Zhang","doi":"10.1016/j.molstruc.2026.145518","DOIUrl":"10.1016/j.molstruc.2026.145518","url":null,"abstract":"<div><div>Herein, several neutral difluoro-substituted cyclometalated Pt(II) complexes incorporating halide/isocyanide ligands, [Pt(<em>κ</em><sup>2</sup>-N^C)(CNXyl)X] (N^<em>C</em> = (−)-3-(4-fluoro-3-(3-fluoropyridin-2-yl)phenyl)-7,7-dimethyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline; CNXyl = 2,6-dimethylphenyl isocyanide; <em>X</em> = Cl (−)-<strong>1</strong>, Br (−)-<strong>2</strong>, or I (−)-<strong>3</strong>), were isolated from the reaction between [Pt(<em>κ</em><sup>3</sup>-N^C^N′)(CNXyl)]OTf and <em>n</em>-Bu<sub>4</sub>NX. The preparation and photoluminescence properties of ionic [Pt(<em>κ</em><sup>3</sup>-N^C^N′)(CNXyl)]OTf precursor and (−)-<strong>1</strong> have been previously reported, and new complexes in this report are the -Br ((−)-<strong>2</strong>) and -I ((−)-<strong>3</strong>) derivatives. Single-crystal X-ray diffraction on (−)-<strong>2</strong> and (−)-<strong>3</strong> revealed a slightly distorted square-planar geometry in a <strong><em>trans-N<sub>C^N</sub>,CNR</em></strong> configuration. All <em>κ</em><sup>2</sup><em>-</em>N^C-coordinated Pt(II) complexes were weakly emissive in CH<sub>2</sub>Cl<sub>2</sub> or THF but emitted bright luminescence with emission quantum yields of up to 77% in rigid media (solid state and PMMA films). A distinct aggregation-induced emission behavior was observed in mixed THF/H<sub>2</sub>O solution. Crystallites of the [Pt(<em>κ<sup>2</sup>-</em>N^C)(CNXyl)X] complexes demonstrated irreversible luminescence thermochromism with a luminescence change from green to red.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145518"},"PeriodicalIF":4.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171086","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 : 2026-01-30DOI: 10.1016/j.molstruc.2026.145517
Jia-Yu Gu , Xin-Ran Chen , Fei Li , Wen-Ya Ding , Jia Cao , Wei-Wei Ge , Kai Chen
Three new coordination polymers based on cucurbit[5]uril (Q[5]) have been successfully synthesized. Their chemical formulas are {[Ni(H2O)2(Q[5])]·(1,5-NDS)}·14H2O (1), {[Co(H2O)2(Q[5])]·(1,5-NDS)}·15H2O (2), and {[Zn(H2O)2(Q[5])]·(1,5-NDS)}·10H2O (3). These polymers were obtained through the self-assembly of Q[5] with the corresponding transition metal salts in the presence of 1,5-naphthalenedisulfonic acid (1,5-H2NDS). Single- crystal X- ray diffraction analysis of these three coordination polymers has unveiled that the deprotonated 1,5-NDS²⁻ anions play a pivotal role in their self - assembly. Within these complexes, 1,5-NDS²⁻ anions facilitate the direct coordination of Ni2+/Co2+/Zn2+ with the carbonyl oxygen atoms at the ports of Q[5], leading to the formation of one - dimensional (1D) supramolecular chains. Moreover, the non - covalent interactions among the 1D chains, along with those arising from the interplay between 1,5 - NDS²⁻ anions and the outer surface of Q[5] within the chains, generate a cooperative effect. This cooperative effect, where the combined action of these interactions is more powerful than the simple sum of their individual contributions, drives the further assembly of the 1D chains into a three-dimensional (3D) supramolecular framework featuring specific channel structures. Performance tests reveal that the Q[5]-Ni2+-based supramolecular assembly has high selective recognition for the antibiotic norfloxacin (NFX).
{"title":"1,5-NDS2−-directed synthesis of transition metal based cucurbit[5]uril supramolecular material for efficient NFX antibiotic detection","authors":"Jia-Yu Gu , Xin-Ran Chen , Fei Li , Wen-Ya Ding , Jia Cao , Wei-Wei Ge , Kai Chen","doi":"10.1016/j.molstruc.2026.145517","DOIUrl":"10.1016/j.molstruc.2026.145517","url":null,"abstract":"<div><div>Three new coordination polymers based on cucurbit[5]uril (Q[5]) have been successfully synthesized. Their chemical formulas are {[Ni(H<sub>2</sub>O)<sub>2</sub>(Q[5])]·(1,5-NDS)}·14H<sub>2</sub>O (<strong>1</strong>), {[Co(H<sub>2</sub>O)<sub>2</sub>(Q[5])]·(1,5-NDS)}·15H<sub>2</sub>O (<strong>2</strong>), and {[Zn(H<sub>2</sub>O)<sub>2</sub>(Q[5])]·(1,5-NDS)}·10H<sub>2</sub>O (<strong>3</strong>). These polymers were obtained through the self-assembly of Q[5] with the corresponding transition metal salts in the presence of 1,5-naphthalenedisulfonic acid (1,5-H<sub>2</sub>NDS). Single- crystal X- ray diffraction analysis of these three coordination polymers has unveiled that the deprotonated 1,5-NDS²⁻ anions play a pivotal role in their self - assembly. Within these complexes, 1,5-NDS²⁻ anions facilitate the direct coordination of Ni<sup>2+</sup>/Co<sup>2+</sup>/Zn<sup>2+</sup> with the carbonyl oxygen atoms at the ports of Q[5], leading to the formation of one - dimensional (1D) supramolecular chains. Moreover, the non - covalent interactions among the 1D chains, along with those arising from the interplay between 1,5 - NDS²⁻ anions and the outer surface of Q[5] within the chains, generate a cooperative effect. This cooperative effect, where the combined action of these interactions is more powerful than the simple sum of their individual contributions, drives the further assembly of the 1D chains into a three-dimensional (3D) supramolecular framework featuring specific channel structures. Performance tests reveal that the Q[5]-Ni<sup>2+</sup>-based supramolecular assembly has high selective recognition for the antibiotic norfloxacin (NFX).</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145517"},"PeriodicalIF":4.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171177","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}
A new heterometallic metal‒organic framework, namely [Zn2Na(μ3O)(H₂ATPA)·DMF]n (Zn-Na-ATPA, H₅ATPA = 2′-acetamido-[1,1′:3′,1′'-terphenyl]-3,3′',5,5′,5′'-pentacarboxylic acid) was successfully constructed using a low-symmetry pentacarboxylic acid ligand incorporating an amide group. Single-crystal X-ray analysis reveals that Zn(II) and Na(I) ions are bridged by carboxylate groups and DMF solvent molecules to form a pentanuclear secondary building unit (SBU) consisting of four Zn(II) and two Na(I) ions. These SBUs are further connected by pentacarboxylic acid ligands to construct a three-dimensional framework. It exhibits a new highly connected (5,10)-c topology. The d¹⁰-configured Zn(II) center confers luminescent properties to the framework, enabling it to function as a versatile fluorescent sensor for detecting nitrobenzene (NB) and iodine. It detects NB in DMF via an inner filter effect with a detection limit of 3.7 mM, demonstrating good selectivity and reusability. More notably, it is capable of iodine sensing in both the aqueous and vapor phases, with a rapid response (quenching within 30 s) and high sensitivity (detection limit of 310 μM in solution). Mechanistic studies revealed that the quenching behavior is attributed to a synergistic combination of the inner filter effect and fluorescence resonance energy transfer (FRET). This work not only presents a unique topological MOF structure but also highlights its significant potential as a multifunctional sensory material for environmental monitoring.
{"title":"A new heterometallic Zn/Na-MOF featuring a (5,10)-connected topology: Structural elucidation and applications in fluorescent sensing","authors":"Hai-Dong Huang , Heng Zhang , Zi-Yuan Huang , An-Qi Chen , Ying Feng , Sheng-Run Zheng","doi":"10.1016/j.molstruc.2026.145510","DOIUrl":"10.1016/j.molstruc.2026.145510","url":null,"abstract":"<div><div>A new heterometallic metal‒organic framework, namely [Zn<sub>2</sub>Na(<em>μ</em><sub>3</sub><sub><img></sub>O)(H₂ATPA)·DMF]<sub>n</sub> (Zn-Na-ATPA, H₅ATPA = 2′-acetamido-[1,1′:3′,1′'-terphenyl]-3,3′',5,5′,5′'-pentacarboxylic acid) was successfully constructed using a low-symmetry pentacarboxylic acid ligand incorporating an amide group. Single-crystal X-ray analysis reveals that Zn(II) and Na(I) ions are bridged by carboxylate groups and DMF solvent molecules to form a pentanuclear secondary building unit (SBU) consisting of four Zn(II) and two Na(I) ions. These SBUs are further connected by pentacarboxylic acid ligands to construct a three-dimensional framework. It exhibits a new highly connected (5,10)-c topology. The d¹⁰-configured Zn(II) center confers luminescent properties to the framework, enabling it to function as a versatile fluorescent sensor for detecting nitrobenzene (NB) and iodine. It detects NB in DMF via an inner filter effect with a detection limit of 3.7 mM, demonstrating good selectivity and reusability. More notably, it is capable of iodine sensing in both the aqueous and vapor phases, with a rapid response (quenching within 30 s) and high sensitivity (detection limit of 310 μM in solution). Mechanistic studies revealed that the quenching behavior is attributed to a synergistic combination of the inner filter effect and fluorescence resonance energy transfer (FRET). This work not only presents a unique topological MOF structure but also highlights its significant potential as a multifunctional sensory material for environmental monitoring.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145510"},"PeriodicalIF":4.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171084","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 : 2026-01-29DOI: 10.1016/j.molstruc.2026.145513
Tenzile Alagoz , Sunay Yilmaz , Eda Mehtap Ozden , Mehmet Abdullah Alagoz , Mustafa Zengin , Hayriye Genc Bilgicli , Ilhami Gulcin
Novel thiosemicarbazide (3a-d), 1,2,4-triazole (4a-d), and 1,3,4-thiadiazole (5a-d) derivatives were obtained in high total yields of 57–66%, 40–51%, and 40–53%, respectively, and they were evaluated for inhibitor activity against acetylcholinesterase, and human carbonic anhydrase isoforms I and II (hCAs I and II). They were demonstrated to have effective inhibition profiles with Ki values of 20.08±4.80–152.41±66.19 nM against hCA I, 64.57±20.74–356.58±176.92 nM against hCA II and 4.55±1.24–61.30±28.60 nM against AChE. On the other hand, acetazolamide showed Ki value of 30.69±9.31 nM against hCA I, and 40.08±6.38 nM against hCA II isoform. Additionally, Tacrine inhibited AChE and demonstrated Ki values of 3.51±1.56 nM. The affinities of the compounds towards hCA I, hCA II and AChE were evaluated by in silico studies. In molecular docking studies, 3c (-7.453 kcal/mol), 3d (-7.380), 5b (-7.372 kcal/mol) showed high affinity towards AChE. In MD simulation studies with the most active compound 3c, it was observed that the compound remained stable in the active site of AChE for 150 ns (Average RMSD < 3.0 Å). The ADMET properties of the synthesized compounds were evaluated in silico. All compounds exhibited pharmacological properties and did not display adverse toxic effects. The inhibition of CA and AChE is a powerful pharmacological tool with diverse clinical applications. By targeting different CA and AChE, inhibitors can treat eye diseases, neurological disorders, metabolic conditions, Alzheimer’s disease and even cancer, highlighting their broad therapeutic potential. MD simulations of the most active compound, 3c, confirmed its stability in the AChE active site for 150 ns (average RMSD < 3.0 Å). Furthermore, in silico ADMET analysis showed that all compounds had favorable pharmacokinetic profiles without significant toxic effects. These results demonstrate that novel 1,3,4-thiadiazole derivatives have considerable potential as selective and potent multitarget enzyme inhibitors and are promising candidates for further pharmaceutical development.
{"title":"2-Methyl-4-nitrophenoxy based thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole compounds as multitarget enzyme inhibitors: Synthesis, biological and computational studies","authors":"Tenzile Alagoz , Sunay Yilmaz , Eda Mehtap Ozden , Mehmet Abdullah Alagoz , Mustafa Zengin , Hayriye Genc Bilgicli , Ilhami Gulcin","doi":"10.1016/j.molstruc.2026.145513","DOIUrl":"10.1016/j.molstruc.2026.145513","url":null,"abstract":"<div><div>Novel thiosemicarbazide (<strong>3a-d</strong>), 1,2,4-triazole (<strong>4a-d</strong>), and 1,3,4-thiadiazole (<strong>5a-d</strong>) derivatives were obtained in high total yields of 57–66%, 40–51%, and 40–53%, respectively, and they were evaluated for inhibitor activity against acetylcholinesterase, and human carbonic anhydrase isoforms I and II (hCAs I and II). They were demonstrated to have effective inhibition profiles with K<sub>i</sub> values of 20.08±4.80–152.41±66.19 nM against hCA I, 64.57±20.74–356.58±176.92 nM against hCA II and 4.55±1.24–61.30±28.60 nM against AChE. On the other hand, acetazolamide showed K<sub>i</sub> value of 30.69±9.31 nM against hCA I, and 40.08±6.38 nM against hCA II isoform. Additionally, Tacrine inhibited AChE and demonstrated K<sub>i</sub> values of 3.51±1.56 nM. The affinities of the compounds towards hCA I, hCA II and AChE were evaluated by in silico studies. In molecular docking studies, <strong>3c</strong> (-7.453 kcal/mol), 3d (-7.380), <strong>5b</strong> (-7.372 kcal/mol) showed high affinity towards AChE. In MD simulation studies with the most active compound 3c, it was observed that the compound remained stable in the active site of AChE for 150 ns (Average RMSD < 3.0 Å). The ADMET properties of the synthesized compounds were evaluated in silico. All compounds exhibited pharmacological properties and did not display adverse toxic effects. The inhibition of CA and AChE is a powerful pharmacological tool with diverse clinical applications. By targeting different CA and AChE, inhibitors can treat eye diseases, neurological disorders, metabolic conditions, Alzheimer’s disease and even cancer, highlighting their broad therapeutic potential. MD simulations of the most active compound, 3c, confirmed its stability in the AChE active site for 150 ns (average RMSD < 3.0 Å). Furthermore, in silico ADMET analysis showed that all compounds had favorable pharmacokinetic profiles without significant toxic effects. These results demonstrate that novel 1,3,4-thiadiazole derivatives have considerable potential as selective and potent multitarget enzyme inhibitors and are promising candidates for further pharmaceutical development.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145513"},"PeriodicalIF":4.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171146","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 : 2026-01-28DOI: 10.1016/j.molstruc.2026.145506
Meiling Nie , Ting Jiao , Lin Wang , Chiyi Wang , Jiahan Jin , Jialu Hu , Yang Li , Hailu Zhang
The study of pharmaceutical cocrystal polymorphism is attracting increasing interest, as variations in intermolecular interactions and packing arrangements between an active pharmaceutical ingredient (API) and the same cocrystal former (CCF) directly impact the extent to which cocrystals can tailor the API’s properties. However, the number of reported cases of cocrystal polymorphism remains relatively limited. Herein, we propose that orientational variability of hydrogen bond donors or acceptors on either the API or the CCF may drive the formation of cocrystal polymorphs. To substantiate this hypothesis, 5-fluorocytosine (5-FC) and L-malic acid (L-MAL) were selected as the model cocrystallization system, and two distinct 2:1 polymorphs (form Ⅰ and form Ⅱ) were ultimately identified. Crystal structural analysis revealed that the two cocrystals share consistent supramolecular interactions; however, the divergent orientations of carbonyl and hydroxyl groups in L-MAL induce distinguishable hydrogen bonding configurations and molecular stacking patterns, which strongly validates the proposed origin of cocrystal polymorphism. Lattice energy calculations, polymorphic transformation studies, and melting point data collectively confirmed that these two polymorphs exhibit a monotropic thermodynamic relationship, with the high-Z’ form Ⅱ (Z’ = 2) being the thermodynamically stable crystalline phase. Under higher relative humidity condition (90 % RH), an obvious phase transformation of form Ⅰ was observed within one week, whereas form Ⅱ maintains its phase stability for at least four weeks. Such performance difference between these two cocrystals further underscores the practical significance of cocrystal polymorph screening.
{"title":"Functional group orientation-dependent conformational polymorphism in 5-fluorocytosine–L-malic acid cocrystals","authors":"Meiling Nie , Ting Jiao , Lin Wang , Chiyi Wang , Jiahan Jin , Jialu Hu , Yang Li , Hailu Zhang","doi":"10.1016/j.molstruc.2026.145506","DOIUrl":"10.1016/j.molstruc.2026.145506","url":null,"abstract":"<div><div>The study of pharmaceutical cocrystal polymorphism is attracting increasing interest, as variations in intermolecular interactions and packing arrangements between an active pharmaceutical ingredient (API) and the same cocrystal former (CCF) directly impact the extent to which cocrystals can tailor the API’s properties. However, the number of reported cases of cocrystal polymorphism remains relatively limited. Herein, we propose that orientational variability of hydrogen bond donors or acceptors on either the API or the CCF may drive the formation of cocrystal polymorphs. To substantiate this hypothesis, 5-fluorocytosine (5-FC) and <em>L</em>-malic acid (<em>L</em>-MAL) were selected as the model cocrystallization system, and two distinct 2:1 polymorphs (form Ⅰ and form Ⅱ) were ultimately identified. Crystal structural analysis revealed that the two cocrystals share consistent supramolecular interactions; however, the divergent orientations of carbonyl and hydroxyl groups in <em>L</em>-MAL induce distinguishable hydrogen bonding configurations and molecular stacking patterns, which strongly validates the proposed origin of cocrystal polymorphism. Lattice energy calculations, polymorphic transformation studies, and melting point data collectively confirmed that these two polymorphs exhibit a monotropic thermodynamic relationship, with the high-<em>Z</em>’ form Ⅱ (<em>Z</em>’ = 2) being the thermodynamically stable crystalline phase. Under higher relative humidity condition (90 % RH), an obvious phase transformation of form Ⅰ was observed within one week, whereas form Ⅱ maintains its phase stability for at least four weeks. Such performance difference between these two cocrystals further underscores the practical significance of cocrystal polymorph screening.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145506"},"PeriodicalIF":4.7,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171132","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 : 2026-01-28DOI: 10.1016/j.molstruc.2026.145508
Heng Guo , Hongjie Shen , Yining Xu , Lan Liu , Zhenger Wu , Senhua Chen
Two new copaene-type norsesquiterpenes, diapoterpenes A (1) and B (2), along with one new biogenetically related cadinane-type sesquiterpenoid, diapoterpene C (3), were isolated from ascidian-derived fungus Diaporthe sp. SYSU-MS4722 collected from the South China Sea. Compounds 1 and 2 represented the first example of copaene-derived norsesquiterpenes, characterized by unique tricyclo[4.4.0.02,7]decane1,2–3-one skeleton. Their structures were elucidated by a combination of spectroscopic analyses (1D/2D NMR, HR-ESIMS, NMR, or ECD calculation) and X-ray crystallography. The unique structure resulted in severe proton signal overlap in the NMR spectra of 1, which significantly complicated the determination of its planar structure and absolute configuration. By applying the modified Mosher’s method, the overlapping proton signals were successfully resolved, enabling the unambiguous assignment of the absolute configuration for 1. Additionally, anti-inflammatory and anti-glioma activities of 1−3 were evaluated, with diapoterpene C (3) showing moderate inhibition of nitric oxide production in LPS-stimulated RAW264.7 cells. Overall, this research not only identifies norsesquiterpenes with novel structure from ascidian-derived fungus but also provides an effective strategy for the structural characterization of complex natural products facing challenges related to proton signal overlap in NMR analysis.
{"title":"Discovery and characterization of two rare copaene-type norsesquiterpenes: Diapoterpenes A and B","authors":"Heng Guo , Hongjie Shen , Yining Xu , Lan Liu , Zhenger Wu , Senhua Chen","doi":"10.1016/j.molstruc.2026.145508","DOIUrl":"10.1016/j.molstruc.2026.145508","url":null,"abstract":"<div><div>Two new copaene-type norsesquiterpenes, diapoterpenes A (<strong>1</strong>) and B (<strong>2</strong>), along with one new biogenetically related cadinane-type sesquiterpenoid, diapoterpene C (<strong>3</strong>), were isolated from ascidian-derived fungus <em>Diaporthe</em> sp. SYSU-MS4722 collected from the South China Sea. Compounds <strong>1</strong> and <strong>2</strong> represented the first example of copaene-derived norsesquiterpenes, characterized by unique tricyclo[4.4.0.0<sup>2</sup><sup>,</sup><sup>7</sup>]decane<sup>1</sup><sup>,</sup><sup>2</sup>–3-one skeleton. Their structures were elucidated by a combination of spectroscopic analyses (1D/2D NMR, HR-ESIMS, NMR, or ECD calculation) and X-ray crystallography. The unique structure resulted in severe proton signal overlap in the NMR spectra of <strong>1</strong>, which significantly complicated the determination of its planar structure and absolute configuration. By applying the modified Mosher’s method, the overlapping proton signals were successfully resolved, enabling the unambiguous assignment of the absolute configuration for <strong>1</strong>. Additionally, anti-inflammatory and anti-glioma activities of <strong>1</strong>−<strong>3</strong> were evaluated, with diapoterpene C (<strong>3</strong>) showing moderate inhibition of nitric oxide production in LPS-stimulated RAW264.7 cells. Overall, this research not only identifies norsesquiterpenes with novel structure from ascidian-derived fungus but also provides an effective strategy for the structural characterization of complex natural products facing challenges related to proton signal overlap in NMR analysis.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145508"},"PeriodicalIF":4.7,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171131","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 : 2026-01-28DOI: 10.1016/j.molstruc.2026.145512
Doaa Domyati , Ranya A. Al-Zahrani , Ehab M.M. Ali , Bambar Davaasuren , Mariusz Jaremko , Mohamed M. El-bendary
The room-temperature self-assembly of Me₃SnCl and 2,2′-dipyridyl ketone (dpk) with K₃[Cu(CN)₄] resulted in a new organotin–copper bimetallic supramolecular coordination polymer, denoted as [Me₃SnCu(CN)₂·dpk], (SCP 1). SCP 1 crystallized as yellow prismatic crystals from an aqueous acetonitrile solution. SCP 1 was comprehensively characterized using elemental analysis, IR spectroscopy, electronic absorption measurements, and 1H/13C NMR spectroscopy. The structure of SCP 1 was unambiguously confirmed by single-crystal X-ray diffraction. SCP 1 consists of infinite 1D zigzag chains formed by [Me₃Sn]⁺ cations linking the anionic [Cu(CN)₂]⁻ units, with dpk ligands bridging between chains. Adjacent chains are further connected through π–π stacking between the pyridine rings of dpk, generating a 2D layered arrangement. Hydrogen bonding between cyanide groups and dpk lignads in neighboring layers further reinforces the assembly, ultimately giving rise to a three-dimensional (3D) honeycomb-like framework. The photoluminescence characteristics of SCP 1 were analyzed and compared with those of the uncoordinated dpk ligand. The newly synthesized bimetallic organotin–copper cyanide SCP 1 was evaluated for its anticancer activity against several cancer cell lines, including liver (HepG2), colon (HCT116), and triple-negative breast cancer (MDA-MB-231). SCP 1 exhibited marked selectivity and potent cytotoxicity, with particularly low IC₅₀ values toward MDA-MB-231 cells (selectivity index, SI = 5.57). Its therapeutic promise is further supported by evidence of necrosis and late-stage apoptosis, along with S-phase and sub-G1 cell-cycle arrest observed in HCT116 colon cancer cells.
{"title":"Design, crystal structure and anticancer activities of a novel bimetallic organotin and copper(I) cyanide with dipyridyl ketone supramolecular coordination polymer","authors":"Doaa Domyati , Ranya A. Al-Zahrani , Ehab M.M. Ali , Bambar Davaasuren , Mariusz Jaremko , Mohamed M. El-bendary","doi":"10.1016/j.molstruc.2026.145512","DOIUrl":"10.1016/j.molstruc.2026.145512","url":null,"abstract":"<div><div>The room-temperature self-assembly of Me₃SnCl and 2,2′-dipyridyl ketone (dpk) with K₃[Cu(CN)₄] resulted in a new organotin–copper bimetallic supramolecular coordination polymer, denoted as <strong>[Me₃SnCu(CN)₂·dpk], (SCP 1). SCP 1</strong> crystallized as yellow prismatic crystals from an aqueous acetonitrile solution. <strong>SCP 1</strong> was comprehensively characterized using elemental analysis, IR spectroscopy, electronic absorption measurements, and <sup>1</sup>H/<sup>13</sup>C NMR spectroscopy. The structure of <strong>SCP 1</strong> was unambiguously confirmed by single-crystal X-ray diffraction. <strong>SCP 1</strong> consists of infinite 1D zigzag chains formed by [Me₃Sn]⁺ cations linking the anionic [Cu(CN)₂]⁻ units, with dpk ligands bridging between chains. Adjacent chains are further connected through π–π stacking between the pyridine rings of dpk, generating a 2D layered arrangement. Hydrogen bonding between cyanide groups and dpk lignads in neighboring layers further reinforces the assembly, ultimately giving rise to a three-dimensional (3D) honeycomb-like framework. The photoluminescence characteristics of <strong>SCP 1</strong> were analyzed and compared with those of the uncoordinated dpk ligand. The newly synthesized bimetallic organotin–copper cyanide <strong>SCP 1</strong> was evaluated for its anticancer activity against several cancer cell lines, including liver (HepG2), colon (HCT116), and triple-negative breast cancer (MDA-MB-231). <strong>SCP 1</strong> exhibited marked selectivity and potent cytotoxicity, with particularly low IC₅₀ values toward MDA-MB-231 cells (selectivity index, SI = 5.57). Its therapeutic promise is further supported by evidence of necrosis and late-stage apoptosis, along with S-phase and sub-G1 cell-cycle arrest observed in HCT116 colon cancer cells.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145512"},"PeriodicalIF":4.7,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171175","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}
A novel resorcynyl-1,3,4-thiadiazole-based Zn(II) complex NTBD-Zn was synthesized and characterized via both experimental and computational studies. The research involved detailed absorption and emission properties measurements and simulations, combined with geometric and electronic structure analyses considering different coordination modes of the metal to the ligand. These studies were further complemented by an assessment of the complex’s potential microbiological activity. The additional UV-Vis absorption intensity centered at ca. 370 nm along with the corresponding emission signal at ca. 460 nm observed for NTBD-Zn vs. NTBD attests to a successful complexation of Zn(II) to the resorcynyl-thiadiazole ligand, which, as confirmed by the calculations, occurs preferentially through one of the nitrogen atoms in the thiadiazole ring and the deprotonated ortho-hydroxyl group in the resorcynyl fragment, with the planar arrangement of the resorcynyl-thiadiazole and an only slightly more favored tetrahedral/pyramidal Zn(II) coordination sphere, preference for which increases upon inclusion of a water molecule in NTBD-Zn. The absorption and emission wavelengths computed for such model solution-phase structures agree with the experimental data in a reasonably satisfactory manner, although an overall blue-shift was observed, and the excitations analysis showed a resorcynyl-thiadiazole-ligand-centered π–π* origin of the dominant electronic transitions with no involvement of the metal orbitals. The experimentally observed appearance of the low-energy absorption intensity and the red-shift of the emission signal for the complex compared to the ligand correlates well with a decrease in the HOMO/LUMO gap occurring upon the complexation. Finally, compared to NTBD, NTBD-Zn demonstrates enhanced biological activity against Gram-positive bacteria, including staphylococci, micrococci, and bacilli, while showing no effect against Gram-negative strains.
{"title":"Structural, spectroscopic and microbiological characterization of a Zn(II) complex based on a 1,3,4-thiadiazole derivative – experimental and computational studies","authors":"Joachim Grzybowski , Iwona Budziak-Wieczorek , Klaudia Rząd , Izabela Korona-Glowniak , Małgorzata Figiel , Dariusz Karcz , Monika Srebro-Hooper , Arkadiusz Matwijczuk","doi":"10.1016/j.molstruc.2026.145498","DOIUrl":"10.1016/j.molstruc.2026.145498","url":null,"abstract":"<div><div>A novel resorcynyl-1,3,4-thiadiazole-based Zn(II) complex NTBD-Zn was synthesized and characterized via both experimental and computational studies. The research involved detailed absorption and emission properties measurements and simulations, combined with geometric and electronic structure analyses considering different coordination modes of the metal to the ligand. These studies were further complemented by an assessment of the complex’s potential microbiological activity. The additional UV-Vis absorption intensity centered at ca. 370 nm along with the corresponding emission signal at ca. 460 nm observed for NTBD-Zn vs. NTBD attests to a successful complexation of Zn(II) to the resorcynyl-thiadiazole ligand, which, as confirmed by the calculations, occurs preferentially through one of the nitrogen atoms in the thiadiazole ring and the deprotonated <em>ortho</em>-hydroxyl group in the resorcynyl fragment, with the planar arrangement of the resorcynyl-thiadiazole and an only slightly more favored tetrahedral/pyramidal Zn(II) coordination sphere, preference for which increases upon inclusion of a water molecule in NTBD-Zn. The absorption and emission wavelengths computed for such model solution-phase structures agree with the experimental data in a reasonably satisfactory manner, although an overall blue-shift was observed, and the excitations analysis showed a resorcynyl-thiadiazole-ligand-centered π–π* origin of the dominant electronic transitions with no involvement of the metal orbitals. The experimentally observed appearance of the low-energy absorption intensity and the red-shift of the emission signal for the complex compared to the ligand correlates well with a decrease in the HOMO/LUMO gap occurring upon the complexation. Finally, compared to NTBD, NTBD-Zn demonstrates enhanced biological activity against Gram-positive bacteria, including staphylococci, micrococci, and bacilli, while showing no effect against Gram-negative strains.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145498"},"PeriodicalIF":4.7,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171126","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}
Malic acid, a prominent organic acid in Rhus coriaria (sumac), a plant widely distributed in Türkiye and traditionally consumed as a food additive, serves as a key raw material across various industries. This study explores the structural features of a calcium complex derived from malic acid extracted from sumac leaves and evaluates its potential to mitigate oxidative damage caused by hydrogen peroxide (H₂O₂) in retinal pigment epithelial (RPE) cells. Characterization techniques include Spectroscopy, Nuclear Magnetic Resonance, Thermal Analysis, and Mass Spectrometry. Additional assessments covered electrochemical behavior, photoluminescence, and thermal stability. Furthermore, the complex's impact on AMD (Age-Related Macular Degeneration) was investigated using ARPE-19 cell lines, with results analyzed statistically. Our findings reveal that the naturally sourced calcium malic acid complex not only exhibits a well-defined structure but also confers protective effects against H₂O₂-mediated oxidative stress in RPE cells, suggesting its potential as a therapeutic agent for retinal disorders.
{"title":"Characterization of calcium malic acid complex synthesized from Rhus coriaria and its protective effects on retinal pigment epithelial cells","authors":"Bilge Alli , Gökhan Ceyhan , Akif Hakan Kurt , Âdem Doğaner","doi":"10.1016/j.molstruc.2026.145486","DOIUrl":"10.1016/j.molstruc.2026.145486","url":null,"abstract":"<div><div>Malic acid, a prominent organic acid in <em>Rhus coriaria</em> (sumac), a plant widely distributed in Türkiye and traditionally consumed as a food additive, serves as a key raw material across various industries. This study explores the structural features of a calcium complex derived from malic acid extracted from sumac leaves and evaluates its potential to mitigate oxidative damage caused by hydrogen peroxide (H₂O₂) in retinal pigment epithelial (RPE) cells. Characterization techniques include Spectroscopy, Nuclear Magnetic Resonance, Thermal Analysis, and Mass Spectrometry. Additional assessments covered electrochemical behavior, photoluminescence, and thermal stability. Furthermore, the complex's impact on AMD (Age-Related Macular Degeneration) was investigated using ARPE-19 cell lines, with results analyzed statistically. Our findings reveal that the naturally sourced calcium malic acid complex not only exhibits a well-defined structure but also confers protective effects against H₂O₂-mediated oxidative stress in RPE cells, suggesting its potential as a therapeutic agent for retinal disorders.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1359 ","pages":"Article 145486"},"PeriodicalIF":4.7,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171083","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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