Journal of Inorganic Biochemistry最新文献

{"title":"Multifunctional Ru(III)/Fe3O4/DNA nanoplatform for photothermal-enhanced photodynamic and chemodynamic cancer therapy","authors":"Jinfeng Zheng ,&nbsp;Xiufeng Wang ,&nbsp;Huan Du ,&nbsp;Ruyan Zhang ,&nbsp;Xiaobing Huo ,&nbsp;Ting Zhou ,&nbsp;Guodong Zhang ,&nbsp;Fang Wang ,&nbsp;Qianxiong Zhou ,&nbsp;Zhiqing Zhang","doi":"10.1016/j.jinorgbio.2024.112771","DOIUrl":"10.1016/j.jinorgbio.2024.112771","url":null,"abstract":"<div><div>Among the many cancer treatment methods, there have been many reports on the use of nanoplatforms with single treatment methods such as photothermal, photodynamic or chemodynamic for cancer treatment. In this study, Ru(III) with photodynamic effect and Fe₃O₄ nanoparticles with photothermal and chemodynamic effects are connected through long DNA chains with efficient active targeting rolling circle amplification to construct Ru(III)/Fe₃O₄/DNA nano-platform realizes the combination of photothermal, photodynamic and chemodynamic treatment, which significantly improves the therapeutic effect of the nano-platform. Its multiple active targeting capabilities reduce the damage to normal cells. Ru(III) has excellent photodynamic effect and can catalyze the respiration product NADH (Nicotinamide adenine dinucleotide)to produce highly oxidizing H₂O₂. Fe₃O₄ NPs has weak absorption at 808 nm indicates that it can perform mild photothermal treatment, and the Fe²⁺ in it can react with H₂O₂ to produce ·OH and participate in chemodynamic treatment. Each repeating unit on the rolling circle amplified DNA long chain is connected to the AS1411 aptamer that can actively target cancer cells. Unlike the passive targeting of other nanomedicines, active and efficient targeting is achieved, and a small amount of drugs can achieve high efficacy. The therapeutic effect also reduces the damage to normal cells. The comprehensive killing effect of Ru(III)/Fe₃O₄/DNA can reach 85.1 %. Its high targeting of cancer cells can also be used for imaging detection of cancer cells. This new nanoplatform provides an idea for the synergy of multiple cancer treatments.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586538","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}

{"title":"Anticancer behavior of cyclometallated iridium(III)-tributyltin(IV) carboxylate schiff base complexes with aggregation-induced emission","authors":"Xicheng Liu,&nbsp;Yiwei Sun,&nbsp;Yuan Gao,&nbsp;Xinru Zhang,&nbsp;Xiaoshuang Li,&nbsp;Wenya Zheng,&nbsp;Mengxian Liu,&nbsp;Ting Zhao,&nbsp;Xiang-Ai Yuan,&nbsp;Mingbo Yue,&nbsp;Zhe Liu","doi":"10.1016/j.jinorgbio.2024.112767","DOIUrl":"10.1016/j.jinorgbio.2024.112767","url":null,"abstract":"<div><div>Cyclometallated iridium(III) and organotin(IV) carboxylate complexes have shown potential application value in the field of anticancer. However, the widespread aggregation-caused quenching (ACQ) effect of these complexes is not conducive to the exploration of their targeting and anticancer mechanism, and the idea of aggregation-induced emission (AIE) effect can effectively solve this problem. Then, AIE-activated cyclometallated iridium(III)-tributyltin(IV) carboxylate Schiff base complexes were designed and prepared in this study. Complexes exhibited AIE effect in highly concentrated solution or aggregative state, which facilitated the investigation of subcellular tissue targeting (mitochondria) and cell morphology. Compared with cyclometallated iridium(III) complex and tributyltin(IV) carboxylate monomers, these complexes showed the better in-vitro anti-proliferative activity toward A549 cells, confirming the favorable synergistic anticancer activity. Even for A549/DDP (cisplatin-resistance) cells, these complexes also exhibited the better activity. In addition, complexes showed a mitochondrial apoptotic pathway. Therefore, cyclometallated iridium(III)-tributyltin(IV) carboxylate Schiff base complexes can be used as the potential substitutes for platinum-based drugs and gain further application.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560633","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}

{"title":"Cetirizine platinum(IV) complexes with antihistamine properties inhibit tumor metastasis by suppressing angiogenesis and boosting immunity","authors":"Yan Chen ,&nbsp;Shuaiqi Feng ,&nbsp;Ming Zhang ,&nbsp;Suying Li ,&nbsp;Ning Zhang ,&nbsp;Jun Han ,&nbsp;Zhifang Liu ,&nbsp;Meifeng Liu ,&nbsp;Qingpeng Wang","doi":"10.1016/j.jinorgbio.2024.112766","DOIUrl":"10.1016/j.jinorgbio.2024.112766","url":null,"abstract":"<div><div>The histamine (HA) in tumors plays critical roles in promoting metastasis. Herein, a series of cetirizine (CTZ) platinum(IV) complexes with antihistamine properties were developed as antimetastatic agents. Dual CTZ platinum(IV) complex with cisplatin core was screened out as a candidate displaying potent antiproliferative activities. More importantly, it exerted promising antimetastatic properties both <em>in vitro</em> and <em>in vivo</em>. Investigation of the mechanism revealed that serious DNA damage was induced, which further led to the upregulation of histone H2AX (<em>γ</em>-H2AX) and P53. The mitochondria-mediated apoptosis was ignited through the B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax)/caspase3 pathway. Moreover, the HA-histamine receptor H1 (HRH1) axis was inhibited, then the key signaling phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) was suppressed. Subsequently, the angiogenesis in tumors was restrained by suppressing the inflammatory and hypoxic microenvironment. Then, the antitumor immunity was reinforced by increasing the CD3⁺ and CD8⁺ T cells and promoting the polarization of macrophages from M2- to M1-type, which was associated with the blockade of programmed cell death ligand-1 (PD-L1) expression in tumors.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542650","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}

{"title":"Water-soluble neutral octahedral chalcogenide tungsten and molybdenum {M6Q8} clusters with P(C2H4CONH2)3 ligand","authors":"Alena D. Gassan ,&nbsp;Tatiana N. Pozmogova ,&nbsp;Ilia V. Eltsov ,&nbsp;Anton A. Ivanov ,&nbsp;Michael A. Shestopalov","doi":"10.1016/j.jinorgbio.2024.112768","DOIUrl":"10.1016/j.jinorgbio.2024.112768","url":null,"abstract":"<div><div>Developing the chemistry of octahedral chalcogenide molybdenum and tungsten cluster complexes in the context of applications in biology and medicine, in this work a series of water-soluble neutral cluster complexes [{M₆Q₈}(P(C₂H₄CONH₂)₃)₆] (M = Mo, W; Q = S, Se) have been obtained by simultaneous replacement of inner and terminal halide ligands in [{M₆I₈}I₆]²⁻ with chalcogenide and organic phosphine ligands and characterized by single-crystal X-ray diffraction analysis, ¹H and ³¹P NMR spectroscopies, elemental analysis, and UV–vis spectroscopy. The amide groups of the organic ligands, on the one hand, contribute to the solubility of the resulting clusters in water and, on the other hand, are able to form an extensive network of hydrogen bonds, leading to the crystallization of the complexes from aqueous solutions. Despite this fact, the complexes have sufficient solubility and stability in aqueous solutions, which made it possible to demonstrate their low cytotoxicity on Hep-2 cells (IC₅₀ were not reached even at concentration up to 4 mM). The resulting clusters are among the most biocompatible of the octahedral clusters studied to date and are the starting point for the development of a new family of X-ray contrast agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566704","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}

{"title":"Ruthenium(II) complexes containing PEGylated N-heterocyclic carbene ligands for tunning biocompatibility in the fight against cancer","authors":"Oscar Barrios ,&nbsp;Claudia Inclán ,&nbsp;Pablo Herrera ,&nbsp;Alicia Bort ,&nbsp;Avelino Martín ,&nbsp;Jesús Cano ,&nbsp;Inés Díaz-Laviada ,&nbsp;Rafael Gómez","doi":"10.1016/j.jinorgbio.2024.112765","DOIUrl":"10.1016/j.jinorgbio.2024.112765","url":null,"abstract":"<div><div>A synthetic procedure was designed for the preparation and characterization of Ag and Ru complexes containing NHC ligands functionalized with PEG fragments. Stability studies were conducted to gain insight of the species in water and other solvents like DMSO, or with reagents like imidazole as representative group for histidine amino acid. The presence of Cl atoms instead of H in the 4,5 positions of the N-heterocyclic carbene afforded higher water stability. The complexes containing PEG units must be considered inactive as anticancer agents. To enhance the anticancer activity of PEG-containing complexes, the balance between hydrophilicity and hydrophobicity was adjusted using a silane moiety, and an anionic carbosilane dendrimer as a lipophilic carrier.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542651","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}

{"title":"A dye-decolorizing peroxidase from Vibrio cholerae can demetallate heme","authors":"Takeshi Uchida ,&nbsp;Sayaka Umetsu ,&nbsp;Miho Sasaki ,&nbsp;Haruka Yoshimura ,&nbsp;Issei Omura ,&nbsp;Koichiro Ishimori","doi":"10.1016/j.jinorgbio.2024.112764","DOIUrl":"10.1016/j.jinorgbio.2024.112764","url":null,"abstract":"<div><div>Iron is an essential element for bacterial survival. Bacterial pathogens have therefore developed methods to obtain iron. <em>Vibrio cholerae</em>, the intestinal pathogen that causes cholera, utilizes heme as an iron source. DyP from <em>V. cholerae</em> (<em>Vc</em>DyP) is a dye-decolorizing peroxidase. When <em>Vc</em>DyP was expressed in <em>Escherichia coli</em> and purified, it was found to contain protoporphyrin IX (PPIX) but not heme, indicating that the protein possesses deferrochelatase activity. Here, we examined the demetallation reaction of <em>Vc</em>DyP using fluorescence spectroscopy. Treatment of heme-reconstituted <em>Vc</em>DyP with sodium dithionite under anaerobic conditions led to an increase in the fluorescence intensity at 624 nm, suggesting the formation of PPIX. Although the same reaction was conducted using myoglobin, horseradish peroxidase and hemin, no increase in the fluorescence was observed. Therefore, demetallation of heme is specific to <em>Vc</em>DyP. This reaction was faster at lower pH, but the amplitudes of the fluorescence increase were larger at pH 6.5–7.5, in clear contrast to the dye-decolorizing activity with the optimal pH of 4.5. In contrast to HutZ from <em>V. cholerae</em>, which is a heme-degrading enzyme that cleaves the heme macrocycle to release iron, <em>Vc</em>DyP can remove iron from heme without degradation. To our knowledge, <em>Vc</em>DyP is the first enzyme whose demetallation activity has been confirmed at neutral pH. Our results show that <em>Vc</em>DyP is a bifunctional protein that degrades anthraquinone dyes and demetallates heme.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542649","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}

{"title":"Catalytic and post-translational maturation roles of a conserved active site serine residue in nitrile hydratases","authors":"Callie Miller ,&nbsp;Kylie Knutson ,&nbsp;Dali Liu ,&nbsp;Brian Bennett ,&nbsp;Richard C. Holz","doi":"10.1016/j.jinorgbio.2024.112763","DOIUrl":"10.1016/j.jinorgbio.2024.112763","url":null,"abstract":"<div><div>A highly conserved second-sphere active site αSer residue in nitrile hydratase (NHase), that forms a hydrogen bond with the axial metal-bound water molecule, was mutated to Ala, Asp, and Thr, in the Co-type NHase from <em>Pseudonocardia thermophila</em> JCM 3095 (<em>Pt</em>NHase) and to Ala and Thr in the Fe-type NHase from <em>Rhodococcus equi</em> TG328–2 (<em>Re</em>NHase). All five mutants were successfully purified; metal analysis via ICP-AES indicated that all three Co-type <em>Pt</em>NHase mutants were in their apo-form while the Fe-type αSer117Ala and αSer117Thr mutants contained 85 and 50 % of their active site Fe(III) ions, respectively. The <em>k</em>_<em>cat</em> values obtained for the <em>Pt</em>NHase mutant enzymes were between 0.03 ± 0.01 and 0.2 ± 0.02 s^{−<strong>1</strong>} amounting to &lt;0.8 % of the <em>k</em>_<em>cat</em> value observed for WT <em>Pt</em>NHase. The Fe-type <em>Re</em>NHase mutants retained some detectable activity with <em>k</em>_<em>cat</em> values of 93 ± 3 and 40 ± 2 s^{−<strong>1</strong>} for the αSer117Ala and αSer117Thr mutants, respectively, which is ∼5 % of WT <em>Re</em>NHase activity towards acrylonitrile. UV–Vis spectra coupled with EPR data obtained on the <em>Re</em>NHase mutant enzymes showed subtle changes in the electronic environment around the active site Fe(III) ions, consistent with altering the hydrogen bonding interaction with the axial water ligand. X-ray crystal structures of the three <em>Pt</em>NHase mutant enzymes confirmed the mutation and the lack of active site metal, while also providing insight into the active site hydrogen bonding network. Taken together, these data confirm that the conserved active site αSer residue plays an important catalytic role but is not essential for catalysis. They also confirm the necessity of the conserved second-sphere αSer residue for the metalation process and subsequent post-translational modification of the α-subunit in Co-type NHases but not Fe-type NHases, suggesting different mechanisms for the two types of NHases.</div></div><div><h3>Synopsis</h3><div>A strictly conserved active site αSer residue in both Co- and Fe-type nitrile hydratases was mutated. This αSer residue was found to play an important catalytic function, but is not essential. In Co-type NHases, it appears to be essential for active site maturation, but not in Fe-type NHases.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492277","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}

{"title":"Interactions of Li+ ions with NCS1: A potential mechanism of Li+ neuroprotective action against psychotic disorders","authors":"Md Shofiul Alam ,&nbsp;Jonathan Cedeño ,&nbsp;Michael A. Reyes ,&nbsp;Sebastian Scavuzzo ,&nbsp;Jaroslava Miksovska","doi":"10.1016/j.jinorgbio.2024.112762","DOIUrl":"10.1016/j.jinorgbio.2024.112762","url":null,"abstract":"<div><div>Li⁺ based drugs have been used for the treatment of psychiatric disorders due to their mood stabilizing role for decades. Recently, several studies reported the protective effect of Li⁺ against severe neuropathologies such as Parkinson's, Alzheimer's, and Huntington's disease. Surprisingly, despite a broad range of Li⁺ effects on neurological conditions, little is known about its molecular mechanism. In this study, we propose that neuronal calcium sensor 1 (NCS1), can be an effective molecular target for Li⁺ action. Here we show that the EF-hands in ApoNCS1 have submillimolar affinity for Li⁺ with K_d = 223 ± 19 μM. Li⁺ binding to ApoNCS1 quenches Trp emission intensity, suggesting distinct Trp sidechains environment in Li⁺NCS1 compared to ApoNCS1 and Ca²⁺NCS1. Li⁺ association also stabilizes the protein α-helical structure, in a similar way to Ca²⁺. Li⁺ association does not promote NCS1 dimerization. Association of Li⁺ increases NCS1 affinity for the D2R receptor binding peptide, in a similar way to Ca²⁺, however, the affinity of NCS1 for chlorpromazine is reduced with respect to Ca²⁺NCS1, possibly due to a decrease in solvent exposed hydrophobic area on the NCS1 surface in the presence of Li⁺. MD simulation data suggests that Li⁺ ions are coordinated by four oxygens from Asp and Glu sidechains and one carbonyl oxygen, in a similar way as reported previously for Li⁺ binding to DREAM. Overall, the data shows that Li⁺ binds to EF-hands of NCS1 and Li⁺NCS1 interactions may be involved in the potential neuroprotective role of Li⁺ against psychotic disorders.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492278","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}

{"title":"Positively charged residues play a significant role in enhancing the antibacterial activity of calcitermin","authors":"Silvia Leveraro ,&nbsp;Maria D'Accolti ,&nbsp;Erika Marzola ,&nbsp;Elisabetta Caselli ,&nbsp;Remo Guerrini ,&nbsp;Magdalena Rowinska-Zyrek ,&nbsp;Maurizio Remelli ,&nbsp;Denise Bellotti","doi":"10.1016/j.jinorgbio.2024.112761","DOIUrl":"10.1016/j.jinorgbio.2024.112761","url":null,"abstract":"<div><div>A systematic study on the human antimicrobial peptide calcitermin (VAIALKAAHYHTHKE) and its carefully designed derivatives was undertaken to verify the impact of divalent copper and zinc ions on the stability, coordination and antimicrobial activity of the formed complexes. In this work we investigate the calcitermin mutants where the alanine in position 7 and 8 is substituted with an arginine residue, with the aim of enhancing the antibacterial activity. Additionally, the analogue where alanine in position 7 is replaced with a histidine is considered, to obtain a chelating sequence with four histidines in alternate position; the aim of this change was to increase the cationic properties of the peptide under acidic conditions and possibly enhance its binding ability towards the metal ions. Through a comprehensive analytical approach involving potentiometric titrations, mass spectrometry, UV–Vis spectrophotometry, NMR and circular dichroism, we delved into the formation equilibria and coordination chemistry of the formed copper(II) and zinc(II) complexes. Antimicrobial assays are also performed to assess the bioactivity of the compounds against a broad spectrum of microorganisms, revealing the pivotal role of positively charged residues in enhancing the antibacterial activity of calcitermin. The obtained results serve as an important stepping stone towards the development of novel metal-based antimicrobial agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454990","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}

{"title":"A tale of two old drugs tetracycline and salicylic acid with new perspectives—Coordination chemistry of their Co(II) and Ni(II) complexes, redox activity of Cu(II) complex, and molecular interactions","authors":"Jinhua Xie ,&nbsp;Shahedul Islam ,&nbsp;Le Wang ,&nbsp;Xiaojing Zheng ,&nbsp;Mengsheng Xu ,&nbsp;Xiqi Su ,&nbsp;Shaohua Huang ,&nbsp;Logan Suits ,&nbsp;Guang Yang ,&nbsp;Prahathees Eswara ,&nbsp;Jianfeng Cai ,&nbsp;Li-June Ming","doi":"10.1016/j.jinorgbio.2024.112757","DOIUrl":"10.1016/j.jinorgbio.2024.112757","url":null,"abstract":"<div><div>Extensive use of the broad-spectrum tetracycline antibiotics (TCs) has resulted their wide spread in the environment and drive new microecological balances, including the infamous antibiotic resistance. TCs require metal ions for their antibiotic activity and resistance via interactions with ribosome and tetracycline repressor TetR, respectively, at specific metal-binding sites. Moreover, the Lewis-acidic metal center(s) in metallo-TCs can interact with Lewis-basic moieties of many bioactive secondary metabolites, which in turn may alter their associated chemical equilibria and biological activities. Thus, it is ultimately important to reveal detailed coordination chemistry of metallo-TC complexes. Herein, we report (a) conclusive specific Co²⁺, Ni²⁺, and Cu²⁺-binding of TC revealed by paramagnetic ¹H NMR, showing different conformations of the coordination and different metal-binding sites in solution and solid state, (b) significant metal-mediated activity of Cu-TC toward catechol oxidation with different mechanisms by air and H₂O₂ (i.e., mono- and di-nuclear pathways, respectively), (c) interactions of metallo-TCs with bioactive salicylic acid and its precursor benzoic acid, and (d) noticeable change of TC antibiotic activity by metal and salicylic acid. The results imply that TCs may play broad and versatile roles in maintaining certain equilibria in microecological environments in addition to their well-established antibiotic activity. We hope the results may foster further exploration of previously unknown metal-mediated activities of metallo-TC complexes and other metalloantibiotics.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445869","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}