Courtney E. Elwell , Emily Stein , Adam Lewis , Stefan Hamaway , Kennedy A. Alexis , Joseph M. Tanski , Timothy J. Barnum , Colleen M. Connelly , Laurie A. Tyler
{"title":"一组含有唑基配体框架的新型 Cu(II) 复合物的合成、表征和生物活性比较","authors":"Courtney E. Elwell , Emily Stein , Adam Lewis , Stefan Hamaway , Kennedy A. Alexis , Joseph M. Tanski , Timothy J. Barnum , Colleen M. Connelly , Laurie A. Tyler","doi":"10.1016/j.jinorgbio.2024.112736","DOIUrl":null,"url":null,"abstract":"<div><div>The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(<em>OMe</em>)BTh) or a methyl group (Py(<em>Me</em>)BTh). Reaction of Py(<em>OMe</em>)BTh with either CuCl<sub>2</sub> or Cu(NO<sub>3</sub>)<sub>2</sub>·2.5 H<sub>2</sub>O yielded the monomeric [Cu(Py(<em>OMe</em>)BTh))<sub>2</sub>(NO<sub>3</sub>)]NO<sub>3</sub>·1.5 MeOH, (<strong>1</strong>·1.5 MeOH) complex or the dimeric [Cu(Py(<em>OMe</em>)BTh)Cl<sub>2</sub>]<sub>2</sub> (<strong>2</strong>), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO<sub>3</sub>)<sub>2</sub>·2.5 H<sub>2</sub>O resulted in the isolation of Cu(Py(<em>Me</em>)BTh)(NO<sub>3</sub>)<sub>2</sub>·0.5 THF (<strong>3</strong>·0.5 THF). Complexes <strong>1</strong>–<strong>3</strong> were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)<sub>2</sub>(H<sub>2</sub>O)](BF<sub>4</sub>)<sub>2</sub> (<strong>4</strong>), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however <strong>2</strong> and <strong>4</strong> were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O<sub>2</sub><sup>−</sup>. Antibacterial studies revealed complex <strong>4</strong> was more potent compared to <strong>1</strong>–<strong>3</strong>. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with <strong>1</strong>–<strong>4</strong>, Cu(QBTh)(NO<sub>3</sub>)<sub>2</sub>(H<sub>2</sub>O) and Cu(PyBIm)<sub>3</sub>(BF<sub>4</sub>)<sub>2</sub>. The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, characterization and comparative biological activity of a novel set of Cu(II) complexes containing azole-based ligand frames\",\"authors\":\"Courtney E. Elwell , Emily Stein , Adam Lewis , Stefan Hamaway , Kennedy A. Alexis , Joseph M. Tanski , Timothy J. Barnum , Colleen M. Connelly , Laurie A. Tyler\",\"doi\":\"10.1016/j.jinorgbio.2024.112736\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(<em>OMe</em>)BTh) or a methyl group (Py(<em>Me</em>)BTh). Reaction of Py(<em>OMe</em>)BTh with either CuCl<sub>2</sub> or Cu(NO<sub>3</sub>)<sub>2</sub>·2.5 H<sub>2</sub>O yielded the monomeric [Cu(Py(<em>OMe</em>)BTh))<sub>2</sub>(NO<sub>3</sub>)]NO<sub>3</sub>·1.5 MeOH, (<strong>1</strong>·1.5 MeOH) complex or the dimeric [Cu(Py(<em>OMe</em>)BTh)Cl<sub>2</sub>]<sub>2</sub> (<strong>2</strong>), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO<sub>3</sub>)<sub>2</sub>·2.5 H<sub>2</sub>O resulted in the isolation of Cu(Py(<em>Me</em>)BTh)(NO<sub>3</sub>)<sub>2</sub>·0.5 THF (<strong>3</strong>·0.5 THF). Complexes <strong>1</strong>–<strong>3</strong> were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)<sub>2</sub>(H<sub>2</sub>O)](BF<sub>4</sub>)<sub>2</sub> (<strong>4</strong>), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however <strong>2</strong> and <strong>4</strong> were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O<sub>2</sub><sup>−</sup>. Antibacterial studies revealed complex <strong>4</strong> was more potent compared to <strong>1</strong>–<strong>3</strong>. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with <strong>1</strong>–<strong>4</strong>, Cu(QBTh)(NO<sub>3</sub>)<sub>2</sub>(H<sub>2</sub>O) and Cu(PyBIm)<sub>3</sub>(BF<sub>4</sub>)<sub>2</sub>. The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.</div></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013424002605\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013424002605","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Synthesis, characterization and comparative biological activity of a novel set of Cu(II) complexes containing azole-based ligand frames
The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(OMe)BTh) or a methyl group (Py(Me)BTh). Reaction of Py(OMe)BTh with either CuCl2 or Cu(NO3)2·2.5 H2O yielded the monomeric [Cu(Py(OMe)BTh))2(NO3)]NO3·1.5 MeOH, (1·1.5 MeOH) complex or the dimeric [Cu(Py(OMe)BTh)Cl2]2 (2), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO3)2·2.5 H2O resulted in the isolation of Cu(Py(Me)BTh)(NO3)2·0.5 THF (3·0.5 THF). Complexes 1–3 were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)2(H2O)](BF4)2 (4), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however 2 and 4 were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O2−. Antibacterial studies revealed complex 4 was more potent compared to 1–3. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with 1–4, Cu(QBTh)(NO3)2(H2O) and Cu(PyBIm)3(BF4)2. The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.
期刊介绍：
The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.
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