{"title":"基于三叉配体的 Cu(II) 复合物与各种胺辅助配体的合成、晶体结构、DNA/蛋白质相互作用和细胞毒性研究","authors":"","doi":"10.1016/j.molstruc.2024.139954","DOIUrl":null,"url":null,"abstract":"<div><p>The present study utilizes a tridentate ligand H<sub>2</sub>L (<strong>1</strong>) derived as a condensation product of dehydroacetic acid and 2-furoic acid hydrazide for the synthesis of a series of copper complexes, namely [Cu(L)(bipy)] (<strong>3</strong>), [Cu(L)(4,4′-Me<sub>2</sub>-bipy)] (<strong>4</strong>), [Cu(L)(6,6′-Me<sub>2</sub>-bipy)] (<strong>5</strong>), [Cu(L)(phen)] (<strong>6</strong>), [Cu(L)(2,9-Me<sub>2</sub>-phen)] (<strong>7</strong>) [Cu(L)(pyrazino[2,3]phen)] (<strong>8</strong>) [Cu(L)(2,2′-dipyridylamine)] (<strong>9</strong>) [Cu(L)(diphenylmethanamine)] (<strong>10</strong>), obtained by reacting Cu(acetate)<sub>2</sub> with the doubly deprotonated ligand and a range of co-ligand amines. All the synthesized compounds were fully structurally characterized using IR, <sup>1</sup>H NMR, HRMS and single-crystal X-ray diffraction studies. The thermal stability and decomposition pattern was investigated using TGA studies. The bio-efficacy of the developed ligand and its complexes was evaluated in anti-cancer assay against SKOV3 cell lines. Copper complexes have been extensively studied for their potential to generate anticancer properties. Most complexes comprise mixed ligands, such as N-N-chelating heterocycles like 2,2’-bipyridine (bpy) and 1,10 phenanthroline (phen), chosen for their chelating and intercalative characteristics. Complex <strong>7</strong> displayed the highest anti-cancer activity with an <em>IC<sub>50</sub></em> value of 0.8 µM compared to standard drug doxorubicin. The impact of complex <strong>7</strong> on DNA fragmentation was also assessed through agarose gel electrophoresis, which indicated that complex <strong>7</strong> promotes observable DNA fragmentation. The serum binding affinity of the complex <strong>7</strong> was also investigated against BSA and HSA protein. The strong binding affinity of complex [Cu(L)(2,9-Me2-phen)] <strong>(7)</strong> with BSA/HSA and its better stability compared to the other investigated complexes were deduced based on its biological activity. The impact of varying concentrations of complex <strong>7</strong> on BSA and HSA was investigated using absorption spectroscopy, revealing the presence of a dynamic quenching mechanism. In silico molecular dynamics and docking, approaches have been utilized to validate the empirical data derived from serum binding studies.</p></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, crystal structure, DNA/protein interactions and cytotoxicity studies of tridentate ligand based Cu(II) complexes with various amine co-ligands\",\"authors\":\"\",\"doi\":\"10.1016/j.molstruc.2024.139954\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The present study utilizes a tridentate ligand H<sub>2</sub>L (<strong>1</strong>) derived as a condensation product of dehydroacetic acid and 2-furoic acid hydrazide for the synthesis of a series of copper complexes, namely [Cu(L)(bipy)] (<strong>3</strong>), [Cu(L)(4,4′-Me<sub>2</sub>-bipy)] (<strong>4</strong>), [Cu(L)(6,6′-Me<sub>2</sub>-bipy)] (<strong>5</strong>), [Cu(L)(phen)] (<strong>6</strong>), [Cu(L)(2,9-Me<sub>2</sub>-phen)] (<strong>7</strong>) [Cu(L)(pyrazino[2,3]phen)] (<strong>8</strong>) [Cu(L)(2,2′-dipyridylamine)] (<strong>9</strong>) [Cu(L)(diphenylmethanamine)] (<strong>10</strong>), obtained by reacting Cu(acetate)<sub>2</sub> with the doubly deprotonated ligand and a range of co-ligand amines. All the synthesized compounds were fully structurally characterized using IR, <sup>1</sup>H NMR, HRMS and single-crystal X-ray diffraction studies. The thermal stability and decomposition pattern was investigated using TGA studies. The bio-efficacy of the developed ligand and its complexes was evaluated in anti-cancer assay against SKOV3 cell lines. Copper complexes have been extensively studied for their potential to generate anticancer properties. Most complexes comprise mixed ligands, such as N-N-chelating heterocycles like 2,2’-bipyridine (bpy) and 1,10 phenanthroline (phen), chosen for their chelating and intercalative characteristics. Complex <strong>7</strong> displayed the highest anti-cancer activity with an <em>IC<sub>50</sub></em> value of 0.8 µM compared to standard drug doxorubicin. The impact of complex <strong>7</strong> on DNA fragmentation was also assessed through agarose gel electrophoresis, which indicated that complex <strong>7</strong> promotes observable DNA fragmentation. The serum binding affinity of the complex <strong>7</strong> was also investigated against BSA and HSA protein. The strong binding affinity of complex [Cu(L)(2,9-Me2-phen)] <strong>(7)</strong> with BSA/HSA and its better stability compared to the other investigated complexes were deduced based on its biological activity. The impact of varying concentrations of complex <strong>7</strong> on BSA and HSA was investigated using absorption spectroscopy, revealing the presence of a dynamic quenching mechanism. In silico molecular dynamics and docking, approaches have been utilized to validate the empirical data derived from serum binding studies.</p></div>\",\"PeriodicalId\":16414,\"journal\":{\"name\":\"Journal of Molecular Structure\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Structure\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022286024024633\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Structure","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022286024024633","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Synthesis, crystal structure, DNA/protein interactions and cytotoxicity studies of tridentate ligand based Cu(II) complexes with various amine co-ligands
The present study utilizes a tridentate ligand H2L (1) derived as a condensation product of dehydroacetic acid and 2-furoic acid hydrazide for the synthesis of a series of copper complexes, namely [Cu(L)(bipy)] (3), [Cu(L)(4,4′-Me2-bipy)] (4), [Cu(L)(6,6′-Me2-bipy)] (5), [Cu(L)(phen)] (6), [Cu(L)(2,9-Me2-phen)] (7) [Cu(L)(pyrazino[2,3]phen)] (8) [Cu(L)(2,2′-dipyridylamine)] (9) [Cu(L)(diphenylmethanamine)] (10), obtained by reacting Cu(acetate)2 with the doubly deprotonated ligand and a range of co-ligand amines. All the synthesized compounds were fully structurally characterized using IR, 1H NMR, HRMS and single-crystal X-ray diffraction studies. The thermal stability and decomposition pattern was investigated using TGA studies. The bio-efficacy of the developed ligand and its complexes was evaluated in anti-cancer assay against SKOV3 cell lines. Copper complexes have been extensively studied for their potential to generate anticancer properties. Most complexes comprise mixed ligands, such as N-N-chelating heterocycles like 2,2’-bipyridine (bpy) and 1,10 phenanthroline (phen), chosen for their chelating and intercalative characteristics. Complex 7 displayed the highest anti-cancer activity with an IC50 value of 0.8 µM compared to standard drug doxorubicin. The impact of complex 7 on DNA fragmentation was also assessed through agarose gel electrophoresis, which indicated that complex 7 promotes observable DNA fragmentation. The serum binding affinity of the complex 7 was also investigated against BSA and HSA protein. The strong binding affinity of complex [Cu(L)(2,9-Me2-phen)] (7) with BSA/HSA and its better stability compared to the other investigated complexes were deduced based on its biological activity. The impact of varying concentrations of complex 7 on BSA and HSA was investigated using absorption spectroscopy, revealing the presence of a dynamic quenching mechanism. In silico molecular dynamics and docking, approaches have been utilized to validate the empirical data derived from serum binding studies.
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