Pub Date : 2025-11-21DOI: 10.1016/j.jinorgbio.2025.113157
Benlian Xue, Youkun Zang, Wang Lv, Yuheng Zhang, Shuangyang Zhang, Xiaoshuang Li, Qinghua Chang, Yongjian Lu, Xicheng Liu, Zhe Liu
Although widely used clinically, the extensive nephrotoxicity and drug resistance of platinum-based metallic anticancer drugs have spurred the research and development of non‑platinum-based metallic anticancer drugs. Half-sandwich iridium(III) (IrIII) complexes have become a research hotspot in this field due to their excellent anticancer activity, structural tunability, and unique mechanism of action different from that of cisplatin. Then two half-sandwich IrIII xanthate complexes with a simple structure were prepared in this study. In vitro anti-proliferative evaluation showed that these two complexes enjoyed favorable activity towards A549 lung cancer cells in comparison to cisplatin, and could also effectively inhibit cell migration. Further research showed that Ir1 could target lysosomes (PCC: 0.85) and lead to lysosomal damage, then disturbing the cell cycle arrest (G0/G1 phase), decreasing mitochondrial membrane potential and inducing the improvement of intracellular reactive oxygen species levels. Western blotting also confirmed the existence of a lysosomal-mitochondrial apoptotic anticancer pathway. Collectively, these structurally simple yet highly active IrIII complexes provide a valuable foundation for the rational design and development of novel non‑platinum-based metallic anticancer drugs.
{"title":"Anticancer behaviour of simplified lysosome-targeted half-sandwich iridium(III) xanthate complexes towards A549 cell lines","authors":"Benlian Xue, Youkun Zang, Wang Lv, Yuheng Zhang, Shuangyang Zhang, Xiaoshuang Li, Qinghua Chang, Yongjian Lu, Xicheng Liu, Zhe Liu","doi":"10.1016/j.jinorgbio.2025.113157","DOIUrl":"10.1016/j.jinorgbio.2025.113157","url":null,"abstract":"<div><div>Although widely used clinically, the extensive nephrotoxicity and drug resistance of platinum-based metallic anticancer drugs have spurred the research and development of non‑platinum-based metallic anticancer drugs. Half-sandwich iridium(III) (Ir<sup>III</sup>) complexes have become a research hotspot in this field due to their excellent anticancer activity, structural tunability, and unique mechanism of action different from that of cisplatin. Then two half-sandwich Ir<sup>III</sup> xanthate complexes with a simple structure were prepared in this study. In vitro anti-proliferative evaluation showed that these two complexes enjoyed favorable activity towards A549 lung cancer cells in comparison to cisplatin, and could also effectively inhibit cell migration. Further research showed that <strong>Ir1</strong> could target lysosomes (PCC: 0.85) and lead to lysosomal damage, then disturbing the cell cycle arrest (G<sub>0</sub>/G<sub>1</sub> phase), decreasing mitochondrial membrane potential and inducing the improvement of intracellular reactive oxygen species levels. Western blotting also confirmed the existence of a lysosomal-mitochondrial apoptotic anticancer pathway. Collectively, these structurally simple yet highly active Ir<sup>III</sup> complexes provide a valuable foundation for the rational design and development of novel non‑platinum-based metallic anticancer drugs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113157"},"PeriodicalIF":3.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.jinorgbio.2025.113156
Yajing Luo , Qixuan Yang , Yabing Gan , Caixia Dou , Haiyan Wang , Qiujun Lu , Guoxing Yin , Fuyou Du , Peng Yin
Sn2+ pollution poses significant risks to ecosystems and human health, necessitating the development of simple detection methods for accurate monitoring of Sn2+ dynamics. Here, we developed a conceptually distinct strategy that exploits the Sn2+-mediated reduction of organic azides rather than conventional chelation mechanism, and constructed a series of azide-based fluorescent probes (A–G) operating via turn-on, ratiometric, or fluorescence resonance energy transfer modality with emissions spanning blue to near-infrared for specific sensing of Sn2+. These probes exhibit exceptional selectivity for Sn2+ over Sn4+ and other biologically relevant species, sub-micromolar detection limits (as low as 13.7 nM), fast response kinetics (t1/2 < 1 min), and full aqueous compatibility. The reduction mechanism was confirmed through radical trapping and product isolation. Probe B enabled direct quantify Sn2+ in real water samples with good recovery (93.5–103.3 %). All designed probes facilitated high-contrast in-situ imaging of Sn2+ in living cells. This work provides a robust platform for deciphering the environmental fate and biological roles of Sn2+.
{"title":"A general strategy for specific sensing of Sn2+ in environmental water samples and in cells","authors":"Yajing Luo , Qixuan Yang , Yabing Gan , Caixia Dou , Haiyan Wang , Qiujun Lu , Guoxing Yin , Fuyou Du , Peng Yin","doi":"10.1016/j.jinorgbio.2025.113156","DOIUrl":"10.1016/j.jinorgbio.2025.113156","url":null,"abstract":"<div><div>Sn<sup>2+</sup> pollution poses significant risks to ecosystems and human health, necessitating the development of simple detection methods for accurate monitoring of Sn<sup>2+</sup> dynamics. Here, we developed a conceptually distinct strategy that exploits the Sn<sup>2+</sup>-mediated reduction of organic azides rather than conventional chelation mechanism, and constructed a series of azide-based fluorescent probes (<strong>A</strong>–<strong>G</strong>) operating via turn-on, ratiometric, or fluorescence resonance energy transfer modality with emissions spanning blue to near-infrared for specific sensing of Sn<sup>2+</sup>. These probes exhibit exceptional selectivity for Sn<sup>2+</sup> over Sn<sup>4+</sup> and other biologically relevant species, sub-micromolar detection limits (as low as 13.7 nM), fast response kinetics (<em>t</em><sub>1/2</sub> < 1 min), and full aqueous compatibility. The reduction mechanism was confirmed through radical trapping and product isolation. Probe B enabled direct quantify Sn<sup>2+</sup> in real water samples with good recovery (93.5–103.3 %). All designed probes facilitated high-contrast in-situ imaging of Sn<sup>2+</sup> in living cells. This work provides a robust platform for deciphering the environmental fate and biological roles of Sn<sup>2+</sup>.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113156"},"PeriodicalIF":3.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.jinorgbio.2025.113153
Ivana R. Scolari, Mario A. Quevedo, Paulina L. Páez, Gladys E. Granero
This paper reports the development of a complex between the antibiotic gentamicin sulfate (GEN), consisting of four major congeners, and zinc ions (Zn(II)GEN complex). The composition of the complex aligns well with the proposed molecular formula [Zn₂+(L)(3H₂O)(2SO₄2−]. The Zn(II)GEN complex significantly enhanced inhibitory and bactericidal activity against S. aureus, E faecalis, P. aeruginosa, and E. coli. Unlike gentamicin sulfate alone, the Zn(II)-GEN complex did not induce drug-resistant mutants. Molecular modeling predicted predominantly hexacoordinated complexes involving three contact points with gentamicin and three with water, which agreed with the spectroscopic studies. The complexes adopted a restricted conformation of gentamicin, resulting in its hydrophilic groups being excluded from the solvent, which is consistent with the higher permeability. Molecular Modeling studies of the Zn(II)GEN complex with 16S RNA revealed a restricted bioactive conformation with stable interactions with residues A1493, G1494, and U1495, a structural requirement for antimicrobial activity. Free energy of binding analyses show that the Zn(II)GEN complex had better pharmacodynamic properties than the pure compound. A favored bioactive conformation formed upon the complexation of gentamicin sulfate with Zn(II) increased the complex's potency against bacteria and allowed it to penetrate bacterial cells. The complex also reduces the likelihood of antimicrobial resistance. The strategy is a good starting point for research into combating bacteria.
{"title":"A zinc (II) gentamicin metalloantibiotic with outstanding antimicrobial activity and reduced susceptibility to bacterial resistance mechanisms: Experimental and theoretical explorations","authors":"Ivana R. Scolari, Mario A. Quevedo, Paulina L. Páez, Gladys E. Granero","doi":"10.1016/j.jinorgbio.2025.113153","DOIUrl":"10.1016/j.jinorgbio.2025.113153","url":null,"abstract":"<div><div>This paper reports the development of a complex between the antibiotic gentamicin sulfate (GEN), consisting of four major congeners, and zinc ions (Zn(II)GEN complex). The composition of the complex aligns well with the proposed molecular formula [Zn<sup>₂+</sup>(L)(3H₂O)(2SO₄<sup>2−</sup>]. The Zn(II)GEN complex significantly enhanced inhibitory and bactericidal activity against <em>S. aureus</em>, <em>E faecalis</em>, <em>P. aeruginosa</em>, and <em>E. coli</em>. Unlike gentamicin sulfate alone, the Zn(II)-GEN complex did not induce drug-resistant mutants. Molecular modeling predicted predominantly hexacoordinated complexes involving three contact points with gentamicin and three with water, which agreed with the spectroscopic studies. The complexes adopted a restricted conformation of gentamicin, resulting in its hydrophilic groups being excluded from the solvent, which is consistent with the higher permeability. Molecular Modeling studies of the Zn(II)GEN complex with 16S RNA revealed a restricted bioactive conformation with stable interactions with residues A1493, G1494, and U1495, a structural requirement for antimicrobial activity. Free energy of binding analyses show that the Zn(<em>II</em>)GEN complex had better pharmacodynamic properties than the pure compound. A favored bioactive conformation formed upon the complexation of gentamicin sulfate with Zn(II) increased the complex's potency against bacteria and allowed it to penetrate bacterial cells. The complex also reduces the likelihood of antimicrobial resistance. The strategy is a good starting point for research into combating bacteria.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113153"},"PeriodicalIF":3.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.jinorgbio.2025.113154
Maria De Fenza , Linda Leone , Matilde Tancredi , Edelberto Oscar Niola , Ornella Maglio , Gerardino D'Errico , Flavia Nastri , Daniele D’Alonzo , Angela Lombardi
Natural peroxidases use 4-halophenols either as substrates in oxidative chemistry or as inhibitors. Herein, we demonstrated that Fe-mimochrome VI*a (Fe-MC6*a), a miniaturized heme-enzyme, is a versatile catalyst as it integrates both these features. We previously reported that Fe-MC6*a catalyzes the chemo- and regio-selective oxidation of 4-halophenols, providing either dehalogenation or oligomerization products, depending on the nature of the halogen atom. In particular, 4-chlorophenol (4-CP) and 4-fluorophenol (4-FP) selectively led to dehalogenation and oligomerization products, respectively. Herein, spin-trapping studies and EPR analysis confirm the ability of Fe-MC6*a into processing halophenols as substrates and provide mechanistic hypothesis for the chemo-divergent reaction outcome. Further, in multiple substrate competition assays, 4-halophenols act as competitive inhibitors of Fe-MC6*a-catalyzed dehalogenation of 2,4,6-trichlorophenol (TCP). Nonetheless, the catalyst retains appreciable turnover in such complex substrate mixtures. Taken together, the combination of substrate-specific selectivity and resilience to the total inhibition position Fe-MC6*a as a promising bioremediation catalyst for simultaneous halophenol detoxification in wastewater-treatment applications.
{"title":"Dehalogenation activity of a miniaturized peroxidase: substrate dependent functional switch","authors":"Maria De Fenza , Linda Leone , Matilde Tancredi , Edelberto Oscar Niola , Ornella Maglio , Gerardino D'Errico , Flavia Nastri , Daniele D’Alonzo , Angela Lombardi","doi":"10.1016/j.jinorgbio.2025.113154","DOIUrl":"10.1016/j.jinorgbio.2025.113154","url":null,"abstract":"<div><div>Natural peroxidases use 4-halophenols either as substrates in oxidative chemistry or as inhibitors. Herein, we demonstrated that Fe-mimochrome VI*a (Fe-MC6*a), a miniaturized heme-enzyme, is a versatile catalyst as it integrates both these features. We previously reported that Fe-MC6*a catalyzes the chemo- and regio-selective oxidation of 4-halophenols, providing either dehalogenation or oligomerization products, depending on the nature of the halogen atom. In particular, 4-chlorophenol (4-CP) and 4-fluorophenol (4-FP) selectively led to dehalogenation and oligomerization products, respectively. Herein, spin-trapping studies and EPR analysis confirm the ability of Fe-MC6*a into processing halophenols as substrates and provide mechanistic hypothesis for the chemo-divergent reaction outcome. Further, in multiple substrate competition assays, 4-halophenols act as competitive inhibitors of Fe-MC6*a-catalyzed dehalogenation of 2,4,6-trichlorophenol (TCP). Nonetheless, the catalyst retains appreciable turnover in such complex substrate mixtures. Taken together, the combination of substrate-specific selectivity and resilience to the total inhibition position Fe-MC6*a as a promising bioremediation catalyst for simultaneous halophenol detoxification in wastewater-treatment applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113154"},"PeriodicalIF":3.2,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.jinorgbio.2025.113152
Emil Thomsen, Parker R. Stow, Maren Cukor, Alison Butler
Bacteria often produce siderophores – small molecules with high affinity for Fe(III) – to acquire the iron that they need to grow. After transport of the Fe(III)-siderophore across the outer membrane of Gram-negative bacteria, a periplasmic binding protein (PBP) generally shuttles the Fe(III)-siderophore through the periplasm to the inner membrane. The fish pathogen Yersinia ruckeri synthesizes the oligoester tris-catecholate siderophore ruckerbactin, (DHB-LArg-LSer)3 (1), to acquire iron during infection. Its biosynthetic gene cluster encodes a single PBP, RupB, which was presumed to bind Fe(III)-ruckerbactin, however, previous fluorescence quenching titrations revealed RupB does not bind Fe(III)-ruckerbactin nor the Fe(III) complexes of its hydrolysis products – the bis- and mono-catecholate siderophores, 2 and 3, respectively – with biologically relevant affinities. Instead, RupB binds the complex of the structurally-related siderophore enterobactin, (DHB-LSer)3, which is surprising since enterobactin is not biosynthesized by Y. ruckeri. RupB inverts the chirality of the Δ-Fe(III)-enterobactin to Λ upon binding. A second PBP, YiuA, which is encoded elsewhere in the genome was established previously to bind the 1:2 Fe(III) complex of the mono-catecholate DHB-LArg-LSer (3), Fe(III)-(3)2, as well as the diastereomeric complex Fe(III)-(4)2 with nanomolar affinities, in which 4 is the monocatechol DHB-DArg-LSer. We show that YiuA recognizes similar siderophore scaffolds containing the alternative cationic amino acids (Lys, Orn), suggesting a broader role in xenosiderophore uptake. YiuA binds its substrate in the Λ isomer regardless of the chirality of the complex presented to it.
细菌经常产生铁载体——一种对铁（III）具有高亲和力的小分子——来获取它们生长所需的铁。铁(III)-铁载体通过革兰氏阴性菌的外膜运输后，周围质结合蛋白（PBP）通常将铁(III)-铁载体通过周质运送到内膜。鱼类病原体拉克氏耶尔森菌在感染过程中合成低聚酯三儿茶酚铁载体拉克巴克蛋白（dhb - lang - lser）3(1)来获取铁。它的生物合成基因簇编码一个单一的PBP， RupB，它被认为可以结合Fe(III)-ruckerbactin，然而，之前的荧光猝灭测定显示，RupB不结合Fe(III)-ruckerbactin，也不结合其水解产物的Fe（III）复合物——双儿茶酚酸和单儿茶酚酸铁载体，2和3——具有生物学上相关的亲和力。相反，RupB与结构相关的铁载体肠杆菌蛋白（DHB-LSer）3的复合物结合，这是令人惊讶的，因为肠杆菌蛋白不是由洛克氏菌生物合成的。RupB在结合后将Δ-Fe(III)-enterobactin的手性反转为Λ。第二个PBP， YiuA，在基因组的其他地方编码，先前被建立结合单儿茶酚dhb - lang - lser(3)的1:2 Fe（III）复合物，Fe(III)-(3)2，以及具有纳米亲和的非对映体复合物Fe(III)-(4)2，其中4是单儿茶酚DHB-DArg-LSer。我们发现YiuA可以识别含有替代阳离子氨基酸（Lys, Orn）的类似铁载体支架，这表明在异种铁载体摄取中具有更广泛的作用。YiuA将其底物结合在Λ同分异构体中，而不考虑提供给它的配合物的手性。
{"title":"Substrate flexibility of the catechol siderophore periplasmic binding proteins, RupB and YiuA from Yersinia ruckeri YRB","authors":"Emil Thomsen, Parker R. Stow, Maren Cukor, Alison Butler","doi":"10.1016/j.jinorgbio.2025.113152","DOIUrl":"10.1016/j.jinorgbio.2025.113152","url":null,"abstract":"<div><div>Bacteria often produce siderophores – small molecules with high affinity for Fe(III) – to acquire the iron that they need to grow. After transport of the Fe(III)-siderophore across the outer membrane of Gram-negative bacteria, a periplasmic binding protein (PBP) generally shuttles the Fe(III)-siderophore through the periplasm to the inner membrane. The fish pathogen <em>Yersinia ruckeri</em> synthesizes the oligoester tris-catecholate siderophore ruckerbactin, (DHB-<sup>L</sup>Arg-<sup>L</sup>Ser)<sub>3</sub> (1), to acquire iron during infection. Its biosynthetic gene cluster encodes a single PBP, RupB, which was presumed to bind Fe(III)-ruckerbactin, however, previous fluorescence quenching titrations revealed RupB does not bind Fe(III)-ruckerbactin nor the Fe(III) complexes of its hydrolysis products – the bis- and mono-catecholate siderophores, 2 and 3, respectively – with biologically relevant affinities. Instead, RupB binds the complex of the structurally-related siderophore enterobactin, (DHB-<sup>L</sup>Ser)<sub>3</sub>, which is surprising since enterobactin is not biosynthesized by <em>Y. ruckeri</em>. RupB inverts the chirality of the Δ-Fe(III)-enterobactin to Λ upon binding. A second PBP, YiuA, which is encoded elsewhere in the genome was established previously to bind the 1:2 Fe(III) complex of the mono-catecholate DHB-<sup>L</sup>Arg-<sup>L</sup>Ser (3), Fe(III)-(3)<sub>2</sub>, as well as the diastereomeric complex Fe(III)-(4)<sub>2</sub> with nanomolar affinities, in which 4 is the monocatechol DHB-<sup>D</sup>Arg-<sup>L</sup>Ser. We show that YiuA recognizes similar siderophore scaffolds containing the alternative cationic amino acids (Lys, Orn), suggesting a broader role in xenosiderophore uptake. YiuA binds its substrate in the Λ isomer regardless of the chirality of the complex presented to it.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113152"},"PeriodicalIF":3.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.jinorgbio.2025.113151
Grace Wang , Jessica Samudio , Hadia Aftab , Lily Le , Fereshteh Zandakrimi , Rebecca K. Donegan
Both Mycobacterium smegmatis and M. abscessus secrete porphyrin throughout their growth, and other species of bacteria have also been shown to secrete porphyrin with various outcomes. However, how the secretion of a heme precursor alters heme levels remains to be seen. Herein we determined that porphyrin levels and heme levels in the mycobacteria are decoupled as an increase in intracellular or extracellular porphyrin does not alter intracellular heme levels. Our findings support a model for heme biosynthesis with multiple points of regulation, further our understanding of how to alter secretion and buildup of endogenous porphyrins in the mycobacteria, and suggest that mycobacteria have a biological purpose for porphyrin secretion.
{"title":"Porphyrin secretion does not alter heme biosynthesis in the nontuberculous mycobacteria","authors":"Grace Wang , Jessica Samudio , Hadia Aftab , Lily Le , Fereshteh Zandakrimi , Rebecca K. Donegan","doi":"10.1016/j.jinorgbio.2025.113151","DOIUrl":"10.1016/j.jinorgbio.2025.113151","url":null,"abstract":"<div><div>Both <em>Mycobacterium smegmatis</em> and <em>M. abscessus</em> secrete porphyrin throughout their growth, and other species of bacteria have also been shown to secrete porphyrin with various outcomes. However, how the secretion of a heme precursor alters heme levels remains to be seen. Herein we determined that porphyrin levels and heme levels in the mycobacteria are decoupled as an increase in intracellular or extracellular porphyrin does not alter intracellular heme levels. Our findings support a model for heme biosynthesis with multiple points of regulation, further our understanding of how to alter secretion and buildup of endogenous porphyrins in the mycobacteria, and suggest that mycobacteria have a biological purpose for porphyrin secretion.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113151"},"PeriodicalIF":3.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.jinorgbio.2025.113148
Wanqing Zhang, Mengyue Tan, Meihua Chen, Weibin Chen, Mei-Jin Li
Cyclometallated Ir(III) complex is a potential photosensitizer for photodynamic therapy (PDT) due to its unique photophysical properties. As an emerging anti-tumor therapy, PDT kills tumor cells by leveraging the toxic reactive oxygen species (ROS) generated by light-activated photosensitizers. In this work, two Ir(III) complexes with aggregation-induced emission (AIE) properties were designed and synthesized. A biosensor based on bovine serum albumin (BSA)-enhanced AIE of Ir(III) complexes for selective sensing of trypsin was constructed and explored. The therapeutic potential of the probes for PDT was evaluated by measuring their ROS generation efficiency, along with their phototoxicity and dark cytotoxicity in HeLa cells. In addition, localization of the two probes on organelles was investigated and the mechanism of apoptosis induced by the probe Ir-2 as a photosensitizer was studied using flow cytometry. The results demonstrated that these AIE-active complexes exhibited high ROS efficiency and good mitochondrial/lysosome dual-organelle targeting capability, which can enhance the efficacy of PDT in cancer treatment. This Ir(III)-AIE theragnostic probe merges enzymatic sensing with organelle-specific PDT, offering dual biomedical applications.
{"title":"Dual-functional AIE-active Ir(III) complexes for trypsin detection and organelle-targeted photodynamic therapy","authors":"Wanqing Zhang, Mengyue Tan, Meihua Chen, Weibin Chen, Mei-Jin Li","doi":"10.1016/j.jinorgbio.2025.113148","DOIUrl":"10.1016/j.jinorgbio.2025.113148","url":null,"abstract":"<div><div>Cyclometallated Ir(III) complex is a potential photosensitizer for photodynamic therapy (PDT) due to its unique photophysical properties. As an emerging anti-tumor therapy, PDT kills tumor cells by leveraging the toxic reactive oxygen species (ROS) generated by light-activated photosensitizers. In this work, two Ir(III) complexes with aggregation-induced emission (AIE) properties were designed and synthesized. A biosensor based on bovine serum albumin (BSA)-enhanced AIE of Ir(III) complexes for selective sensing of trypsin was constructed and explored. The therapeutic potential of the probes for PDT was evaluated by measuring their ROS generation efficiency, along with their phototoxicity and dark cytotoxicity in HeLa cells. In addition, localization of the two probes on organelles was investigated and the mechanism of apoptosis induced by the probe Ir-2 as a photosensitizer was studied using flow cytometry. The results demonstrated that these AIE-active complexes exhibited high ROS efficiency and good mitochondrial/lysosome dual-organelle targeting capability, which can enhance the efficacy of PDT in cancer treatment. This Ir(III)-AIE theragnostic probe merges enzymatic sensing with organelle-specific PDT, offering dual biomedical applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113148"},"PeriodicalIF":3.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.jinorgbio.2025.113150
Anthony J. Chavez , Peter C. Ford , Nadia G. Léonard , Mahdi M. Abu-Omar
Mixed-valence multi-metallic complexes, in which the metal is present in more than one oxidation state, provide crucial insight into how electron transfer operates in both biological proteins/enzymes and synthetic inorganic compounds. Nature offers striking examples, such as the oxygen-evolving complex (OEC) of photosystem II, where mixed valency plays an essential role in facilitating proton-coupled electron transfer (PCET) The degree of electronic delocalization between redox sites is subdivided into three groups (Class I, Class II, and Class III) by the Robin-Day classification. Elucidating electronic structure and the function of such systems serves as a foundation for the design of bioinspired catalysts. Nickel, with its rich redox flexibility, is well positioned to form mixed-valent binuclear complexes across several oxidation states, including Ni₂(I,0), Ni₂(I,II), and Ni₂(II,III) dinuclear complexes. Several such systems mirror the redox profiles of enzymes like acetyl-CoA synthase, which is central to C1 metabolism. This perspective highlights the emerging landscape of multinuclear nickel complexes, focusing on their structural classification and redox behavior. Special attention is given to a newly characterized family of Class III Ni₂(I,II) complexes, which exhibit fully delocalized valency. Collectively, this work underscores how mixed-valent states not only advance our understanding of electron transfer mechanisms but can also guide the development of new redox-active materials for catalysis.
{"title":"Mixed-valency in multinuclear nickel complexes: From fundamentals to nickel enzymes","authors":"Anthony J. Chavez , Peter C. Ford , Nadia G. Léonard , Mahdi M. Abu-Omar","doi":"10.1016/j.jinorgbio.2025.113150","DOIUrl":"10.1016/j.jinorgbio.2025.113150","url":null,"abstract":"<div><div>Mixed-valence multi-metallic complexes, in which the metal is present in more than one oxidation state, provide crucial insight into how electron transfer operates in both biological proteins/enzymes and synthetic inorganic compounds. Nature offers striking examples, such as the oxygen-evolving complex (OEC) of photosystem II, where mixed valency plays an essential role in facilitating proton-coupled electron transfer (PCET) The degree of electronic delocalization between redox sites is subdivided into three groups (Class I, Class II, and Class III) by the Robin-Day classification. Elucidating electronic structure and the function of such systems serves as a foundation for the design of bioinspired catalysts. Nickel, with its rich redox flexibility, is well positioned to form mixed-valent binuclear complexes across several oxidation states, including Ni₂(I,0), Ni₂(I,II), and Ni₂(II,III) dinuclear complexes. Several such systems mirror the redox profiles of enzymes like acetyl-CoA synthase, which is central to C1 metabolism. This perspective highlights the emerging landscape of multinuclear nickel complexes, focusing on their structural classification and redox behavior. Special attention is given to a newly characterized family of Class III Ni₂(I,II) complexes, which exhibit fully delocalized valency. Collectively, this work underscores how mixed-valent states not only advance our understanding of electron transfer mechanisms but can also guide the development of new redox-active materials for catalysis.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113150"},"PeriodicalIF":3.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.jinorgbio.2025.113149
Qinglin Chen, Hong Zeng, Jie Wu, Yuanyan Li, Yibao Li, Yongquan Wu
As a photochemical-based treatment approach, photodynamic therapy (PDT) relies on a photosensitiser (PS) that produces reactive oxygen species (ROS) after irradiation, which lead to irreparable cell damage and hence cell death. Cyclometalated iridium(III) complexes are often used in the development of PSs attributed to their rich photophysical properties with high quantum yields, large Stokes shifts, long-lived phosphorescence and good photostability. In addition, phenothiazine has excellent electron-donating ability and good rigid structure, its derivatives have been shown to possess activity against bacteria, malignant cells, and protozoa. In this work, we designed and synthesized two iridium(III) complexes DF-Ir-CHO and DF-Ir-PTZ. The DF-Ir-PTZ contains a novel ligand functionalized with phenothiazine. DF-Ir-PTZ has a better singlet oxygen (1O2) production quantum yield of 0.357 upon light irradiation and negligible dark cytotoxicity, suggesting that its biological safety is favorable. In addition, DF-Ir-PTZ was able to generate 1O2 and ROS in cancer cells under light conditions, leading to cell apoptosis of MCF-7.
{"title":"Exploring the singlet oxygen generation of iridium(III) complex containing phenothiazine for photodynamic therapy","authors":"Qinglin Chen, Hong Zeng, Jie Wu, Yuanyan Li, Yibao Li, Yongquan Wu","doi":"10.1016/j.jinorgbio.2025.113149","DOIUrl":"10.1016/j.jinorgbio.2025.113149","url":null,"abstract":"<div><div>As a photochemical-based treatment approach, photodynamic therapy (PDT) relies on a photosensitiser (PS) that produces reactive oxygen species (ROS) after irradiation, which lead to irreparable cell damage and hence cell death. Cyclometalated iridium(III) complexes are often used in the development of PSs attributed to their rich photophysical properties with high quantum yields, large Stokes shifts, long-lived phosphorescence and good photostability. In addition, phenothiazine has excellent electron-donating ability and good rigid structure, its derivatives have been shown to possess activity against bacteria, malignant cells, and protozoa. In this work, we designed and synthesized two iridium(III) complexes DF-Ir-CHO and DF-Ir-PTZ. The DF-Ir-PTZ contains a novel ligand functionalized with phenothiazine. DF-Ir-PTZ has a better singlet oxygen (<sup>1</sup>O<sub>2</sub>) production quantum yield of 0.357 upon light irradiation and negligible dark cytotoxicity, suggesting that its biological safety is favorable. In addition, DF-Ir-PTZ was able to generate <sup>1</sup>O<sub>2</sub> and ROS in cancer cells under light conditions, leading to cell apoptosis of MCF-7.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113149"},"PeriodicalIF":3.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.jinorgbio.2025.113137
Milica G. Paunović , Miloš M. Matić , Ana D. Obradović , Vesna D. Stanković , Verica V. Jevtić , Branka I. Ognjanović
Due to cisplatin's limited efficacy and adverse effects on healthy tissues, particularly the kidneys, its use is restricted. The objective of this research was to investigate the impact of new Pt(IV) complexes that contain ethyl- propyl- and butyl-esters of the ethylenediamine-N,N′-di-S,S-(2,2′-dibenzyl) acetic acid, as well as possible advantages of resveratrol co-treatment, on the kidneys of female Wistar albino rats by detecting kidney injury markers, oxidative stress parameters and morphological tissue changes. The rats, divided into ten groups, received a single intraperitoneal dosage of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg), and/or resveratrol (25 mg/kg), whereas the control animals received only an ip injection of saline. Acute complexes treatments increased Chl value while decreasing Gl, Cre, and Urea levels, suggesting kidney injury. Novel compounds considerably decreased the levels of O2•−, H2O2 and GSSG, while raising the levels of NO2−, LPO and GSH. In addition, the activities of SOD, GSH-Px, and GST were increased, while the activities of CAT and GR were alleviated. Regarding morphological changes in kidney tissue, they were mostly of mild intensity. Results indicate that used complexes might trigger an imbalance of redox equilibrium of kidney cells and that the renal tissue was more vulnerable to the negative effects of Pt(IV) complexes than to cisplatin. Resveratrol's nephroprotective benefits were not shown. Additionally, a prooxidative effect was registered after co-treatments. These findings could be useful for future studies in clarifying how the investigated compounds act in the estradiol-rich environment and how they affect the tissues of male rats.
{"title":"Assessment of the novel platinum(IV) complexes effects on female rats' kidneys: Possible nephroprotection of resveratrol","authors":"Milica G. Paunović , Miloš M. Matić , Ana D. Obradović , Vesna D. Stanković , Verica V. Jevtić , Branka I. Ognjanović","doi":"10.1016/j.jinorgbio.2025.113137","DOIUrl":"10.1016/j.jinorgbio.2025.113137","url":null,"abstract":"<div><div>Due to cisplatin's limited efficacy and adverse effects on healthy tissues, particularly the kidneys, its use is restricted. The objective of this research was to investigate the impact of new Pt(IV) complexes that contain ethyl- propyl- and butyl-esters of the ethylenediamine-<em>N,N′</em>-di-<em>S,S</em>-(2,2′-dibenzyl) acetic acid, as well as possible advantages of resveratrol co-treatment, on the kidneys of female Wistar albino rats by detecting kidney injury markers, oxidative stress parameters and morphological tissue changes. The rats, divided into ten groups, received a single intraperitoneal dosage of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg), and/or resveratrol (25 mg/kg), whereas the control animals received only an ip injection of saline. Acute complexes treatments increased Chl value while decreasing Gl, Cre, and Urea levels, suggesting kidney injury. Novel compounds considerably decreased the levels of O<sub>2</sub><sup>•−</sup>, H<sub>2</sub>O<sub>2</sub> and GSSG, while raising the levels of NO<sub>2</sub><sup>−</sup>, LPO and GSH. In addition, the activities of SOD, GSH-Px, and GST were increased, while the activities of CAT and GR were alleviated. Regarding morphological changes in kidney tissue, they were mostly of mild intensity. Results indicate that used complexes might trigger an imbalance of redox equilibrium of kidney cells and that the renal tissue was more vulnerable to the negative effects of Pt(IV) complexes than to cisplatin. Resveratrol's nephroprotective benefits were not shown. Additionally, a prooxidative effect was registered after co-treatments. These findings could be useful for future studies in clarifying how the investigated compounds act in the estradiol-rich environment and how they affect the tissues of male rats.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113137"},"PeriodicalIF":3.2,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517373","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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