Pub Date : 2024-10-12DOI: 10.1016/j.jinorgbio.2024.112760
Tao Shao , Zhihui Feng , Yu Shen , Dandan Chen , Pan Xiang , Qiong Zhang , Shao Ma , Yupeng Tian , Xiaohe Tian
Cyclometalated iridium(III) complexes have emerged as versatile candidates for cancer theranostics, offering integrated diagnostic imaging and potent singlet oxygen (1O2) generation for photodynamic therapy (PDT). However, their application has been limited by subdued photoluminescence, primarily due to intramolecular motion-induced excited energy dissipation. In this study, we address these limitations through the design and synthesis of five novel iridium(III) complexes: IrC2, IrC4, IrC6, IrC8, and IrC12. Our approach employs meticulous side-chain extending strategy to modulate side-chain length, thereby reducing intramolecular motion and significantly enhancing both one- and three-photon emissions and 1O2 production in the aggregated state. Detailed photophysical investigations, supported by crystallographic insights, reveal that side-chain elongation substantially amplifies these properties. Among the synthesized complexes, IrC8 stands out as a superior candidate for image-guided photodynamic therapy in cellular and 3D tumor spheroid models. This investigation pioneers the simultaneous enhancement of dual-photon emissions and PDT efficacy through a novel side-chain extension strategy in iridium(III) complexes, paving the way for their translational application in clinical theranostics.
{"title":"Fine-tuning the side-chain length of iridium(III) complexes for enhanced Photophysical properties in Cancer Theranostics","authors":"Tao Shao , Zhihui Feng , Yu Shen , Dandan Chen , Pan Xiang , Qiong Zhang , Shao Ma , Yupeng Tian , Xiaohe Tian","doi":"10.1016/j.jinorgbio.2024.112760","DOIUrl":"10.1016/j.jinorgbio.2024.112760","url":null,"abstract":"<div><div>Cyclometalated iridium(III) complexes have emerged as versatile candidates for cancer theranostics, offering integrated diagnostic imaging and potent singlet oxygen (<sup>1</sup>O<sub>2</sub>) generation for photodynamic therapy (PDT). However, their application has been limited by subdued photoluminescence, primarily due to intramolecular motion-induced excited energy dissipation. In this study, we address these limitations through the design and synthesis of five novel iridium(III) complexes: <strong>IrC2</strong>, <strong>IrC4</strong>, <strong>IrC6</strong>, <strong>IrC8</strong>, and <strong>IrC12</strong>. Our approach employs meticulous side-chain extending strategy to modulate side-chain length, thereby reducing intramolecular motion and significantly enhancing both one- and three-photon emissions and <sup>1</sup>O<sub>2</sub> production in the aggregated state. Detailed photophysical investigations, supported by crystallographic insights, reveal that side-chain elongation substantially amplifies these properties. Among the synthesized complexes, <strong>IrC8</strong> stands out as a superior candidate for image-guided photodynamic therapy in cellular and 3D tumor spheroid models. This investigation pioneers the simultaneous enhancement of dual-photon emissions and PDT efficacy through a novel side-chain extension strategy in iridium(III) complexes, paving the way for their translational application in clinical theranostics.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442299","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 work, mixed ligand Cu(II) complexes containing hydrazone and bipyridine ligands (CB1-CB5), or hydrazone and phenanthroline ligands (CP1-CP5) have been synthesized and characterized by spectroscopic and analytical techniques. Single crystal X-ray structure of complex CB1 revealed that two nitrogen atoms from bipyridine, one carbonyl oxygen, one azomethine nitrogen and one hydroxyl oxygen from the hydrazone ligand coordinated to Cu(II) ion, adopting a distorted square pyramidal geometry. Interaction of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA) was analyzed by absorption and emission studies. Further, the in vitro anticancer activity of the complexes was investigated exclusively against the breast cancer cells namely MCF7, T47D and MDA MB 231, and a normal breast MCF 10a cell line. The phenanthroline bearing complexes (CP1-CP5) displayed better activity than their bipyridine counterparts as seen from the IC50 values. In addition, the most active complex CP1 having an IC50 value of 5.8 ± 0.3 μM against T47D cancer cells was investigated for its mode of cell death through acridine orange/ethidium bromide(AO/EB), 4′,6-diamidino-2-phenylindole (DAPI) and Annexin-V fluorescein isothiocyanate (FITC) staining assays which revealed apoptosis. Lastly, the cell cycle analysis revealed that complex CP1 induced cell death in T47D cancer cells at the G0/G1 phase.
{"title":"Copper(II) complexes containing hydrazone and bipyridine/phenanthroline ligands for anticancer application against breast cancer cells","authors":"Dorothy Priyanka Dorairaj , Prashant Kumar , Haritha Rajasekaran , Nattamai Bhuvanesh , Sodio C.N. Hsu , Ramasamy Karvembu","doi":"10.1016/j.jinorgbio.2024.112759","DOIUrl":"10.1016/j.jinorgbio.2024.112759","url":null,"abstract":"<div><div>In this work, mixed ligand Cu(II) complexes containing hydrazone and bipyridine ligands (<strong>CB1</strong>-<strong>CB5</strong>), or hydrazone and phenanthroline ligands (<strong>CP1</strong>-<strong>CP5</strong>) have been synthesized and characterized by spectroscopic and analytical techniques. Single crystal X-ray structure of complex <strong>CB1</strong> revealed that two nitrogen atoms from bipyridine, one carbonyl oxygen, one azomethine nitrogen and one hydroxyl oxygen from the hydrazone ligand coordinated to Cu(II) ion, adopting a distorted square pyramidal geometry. Interaction of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA) was analyzed by absorption and emission studies. Further, the <em>in vitro</em> anticancer activity of the complexes was investigated exclusively against the breast cancer cells namely MCF7, T47D and MDA MB 231, and a normal breast MCF 10a cell line. The phenanthroline bearing complexes (<strong>CP1</strong>-<strong>CP5</strong>) displayed better activity than their bipyridine counterparts as seen from the IC<sub>50</sub> values. In addition, the most active complex <strong>CP1</strong> having an IC<sub>50</sub> value of 5.8 ± 0.3 μM against T47D cancer cells was investigated for its mode of cell death through acridine orange/ethidium bromide(AO/EB), 4′,6-diamidino-2-phenylindole (DAPI) and Annexin-V fluorescein isothiocyanate (FITC) staining assays which revealed apoptosis. Lastly, the cell cycle analysis revealed that complex <strong>CP1</strong> induced cell death in T47D cancer cells at the G0/G1 phase.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454988","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}
The interest in the antineoplastic and binding properties shown by the bis-maltol polyamine family, particularly Malten and Maltonis, prompted us to study the Pd2+ complexes of these latter from both a biological and metallo-receptor point of view. The Malten-Pd2+ complex can lodge hard species such as Sr2+ in its coordination-driven preorganized pocket, as confirmed by X-ray diffraction. UV–Vis and NMR data showed that Malten-Pd2+ forms even at acidic pH and exists in aqueous solution in a wide range of pH. The mononuclear complex is stable enough not to release Pd2+ in solution for a long period of time (at least one week), thus Malten-Pd2+, similarly to Maltonis-Pd2+, is suitable to be tested in biological analyses. Studies on the U937 cell line revealed that the effect on cell survival reduction induced by Malten is partially lost in Malten-Pd2+, while no differences where monitored between the effects of Maltonis-Pd2+ and Maltonis, suggesting that the availability of free maltol moieties, that is retained in Maltonis-Pd2+, but not in Malten-Pd2+, is crucial to guarantee the biological activity of these compounds.
{"title":"Two bis-maltol-polyamines: Synthesis, characterization and studies of their palladium(II) complexes exploring their potential anticancer activity","authors":"Daniele Paderni , Eleonora Macedi , Enrica Sordini , Stefano Amatori , Patrizia Rossi , Mauro Formica , Luca Giorgi , Paola Paoli , Mirco Fanelli , Vieri Fusi","doi":"10.1016/j.jinorgbio.2024.112758","DOIUrl":"10.1016/j.jinorgbio.2024.112758","url":null,"abstract":"<div><div>The interest in the antineoplastic and binding properties shown by the bis-maltol polyamine family, particularly Malten and Maltonis, prompted us to study the Pd<sup>2+</sup> complexes of these latter from both a biological and metallo-receptor point of view. The Malten-Pd<sup>2+</sup> complex can lodge hard species such as Sr<sup>2+</sup> in its coordination-driven preorganized pocket, as confirmed by X-ray diffraction. UV–Vis and NMR data showed that Malten-Pd<sup>2+</sup> forms even at acidic pH and exists in aqueous solution in a wide range of pH. The mononuclear complex is stable enough not to release Pd<sup>2+</sup> in solution for a long period of time (at least one week), thus Malten-Pd<sup>2+</sup>, similarly to Maltonis-Pd<sup>2+</sup>, is suitable to be tested in biological analyses. Studies on the U937 cell line revealed that the effect on cell survival reduction induced by Malten is partially lost in Malten-Pd<sup>2+</sup>, while no differences where monitored between the effects of Maltonis-Pd<sup>2+</sup> and Maltonis, suggesting that the availability of free maltol moieties, that is retained in Maltonis-Pd<sup>2+</sup>, but not in Malten-Pd<sup>2+</sup>, is crucial to guarantee the biological activity of these compounds.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 μg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.
{"title":"AIE-based ruthenium complexes as photosensitizers for specifically photo-inactivate gram-positive bacteria","authors":"Hai-Yan Huang , Run-Yu Xue , Su-Xin Xiao , Li-Ting Huang , Xiang-Wen Liao , Jin-Tao Wang , Xue-Min Duan , Ru-Jian Yu , Yan-Shi Xiong","doi":"10.1016/j.jinorgbio.2024.112755","DOIUrl":"10.1016/j.jinorgbio.2024.112755","url":null,"abstract":"<div><div>The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, <em>Staphylococcus aureus</em> as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed <em>S. aureus</em> unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, <strong>Ru1</strong> at only 4 μg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between <strong>Ru1</strong> and bacteria enhanced the possibility of antibacterial. Under light irradiation, <strong>Ru1</strong> could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, <strong>Ru1</strong> possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398990","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 : 2024-10-06DOI: 10.1016/j.jinorgbio.2024.112756
Wujiu Jiang , Qing Luo , Wei Huang , Yuxing Tan , Yiyuan Peng
Diorganotin acylhydrazone complexes with mitochondrial targeting demonstrate significant potential as replacements for platinum-based complexes due to their potent anticancer properties. Twelve methylphenyltin arylformylhydrazone complexes have been synthesized by microwave “one-pot” reaction. The complexes have been characterized by FT-IR, multinuclear NMR (1H, 13C, and 119Sn), TGA, and HRMS. Crystal structures were determined for 10 out of the 12 complexes under study. Structures 1 through 8, 10 and 12 possessed a central symmetric structure of a di-nuclear Sn2O2 tetrahedral ring. All complexes were tested for their inhibitory activity against human cell lines NCI-H460, MCF-7, and HepG2. Complex 8 exhibited the most effective inhibitory effect on HepG2 cells, with an IC50 value of 1.34 ± 0.04 μM. Preliminary studies on the anticancer mechanism suggest that complex 8 induces apoptosis in HepG2 cells via the mitochondrial pathway, accompanied by G2/M phase cell cycle arrest.
{"title":"Synthesis, anticancer activity, and mechanistic investigations of aryl-alkyl diorganotin arylformylhydrazone complexes","authors":"Wujiu Jiang , Qing Luo , Wei Huang , Yuxing Tan , Yiyuan Peng","doi":"10.1016/j.jinorgbio.2024.112756","DOIUrl":"10.1016/j.jinorgbio.2024.112756","url":null,"abstract":"<div><div>Diorganotin acylhydrazone complexes with mitochondrial targeting demonstrate significant potential as replacements for platinum-based complexes due to their potent anticancer properties. Twelve methylphenyltin arylformylhydrazone complexes have been synthesized by microwave “one-pot” reaction. The complexes have been characterized by FT-IR, multinuclear NMR (<sup>1</sup>H, <sup>13</sup>C, and <sup>119</sup>Sn), TGA, and HRMS. Crystal structures were determined for <strong>10</strong> out of the <strong>12</strong> complexes under study. Structures <strong>1</strong> through <strong>8</strong>, <strong>10</strong> and <strong>12</strong> possessed a central symmetric structure of a di-nuclear Sn<sub>2</sub>O<sub>2</sub> tetrahedral ring. All complexes were tested for their inhibitory activity against human cell lines NCI-H460, MCF-7, and HepG2. Complex <strong>8</strong> exhibited the most effective inhibitory effect on HepG2 cells, with an IC<sub>50</sub> value of 1.34 ± 0.04 μM. Preliminary studies on the anticancer mechanism suggest that complex <strong>8</strong> induces apoptosis in HepG2 cells <em>via</em> the mitochondrial pathway, accompanied by G2/M phase cell cycle arrest.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398991","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 : 2024-10-05DOI: 10.1016/j.jinorgbio.2024.112754
Anastasia A. Antonets , Ekaterina V. Spitsyna , Vladimir Yu. Tyurin , Dmitrii M. Mazur , Dmitry S. Yakovlev , Denis A. Babkov , Mariya S. Pshenichnikova , Alexander A. Spasov , Elena R. Milaeva , Alexey A. Nazarov
This study is dedicated to the development of multimodal anticancer agents. We have obtained ruthenium complexes conjugated with the steroid-type antitumor drug abiraterone acetate in order to take advantage of the dual antitumor properties of both ruthenium and abiraterone. The compounds exhibit good antiproliferative activity against cancer cells, with selectivity over primary fibroblasts. Real-time cell analysis revealed that compound dichlorido(η66-p-cymene)(abiraterone acetate)ruthenium(II) had pronounced antiproliferation activity compared to abiraterone acetate. Flow cytometric studies on the mechanism of cell death have revealed that the most active compound induces apoptosis more effectively than abiraterone acetate. Our findings demonstrate the potential of this novel dual-action compound as promising candidates for further development as anticancer agents.
{"title":"Ruthenium complexes with abiraterone acetate as antiproliferative agents","authors":"Anastasia A. Antonets , Ekaterina V. Spitsyna , Vladimir Yu. Tyurin , Dmitrii M. Mazur , Dmitry S. Yakovlev , Denis A. Babkov , Mariya S. Pshenichnikova , Alexander A. Spasov , Elena R. Milaeva , Alexey A. Nazarov","doi":"10.1016/j.jinorgbio.2024.112754","DOIUrl":"10.1016/j.jinorgbio.2024.112754","url":null,"abstract":"<div><div>This study is dedicated to the development of multimodal anticancer agents. We have obtained ruthenium complexes conjugated with the steroid-type antitumor drug abiraterone acetate in order to take advantage of the dual antitumor properties of both ruthenium and abiraterone. The compounds exhibit good antiproliferative activity against cancer cells, with selectivity over primary fibroblasts. Real-time cell analysis revealed that compound dichlorido(η<sup>6</sup><span><span>6</span></span>-p-cymene)(abiraterone acetate)ruthenium(II) had pronounced antiproliferation activity compared to abiraterone acetate. Flow cytometric studies on the mechanism of cell death have revealed that the most active compound induces apoptosis more effectively than abiraterone acetate. Our findings demonstrate the potential of this novel dual-action compound as promising candidates for further development as anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387007","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 : 2024-10-01DOI: 10.1016/j.jinorgbio.2024.112752
Gabriele de Menezes Pereira , Julia H. Bormio Nunes , Vinicius Souza Macedo , Douglas Henrique Pereira , Kaio Eduardo Buglio , Daniele D. Affonso , Ana Lucia T.G. Ruiz , João Ernesto de Carvalho , Silmara Cristina L. Frajácomo , Wilton R. Lustri , Carmen Silvia Passos Lima , Fernando R.G. Bergamini , Alexandre Cuin , Norberto Masciocchi , Pedro Paulo Corbi
New silver(I) complexes of 5-(trifluoromethyl)uracil (5TFMU) and 6-(trifluoromethyl)uracil (6TFMU) isomers were synthesized, characterized, and evaluated as antibacterial and antiproliferative agents. Based on elemental and thermogravimetric analyses, the Ag-5TFMU and Ag-6TFMU species are formulated as AgC5H2F3N2O2 and Ag2C5HF3N2O2, respectively. Infrared and 13C solid-state nuclear magnetic resonance spectroscopies suggest coordination of the trifluoromethyluracil isomers to silver by both nitrogen and oxygen atoms. Confirmation of their structure and connectivity was achieved, in the absence of single crystals of suitable quality, by state-of-the-art structural powder diffraction methods. In Ag-5TFMU, the organic ligand is tridentate and two distinct metal coordination environments are found (linear AgN2 as well as C2v AgO4 geometries), whereas Ag-6TFMU contains a complex polymeric structure with tetradentate dianionic 6TFMU moieties and five distinct AgX2 (X = N, O) fragments, further stabilized by ancillary (longer) Ag…O contacts. These species presented modest activity over Gram-positive and Gram-negative bacterial strains, whereas Ag-6TFMU was active over a set of tumor cells, with the best activity over prostate (PC-3) and kidney cell lines and selectivity indices of 4.6 and 1.3, respectively. On the other hand, Ag-5TFMU was active over all considered tumor cells except MCF-7 (breast cancer). The best activity was found for PC-3 cells, but no selectivity was observed. The Ag-5TFMU and Ag-6TFMU species also reduced the proliferation of tongue squamous cell carcinoma cell lines SCC − 4 and SCC-15. Preliminary biophysical assays by circular dichroism suggest that the Ag-5TFMU complex interacts with DNA by intercalation, an effect not seen in Ag-6TFMU.
{"title":"Antibacterial profile and antiproliferative activities over human tumor cells of new silver(I) complexes containing two distinct trifluoromethyl uracil isomers","authors":"Gabriele de Menezes Pereira , Julia H. Bormio Nunes , Vinicius Souza Macedo , Douglas Henrique Pereira , Kaio Eduardo Buglio , Daniele D. Affonso , Ana Lucia T.G. Ruiz , João Ernesto de Carvalho , Silmara Cristina L. Frajácomo , Wilton R. Lustri , Carmen Silvia Passos Lima , Fernando R.G. Bergamini , Alexandre Cuin , Norberto Masciocchi , Pedro Paulo Corbi","doi":"10.1016/j.jinorgbio.2024.112752","DOIUrl":"10.1016/j.jinorgbio.2024.112752","url":null,"abstract":"<div><div>New silver(I) complexes of 5-(trifluoromethyl)uracil (5TFMU) and 6-(trifluoromethyl)uracil (6TFMU) isomers were synthesized, characterized, and evaluated as antibacterial and antiproliferative agents. Based on elemental and thermogravimetric analyses, the Ag-5TFMU and Ag-6TFMU species are formulated as AgC<sub>5</sub>H<sub>2</sub>F<sub>3</sub>N<sub>2</sub>O<sub>2</sub> and Ag<sub>2</sub>C<sub>5</sub>HF<sub>3</sub>N<sub>2</sub>O<sub>2</sub>, respectively. Infrared and <sup>13</sup>C solid-state nuclear magnetic resonance spectroscopies suggest coordination of the trifluoromethyluracil isomers to silver by both nitrogen and oxygen atoms. Confirmation of their structure and connectivity was achieved, in the absence of single crystals of suitable quality, by state-of-the-art structural powder diffraction methods. In Ag-5TFMU, the organic ligand is tridentate and two distinct metal coordination environments are found (linear AgN<sub>2</sub> as well as <em>C</em><sub><em>2v</em></sub> AgO<sub>4</sub> geometries), whereas Ag-6TFMU contains a complex polymeric structure with tetradentate dianionic 6TFMU moieties and <em>five</em> distinct AgX<sub>2</sub> (X = N, O) fragments, further stabilized by ancillary (longer) Ag<sup>…</sup>O contacts. These species presented modest activity over Gram-positive and Gram-negative bacterial strains, whereas Ag-6TFMU was active over a set of tumor cells, with the best activity over prostate (PC-3) and kidney cell lines and selectivity indices of 4.6 and 1.3, respectively. On the other hand, Ag-5TFMU was active over all considered tumor cells except MCF-7 (breast cancer). The best activity was found for PC-3 cells, but no selectivity was observed. The Ag-5TFMU and Ag-6TFMU species also reduced the proliferation of tongue squamous cell carcinoma cell lines SCC − 4 and SCC-15. Preliminary biophysical assays by circular dichroism suggest that the Ag-5TFMU complex interacts with DNA by intercalation, an effect not seen in Ag-6TFMU.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374875","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 : 2024-09-30DOI: 10.1016/j.jinorgbio.2024.112750
Tushar S. Basu Baul , Swmkwr Brahma , Rupen Tamang , Andrew Duthie , Biplob Koch , Sean Parkin
Diorganotin complexes of the compositions [Me2Sn(L)] (1), [n-Bu2Sn(L)] (2), [Ph2Sn(L)]⋅C6H6 (3), [Bz2Sn(L)]⋅C6H6 (4) and [n-Oct2Sn(L)] (5) were synthesized by reacting R2SnO (R = Me, n-Bu, Ph, Bz or n-Oct) with the N2,N6-di(thiazol-2-yl)pyridine-2,6-dicarboxamide (H2L, where H2 denotes the two acidic protons) in refluxing toluene. Additionally, the mono-n-butyltin complex [n-BuSn(HL)Cl2]·H2O (6) was synthesized from n-BuSnCl3 and H2L in acetonitrile. Compounds were characterized by FT-IR, 1H, 13C and 119Sn NMR spectroscopy, while their solid-state structures were examined using single-crystal X-ray diffraction studies. In diorganotin compounds 1–5, the dianionic tridentate ligands (Npy, N−, N−) act as κ-N3 chelators. In 6, the L moiety (O, Npy, N−) acts as a κ-ON2 tridentate chelator, with involvement of one of the carboxamide oxygen atoms. The coordination polyhedron around the Sn(IV) ion is completed either by two axial Sn-R ligands in compounds 1–5 or by n-Bu and Cl ligands in compound 6, giving rise to distorted trigonal bipyramid or octahedral structures, respectively. The tin NMR results show that the penta-coordinated structures of compounds 1–5 and the hexacoordinated structure of compound 6, observed in the solid-state, are retained in solution. The in vitro antitumor activities of 1–5 were tested on T-47D breast cancer cells. Of these, diphenyltin compound 3 showed the highest anti-proliferative effect, with an IC50 of 10 ± 1.60 μM. Compound 3 exhibited selective toxicity, potentially inducing apoptosis via reactive oxygen species generation and nuclear changes, indicating promise as a breast cancer treatment. This study is the first to explore thiazole-appended organotin compounds for cytotoxicity.
{"title":"Synthesis, structures, and cytotoxicity insights of organotin(IV) complexes with thiazole-appended pincer ligand","authors":"Tushar S. Basu Baul , Swmkwr Brahma , Rupen Tamang , Andrew Duthie , Biplob Koch , Sean Parkin","doi":"10.1016/j.jinorgbio.2024.112750","DOIUrl":"10.1016/j.jinorgbio.2024.112750","url":null,"abstract":"<div><div>Diorganotin complexes of the compositions [Me<sub>2</sub>Sn(L)] (<strong>1</strong>), [<em>n</em>-Bu<sub>2</sub>Sn(L)] (<strong>2</strong>), [Ph<sub>2</sub>Sn(L)]⋅C<sub>6</sub>H<sub>6</sub> (<strong>3</strong>), [Bz<sub>2</sub>Sn(L)]⋅C<sub>6</sub>H<sub>6</sub> (<strong>4</strong>) and [<em>n</em>-Oct<sub>2</sub>Sn(L)] (<strong>5</strong>) were synthesized by reacting R<sub>2</sub>SnO (R = Me, <em>n</em>-Bu, Ph, Bz or <em>n</em>-Oct) with the <em>N</em><sup><em>2</em></sup>,<em>N</em><sup><em>6</em></sup>-di(thiazol-2-yl)pyridine-2,6-dicarboxamide (H<sub>2</sub>L, where H<sub>2</sub> denotes the two acidic protons) in refluxing toluene. Additionally, the mono-<em>n</em>-butyltin complex [<em>n</em>-BuSn(HL)Cl<sub>2</sub>]·H<sub>2</sub>O (<strong>6</strong>) was synthesized from <em>n</em>-BuSnCl<sub>3</sub> and H<sub>2</sub>L in acetonitrile. Compounds were characterized by FT-IR, <sup>1</sup>H, <sup>13</sup>C and <sup>119</sup>Sn NMR spectroscopy, while their solid-state structures were examined using single-crystal X-ray diffraction studies. In diorganotin compounds <strong>1</strong>–<strong>5</strong>, the dianionic tridentate ligands (N<sub>py</sub>, N<sup>−</sup>, N<sup>−</sup>) act as κ-<em>N</em><sup><em>3</em></sup> chelators. In <strong>6</strong>, the L moiety (O, N<sub>py</sub>, N<sup>−</sup>) acts as a κ-<em>ON</em><sup><em>2</em></sup> tridentate chelator, with involvement of one of the carboxamide oxygen atoms. The coordination polyhedron around the Sn(IV) ion is completed either by two axial Sn-R ligands in compounds <strong>1</strong>–<strong>5</strong> or by <em>n</em>-Bu and Cl ligands in compound <strong>6</strong>, giving rise to distorted trigonal bipyramid or octahedral structures, respectively. The tin NMR results show that the penta-coordinated structures of compounds <strong>1</strong>–<strong>5</strong> and the hexacoordinated structure of compound <strong>6</strong>, observed in the solid-state, are retained in solution. The <em>in vitro</em> antitumor activities of <strong>1</strong>–<strong>5</strong> were tested on T-47D breast cancer cells. Of these, diphenyltin compound <strong>3</strong> showed the highest anti-proliferative effect, with an IC<sub>50</sub> of 10 ± 1.60 μM. Compound <strong>3</strong> exhibited selective toxicity, potentially inducing apoptosis via reactive oxygen species generation and nuclear changes, indicating promise as a breast cancer treatment. This study is the first to explore thiazole-appended organotin compounds for cytotoxicity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387008","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 : 2024-09-30DOI: 10.1016/j.jinorgbio.2024.112751
Marcin Wysocki , Daniel Ziental , Zekeriya Biyiklioglu , Malgorzata Jozkowiak , Hüseyin Baş , Jolanta Dlugaszewska , Hanna Piotrowska-Kempisty , Emre Güzel , Lukasz Sobotta
The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran – DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and S. epidermidis. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications.
{"title":"Non-peripheral octasubstituted zinc(II) phthalocyanines bearing pyridinepropoxy substituents – Antibacterial, anticancer photodynamic and sonodynamic activity","authors":"Marcin Wysocki , Daniel Ziental , Zekeriya Biyiklioglu , Malgorzata Jozkowiak , Hüseyin Baş , Jolanta Dlugaszewska , Hanna Piotrowska-Kempisty , Emre Güzel , Lukasz Sobotta","doi":"10.1016/j.jinorgbio.2024.112751","DOIUrl":"10.1016/j.jinorgbio.2024.112751","url":null,"abstract":"<div><div>The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran – DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and <em>S. epidermidis</em>. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}