Journal of Inorganic Biochemistry最新文献

英文中文

A highly positively charged Ru(II) complex with photo-labile ligands for selective and efficient photo-inactivation of intracellular Staphylococcus aureus 带有光敏配体的高正电荷 Ru(II) 复合物可选择性地高效光灭活细胞内的金黄色葡萄球菌

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-04-04 DOI: 10.1016/j.jinorgbio.2025.112908

Yunli Xu , Xuwen Da , Yao Jian , Wanpeng Zhou , Aifeng Wu , Yao Wu , Yatong Peng , Xiulian Liu , Yu Shi , Xuesong Wang , Qianxiong Zhou

Due to the protection afforded by host cells, intracellular Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), poses a significantly greater challenge to eliminate compared to the extracellular counterparts. It is highly desirable to develop novel antibacterial agents which are capable of selectively and efficiently eradicating intracellular bacteria, including drug-resistant strains, while being less prone to induce bacterial resistance. In this work, two Ru(II) complexes (Ru1 and Ru2) with photo-labile ligands were designed and synthesized. Both Ru1 and Ru2 could covalently bind to DNA after photo-induced ligand dissociation. Compared to Ru1, the incorporation of a triphenylamine group adorned with two positively charged cationic pyridine units significantly boosts the DNA binding constant, bacterial binding/uptake level, and subsequently, the antibacterial activity of Ru2. Ru2 could selectively photo-inactivate intracellular S. aureus and MRSA, being more efficient than vancomycin both in vitro and in vivo. Interestingly, after 20 days' treatment at sublethal concentrations, S. aureus cells exhibited no obvious drug resistance towards Ru2 upon irradiation. Such appealing results may provide new sights for developing novel antibacterial agents against intractable intracellular pathogens and also prevalent drug resistance.

{"title":"A highly positively charged Ru(II) complex with photo-labile ligands for selective and efficient photo-inactivation of intracellular Staphylococcus aureus","authors":"Yunli Xu , Xuwen Da , Yao Jian , Wanpeng Zhou , Aifeng Wu , Yao Wu , Yatong Peng , Xiulian Liu , Yu Shi , Xuesong Wang , Qianxiong Zhou","doi":"10.1016/j.jinorgbio.2025.112908","DOIUrl":"10.1016/j.jinorgbio.2025.112908","url":null,"abstract":"<div><div>Due to the protection afforded by host cells, intracellular <em>Staphylococcus aureus</em> (<em>S. aureus</em>), particularly methicillin-resistant <em>S. aureus</em> (MRSA), poses a significantly greater challenge to eliminate compared to the extracellular counterparts. It is highly desirable to develop novel antibacterial agents which are capable of selectively and efficiently eradicating intracellular bacteria, including drug-resistant strains, while being less prone to induce bacterial resistance. In this work, two Ru(II) complexes (Ru1 and Ru2) with photo-labile ligands were designed and synthesized. Both Ru1 and Ru2 could covalently bind to DNA after photo-induced ligand dissociation. Compared to Ru1, the incorporation of a triphenylamine group adorned with two positively charged cationic pyridine units significantly boosts the DNA binding constant, bacterial binding/uptake level, and subsequently, the antibacterial activity of Ru2. Ru2 could selectively photo-inactivate intracellular <em>S. aureus</em> and MRSA, being more efficient than vancomycin both <em>in vitro</em> and <em>in vivo</em>. Interestingly, after 20 days' treatment at sublethal concentrations, <em>S. aureus</em> cells exhibited no obvious drug resistance towards Ru2 upon irradiation. Such appealing results may provide new sights for developing novel antibacterial agents against intractable intracellular pathogens and also prevalent drug resistance.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112908"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800406","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}

引用次数: 0

Intrinsically photoluminescent hydrogels to measure peptides‑copper binding affinities

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-04-04 DOI: 10.1016/j.jinorgbio.2025.112914

Alessia Distefano , Paolo Corsaro , Nunzio Tuccitto , Francesca Laneri , Olivier Monasson , Elisa Peroni , Giuseppe Grasso

NH₂ decorated intrinsically photoluminescent hydrogels (IPH-NH₂) were functionalized with the addition of various peptides via EDC/NHS coupling method. These peptidic devices bind copper with binding affinities depending on surface functionalization. Particularly, fluorescence analysis of copper titrations, alongside the determination of quenching efficiency and lifetime measurements, allowed to assess binding constants and to elucidate the underlying binding mechanism. Various peptides, having the same copper binding amino acidic residues (GHK) but different chain lengths, were tested and it was found that increasing the distance of the GHK sequence from the IPH-NH₂ surface resulted in a decrease in the binding constant, as well as a reduction in quenching efficiency, whereas the binding mechanism remained unchanged as indicated by lifetime measurements. This method not only provides binding constants for peptides immobilized on biosensor surfaces or pre-fabricated devices without altering their structure, but also contributes to the optimization of biosensor design, tailoring it to its intended application.

{"title":"Intrinsically photoluminescent hydrogels to measure peptides‑copper binding affinities","authors":"Alessia Distefano , Paolo Corsaro , Nunzio Tuccitto , Francesca Laneri , Olivier Monasson , Elisa Peroni , Giuseppe Grasso","doi":"10.1016/j.jinorgbio.2025.112914","DOIUrl":"10.1016/j.jinorgbio.2025.112914","url":null,"abstract":"<div><div>NH<sub>2</sub> decorated intrinsically photoluminescent hydrogels (IPH-NH<sub>2</sub>) were functionalized with the addition of various peptides via EDC/NHS coupling method. These peptidic devices bind copper with binding affinities depending on surface functionalization. Particularly, fluorescence analysis of copper titrations, alongside the determination of quenching efficiency and lifetime measurements, allowed to assess binding constants and to elucidate the underlying binding mechanism. Various peptides, having the same copper binding amino acidic residues (GHK) but different chain lengths, were tested and it was found that increasing the distance of the GHK sequence from the IPH-NH<sub>2</sub> surface resulted in a decrease in the binding constant, as well as a reduction in quenching efficiency, whereas the binding mechanism remained unchanged as indicated by lifetime measurements. This method not only provides binding constants for peptides immobilized on biosensor surfaces or pre-fabricated devices without altering their structure, but also contributes to the optimization of biosensor design, tailoring it to its intended application.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112914"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791270","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}

引用次数: 0

Recent advances in Schiff bases and Cu(II) complexes: Applications in fluorescence imaging and anticancer therapy (2020–2024)

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-04-03 DOI: 10.1016/j.jinorgbio.2025.112909

Alaa Shafie , Amal Adnan Ashour

Schiff base derivatives have garnered significant attention for their bioimaging and anticancer potentials. In the realm of bioimaging, Schiff base derivatives have shown exceptional capabilities in detecting various metal ions, due to their strong binding affinities and fluorescence properties. Moreover, the potential Schiff bases and their Cu(II) complexes as anticancer agents is being actively explored, with studies demonstrating their ability to induce apoptosis and inhibit cell proliferation in various cancer cell lines. This review article provides a comprehensive overview of recent advancements in the field of cell imaging utilizing Schiff base derivatives for the recognition of Cu²⁺ in living cells and organisms. From 2022 to 2024, significant progress has been made in understanding the applications of Schiff bases in cell imaging techniques, ranging from fluorescence microscopy to molecular imaging modalities. Additionally, article has focused on leveraging the unique properties of Schiff base Cu(II) complexes to expand the anticancer efficacy. The article offering insights into the mechanisms underlying enhanced anticancer activity and the development of novel anticancer agents.

{"title":"Recent advances in Schiff bases and Cu(II) complexes: Applications in fluorescence imaging and anticancer therapy (2020–2024)","authors":"Alaa Shafie , Amal Adnan Ashour","doi":"10.1016/j.jinorgbio.2025.112909","DOIUrl":"10.1016/j.jinorgbio.2025.112909","url":null,"abstract":"<div><div>Schiff base derivatives have garnered significant attention for their bioimaging and anticancer potentials. In the realm of bioimaging, Schiff base derivatives have shown exceptional capabilities in detecting various metal ions, due to their strong binding affinities and fluorescence properties. Moreover, the potential Schiff bases and their Cu(II) complexes as anticancer agents is being actively explored, with studies demonstrating their ability to induce apoptosis and inhibit cell proliferation in various cancer cell lines. This review article provides a comprehensive overview of recent advancements in the field of cell imaging utilizing Schiff base derivatives for the recognition of Cu<sup>2+</sup> in living cells and organisms. From 2022 to 2024, significant progress has been made in understanding the applications of Schiff bases in cell imaging techniques, ranging from fluorescence microscopy to molecular imaging modalities. Additionally, article has focused on leveraging the unique properties of Schiff base Cu(II) complexes to expand the anticancer efficacy. The article offering insights into the mechanisms underlying enhanced anticancer activity and the development of novel anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112909"},"PeriodicalIF":3.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785777","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}

引用次数: 0

Repaglinide platinum(IV) conjugates: Enhancing p53 signaling for antitumor and antimetastatic efficacy

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-04-03 DOI: 10.1016/j.jinorgbio.2025.112910

Suying Li , Zhifang Liu , Yan Chen , Shuaiqi Feng , Hengye Chen , Yanna Zhao , Yanqin He , Qingpeng Wang

The tumor suppressor p53 plays multiple roles at the crossroads of suppressing tumor development and metastasis. Here, a series of Repaglinide platinum(IV) conjugates promoting the p53 pathway were designed and prepared, which displayed potent antiproliferative and antimetastatic activities both in vitro and in vivo. Mechanistically, the expression of p53 was upregulated by the synergistic functions of the platinum core through causing severe DNA damage, and the RPG ligand via stimulating the lumican/p53/p21 pathway. The mitochondria-mediated apoptosis was initiated, involving the Bcl-2/Bax/caspase pathway. Pro-death autophagy was initiated with the upregulation of LC3II and down regulation of p62. Additionally, angiogenesis was suppressed by reversing tumor inflammation through the inhibition of key enzymes COX-2, MMP9, and VEGFA. Furthermore, antitumor immunity was enhanced by blocking the immune checkpoint PD-L1, which led to an increased presence of CD3⁺ and CD8⁺ T-cells within the tumor microenvironment.

{"title":"Repaglinide platinum(IV) conjugates: Enhancing p53 signaling for antitumor and antimetastatic efficacy","authors":"Suying Li , Zhifang Liu , Yan Chen , Shuaiqi Feng , Hengye Chen , Yanna Zhao , Yanqin He , Qingpeng Wang","doi":"10.1016/j.jinorgbio.2025.112910","DOIUrl":"10.1016/j.jinorgbio.2025.112910","url":null,"abstract":"<div><div>The tumor suppressor p53 plays multiple roles at the crossroads of suppressing tumor development and metastasis. Here, a series of Repaglinide platinum(IV) conjugates promoting the p53 pathway were designed and prepared, which displayed potent antiproliferative and antimetastatic activities both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, the expression of p53 was upregulated by the synergistic functions of the platinum core through causing severe DNA damage, and the RPG ligand <em>via</em> stimulating the lumican/p53/p21 pathway. The mitochondria-mediated apoptosis was initiated, involving the Bcl-2/Bax/caspase pathway. Pro-death autophagy was initiated with the upregulation of LC3II and down regulation of p62. Additionally, angiogenesis was suppressed by reversing tumor inflammation through the inhibition of key enzymes COX-2, MMP9, and VEGFA. Furthermore, antitumor immunity was enhanced by blocking the immune checkpoint PD-L1, which led to an increased presence of CD3<sup>+</sup> and CD8<sup>+</sup> T-cells within the tumor microenvironment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112910"},"PeriodicalIF":3.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791269","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}

引用次数: 0

Unraveling the unfolding mechanism of pseudoazurin: Insights into stabilizing cupredoxin fold as a common domain of Cu-containing proteins

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-04-02 DOI: 10.1016/j.jinorgbio.2025.112907

Takahide Yamaguchi , Attila Taborosi , Kiyokazu Tsugane , Kathleen Wood , Andrew E. Whitten , Seiji Mori , Takamitsu Kohzuma

Understanding protein unfolding mechanisms is crucial for comprehending protein-folding related diseases, developing diagnostic methods, and designing proteins with desired stability for medicinal or industrial applications. However, investigating structures at atomic resolution is often difficult due to the flexibility and transiency of unfolding intermediate states. Pseudoazurin (PAz) is a well-characterized simple cupredoxin composed of a small polypeptide (124 amino acids) and a single metal cofactor (Cu²⁺), making it suitable to study the unfolding mechanism. In this study, combining the merits of structure determination by small-angle neutron scattering (SANS) and molecular dynamics (MD) simulations enabled us to access the details of the unfolding mechanism. The unfolding of PAz proceeds through a two-step mechanism involving the “native”, “open-domain”, and “random-coil” states. Several amino acid residues at the vicinity of Cu²⁺ ion are involved in the structural transitions, where the interactions among these residues are important in controlling the stability of PAz. These findings may be applicable to stabilizing metalloproteins with cupredoxin domain structures.

{"title":"Unraveling the unfolding mechanism of pseudoazurin: Insights into stabilizing cupredoxin fold as a common domain of Cu-containing proteins","authors":"Takahide Yamaguchi , Attila Taborosi , Kiyokazu Tsugane , Kathleen Wood , Andrew E. Whitten , Seiji Mori , Takamitsu Kohzuma","doi":"10.1016/j.jinorgbio.2025.112907","DOIUrl":"10.1016/j.jinorgbio.2025.112907","url":null,"abstract":"<div><div>Understanding protein unfolding mechanisms is crucial for comprehending protein-folding related diseases, developing diagnostic methods, and designing proteins with desired stability for medicinal or industrial applications. However, investigating structures at atomic resolution is often difficult due to the flexibility and transiency of unfolding intermediate states. Pseudoazurin (PAz) is a well-characterized simple cupredoxin composed of a small polypeptide (124 amino acids) and a single metal cofactor (Cu<sup>2+</sup>), making it suitable to study the unfolding mechanism. In this study, combining the merits of structure determination by small-angle neutron scattering (SANS) and molecular dynamics (MD) simulations enabled us to access the details of the unfolding mechanism. The unfolding of PAz proceeds through a two-step mechanism involving the “native”, “open-domain”, and “random-coil” states. Several amino acid residues at the vicinity of Cu<sup>2+</sup> ion are involved in the structural transitions, where the interactions among these residues are important in controlling the stability of PAz. These findings may be applicable to stabilizing metalloproteins with cupredoxin domain structures.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112907"},"PeriodicalIF":3.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791271","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}

引用次数: 0

Rationalizing the structural basis of organic-platinum hybrid complexes binding towards quadruplex-duplex hybrids through all-atom simulations

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-04-01 DOI: 10.1016/j.jinorgbio.2025.112904

Salvatore Muscarella, Irene Treccarichi, Luisa D'Anna, Angelo Spinello

Guanine-rich sequences containing complementary base pairs can fold into non-canonical quadruplex-duplex hybrid (QDH) conformations. These structures possess unique structural features, leading to the presence of a peculiar binding pocket that can be distinguished from a canonical double helix or a G-quadruplex (G4) structure. Recently, two organic-metal hybrid platinum complexes, able to selectively and strongly recognize a particular type of QDH with a lateral duplex stem-loop, were reported in the literature. However, solution structures are not available for all the investigated compounds, leaving unanswered questions on the structural traits underlying the different binding affinity of these complexes. In this work, we address this gap using all-atom simulations to unravel the key features driving the high selectivity of these organic‑platinum hybrid complexes at an atomistic level. In particular, their binding affinity depends on a delicate balance between the extended π-π stacking interactions performed in the G4-duplex binding pocket and the capacity to form stable hydrogen bonds with the surrounding nucleobases. Thus, our findings provide essential insights to guide the rational design of novel compounds that selectively target QDH structures.

{"title":"Rationalizing the structural basis of organic-platinum hybrid complexes binding towards quadruplex-duplex hybrids through all-atom simulations","authors":"Salvatore Muscarella, Irene Treccarichi, Luisa D'Anna, Angelo Spinello","doi":"10.1016/j.jinorgbio.2025.112904","DOIUrl":"10.1016/j.jinorgbio.2025.112904","url":null,"abstract":"<div><div>Guanine-rich sequences containing complementary base pairs can fold into non-canonical quadruplex-duplex hybrid (QDH) conformations. These structures possess unique structural features, leading to the presence of a peculiar binding pocket that can be distinguished from a canonical double helix or a G-quadruplex (G4) structure. Recently, two organic-metal hybrid platinum complexes, able to selectively and strongly recognize a particular type of QDH with a lateral duplex stem-loop, were reported in the literature. However, solution structures are not available for all the investigated compounds, leaving unanswered questions on the structural traits underlying the different binding affinity of these complexes. In this work, we address this gap using all-atom simulations to unravel the key features driving the high selectivity of these organic‑platinum hybrid complexes at an atomistic level. In particular, their binding affinity depends on a delicate balance between the extended π-π stacking interactions performed in the G4-duplex binding pocket and the capacity to form stable hydrogen bonds with the surrounding nucleobases. Thus, our findings provide essential insights to guide the rational design of novel compounds that selectively target QDH structures.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112904"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785778","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}

引用次数: 0

Bioinspired copper(II) complexes catalyzed oxidative coupling of aminophenols with broader substrate scope

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-03-28 DOI: 10.1016/j.jinorgbio.2025.112906

Thasnim P Mohammed , Marappan Velusamy , Muniyandi Sankaralingam

The strategic selection of ligand systems in metal complexes has demonstrated a profound impact on the efficiency and specificity of biomimetic reactions. In this work, we introduce a series of aminoquinoline-based copper(II) complexes (1–4) distinguished by systematic variation in terminal amine substituents: di-n-methyl (L1(H)), di-n-ethyl (L2(H)), di-n-propyl (L3(H)), and di-n-butyl (L4(H)). These complexes are synthesized, characterized, and evaluated as the catalyst for the oxidative coupling of different aminophenol derivatives. Remarkably, complex 1, featuring a methyl substituent, exhibited unparalleled catalytic performance, achieving an 86 % (K_cat - 9.7 × 10⁴ h⁻¹) conversion of o-aminophenol to the desired product, 2-amino-phenoxazin-3-one, alongside water and hydrogen peroxide as byproducts. Notably, complex 1 demonstrated exceptional versatility, extending its catalytic activity to other substrates with remarkable activity. Mechanistic investigations, supported by mass-spectrometric analysis, revealed the formation of a complex-substrate adduct with all substrates, enabling us to propose a detailed reaction pathway. The work highlights the benefits of ligand design in improving catalytic performance and sets a new standard for aminoquinoline-based copper(II) complexes in oxidative coupling reactions. To the best of our knowledge, this work is the first to report a wider substrate scope for PHS activity with copper(II) complexes.

金属配合物中配体系统的策略性选择对仿生反应的效率和特异性有着深远的影响。在这项工作中，我们介绍了一系列基于氨基喹啉的铜（II）配合物（1-4），这些配合物通过末端胺取代基的系统变化而有所区别：二-正甲基（L1(H)）、二-正乙基（L2(H)）、二-正丙基（L3(H)）和二-正丁基（L4(H)）。这些配合物作为不同氨基苯酚衍生物氧化偶联的催化剂进行了合成、表征和评估。值得注意的是，以甲基取代基为特征的复合物 1 表现出了无与伦比的催化性能，它能将邻氨基苯酚转化为所需产物 2-氨基苯并恶嗪-3-酮，转化率高达 86%（Kcat - 9.7 × 104 h-1），同时副产物为水和过氧化氢。值得注意的是，复合物 1 表现出了非凡的多功能性，其催化活性可扩展到其他底物，且活性显著。在质谱分析的支持下进行的机理研究发现，所有底物都会形成复合物与底物的加合物，从而使我们能够提出详细的反应途径。这项工作凸显了配体设计在提高催化性能方面的优势，并为氧化偶联反应中的氨基喹啉基铜（II）配合物设定了新标准。据我们所知，这项研究首次报告了铜(II)配合物在 PHS 活性方面更广泛的底物范围。

{"title":"Bioinspired copper(II) complexes catalyzed oxidative coupling of aminophenols with broader substrate scope","authors":"Thasnim P Mohammed , Marappan Velusamy , Muniyandi Sankaralingam","doi":"10.1016/j.jinorgbio.2025.112906","DOIUrl":"10.1016/j.jinorgbio.2025.112906","url":null,"abstract":"<div><div>The strategic selection of ligand systems in metal complexes has demonstrated a profound impact on the efficiency and specificity of biomimetic reactions. In this work, we introduce a series of aminoquinoline-based copper(II) complexes (<strong>1</strong>–<strong>4</strong>) distinguished by systematic variation in terminal amine substituents: di-<em>n</em>-methyl (<strong>L1</strong>(H)), di-<em>n</em>-ethyl (<strong>L2</strong>(H)), di-<em>n</em>-propyl (<strong>L3</strong>(H)), and di-<em>n</em>-butyl (<strong>L4</strong>(H)). These complexes are synthesized, characterized, and evaluated as the catalyst for the oxidative coupling of different aminophenol derivatives. Remarkably, complex <strong>1</strong>, featuring a methyl substituent, exhibited unparalleled catalytic performance, achieving an 86 % (<em>K</em><sub>cat</sub> - 9.7 × 10<sup>4</sup> h<sup>−1</sup>) conversion of <em>o</em>-aminophenol to the desired product, 2-amino-phenoxazin-3-one, alongside water and hydrogen peroxide as byproducts. Notably, complex <strong>1</strong> demonstrated exceptional versatility, extending its catalytic activity to other substrates with remarkable activity. Mechanistic investigations, supported by mass-spectrometric analysis, revealed the formation of a complex-substrate adduct with all substrates, enabling us to propose a detailed reaction pathway. The work highlights the benefits of ligand design in improving catalytic performance and sets a new standard for aminoquinoline-based copper(II) complexes in oxidative coupling reactions. To the best of our knowledge, this work is the first to report a wider substrate scope for PHS activity with copper(II) complexes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112906"},"PeriodicalIF":3.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829668","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}

引用次数: 0

Ascorbic acid potentiates the formation of IgG-enriched protein aggregates in plasma in a Cu(II)-mediated manner

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-03-24 DOI: 10.1016/j.jinorgbio.2025.112905

Christian Saporito-Magriña , Lila Lopez-Montañana , María Laura Facio , Guadalupe Pagano , Topp Nicole , Ariana Danzi , Juan Ignacio Bellida , Agustín Silva , Matías Albizzati , Marisa Gabriela Repetto

Protein aggregates have been reported in disease but also in physiological contexts in tissues as well as circulating protein aggregates in the bloodstream. Free Cu(II) induces the aggregation of serum proteins and this metal yields highly oxidant species upon reaction with hydrogen peroxide and also reacts with ascorbic acid (AA). A broad population is exposed to high doses of AA as second line therapy for different pathologies or as nutritional supplementation. This study addresses the effect of AA on the formation of plasma protein aggregates, observed by optic density, protein quantification and electrophoresis (SDS-PAGE) that, contrary to hampering the Cu(II)-induced plasma protein aggregation, AA potentiates their formation. Free Cu(II) induces the formation of IgG-enriched plasma protein aggregates but the combination with AA potentiates the incorporation of gamma-globulin (IgG) whereas other proteins such as albumin become depleted. The potentiating effect of Cu(II) and AA was corroborated employing isolated IgG. This effect of AA on Cu(II)-induced protein aggregation is not reproduced with isolated albumin. Additionally, AA does not potentiate Fe(III)-mediated aggregation of IgG, albumin or human plasma. Finally, it was shown that in healthy subjects which were administered high doses of intravenous AA, the aggregates can be obtained from the centrifuged plasma after 30 min of the administration of the antioxidant. Aggregated IgG have been shown to activate Fc receptors, involved in oxidative burst and inflammatory processes observed in neutrophils. Thus, the effect of AA on the immune system could be linked to the accumulation of protein aggregates enriched in specific proteins.

{"title":"Ascorbic acid potentiates the formation of IgG-enriched protein aggregates in plasma in a Cu(II)-mediated manner","authors":"Christian Saporito-Magriña , Lila Lopez-Montañana , María Laura Facio , Guadalupe Pagano , Topp Nicole , Ariana Danzi , Juan Ignacio Bellida , Agustín Silva , Matías Albizzati , Marisa Gabriela Repetto","doi":"10.1016/j.jinorgbio.2025.112905","DOIUrl":"10.1016/j.jinorgbio.2025.112905","url":null,"abstract":"<div><div>Protein aggregates have been reported in disease but also in physiological contexts in tissues as well as circulating protein aggregates in the bloodstream. Free Cu(II) induces the aggregation of serum proteins and this metal yields highly oxidant species upon reaction with hydrogen peroxide and also reacts with ascorbic acid (AA). A broad population is exposed to high doses of AA as second line therapy for different pathologies or as nutritional supplementation. This study addresses the effect of AA on the formation of plasma protein aggregates, observed by optic density, protein quantification and electrophoresis (SDS-PAGE) that, contrary to hampering the Cu(II)-induced plasma protein aggregation, AA potentiates their formation. Free Cu(II) induces the formation of IgG-enriched plasma protein aggregates but the combination with AA potentiates the incorporation of gamma-globulin (IgG) whereas other proteins such as albumin become depleted. The potentiating effect of Cu(II) and AA was corroborated employing isolated IgG. This effect of AA on Cu(II)-induced protein aggregation is not reproduced with isolated albumin. Additionally, AA does not potentiate Fe(III)-mediated aggregation of IgG, albumin or human plasma. Finally, it was shown that in healthy subjects which were administered high doses of intravenous AA, the aggregates can be obtained from the centrifuged plasma after 30 min of the administration of the antioxidant. Aggregated IgG have been shown to activate Fc receptors, involved in oxidative burst and inflammatory processes observed in neutrophils. Thus, the effect of AA on the immune system could be linked to the accumulation of protein aggregates enriched in specific proteins.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112905"},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705198","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}

引用次数: 0

Coiled coils as ligands for inclusion in the inorganic chemist's toolbox – For advances in MRI contrast agent design

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-03-23 DOI: 10.1016/j.jinorgbio.2025.112903

Anna F.A. Peacock

Ligands are essential tools in synthetic inorganic chemistry, enabling the fine-tuning of metal ion properties to optimize performance. Spanning from small molecules to macromolecular proteins, ligands vary widely in structure and function. De novo designed coiled coils serve as a unique bridge between these extremes, offering precise control over metal coordination. Here, we explore the application of coiled coil ligands in MRI contrast agent design, leveraging their versatility to systematically modulate the coordination chemistry and hydration state of gadolinium - the metal used in most clinical MRI contrast agents. This novel class of gadolinium-based agents demonstrates superior performance compared to existing clinical agents, highlighting the potential of coiled coil ligands. Furthermore, when coordinated to copper, these ligands form complexes that challenge the conventional notion that copper is unsuitable for MRI contrast agents. These findings establish coiled coil ligands as a powerful platform for advancing contrast agent design.

引用次数: 0

Novel erbium complex with anticancer activity against radiation resistant lung adenocarcinoma cells

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-03-19 DOI: 10.1016/j.jinorgbio.2025.112902

Hao Wang , Guozhu Ren , Yue Xu , Ruiping Deng , Rui Wang , Liang Zhou

In this work, novel erbium complex with anticancer activity against radiation resistant lung adenocarcinoma cells was obtained and demonstrated. Firstly, stronger inhibitory effect of Er³⁺ on non-small cell lung cancer (NSCLC) cells and NSCLC- radiation resistant (RR) cells was experimentally confirmed. Then, by selecting highly biocompatible porphyrins as ligands, a novel erbium complex tetraphenylporphyrin erbium acetylacetonate (Er(acac)TPP) was synthesized and purified. Compared with Cisplatin, notably, Er(acac)TPP exhibits relatively higher inhibitory efficiency on NSCLC-RR cells. Moreover, the toxicities of Er(acac)TPP to normal cells are much lower than that of cancer cells. Subsequently, cell expansion, increased apoptosis, a decline in mitochondrial membrane potential (MMP), an accumulation of intracellular reactive oxygen species (ROS), increased Caspase-9 protein level and G2/M arrest were seen. These data all pointed to Er(acac)TPP as a possible candidate for more research and development as a chemotherapeutic drug.

{"title":"Novel erbium complex with anticancer activity against radiation resistant lung adenocarcinoma cells","authors":"Hao Wang , Guozhu Ren , Yue Xu , Ruiping Deng , Rui Wang , Liang Zhou","doi":"10.1016/j.jinorgbio.2025.112902","DOIUrl":"10.1016/j.jinorgbio.2025.112902","url":null,"abstract":"<div><div>In this work, novel erbium complex with anticancer activity against radiation resistant lung adenocarcinoma cells was obtained and demonstrated. Firstly, stronger inhibitory effect of Er<sup>3+</sup> on non-small cell lung cancer (NSCLC) cells and NSCLC- radiation resistant (RR) cells was experimentally confirmed. Then, by selecting highly biocompatible porphyrins as ligands, a novel erbium complex tetraphenylporphyrin erbium acetylacetonate (Er(acac)TPP) was synthesized and purified. Compared with Cisplatin, notably, Er(acac)TPP exhibits relatively higher inhibitory efficiency on NSCLC-RR cells. Moreover, the toxicities of Er(acac)TPP to normal cells are much lower than that of cancer cells. Subsequently, cell expansion, increased apoptosis, a decline in mitochondrial membrane potential (MMP), an accumulation of intracellular reactive oxygen species (ROS), increased Caspase-9 protein level and G2/M arrest were seen. These data all pointed to Er(acac)TPP as a possible candidate for more research and development as a chemotherapeutic drug.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112902"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682899","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}

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Journal of Inorganic Biochemistry

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀