Journal of Inorganic Biochemistry最新文献

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Copper(II) carboxylate complexes inhibit Staphylococcus aureus biofilm formation by targeting extracellular proteins

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-30 DOI: 10.1016/j.jinorgbio.2025.112835

Hazrat Bilal , Cai-Xiang Zhang , Muhammad Iqbal Choudhary , Sukanya Dej-adisai , Yanghan Liu , Zhen-Feng Chen

Three copper(II) complexes of diphenyl acetic acid (DPAA) pyridine (py), 2,2΄-dipyridylamine (dpa), and 4,7-diphenyl, 1,10-phenanthrline (di-phen), [Cu₂(DPAA)₄(py)₂] (Cu-1), [Cu(DPAA)₂(dpa)] (Cu-2), and [Cu₂(DPAA)₄(di-phen)₂] (Cu-3) were synthesized and characterized. Their antibacterial activities were evalvated. The minimum inhibitory concentrations (MIC) of these complexes against six tested microbial strains ranged from 1 to 128 μg/mL, and that of vancomycin antibiotic ranged from 0.5 to 2 μg/mL. The bactericidal effects of Cu-1, Cu-2 and Cu-3 and vancomycin against Staphylococcus aureus (S. aureus) were determined by colony count assay. Cu-1, Cu-2, and vancomycin showed relatively weaker antibiofilm formation activities; however, Cu-3 showed enhanced activity against S. aureus proliferation and biofilm formation as confirmed by microscopic analysis. In antibiofilm assays, Cu-1, Cu-2 and Cu-3 demonstrated high inhibition ability (23–75 %), of mature biofilm formation at concentrations of 5 to 15 μg/mL, and vancomycin at 15 μg/mL inhibited only 47 %. Cu-3 also effectively killed S. aureus within biofilms at doses up to 2 × MIC μg/mL. Further analysis of extracellular proteins (ECPs) expression revealed, that Cu-3 had significant potential in suppressing ECPs production. Molecular docking (MD) studies with biofilm associated protein (Bap) and SARS-CoV-2 receptors showed high interactions by several bonding types, where Cu-2 found as potent antiviral agent. Collectively, these findings highlighted the copper complexes potential in antibacterial applications, with Cu-3 emerging as a potent candidate for S. aureus biofilm inhibition.

{"title":"Copper(II) carboxylate complexes inhibit Staphylococcus aureus biofilm formation by targeting extracellular proteins","authors":"Hazrat Bilal , Cai-Xiang Zhang , Muhammad Iqbal Choudhary , Sukanya Dej-adisai , Yanghan Liu , Zhen-Feng Chen","doi":"10.1016/j.jinorgbio.2025.112835","DOIUrl":"10.1016/j.jinorgbio.2025.112835","url":null,"abstract":"<div><div>Three copper(II) complexes of diphenyl acetic acid (DPAA) pyridine (py), 2,2΄-dipyridylamine (dpa), and 4,7-diphenyl, 1,10-phenanthrline (di-phen), [Cu₂(DPAA)₄(py)2] (Cu-1), [Cu(DPAA)₂(dpa)] (Cu-2), and [Cu₂(DPAA)₄(di-phen)₂] (Cu-3) were synthesized and characterized. Their antibacterial activities were evalvated. The minimum inhibitory concentrations (MIC) of these complexes against six tested microbial strains ranged from 1 to 128 μg/mL, and that of vancomycin antibiotic ranged from 0.5 to 2 μg/mL. The bactericidal effects of Cu-1, Cu-2 and Cu-3 and vancomycin against Staphylococcus aureus (S. aureus) were determined by colony count assay. Cu-1, Cu-2, and vancomycin showed relatively weaker antibiofilm formation activities; however, Cu-3 showed enhanced activity against S. aureus proliferation and biofilm formation as confirmed by microscopic analysis. In antibiofilm assays, Cu-1, Cu-2 and Cu-3 demonstrated high inhibition ability (23–75 %), of mature biofilm formation at concentrations of 5 to 15 μg/mL, and vancomycin at 15 μg/mL inhibited only 47 %. Cu-3 also effectively killed S. aureus within biofilms at doses up to 2 × MIC μg/mL. Further analysis of extracellular proteins (ECPs) expression revealed, that Cu-3 had significant potential in suppressing ECPs production. Molecular docking (MD) studies with biofilm associated protein (Bap) and SARS-CoV-2 receptors showed high interactions by several bonding types, where Cu-2 found as potent antiviral agent. Collectively, these findings highlighted the copper complexes potential in antibacterial applications, with Cu-3 emerging as a potent candidate for S. aureus biofilm inhibition.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"266 ","pages":"Article 112835"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143356051","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

Jim Kincaid and heme proteins: The Princeton years and beyond

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-25 DOI: 10.1016/j.jinorgbio.2025.112834

Thomas G. Spiro

This article is a personal chronical of Jim Kincaid's scientific career from his postdoctoral years in my laboratory at Princeton, to his final years in his lab at Marquette. He devoted himself to the study of heme proteins, using Raman spectroscopy as a probe of structure and function, producing many notable advances in our understanding of these key biological molecules. Along the way, Jim supported and encouraged many aspiring scientists. Reminiscences from his students and colleagues affirm his enthusiasm for science and for friendship, his generosity of time and attention, his puckish sense of humor, his unfailing kindness and his concern for the well-being of those around him, to the very end of his life. I was fortunate to have him as a student, collaborator, and life-long friend.

引用次数: 0

Two multifunctional zero-dimensional Gd(III) complexes: magnetocaloric effect and anticancer mechanisms for lung cancer

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-22 DOI: 10.1016/j.jinorgbio.2025.112832

Shouying Cao, Yaqing Xie, Xiaotong Lu, Zijie Zhao, Feiya Zhou, Jie Wang, Lili Liang

Two Gd(III) complexes [GdL(H₂O)(NO₃)₂(CH₃OH)_0.75(CH₃CH₂OH)_0.25] (Gd1) and [Gd₂(OOCCH₃)₂L₂(H₂O)₆]•2(H₂O) (Gd2) (HL = 2-pyridylcarboxaldehyde isonicotinoylhydrazone) were synthesized with a Schiff base ligand. Crystallographic study reveals both Gd1 and Gd2 have a zero-dimensional mononuclear or binuclear structure. Magnetic investigations demonstrate that Gd1 and Gd2 exhibit potential magnetocaloric effects due to Gd(III) ions, which provide negligible magnetic anisotropy, and possess low-lying excited spin states. The antiproliferative activity of Gd1 and Gd2 to three tumor cell lines was conducted and the results showed Gd1 and Gd2 showed more pronounced antiproliferative activity to A549 cells better than cisplatin. The administration of Gd1 and Gd2 led to an increase in apoptosis among A549 cells in a concentration-dependent manner, along with a corresponding rise in the levels of reactive oxygen species (ROS) within the cells. Besides, Gd1 and Gd2 were able to significantly inhibit tumor cell migration. Cell cycle assay in A549 cells revealed that cell cycle was arrested of G0/G1 phase. Western blotting analysis showed that Gd1 and Gd2 complexes could promote apoptosis in A549 cells by modulating the expression of Bcl-2 and Bax proteins.

{"title":"Two multifunctional zero-dimensional Gd(III) complexes: magnetocaloric effect and anticancer mechanisms for lung cancer","authors":"Shouying Cao, Yaqing Xie, Xiaotong Lu, Zijie Zhao, Feiya Zhou, Jie Wang, Lili Liang","doi":"10.1016/j.jinorgbio.2025.112832","DOIUrl":"10.1016/j.jinorgbio.2025.112832","url":null,"abstract":"<div><div>Two Gd(III) complexes [GdL(H2O)(NO3)2(CH3OH)0.75(CH3CH2OH)0.25] (Gd1) and [Gd2(OOCCH3)2L2(H2O)6]•2(H2O) (Gd2) (HL = 2-pyridylcarboxaldehyde isonicotinoylhydrazone) were synthesized with a Schiff base ligand. Crystallographic study reveals both Gd1 and Gd2 have a zero-dimensional mononuclear or binuclear structure. Magnetic investigations demonstrate that Gd1 and Gd2 exhibit potential magnetocaloric effects due to Gd(III) ions, which provide negligible magnetic anisotropy, and possess low-lying excited spin states. The antiproliferative activity of Gd1 and Gd2 to three tumor cell lines was conducted and the results showed Gd1 and Gd2 showed more pronounced antiproliferative activity to A549 cells better than cisplatin. The administration of Gd1 and Gd2 led to an increase in apoptosis among A549 cells in a concentration-dependent manner, along with a corresponding rise in the levels of reactive oxygen species (ROS) within the cells. Besides, Gd1 and Gd2 were able to significantly inhibit tumor cell migration. Cell cycle assay in A549 cells revealed that cell cycle was arrested of G0/G1 phase. Western blotting analysis showed that Gd1 and Gd2 complexes could promote apoptosis in A549 cells by modulating the expression of Bcl-2 and Bax proteins.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112832"},"PeriodicalIF":3.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057437","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

Copper-nitrite complexes release nitric oxide and selectively induce oral precancer and cancer cell apoptosis

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-20 DOI: 10.1016/j.jinorgbio.2025.112833

Yen-Yun Wang , Pang-Yu Chen , Naorem Jemes Meitei , Yu-Ren Lin , Tsai-Te Lu , Hieu D.H. Nguyen , Sodio C.N. Hsu , Shyng-Shiou F. Yuan

Nitric oxide (NO) is a small, short-lived gas molecule that influences various critical functions in living organisms. It involves multiple physiological processes, including cardiovascular function, metabolism, neurotransmission, immunity, and aberrant NO signaling leads to various disorders such as cardiovascular diseases, diabetes, and cancers. In this study, we explored the potential application of copper-nitrite complexes in treating oral precancer and cancer. The copper-nitrite complexes, L₁Cu(NO₂) and L₂Cu(NO₂), were shown to release NO into cells and selectively induce cytotoxicity to oral precancer and cancer cells. Notably, L₁Cu(NO₂) inhibited oral cancer cell proliferation by causing G0/G1 phase cell cycle arrest. Furthermore, L₁Cu(NO₂) induced cell apoptosis and upregulated the expression of p-PRAS40 (proline-rich Akt substrate of 40 kDa) in oral cancer cells. All these results reveal the therapeutic potential of copper-nitrite complexes, especially L₁Cu(NO₂), to be developed as a targeted therapy against oral precancer and cancer.

{"title":"Copper-nitrite complexes release nitric oxide and selectively induce oral precancer and cancer cell apoptosis","authors":"Yen-Yun Wang , Pang-Yu Chen , Naorem Jemes Meitei , Yu-Ren Lin , Tsai-Te Lu , Hieu D.H. Nguyen , Sodio C.N. Hsu , Shyng-Shiou F. Yuan","doi":"10.1016/j.jinorgbio.2025.112833","DOIUrl":"10.1016/j.jinorgbio.2025.112833","url":null,"abstract":"<div><div>Nitric oxide (NO) is a small, short-lived gas molecule that influences various critical functions in living organisms. It involves multiple physiological processes, including cardiovascular function, metabolism, neurotransmission, immunity, and aberrant NO signaling leads to various disorders such as cardiovascular diseases, diabetes, and cancers. In this study, we explored the potential application of copper-nitrite complexes in treating oral precancer and cancer. The copper-nitrite complexes, L1Cu(NO2) and L2Cu(NO2), were shown to release NO into cells and selectively induce cytotoxicity to oral precancer and cancer cells. Notably, L1Cu(NO2) inhibited oral cancer cell proliferation by causing G0/G1 phase cell cycle arrest. Furthermore, L1Cu(NO2) induced cell apoptosis and upregulated the expression of p-PRAS40 (proline-rich Akt substrate of 40 kDa) in oral cancer cells. All these results reveal the therapeutic potential of copper-nitrite complexes, especially L1Cu(NO2), to be developed as a targeted therapy against oral precancer and cancer.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112833"},"PeriodicalIF":3.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035694","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

Large-capacity DNA vectors based on rolling circle amplification with multivalent aptamers delivery copper sulfide for the synergistic treatment of Cancer through chemo/Photothermal/Chemodynamic therapy in vitro

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-17 DOI: 10.1016/j.jinorgbio.2025.112831

Huan Du, Fang Wang, Ruyan Zhang, Yan Ma, Xiaobing Huo, Gan Ning, Xiufeng Wang, Ting Zhou, Guodong Zhang, Zhiqing Zhang

Developing multifunctional nanomedicines represents a frontier. We have engineered a high-capacity DNA vector basing rolling circle amplification for the delivery of copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), coupled with multivalent aptamers (MA) that precisely target tumors, culminating in a multifunctional nanoplatform (RMAL₁Cu@DOX), which combines the chemotherapy (CT)/photothermal therapy (PTT)/chemodynamic therapy (CDT). The vector (RMAL₁) boasts exceptional biocompatibility and incorporates multiple copy units, enabling the precise loading of numerous CuS NPs, forming RMAL₁Cu which possesses a robust photothermal effect and superior Fenton-like catalytic activity, heralding a project of minimally invasive dual-mode (PTT/CDT) therapy. Furthermore, the abundance of G-C of RMAL₁ enabled effective DOX encapsulation through π-π interactions to construct RMAL₁Cu@DOX. The MA integrated into RMAL₁Cu@DOX is pivotal in enhancing the targeting of tumors and in preventing non-specific release of CuS and DOX, enabling an integrated CT/PTT/CDT. Data indicate that 1 nM of RMAL₁Cu could load 270 nM of DOX with an impressive loading capacity of 77 %, and modification with MA, its tumor-targeting ability was amplified by 51-fold and significantly bolstered in vitro imaging outcomes, and the synergistic killing of B16 was as 67.3 %. This innovative nanoplatform offers a comprehensive and holistic strategy for the treatment of malignant tumors.

{"title":"Large-capacity DNA vectors based on rolling circle amplification with multivalent aptamers delivery copper sulfide for the synergistic treatment of Cancer through chemo/Photothermal/Chemodynamic therapy in vitro","authors":"Huan Du, Fang Wang, Ruyan Zhang, Yan Ma, Xiaobing Huo, Gan Ning, Xiufeng Wang, Ting Zhou, Guodong Zhang, Zhiqing Zhang","doi":"10.1016/j.jinorgbio.2025.112831","DOIUrl":"10.1016/j.jinorgbio.2025.112831","url":null,"abstract":"<div><div>Developing multifunctional nanomedicines represents a frontier. We have engineered a high-capacity DNA vector basing rolling circle amplification for the delivery of copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), coupled with multivalent aptamers (MA) that precisely target tumors, culminating in a multifunctional nanoplatform (RMAL1Cu@DOX), which combines the chemotherapy (CT)/photothermal therapy (PTT)/chemodynamic therapy (CDT). The vector (RMAL1) boasts exceptional biocompatibility and incorporates multiple copy units, enabling the precise loading of numerous CuS NPs, forming RMAL1Cu which possesses a robust photothermal effect and superior Fenton-like catalytic activity, heralding a project of minimally invasive dual-mode (PTT/CDT) therapy. Furthermore, the abundance of G-C of RMAL1 enabled effective DOX encapsulation through π-π interactions to construct RMAL1Cu@DOX. The MA integrated into RMAL1Cu@DOX is pivotal in enhancing the targeting of tumors and in preventing non-specific release of CuS and DOX, enabling an integrated CT/PTT/CDT. Data indicate that 1 nM of RMAL1Cu could load 270 nM of DOX with an impressive loading capacity of 77 %, and modification with MA, its tumor-targeting ability was amplified by 51-fold and significantly bolstered in vitro imaging outcomes, and the synergistic killing of B16 was as 67.3 %. This innovative nanoplatform offers a comprehensive and holistic strategy for the treatment of malignant tumors.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112831"},"PeriodicalIF":3.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035696","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

Binding a C12-appended rhenium-(Bispyridine) carbonyl complex to β-Lactoglobulin: Effects of pH & cysteine modification on calyx affinity 将 C12 添加的铼-（双吡啶）羰基复合物与 β-乳球蛋白结合：pH 值和半胱氨酸修饰对花萼亲和力的影响。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-13 DOI: 10.1016/j.jinorgbio.2025.112828

Emily E. Stumbo , Sean T. Goralski , Phillip R. Leclair, Spencer Kerns, Michael J. Rose

Due to its commercial availability and well-defined structure, the interaction between bovine protein β-lactoglobulin (βLG) and a wide variety of non-native ligands — including transition metal complexes — has been explored, but its application as an artificial metalloenzyme scaffold is limited. This protein is hypothesized to transport fatty acids and other nutrients during juvenile development, and it binds hydrophobic ligands inside a binding pocket constructed upon an 8-stranded β-barrel, called the ‘calyx’. Herein, we compare the binding behavior of two rhenium(anthracene-bispyridine) (‘Anth-py₂’) tricarbonyl complexes, one with a 12‑carbon chain appended to the ligand scaffold (‘^C12Anth-py₂’) to βLG. We investigate (i) how calyx-binding specificity is affected by pH (which controls βLG structure at the entrance to the calyx) and (ii) modification of a free cysteine residue located in a putative second binding site of βLG (SMe-βLG). The binding affinities of [Re(^C12Anth-py₂)(CO)₃(solv)]⁺ (ReC₁₂) and [Re(Anth-py₂)(CO)₃(solv)]⁺ (ReCH) for βLG at pH 7.3 were similar at 36 ± 2 μM and 43 ± 1 μM, respectively. The K_D of ReC₁₂ decreased by ∼13 μM at pH 6.1 due to a well-known conformational change (Tanford transition) at the entrance to the calyx; the K_D value was not significantly affected by Cys121 modification, indicating β-barrel calyx binding specificity. In contrast, ReCH experienced a decrease in K_D in response to blocking the second binding (SMe-βLG), but was also unaffected by pH. The results show an increase in binding affinity and specificity as a result of targeted ligand design and utilization of native protein characteristics. The findings will inform and improve the design of future βLG-derived ArMs.

{"title":"Binding a C12-appended rhenium-(Bispyridine) carbonyl complex to β-Lactoglobulin: Effects of pH & cysteine modification on calyx affinity","authors":"Emily E. Stumbo , Sean T. Goralski , Phillip R. Leclair, Spencer Kerns, Michael J. Rose","doi":"10.1016/j.jinorgbio.2025.112828","DOIUrl":"10.1016/j.jinorgbio.2025.112828","url":null,"abstract":"<div><div>Due to its commercial availability and well-defined structure, the interaction between bovine protein β-lactoglobulin (βLG) and a wide variety of non-native ligands — including transition metal complexes — has been explored, but its application as an artificial metalloenzyme scaffold is limited. This protein is hypothesized to transport fatty acids and other nutrients during juvenile development, and it binds hydrophobic ligands inside a binding pocket constructed upon an 8-stranded β-barrel, called the ‘calyx’. Herein, we compare the binding behavior of two rhenium(anthracene-bispyridine) (‘Anth-py2’) tricarbonyl complexes, one with a 12‑carbon chain appended to the ligand scaffold (‘C12Anth-py2’) to βLG. We investigate (i) how calyx-binding specificity is affected by pH (which controls βLG structure at the entrance to the calyx) and (ii) modification of a free cysteine residue located in a putative second binding site of βLG (SMe-βLG). The binding affinities of [Re(C12Anth-py2)(CO)3(solv)]+ (ReC12) and [Re(Anth-py2)(CO)3(solv)]+ (ReCH) for βLG at pH 7.3 were similar at 36 ± 2 μM and 43 ± 1 μM, respectively. The KD of ReC12 decreased by ∼13 μM at pH 6.1 due to a well-known conformational change (Tanford transition) at the entrance to the calyx; the KD value was not significantly affected by Cys121 modification, indicating β-barrel calyx binding specificity. In contrast, ReCH experienced a decrease in KD in response to blocking the second binding (SMe-βLG), but was also unaffected by pH. The results show an increase in binding affinity and specificity as a result of targeted ligand design and utilization of native protein characteristics. The findings will inform and improve the design of future βLG-derived ArMs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112828"},"PeriodicalIF":3.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035690","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

Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-11 DOI: 10.1016/j.jinorgbio.2025.112829

Paolo Ascenzi , Giovanna De Simone , Gabriele Antonio Zingale , Massimo Coletta

Nitrite (NO₂⁻) interacts with myoglobin (Mb) and hemoglobin (Hb) behaving as a ligand of both the ferrous (i.e., Mb(II) and Hb(II)) and ferric (i.e., Mb(III) and Hb(III)) forms. However, while the binding to the Fe(III) species corresponds to the formation of a stable complex (i.e., Mb(III)-NO₂⁻ and Hb(III)-NO₂⁻), in the case of the ferrous forms the reaction proceeds with a nitrite reductase redox process, leading to the oxidation of the heme-protein with the reduction of NO₂⁻ to NO. This event is of the utmost importance for the rapid production of NO in vivo in the blood stream and in striated muscles, being crucial for the regulation of the blood flow, and thus for O₂ supply to poorly oxygenated tissues, such as the eye's retina. Further, NO₂⁻ interacts with Mb(II)-O₂ and Hb(II)-O₂, inducing their oxidation with a complex mechanism, which has been only partially elucidated. Mb and Hb form the complex with NO₂⁻ through the O-nitrito binding mode (i.e., Fe-ONO⁻), which is regulated by residues paving the heme distal side; thus, in a site-directed mutant, where HisE7 is substituted by Val, the interaction occurs in the N-nitro binding mode (i.e., Fe-N(O)O⁻), like in most other heme-proteins. The structure-function relationships of the interaction of NO₂⁻ with both ferric and ferrous forms of Mb and Hb are discussed here.

{"title":"Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects","authors":"Paolo Ascenzi , Giovanna De Simone , Gabriele Antonio Zingale , Massimo Coletta","doi":"10.1016/j.jinorgbio.2025.112829","DOIUrl":"10.1016/j.jinorgbio.2025.112829","url":null,"abstract":"<div><div>Nitrite (NO2−) interacts with myoglobin (Mb) and hemoglobin (Hb) behaving as a ligand of both the ferrous (i.e., Mb(II) and Hb(II)) and ferric (i.e., Mb(III) and Hb(III)) forms. However, while the binding to the Fe(III) species corresponds to the formation of a stable complex (i.e., Mb(III)-NO2− and Hb(III)-NO2−), in the case of the ferrous forms the reaction proceeds with a nitrite reductase redox process, leading to the oxidation of the heme-protein with the reduction of NO2− to NO. This event is of the utmost importance for the rapid production of NO in vivo in the blood stream and in striated muscles, being crucial for the regulation of the blood flow, and thus for O2 supply to poorly oxygenated tissues, such as the eye's retina. Further, NO2− interacts with Mb(II)-O2 and Hb(II)-O2, inducing their oxidation with a complex mechanism, which has been only partially elucidated. Mb and Hb form the complex with NO2− through the O-nitrito binding mode (i.e., Fe-ONO−), which is regulated by residues paving the heme distal side; thus, in a site-directed mutant, where HisE7 is substituted by Val, the interaction occurs in the N-nitro binding mode (i.e., Fe-N(O)O−), like in most other heme-proteins. The structure-function relationships of the interaction of NO2− with both ferric and ferrous forms of Mb and Hb are discussed here.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112829"},"PeriodicalIF":3.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035710","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

Palladium(II) complexes containing andrographolide appended N,O heterocyclic chelators: Investigation of anti-oxidant, anti-cancer and apoptotic activities

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-11 DOI: 10.1016/j.jinorgbio.2025.112830

Priya Prasad , S. Parveen , Abdullah A. Alarfaj , Abdurahman Hajinur Hirad , M. Mohamed Subarkhan , S. Dhanapal , G. Kalaiarasi

A series of new Pd(II) complexes were synthesized from the reaction of andrographolide appended hydrazide derivatives with potassium tetrachloropalladate K₂[PdCl₄]. The formation of the complexes was confirmed through structural assessments conducted using various spectroscopic techniques. From the spectral studies we confirmed that the ligands coordinated to Pd(II) ion via amine nitrogen and enone oxygen. The complexes were assessed for their antioxidant properties, demonstrating significant radical scavenging activity with a series of free radicals such as 1,1-diphenyl-2-picrylhydrazyl (DPPH^•), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS^•+), Super oxide (O²⁻) and Nitric oxide (NO^•) radicals compared with standard antioxidants. Moreover, in vitro antiproliferative investigations conducted on A549 (human lung cancer) and HeLa (human cervical cancer) cell lines revealed significant cytotoxicity of the complexes, with lower IC₅₀ values compared to the standard metallo-drug cisplatin. Morphological alterations observed in HeLa and A549 cells when treated with IC₅₀ concentrations of the complexes, as examined through Acridine Orange-Ethidium Bromide (AO-EB) and 4′,6-diamidino-2-phenylindole (DAPI) staining techniques, indicated cell death via apoptosis. Biological studies indicated that AGC-Pd exhibited superior activity among others, further the percentages of the apoptotic and necrotic cells were determined by flow cytometric technique.

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引用次数: 0

Accessing iridium Cp* as a cofactor for artificial metalloenzymes 获得铱Cp*作为人工金属酶的辅助因子。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-03 DOI: 10.1016/j.jinorgbio.2024.112820

Oskar James Klein, Armando Albert-Flores, Matthew G. Wheeler, Katherine Rojales, Andrew D. Bond, Sally R. Boss, Paul D. Barker

By introducing new-to-nature transformations, artificial metalloenzymes hold great potential for expanding the biosynthetic toolbox. The chemistry of an active cofactor in these enzymes is highly dependent on how the holoprotein is assembled, potentially limiting the choice of organometallic complexes amenable to incorporation and ability of the protein structure to influence the metal centre. We have previously reported a method utilising ligand exchange as a means to introduce ruthenium-arene fragments into a four-helix bundle protein. In this work we expand the scope of this method to incorporate an iridium pentamethylcyclopentadienyl fragment into a four-helix bundle, yielding an artificial metalloenzyme with improved transfer hydrogenation properties, highlighting that understanding ligand exchange reactions is important for speciation control.

通过引入新的自然转化，人工金属酶具有扩大生物合成工具箱的巨大潜力。这些酶中活性辅助因子的化学性质高度依赖于全蛋白的组装方式，这可能限制了适合结合的有机金属配合物的选择以及蛋白质结构影响金属中心的能力。我们以前曾报道过一种利用配体交换将钌-芳烃片段引入四螺旋束蛋白的方法。在这项工作中，我们扩展了该方法的范围，将五甲基环戊二烯铱片段纳入四螺旋束，产生具有改善转移氢化性能的人工金属酶，强调了解配体交换反应对物种形成控制的重要性。

引用次数: 0

Ruthenium(II)-mercapto complexes induce cell damage via apoptosis pathway on ovarian cancer cells 钌(II)-巯基复合物通过凋亡途径诱导卵巢癌细胞损伤。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2024-12-30 DOI: 10.1016/j.jinorgbio.2024.112819

Marcos V. Palmeira-Mello , Tamara Teixeira , Matheus Reis Santos de Melo , Heloiza Diniz Nicolella , Jocely L. Dutra , Marcia R. Cominetti , Fillipe Vieira Rocha , Denise Crispim Tavares , Alzir A. Batista

Ovarian cancer represents a leading cause of cancer-related deaths in women worldwide. Chemotherapeutic agents are usually employed to treat the patients, and Ruthenium(II)-based compounds have been investigated as possible substitutes for platinum drugs. In this work, we studied three different Ru(II)-phosphine-mercapto complexes (1–3) as potential cytotoxic agents against A2780 and A2780-cisR ovarian cancer cells. A time-dependent cytotoxicity was observed for 2, which also exhibited better selectivity than cisplatin control. A similar cytotoxic behavior was observed on 3D tumor spheroids. Although no changes were observed in cell cycle distribution, compound 2 affected the mitochondrial membrane potential on A2780 cells, and caused cell death via apoptotic pathway, which was confirmed by flow cytometry assay. Western blotting experiments revealed that 2 affected the expression of p53, PCNA, γH2AX and cleaved caspase-3, making it a promising anticancer agent for ovarian cancer.

卵巢癌是全世界妇女癌症相关死亡的主要原因。化疗药物通常用于治疗患者，钌（II）基化合物已被研究作为铂类药物的可能替代品。在这项工作中，我们研究了三种不同的Ru(II)-膦-巯基络合物（1-3）作为抗A2780和A2780- cisr卵巢癌细胞的潜在细胞毒性药物。观察到2的时间依赖性细胞毒性，也表现出比顺铂对照组更好的选择性。在三维肿瘤球体上观察到类似的细胞毒性行为。虽然没有观察到细胞周期分布的变化，但化合物2影响了A2780细胞的线粒体膜电位，并通过凋亡途径引起细胞死亡，流式细胞术实验证实了这一点。Western blotting实验显示，2能影响p53、PCNA、γ - h2ax和cleaved caspase-3的表达，是一种很有前景的卵巢癌抗癌药物。

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引用次数: 0

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