Journal of Inorganic Biochemistry最新文献

{"title":"Loss of chromium(III) from mixed Cr(III),Fe(III) serum Transferrins","authors":"Dylan R. Graham,&nbsp;Kyle C. Edwards,&nbsp;Susan Darby Keith,&nbsp;Michael W. Gannon,&nbsp;John B. Vincent","doi":"10.1016/j.jinorgbio.2025.113046","DOIUrl":"10.1016/j.jinorgbio.2025.113046","url":null,"abstract":"<div><div>Trivalent chromium has been shown to be transported <em>in vivo</em> from the bloodstream to the tissues <em>via</em> endocytosis by transferrin (Tf), the major iron transport protein in the blood. Recent <em>in vitro</em> studies using Cr(III)₂-Tf have shown that under physiologically relevant conditions, the binding of Cr(III) to Tf and the loss of Cr(III) from the Cr(III)₂-Tf/Tf receptor complex are rapid. However, the major form of transferrin in the bloodstream is monoferric Tf. Thus, given the low concentrations of Cr(III) in the bloodstream, the form of Cr(III)-containing transferrin in the bloodstream that is transported <em>via</em> endocytosis is monochromic, monoferric-Tf (Cr(III),Fe(III)-Tf). Given that Tf has two specific metal-binding sites, one in both the C-terminal and the N-terminal lobes of Tf, two forms of Cr(III),Fe(III)-Tf can form. The loss of Cr(III) from both forms of Cr(III),Fe(III)-Tf have been examined for the first time. The mixed metal Tf's lose Cr(III) in similar fashions to Cr(III) losses from Cr(III)₂-Tf itself or from the Cr(III)₂-Tf/Tf receptor complex.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113046"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908486","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":"Knowledge graph-driven curation of heme-TLR4 interactions in inflammatory pathways","authors":"Dhruv C. Rathod ,&nbsp;Negin Sadat Babaiha ,&nbsp;Elena Kullmann ,&nbsp;Martin Hofmann-Apitius ,&nbsp;Diana Imhof","doi":"10.1016/j.jinorgbio.2025.113040","DOIUrl":"10.1016/j.jinorgbio.2025.113040","url":null,"abstract":"<div><div>Heme, a vital iron-containing molecule, serves fundamental roles in oxygen transport and electron transfer but also acts as an extracellular signaling entity, significantly influencing inflammatory responses. Elevated levels of labile heme resulting from hemolytic events or therapeutic treatments may activate inflammatory signaling pathways, particularly through the Toll-like receptor 4 (TLR4). In this study, we systematically expanded the previously developed Heme Knowledge Graph (HemeKG) to comprehensively incorporate recent findings regarding heme-TLR4 interactions. By employing rigorous literature curation and validation using Biological Expression Language (BEL) standards and the e:BEL Python package, we successfully integrated newly identified molecular entities, notably activator protein 1 (AP-1), interleukin-12 (IL-12), cluster of differentiation 80 (CD80), cluster of differentiation 86 (CD86), and chemokine (C-X-C motif) ligand 1 (CXCL1), into the existing HemeKG framework. Pathway enrichment analysis across Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and WikiPathways databases robustly supported these integrations, consistently identifying significant enrichment of the TLR4 signaling cascade. The updated HemeKG thus provides an integrated and predictive platform, enhancing our understanding of the complex interactions between heme-driven inflammatory pathways and metabolic dysregulation.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113040"},"PeriodicalIF":3.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902738","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":"Special Issue ISMEC 2023: 51st International symposium of metal complexes","authors":"Mauro Formica,&nbsp;Vieri Fusi","doi":"10.1016/j.jinorgbio.2025.113043","DOIUrl":"10.1016/j.jinorgbio.2025.113043","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113043"},"PeriodicalIF":3.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938144","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":"Synthesis, characterization, inhibition of β-hematin formation, lipophilicity, and antimalarial activity of metal-amodiaquine complexes","authors":"Luana Daniel ,&nbsp;Giovana Pimentel ,&nbsp;Carolina Brandi Marques ,&nbsp;Mariana da Cruz Borges Silva ,&nbsp;Diogo Rodrigo M. Moreira ,&nbsp;Letícia Ferreria Machado ,&nbsp;Kézia Katiani Gorza Scopel ,&nbsp;Adolfo Horn Jr. ,&nbsp;Maribel Navarro","doi":"10.1016/j.jinorgbio.2025.113041","DOIUrl":"10.1016/j.jinorgbio.2025.113041","url":null,"abstract":"<div><div>Malaria kills more people than any other infectious disease. It claims over 600,000 lives each year. Despite ongoing efforts, an effective scientific endeavor to eradicate it has yet to be realized. In line with our strategy of searching for a rational alternative treatment, we have developed five new coordination compounds containing amodiaquine (AQ): [Zn(AQ)Cl₂]₂ (<strong>1</strong>); [Zn(AQ)(OH)₂(H₂O)] (<strong>2</strong>); [Zn(AQ)(Ac)₂] (<strong>3</strong>); [Cu(AQ)(Ac)₂] (<strong>4</strong>) and [Ag(AQ)(PPh₃)₂(H₂O)]NO₃ (<strong>5</strong>) which were synthesized under mild conditions. The M-AQ complexes were characterized using a combination of conductivity measurements, elemental and thermal analyses, electronic, infrared, and NMR spectroscopies, ESI–MS spectrometry and EPR. AQ is coordinated to the metal by the nitrogen atom of the quinoline ring. Overall, compounds <strong>1</strong>, <strong>2</strong>, and <strong>3</strong> demonstrated greater inhibitory efficacy compared to amodiaquine alone. Based on these IC₅₀ values, we can infer that these metal-AQ complexes are as potent in inhibiting β-hematin formation as AQ, consistent with their strong binding affinity to Fe(<em>III</em>)PPIX (protoporphyrin IX). All metal-AQ complexes exhibited negative log D values at pH 5 indicating a more hydrophilic character. All the Metal-AQ complexes exhibited <em>in vitro</em> activity against CQ-resistant strains of <em>P. falciparum</em>. The Zn-AQ complexes were the most active in the series, comparable to AQ and more active than chloroquine diphosphate against the CQ-resistant strain PfW2. At a dose of 30 mg/kg, treatment with complex <strong>1</strong> increased the median survival time of the mice by 75 %. This may be due to the presence of two amodiaquine molecules in its composition.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113041"},"PeriodicalIF":3.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903357","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":"The new optical test system for semi-quantitative determination of antioxidant capacity using complexes of the iron with 2,2′-bipyridine derivatives","authors":"Elena Salimgareeva ,&nbsp;Maria Konovalova ,&nbsp;Maria Lykova ,&nbsp;Elena Gerasimova ,&nbsp;Alla Ivanova ,&nbsp;Dmitry Kopchuk ,&nbsp;Aleksey Krinochkin ,&nbsp;Aluru Rammohan ,&nbsp;Olga Shabunina ,&nbsp;Grigory Zyryanov","doi":"10.1016/j.jinorgbio.2025.113039","DOIUrl":"10.1016/j.jinorgbio.2025.113039","url":null,"abstract":"<div><div>This work introduces the semi-quantitative optical test system for determining the antioxidant capacity (AOC) of various substances using coordination compounds as model oxidizers. The test system consists of the plastic plate with paper sensors impregnated with a model oxidant, and the calibration strip. In order to determine AOC, the sensor color must be compared with the color of the calibration strip. For more accurate color identification, a Python-based software has been developed. Iron complexes with 2,2′-bipyridine and its derivatives were used as the model oxidant. Directed synthesis of 2,2′-bipyridine derivatives was carried out using various modifications of the “1,2,4-triazine\" methodology in order to select a model oxidizing agent, which must have high stability under assay conditions, a high molar absorptivity coefficient, and good solubility in solvents. It was shown that complex-forming ability, especially with Fe(III), increases when halogens are introduced into the 2,2′-bipyridine. Characteristics of the complex compounds were evaluated both in solution and in thin layers. Promising complex compounds were identified. Properties of the complexes, such as high stability, contrast, and solubility, enable their use in portable devices and ensure reliable results. AOC was determined for a number of model antioxidant solutions, ethanol extracts of plant materials, and supplements, containing ascorbic acid and α-tocopherol, using the test system. Comparative studies with spectrophotometry using selected complex showed a high level of concordance between the results. Thus, the semi-quantitative test system allows for express and accurate in site analysis. It can be used for analyzing a wide variety of substances.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113039"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890333","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":"Potent inhibition of SARS-CoV-2 proteases PLpro and 3CLpro by selected gold(III)-dithiocarbamato complexes showing strong and selective antiviral activity against HCoV-OC43","authors":"Maria Gil-Moles ,&nbsp;Judith Füllborn-Ott ,&nbsp;Federica Brescia ,&nbsp;Luca Ronconi ,&nbsp;Ingo Ott","doi":"10.1016/j.jinorgbio.2025.113042","DOIUrl":"10.1016/j.jinorgbio.2025.113042","url":null,"abstract":"<div><div>Selected gold(III)-dithiocarbamato complexes were identified as potent inhibitors of two critical enzymes involved in the SARS-CoV-2 replication cycle, the papain-line protease (PL^pro) and the 3-chymotrypsin-like protease (3CL^pro), showing exceptional inhibition of PL^pro with IC₅₀ values in the range of 0.1–0.2 μM and rather moderate activity against 3CL^pro (IC₅₀ values 8–9 μM). Crucially, the inhibitory activity could be attributed to the presence of the gold(III) centre, as the gold-free dithiocarbamato ligand showed no significant activity against either proteases. The toxicity toward host cells, cellular uptake, and antiviral activity against the HCoV-OC43 coronavirus of the complexes were generally in good correlation to one another. Complexes <strong>Au-1</strong> and <strong>Au-2</strong> stood out as a highly active antiviral agents with a selectivity index above 90.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113042"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908488","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":"Synthesis, structural characterization, and investigation of anti-glioblastoma activity of copper complexes supported by bis(pyrazol-1-yl)acetate ligands functionalized with memantine","authors":"Miriam Caviglia ,&nbsp;Fabio Del Bello ,&nbsp;Carlo Santini ,&nbsp;Sofia Migani ,&nbsp;Wilma Quaglia ,&nbsp;Jo’ Del Gobbo ,&nbsp;Federica Matteucci ,&nbsp;Maria Beatrice Morelli ,&nbsp;Laura Zeppa ,&nbsp;Cristina Aguzzi ,&nbsp;Giuseppina Bozzuto ,&nbsp;Annarita Stringaro ,&nbsp;Chiara Battocchio ,&nbsp;Giovanna Iucci ,&nbsp;Iole Venditti ,&nbsp;Carlo Meneghini ,&nbsp;Simone Amatori ,&nbsp;Alessandro Dolmella ,&nbsp;Maura Pellei","doi":"10.1016/j.jinorgbio.2025.113035","DOIUrl":"10.1016/j.jinorgbio.2025.113035","url":null,"abstract":"<div><div>The new ligand bis(1H-pyrazol-1-yl)acetyl-3,5-dimethyladamantane-1-amide (L^Mem) was synthesized by conjugating the drug memantine with the bifunctional species bis(pyrazol-1-yl)acetic acid and used as supporting ligand of copper(II) and copper(I) complexes <strong>1–7</strong>. In the synthesis of the Cu^I complexes, the lipophilic triphenylphosphine (PPh₃) and hydrophilic 1,3,5-triaza-7-phosphaadamantane (PTA) were selected as co-ligands, in order to stabilize copper in +1 oxidation state and to confer different solubility properties to the corresponding metal complexes. The electronic and molecular structures of Cu^I and Cu^II coordination compounds were investigated by high resolution Synchrotron Radiation-induced X-ray Photoelectron Spectroscopy (SR-XPS), Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy. The local structure around the copper ion sites was studied combining Density Functional Theory (DFT) modelling and X-ray Absorption Fine Structure (XAFS) spectroscopy, in both X-ray Absorption Near Edge Spectroscopy (XANES) and Extended X-ray Absorption Fine Structures (EXAFS) regions. X-ray diffraction (XRD) studies were carried out on suitable crystals to describe the molecular structure and the intermolecular contacts of the L^Mem ligand. Among all Cu complexes tested, compounds <strong>4</strong> and <strong>5</strong> exhibited potent antiproliferative and cytotoxic effects in U87, T98, and U251 glioma cell lines. These effects were associated with increased reactive oxygen species (ROS) production and mitochondrial dysfunction, as evidenced by mitochondrial depolarization and altered intracellular distribution. Furthermore, the cytotoxic activity of these compounds was shown to be Cu-dependent, as it was effectively inhibited by the Cu chelator tetrathiomolybdate, confirming the essential role of copper in their mechanism of action.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113035"},"PeriodicalIF":3.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861128","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":"Discovery of a dual-action compound for metallo-β-lactamase inhibition and biofilm clearance to reverse CRE resistance","authors":"Mingjun Liu ,&nbsp;Chen Wu ,&nbsp;Xuanliang Zhang ,&nbsp;Yushi Wang ,&nbsp;Yuxuan Wei ,&nbsp;Yuzhou Hu ,&nbsp;Zouyi Sun ,&nbsp;Cheng Chen ,&nbsp;Youzhen Ma","doi":"10.1016/j.jinorgbio.2025.113028","DOIUrl":"10.1016/j.jinorgbio.2025.113028","url":null,"abstract":"<div><div>The emergence of carbapenem-resistant Enterobacteriaceae (CRE) poses a severe threat to global public health due to its multidrug resistance and limited treatment options. In this study, QA, a zinc ion chelator with potent inhibitory activity against metallo-β-lactamases (MBLs), was identified through high-throughput screening and biochemical analysis. QA effectively inhibits MBLs by chelating zinc ions and demonstrates potent biofilm clearance capabilities, ultimately reversing carbapenem-resistant Enterobacteriaceae (CRE) resistance. Synergistic antibacterial effects were observed when QA was combined with meropenem and other β-lactam antibiotics, significantly enhancing their efficacy. These findings highlight the dual-action potential of QA as a zinc ion chelator and biofilm disruptor, offering a promising strategy for combating CRE infections and multidrug-resistant bacteria.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113028"},"PeriodicalIF":3.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842410","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":"Cytotoxic binuclear η6-arene-Ru(II) complexes: DNA sequence specific helix unwinding and binding properties","authors":"Dimitrios Thomos ,&nbsp;Theodoros Tsolis ,&nbsp;Achilleas Garoufis","doi":"10.1016/j.jinorgbio.2025.113027","DOIUrl":"10.1016/j.jinorgbio.2025.113027","url":null,"abstract":"<div><div>Cytotoxic bifunctional DNA binders of the general formula {[(η⁶-cym)Ru(phe)]₂(<em>μ</em>-BL)}Cl₄, where cym = p-cymene, phe = 1,10-phenanthroline, BL = 4,4′-bipyridine (BL-1), (<strong>1</strong>), 1,2-bis(4-pyridyl)ethane (BL-2), (<strong>2</strong>) and 1,3-bis(4-pyridyl)propane (BL-3), (<strong>3</strong>), were investigated for their binding properties with B-type DNA sequences d(5′-CGCGCG-3′), d(5′-CTTTTGCAAAAG-3′) and CT-DNA using NMR spectroscopy and fluorescence titrations. The results revealed distinct binding modes and affinities, significantly influenced by both the DNA sequence and the length of the BL. The interactions were non-selective and occurred through multiple binding modes. Complex (<strong>1</strong>) was found to disrupt the W.-C. imino hydrogen bonds at both C·G and A·T base pairs, effectively mimicking the DNA strand separation mechanism by helicase enzymes. In contrast, the binding of (<strong>2</strong>) does not disrupt the C.-W. GN1-H imino hydrogen bonds in the G·C-only sequence d(5′-CGCGCG-3′)₂ but it selectively disrupts the T2N3H imino hydrogen bond of the T2·A11 base pair in the AT-rich sequence d(5′-CTTTTGCAAAAG-3′). Complex (<strong>3</strong>) induced localized unwinding of the helix near the center of the d(5′-CGCGCG-3′)₂. The DNA binding affinities of complexes (<strong>1</strong>)–(<strong>3</strong>) exhibit strong sequence dependence, with binding constants (K_b) ranging from 1.23 × 10³ M⁻¹ to 6.34 × 10⁵ M⁻¹.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113027"},"PeriodicalIF":3.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829837","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":"Engineered hemoproteins containing non-canonical cofactors toward artificial metalloenzymes","authors":"Koji Oohora","doi":"10.1016/j.jinorgbio.2025.113026","DOIUrl":"10.1016/j.jinorgbio.2025.113026","url":null,"abstract":"<div><div>Hemoproteins have emerged as versatile scaffolds for the construction of artificial metalloenzymes. Through directed evolution via random and/or site-saturation mutagenesis, these proteins can be repurposed to catalyze abiological transformations. Their catalytic scope can be further expanded by introducing non-canonical molecular components. One approach involves the incorporation of non-canonical amino acid residues, such as methylhistidine, into the protein scaffold. Another strategy replaces the native heme with synthetic cofactors. While natural heme cofactors are generally restricted to porphyrins, synthetic chemistry has enabled access to a variety of porphyrin derivatives and artificial porphyrinoids with diverse core structures and peripheral functionalities. This review highlights recent efforts in designing such non-canonical cofactors and engineering complementary protein mutants to achieve challenging transformations, including C–H hydroxylation/amination and olefin cyclopropanation. Expanding the chemical space of hemoproteins through the integration of non-canonical cofactors represents a promising direction toward artificial metalloenzymes with novel and valuable catalytic functions.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113026"},"PeriodicalIF":3.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861992","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}