Journal of Inorganic Biochemistry最新文献

{"title":"Ruthenium(II) Paracymene complexes of phenolic acids: Synthesis, chemical characterization, in-silico biomolecular interaction and cytotoxicity studies","authors":"Sabyasachi Banerjee ,&nbsp;Sourav De ,&nbsp;S.K. Ashok Kumar ,&nbsp;Sankhadip Bose ,&nbsp;Subhasis Banerjee","doi":"10.1016/j.jinorgbio.2025.113080","DOIUrl":"10.1016/j.jinorgbio.2025.113080","url":null,"abstract":"<div><div>Presently, Ruthenium (Ru) complexes drawn a significant attention in medicinal chemistry researchowing to their promising anti-cancer potential. The present research dealt with design, synthesis, and chemical characterization of two ruthenium (II)-p-cymene based phenolic acid. The structural analysis revealsthat the Ru(II) complexes acquire a ‘piano stool’ coordination geometry comprises of one bound arene, two sigma bonded esteric oxygen atoms, and labile chlorine linked to Ru(II). The optical properties of these complexes were studied,which showed absorption peaks at 270 nm and 320 nm, which are due to the contribution of intra-ligand charge transitions and metal-to-ligand charge transitions, respectively. The binding interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) is non-covalent in nature and the binding constants of <strong>Ru-1</strong> and <strong>Ru-2</strong> complexes with CT-DNA and BSA were found to be 3.6 × 10³ M⁻¹,2.5 × 10⁶ M⁻¹ and 1 × 10⁶ M⁻¹, 9.9 × 10⁴ M⁻¹respectively. It is also observed that in presence of Ru(II) complexes, ethidium bromide (EtBr) was competitively displaced from CT-DNA through intercalation, which is well supported by viscosity and in silico studies. The cytotoxicity study of these Ru(II) complexes was conducted with multiple cancer cell lines (HeLa, MDA-MB-231, MCF-7, Hep G2) and one human embryonic kidney cell (HEK-293). Both Ru(II) complexes were investigated in-vitro for cytotoxicity against HeLa, MCF-7, Hep G2 and MDA-MB-231 cells. The obtained results show that <strong>Ru-1</strong> and <strong>Ru-2</strong> (ranging from 2.5 to 8.4 μM) exhibits considerable potency and selectivity towards cancer cell lines in compare to cisplatin.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113080"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155112","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":"Developing a novel Cu(II) complex: Crystal structure, cyclic voltammetry, biomolecular interactions, anticancer activity, and computational investigations","authors":"Hagar E. Badr ,&nbsp;Mohamed M. Aboelnga ,&nbsp;Abdelaziz Elgamouz ,&nbsp;Abdel-Nasser Kawde ,&nbsp;Ahmed M. El-Hendawy ,&nbsp;Shadia A. Elsayed","doi":"10.1016/j.jinorgbio.2025.113079","DOIUrl":"10.1016/j.jinorgbio.2025.113079","url":null,"abstract":"<div><div>A new copper(II) Schiff base complex [Cu(L)₂] derived from 2-hydroxybenzaldehyde-4-aminomethylbenzoate (HL) has been synthesized. The Characterization was performed by single crystal X-ray crystallography, FTIR, (¹H,¹³C) NMR (for the ligand), Electrospray Ionization Mass Spectrometry (ESI-MS), UV–visible spectra, thermogravimetric analysis (TGA), cyclic voltammetry (CV) measurements, and DFT calculations. The analyses showed that the copper(II) complex has a distorted square planar geometry with two ligand molecules coordinated through the deprotonated phenolate oxygen and azomethine nitrogen (NO-donor). The stacking interaction of the ligand and the complex with calf thymus (ctDNA) and bovine serum albumin (BSA) was confirmed by UV–visible and fluorescence spectroscopy. The obtained data revealed that the Cu(II) complex is binding more strongly (1.77 × 10⁵ M⁻¹) to the ctDNA than the ligand (3.6 × 10⁴ M⁻¹) as an example. The interaction of the complex with ctDNA and BSA was also confirmed by cyclic voltammetry and an extended study for L-tyrosine, lysozyme, and glutathione. Molecular docking was also performed to obtain deeper structural insights into these interactions with BSA and DNA. Furthermore, <em>in vitro</em> cytotoxic activity against human normal lung cells (WI38), colorectal carcinoma (HCT116), and breast cancer (MDA-MB-231) was studied using cisplatin as a standard drug. The IC₅₀ and selective index (SI) data showed that the Cu(II) complex is more active and selective toward both cancer cells compared to the free ligand, particularly in MDA-MB-231 cell lines, and flow cytometry analysis showed that the Cu(II) complex induces apoptosis in these cells. The treatment with the Cu(II) complex increases <em>caspase3</em> and reduces PCNA expression. Moreover, it reduces metastasis in MDA-MB-231 cells after 48 h of treatment, probably due to its strong binding affinity to cancer cell DNA.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113079"},"PeriodicalIF":3.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184466","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":"Contribution of copper(II) and zinc(II) to the electrochemical and biological properties of 5-nitroimidazole coordination compounds. An experimental and theoretical approach","authors":"Rubí Navarro-Peñaloza ,&nbsp;Bruno Landeros-Rivera ,&nbsp;Jesús I. Palacios-Ramírez ,&nbsp;Francisco Sánchez-Bartéz ,&nbsp;Isabel Gracia-Mora ,&nbsp;Felipe J. González ,&nbsp;Norah Barba-Behrens","doi":"10.1016/j.jinorgbio.2025.113075","DOIUrl":"10.1016/j.jinorgbio.2025.113075","url":null,"abstract":"<div><div>Coordination compounds of copper(II) and zinc(II) with the 5-nitroimidazole derivatives 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (<em>cenz</em>) and 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (<em>onz</em>) have shown antiparasitic activity against <em>Toxoplasma gondii</em>. This study combines electrochemical and theoretical approaches to evaluate the role of the metal ion in the formation and stability of redox species potentially involved in their mechanism of action. The free ligands exhibited oxidation and reduction peaks corresponding to the formation of nitro radical anion and hydroxylamine species, associated with their biological activity. In the coordination compounds, the metal ion influenced these processes by different mechanisms. Theoretical analysis revealed that the nitro radical anion can be stabilized by intramolecular hydrogen bonding or by lone pair···π hole interactions. In the copper(II) complexes, these interactions were further enhanced by a redox-driven structural rearrangement in which the coordination geometry shifts from distorted tetrahedral to trigonal planar upon Cu^II/Cu^I reduction. This geometrical change promotes stabilization of the nitro radical and facilitates redox cycling, which may contribute to antiparasitic activity. In contrast, the zinc(II) complexes maintain a regular tetrahedral geometry and present an intramolecular redox mechanism, where the nitro group is reduced via a transient state. To explore their potential anticancer activity, in vitro assays were conducted against HeLa, HCT-15 and A549 human cancer cell lines and L929 healthy fibroblast. Additionally acute toxicity studies were performed. The results support the potential of these coordination compounds as antiparasitic and anticancer agents, highlighting the key role of metal-induced structural and electronic effects into modulating biological activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113075"},"PeriodicalIF":3.2,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155111","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":"Conformation of six-membered vanadium chelate rings","authors":"Skyler A. Markham ,&nbsp;Kendall E. Jenkins ,&nbsp;Avery M. Gibson ,&nbsp;Craig C. McLauchlan ,&nbsp;Debbie C. Crans","doi":"10.1016/j.jinorgbio.2025.113078","DOIUrl":"10.1016/j.jinorgbio.2025.113078","url":null,"abstract":"<div><div>Vanadium complexes have many desirable catalytic and biological properties across a wide variety of chelate types with coordination moieties typically being oxygen and nitrogen. In this work, we carried out a data mining analysis investigating the conformation of six-membered rings formed between a ligand and a vanadium atom with the objective to understand how much the ligand conformation impacted the structure and stability of the coordination complex. There are 104 structures with the NVN unit in the Cambridge Crystallographic Data Centre (CCDC), 28 structures with OVN unit, 386 structures with the OVO unit, and 11 structures with NVN(sp²)C(sp²) unit, with the remainder of the six-membered ring being three C atoms. The structures containing NVN, OVN, OVO, and NVN(sp²)C(sp²) units show chelate geometries including chair, twist-boat, boat, and half-chair. Out of the total 529 structures, there were 315 chairs (60 %), 91 twist-boats (17 %), 86 boats (16 %), 4 half-chairs (1 %), 2 planar (0.5 %), 13 complexes that contained more than one 6-membered ring and the complex having more than one chelate conformation (2.5 %), and 16 complexes where the structures are not deposited in the CCDC (3 %). Based on the analysis, there is a distinct correlation between the conformation of the ring and the composition of the chelate of the mononuclear, dinuclear and polyoxidovanadate complexes containing NVN, OVN, OVO and NVN(sp²)C(sp²) groups. Therefore, it appears that the chelate composition impacts the conformation of the six-membered ring and thus the stability of the complex.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113078"},"PeriodicalIF":3.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205035","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":"Horse heart mini- and full length-myoglobin: pH effects on CO binding","authors":"Massimo Coletta ,&nbsp;Gabriele Antonio Zingale ,&nbsp;Giovanna De Simone ,&nbsp;Giampiero De Sanctis ,&nbsp;Virginia Quadrotta ,&nbsp;Fabio Polticelli ,&nbsp;Paolo Ascenzi","doi":"10.1016/j.jinorgbio.2025.113081","DOIUrl":"10.1016/j.jinorgbio.2025.113081","url":null,"abstract":"<div><div>Mini-myoglobin (mini-HH-Mb) is a proteolytic fragment of horse heart myoglobin (HH-Mb) comprising residues 32–139, grossly corresponding to the central exon of the HH-Mb gene, which encodes residues 31–105. Unlike HH-Mb, which displays a single exponential for both CO association and CO dissociation kinetics, mini-HH-Mb shows a biphasic kinetic behavior for both processes, indicating the presence of at least two distinct conformations which are in a very slow (or no) equilibrium with each other. Between pH 2 and 12, CO association to both species of mini-HH-Mb shows two proton-linked transitions, one in the neutral-alkaline pH range (not observed for HH-Mb) and a second one in the acidic region displaying a p<em>K</em>_a of 2.9 like that observed in HH-Mb (p<em>K</em>_a = 2.7). Kinetics of CO dissociation from both species of mini-HH-Mb-CO was investigated between pH 5.5 and 10.5 only, since outside this pH range the slow CO dissociation kinetics are affected by protein denaturation, which shows up after few seconds. The CO dissociation rate shows a bell-shaped pH dependence for both conformations, while ligand dissociation from HH-Mb-CO is pH-independent. These features find a structural basis on molecular modelling, displaying a higher flexibility of both the proximal and distal side of the heme pocket in mini-HH-Mb, envisaging multiple conformations with different reactivity. This indicates that mini-HH-Mb differs from HH-Mb, suggesting a significant structural-functional role for the <em>N</em>- and <em>C</em>-terminal regions in O₂ supply to highly demanding tissues, like the retina, with implications for improving retinal blood flow in ocular pathologies.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113081"},"PeriodicalIF":3.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109449","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":"Influence of Bathophenanthroline in Cu-Naringenin complexes on 3D culture anticancer activity, antimetastatic properties and synergy with the antidepressant paroxetine","authors":"Janetsi Y. Caro Ramírez,&nbsp;Patricia A.M. Williams,&nbsp;Evelina G. Ferrer,&nbsp;Luciana G. Naso","doi":"10.1016/j.jinorgbio.2025.113072","DOIUrl":"10.1016/j.jinorgbio.2025.113072","url":null,"abstract":"<div><div>Cancer is responsible for about 22.8 % of global deaths from noncommunicable diseases, with lung cancer the most diagnosed in 2022. Non-small cell lung cancer (NSCLC) accounts for 85–90 % of cases. Conventional treatments like chemotherapy have limitations, including low bioavailability and drug resistance. Drug repositioning, where existing medications are used for new purposes, has emerged as a promising approach. This study advances the understanding of antitumor effects of the copper-naringenin (Cu-Nar) complexes: CuNar, CuNarPhen, CuNarBatho [CuNarPhen and CuNarBatho feature CuNar containing phenanthroline (Phen) or bathophenanthroline (Batho)] in lung cancer cells (A549). Clonogenic assays in 2D cultures showed that CuNarBatho was the most effective complex in inhibiting colony formation. Likewise, in a 3D culture model, CuNarBatho disrupted tumor spheroids and demonstrated significant cytotoxicity, with an IC₅₀ value of 11.72 μM. The effect on metastatic processes was also studied, revealing that the complexes significantly reduced cell migration, adhesion, and invasion, particularly CuNarBatho. Zymography assays showed that this complex inhibited the activity of matrix metalloproteinases (MMP-2 and MMP-9), key enzymes involved in cancer metastasis. Additionally, the cytotoxic effects of the three complexes in combination with the antidepressant agent paroxetine, a selective serotonin reuptake inhibitor, were studied, and its inhibitory effect in A549 cells was also determined. When paroxetine and the copper complexes were combined, different degrees of synergy were observed, with CuNarBatho exhibiting the most impactful synergistic effect. These findings suggest that CuNarBatho has potential as a novel therapeutic strategy for lung cancer.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113072"},"PeriodicalIF":3.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109562","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":"Vanadium(IV) complexes of acetophenone isoniazid hydrazones: Synthesis, characterization, stability assay, antidiabetic activity, histopathology and bioaccumulation","authors":"Selma Fetahović ,&nbsp;Muhamed Fočak ,&nbsp;Aleksandar Višnjevac ,&nbsp;Sunčica Roca ,&nbsp;Višnja Muzika ,&nbsp;Dijana Žilić ,&nbsp;Lucija Vujević ,&nbsp;Sabina Žero ,&nbsp;Walter Gössler ,&nbsp;Lorenz Steiner ,&nbsp;Debbie C. Crans ,&nbsp;Adnan Zahirović","doi":"10.1016/j.jinorgbio.2025.113074","DOIUrl":"10.1016/j.jinorgbio.2025.113074","url":null,"abstract":"<div><div>Four new heteroleptic neutral paramagnetic mononuclear oxidovanadium(IV) complexes, designated as [VOL(phen)], where L corresponds to acetophenone isoniazid hydrazone or its 5-halogenated derivatives and phen stands for 1,10-phenanthroline, were synthesized and thoroughly characterized using chemical analysis, various spectroscopic techniques, and diffraction methods. Single-crystal X-ray diffraction revealed the molecular and crystal structures of two complexes, showing an octahedral coordination environment around the vanadium(IV) center. The coordination includes a tridentate ONO donor hydrazone ligand in its deprotonated enol-imine form, 1,10-phenanthroline as a bidentate NN donor ternary ligand, and one terminal oxygen atom. The biochemical and hematological effects of these complexes were evaluated in a streptozotocin-induced diabetic rat model. All synthesized complexes showed cholesterol-lowering effects compared to the diabetic rat group, with the vanadium complex lacking a substituent on the acetophenone ring of hydrazone showing the strongest effect. Complexes exhibited comparable and significant antidiabetic activity <em>in vivo</em>, effectively reducing hyperglycemia within 1 week of treatment. Additionally, the histopathological effects of complex (<strong>4</strong>) on liver, kidney, and brain tissues were investigated. All four complexes were found to have low bioaccumulation levels, with total absolute bioaccumulation in all tested organs less than 0.35% of the administered dose.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113074"},"PeriodicalIF":3.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155122","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":"Restoring nitric oxide/Peroxynitrite equilibrium in impaired human neural progenitor cells: Nanomedical approaches and their potential impact on neurodegenerative disease treatment","authors":"Nouf Alsiraey ,&nbsp;Howard D. Dewald","doi":"10.1016/j.jinorgbio.2025.113073","DOIUrl":"10.1016/j.jinorgbio.2025.113073","url":null,"abstract":"<div><div>Nitric oxide (NO), an essential inorganic signaling molecule, involved in many physiological processes and has promising therapeutic potential Its oxidation product, peroxynitrite (ONOO^¯), is cytotoxic, and elevated ONOO^¯ levels induce nitroxidative stress, a factor implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Through pharmacological modulation of NO and ONOO^¯ levels in human neural progenitor cell (hNPCs), this study explores the potential pharmaceutical interventions targeting the NO and the neuronal nitric oxide synthase (nNOS) pathway, (NO/nNOS), to prevent or reduce AD progression by restoring the [NO]/[ONOO^¯] balance. To achieve this, metalloporphyrin nanosensors have been effectively employed for real-time, <em>in-situ</em> measurement of NO and ONOO^¯ concentrations (200–300 nm diameter) were applied and precisely positioned 4–5 ± 1 μm from hNPCs membranes, enabling precise investigation of the [NO]/[ONOO^¯] ratio. The [NO]/[ONOO^¯] ratio emerged as a critical biomarker for the evaluation of nNOS coupling/uncoupling to the hNPC functioning/dysfunction. In healthy cells, this ratio was around 0.25 ± 0.005, While dysfunctional hNPCs treated to amyloid beta 42 (Aβ₄₂)—a hallmark of AD—caused a dramatic 94 % drop, signaling severe cellular dysfunction. Based on these findings, potential pharmacological interventions have been proposed to prevent or reduce AD progression by restoring the [NO]/[ONOO^¯] balance. Notably, a co-treatment of sepiapterin (SEP), a cofactor precursor for NO synthesis, with VAS 2870 (an NADPH oxidase inhibitor) partially restored the ratio to 0.1, indicating improved nNOS function.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113073"},"PeriodicalIF":3.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084763","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 and evaluation of HOPO-O8-Methyl-tetrazine as a bifunctional chelator for use in [89Zr]Zr4+, [161Tb]Tb3+ and [227Th]Th4+ radioimmunoconjugates","authors":"Imma Carbo-Bague ,&nbsp;Parmissa Randhawa ,&nbsp;Marianna Tosato ,&nbsp;Brooke L. McNeil ,&nbsp;Milena Čolović ,&nbsp;Lucas London ,&nbsp;Cristina Rodríguez-Rodríguez ,&nbsp;Maryam Osooly ,&nbsp;Luke Wharton ,&nbsp;Helen Merkens ,&nbsp;Michiel Van De Voorde ,&nbsp;Maarten Ooms ,&nbsp;Hua Yang ,&nbsp;François Bénard ,&nbsp;Caterina F. Ramogida","doi":"10.1016/j.jinorgbio.2025.113077","DOIUrl":"10.1016/j.jinorgbio.2025.113077","url":null,"abstract":"<div><div>The growing availability of new radiometals with favorable decay properties for cancer diagnosis and therapy highlights the need for chelators that can stably bind a variety of metal ions. 1-Hydroxy-2(<em>1</em>H)-pyridinones (1,2-HOPOs) are effective bidentate ligands with strong affinity for trivalent and tetravalent metals. In this study, we developed a bifunctional octadentate 1,2-HOPO chelator with a methyl tetrazine (Me-Tz) moiety, HOPO-O₈-Me-Tz, and evaluated its coordination to [⁸⁹Zr]Zr⁴⁺, [¹⁶¹Tb]Tb³⁺, and [²²⁷Th]Th⁴⁺ for theranostic applications. HOPO-O₈-Me-Tz was conjugated to HER2/<em>neu</em> targeting antibody Trastuzumab (Tmab), modified with transcyclooctene (TCO), using the inverse electron demand Diels-Alder (IEDDA) click reaction to yield HOPO-O₈-Tmab. Radiolabeled conjugates were synthesized under mild conditions (30 min, ambient temperature) and evaluated <em>in vitro</em> and <em>in vivo</em> in SKOV-3 tumour-bearing nude mice. All radiometal complexes demonstrated high stability in serum over 7 days. <em>In vivo</em>, [⁸⁹Zr]Zr-, [¹⁶¹Tb]Tb- and [²²⁷Th]Th-HOPO-O₈-Tmab showed high tumour uptake (9.87 ± 3.57, 11.29 ± 4.14 and 19.40 ± 5.40 %ID/g, respectively). Notably, [¹⁶¹Tb]Tb- and [²²⁷Th]Th-conjugates exhibited low bone uptake at 96 h post-injection, indicating excellent <em>in vivo</em> stability. The potential redistribution of the alpha-emitting daughter nuclide [²²³Ra]Ra²⁺ from [²²⁷Th]Th-HOPO-O₈-Tmab was assessed, revealing elevated ²²³Ra in the bone and joint. These findings underscore the promise of HOPO-O₈-Me-Tz as a versatile bifunctional chelator for next-generation theranostic radioimmunoconjugates, while also highlighting the importance of managing daughter radionuclide redistribution in alpha therapy.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"Article 113077"},"PeriodicalIF":3.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090946","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":"Structural and sequence basis for substrate selection in the cellular trafficking of Fe-S clusters, hemes and glutathione-complexed metals through membrane transporters.","authors":"J A Cowan","doi":"10.1016/j.jinorgbio.2025.113076","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2025.113076","url":null,"abstract":"<p><p>Cellular mobilization of heme and iron‑sulfur cluster cofactors has been a topic of interest for over a decade. Recognition of glutathione-complexed clusters as viable mediators of intracellular trafficking of [2Fe-2S] cofactors and other metallosubstrates for transmembrane localization has been demonstrated both biochemically and by structural studies, and is supported by genetic analysis. Sequence and structural correlations of both eukaryotic and prokaryotic ATP-binding cassette (ABC) membrane transporter families (ABCB7 and ABCB6) reveals connections that address possible roles for ABCB6 in Fe-S cluster cellular mobilization and further clarify its role in heme transport. This review expands on these themes by correlating structural and sequence relationships between Fe-S cluster and heme transporters, and broader roles in mediating drug resistance and elimination of toxic metals.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"274 ","pages":"113076"},"PeriodicalIF":3.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249161","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}