Journal of Inorganic Biochemistry最新文献

{"title":"Preparation of diverse porphyrins-based hydrogen-bonded organic frameworks for photodynamic cancer therapy","authors":"Luwen Zhang,&nbsp;Jiarui Qiao,&nbsp;Junhe Ou,&nbsp;Yan Wang,&nbsp;Tingyan Jiang,&nbsp;Xianhao Wei,&nbsp;Maolin Pang","doi":"10.1016/j.jinorgbio.2026.113226","DOIUrl":"10.1016/j.jinorgbio.2026.113226","url":null,"abstract":"<div><div>As a promising noninvasive approach, photodynamic therapy (PDT) has received considerable attention attributed to its preciseness and low toxicity. However, its therapeutic efficacy is largely dependent on the ability of photosensitizers to generate reactive oxygen species (ROS). In this study, a systematic comparison of hydrogen-bonded organic frameworks (HOFs) constructed from different porphyrin units demonstrated that TCPP-Cu-HOF exhibited the narrowest bandgap and the highest ROS generation efficiency under 650 nm laser irradiation, leading to outstanding PDT performance at the cellular level. Based on these results, TCPP-Cu-HOF was further selected for <em>in vivo</em> evaluation, where effective antitumor efficacy was achieved. This work provides a facile synthesis method for HOF nanoparticles and further expands their potential applications in biomedical fields.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113226"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951051","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 basis for organism-dependent effects on spectroscopic properties of type 1 copper azurin by the same axial methionine to histidine mutation","authors":"Jiaqing Xu ,&nbsp;Lu Yu ,&nbsp;Sheng-Song Yu ,&nbsp;Yiwei Liu ,&nbsp;Jing-Xiang Wang ,&nbsp;Jun-Jie Li ,&nbsp;Casey Van Stappen ,&nbsp;Han-Qing Yu ,&nbsp;Mark J. Nilges ,&nbsp;Yi Lu","doi":"10.1016/j.jinorgbio.2025.113209","DOIUrl":"10.1016/j.jinorgbio.2025.113209","url":null,"abstract":"<div><div>Cupredoxins are a family of copper proteins that mediate electron transfer in key biological processes, and understanding structural features responsible for their spectroscopic properties is important for elucidating structure–function relationships. Here, we characterize the effect of mutation of the axial methionine to histidine in azurin from <em>Pseudomonas aeruginosa</em> (M121HAz-PA) using UV–Vis absorption, electron paramagnetic resonance (EPR) spectroscopy, and X-ray crystallography to examine how the same M121H mutation affects spectroscopic properties differently from its homolog in <em>Alcaligenes denitrificans</em> (M121HAz-AD). M121HAz-PA shows a pH-dependent UV–vis spectral change from pH 4 to pH 8, with unusual EPR features, indicating changes in coordination electronic structure. Azide binding titrations produce EPR spectra intermediate between type 1 copper (T1Cu) and type 2 copper (T2Cu), supporting that changes of (exogenous) ligand coordination drive significant geometric and electronic rearrangements. X-ray crystallography reveals differences in axial His121 coordination mode to Cu^II and its orientation between M121HAz-PA and M121HAz-AD, providing a structural basis for the observed spectroscopic differences. These findings provide insights into how subtle variations in ligand coordination affect the electronic structure in Cu-binding sites, offering a basis for the rational design of metalloproteins.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113209"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921997","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":"Ascorbate-enabled C-H bond amination catalyzed by myoglobin reconstituted with a trifluoromethyl-substituted Iron porphyrin","authors":"Chihiro Sonoda,&nbsp;Takashi Hayashi","doi":"10.1016/j.jinorgbio.2025.113207","DOIUrl":"10.1016/j.jinorgbio.2025.113207","url":null,"abstract":"<div><div>Nitrogen-containing organic molecules are essential structural motifs in bioactive compounds, pharmaceuticals and functional materials. Direct C-H amination via nitrene transfer provides an efficient and atom-economical route for C-N bond formation. However, most hemoprotein-based catalysts require strong reductants such as dithionite to generate the metal–nitrene intermediate. Here, we report myoglobin reconstituted with an iron complex (FePor(CF₃)₂) bearing two trifluoromethyl groups at the pyrrole β-positions of the porphyrin framework. This arrangement promotes intramolecular benzylic C-H bond amination under mild conditions using sodium <span>l</span>-ascorbate as the sole reductant. The FePor(CF₃)₂ cofactor exhibits a positively shifted Fe(III)/Fe(II) redox potential that allows efficient reduction to occur in the protein scaffold and suppresses noncatalytic substrate reduction, leading to improved chemoselectivity for secondary C-H bond amination. The H64A mutant of myoglobin reconstituted with FePor(CF₃)₂ achieved a turnover number (TON) of 133 for tertiary benzylic C-H amination. Kinetic studies revealed that the reaction rate is inversely correlated with the C-H bond dissociation energy, with a smaller negative slope in the bond dissociation energies (BDEs) plot compared to a synthetic cofactor with a negative redox potential. This suggests that there is a mechanistic shift in the rate-determining step from hydrogen atom transfer to nitrene formation. These findings highlight the potential of cofactor redox tuning to control reactivity and selectivity in artificial heme enzymes for abiological C-H bond functionalization.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113207"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909877","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 cobalamin-binding domain of cobalamin-dependent radical S-adenosylmethionine enzymes: Familiarity in unfamiliar places","authors":"Dante M. Avalos ,&nbsp;Catherine L. Drennan","doi":"10.1016/j.jinorgbio.2025.113204","DOIUrl":"10.1016/j.jinorgbio.2025.113204","url":null,"abstract":"<div><div>Cobalamin (Cbl)-dependent Radical <em>S</em>-adenosylmethionine (RS) enzymes are well known for their use of two powerful cofactors to catalyze chemically challenging reactions, such as methylations on unactivated carbons and phosphorus centers, ring contractions, ring formations, and thioether bond formations. Our repertoire of Cbl-dependent RS enzyme structures has grown since the first solved structure of the oxetanocin A biosynthetic enzyme OxsB in 2017, which has provided insight into the structural basis of catalysis. In particular, the Cbl-binding domains of these RS enzymes have been found to have interesting structural variations that seem to correlate with enzymatic function, at least for the small number of enzymes that have been characterized. In this review, we highlight the recent research about the Cbl cofactor in Cbl-dependent RS enzymes. We compare modes of Cbl binding and demonstrate a previously undetected connection between a subgroup of Cbl-dependent RS enzymes and the corrinoid iron‑sulfur protein (CFeSP) from the Wood-Ljungdahl pathway of reductive acetogenesis. Additionally, we discuss recent mechanistic findings on Cbl-dependent RS enzymes OxsB and its close homolog AlsB, which have not been recently reviewed. As Cbl-dependent RS enzymes are involved in making antiviral and antibiotic compounds, herbicides, and other molecules of value, understanding and manipulating enzyme activity has implications in both medicine and agriculture.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113204"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881772","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":"Thiodiacetate vs. oxydiacetate: physicochemical and biological properties of new heteroligand (acetylacetonate)oxidovanadium(IV) complexes","authors":"Dariusz Wyrzykowski ,&nbsp;Katarzyna Chmur ,&nbsp;Jakub Brzeski ,&nbsp;Artur Sikorski ,&nbsp;Olga Tovchiga ,&nbsp;Justyna Budka ,&nbsp;Iwona Inkielewicz-Stępniak ,&nbsp;Aleksandra Tesmar","doi":"10.1016/j.jinorgbio.2025.113155","DOIUrl":"10.1016/j.jinorgbio.2025.113155","url":null,"abstract":"<div><div>This research aimed to compare the crystal structure, physicochemical, and biological properties of novel (acetylacetonate)(thiodiacetato)oxidovanadium(IV) complex salts, namely [QH][VO(acac)(tda)] (<strong>1</strong>) and [(acr)H][VO(acac)(tda)] (<strong>2</strong>) (acac = acetylacetonate, tda²⁻ = thiodiacetate, Q = quinoline, acr = acridine) with previously reported oxydiacetate (oda⁻) analogues: [QH][VO(acac)(oda)] (<strong>3</strong>) and [(acr)H][VO(acac)(oda)](H₂O)₂ (<strong>4</strong>). A combination of experimental data, including X-ray crystallography, IR spectroscopy, potentiometric measurements and ESI-MS, and density functional theory (DFT) calculations enables thorough characterization of the complexes in the solid state and in solution. It has been demonstrated that the observed differences in the nature of <em>V</em><img>S (thioether) and V<img>O (ether) dative bonds have only a slight impact on orbital energy levels and spin density distribution. At the same time, these minor differences do not significantly affect the thermodynamic stability of the complexes: log<em>ß</em>₁₁₁₀ {[VO(acac)(tda)]⁻} = 16.91 and log<em>ß</em>₁₁₁₀ {[VO(acac)(oda)]⁻} = 16.45. Additionally, the calculated thermodynamic parameters for the formation of these complexes (∆<em>H</em>, T∆<em>S</em>, ∆<em>G</em> in kcal mol⁻¹, at 298 K) are −66.72, −16.38, and − 50.34 for [VO(acac)(tda)]⁻, and − 68.47, −15.64, and − 52.82 for [VO(acac)(oda)]⁻, respectively. The biological evaluations showed promising selective cytotoxic activity of the investigated complex salts against the human osteosarcoma cell line MG-63. The mechanism of biological action of these complexes appears to involve disruption of cell cycle regulation and induction of apoptosis. The counterions (acridine and quinoline) alone do not significantly affect cell cycle distribution, suggesting that the cytotoxic and cell cycle effects are primarily due to the [VO(acac)(tda)]⁻ and [VO(acac)(oda)]⁻ species.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113155"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600641","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":"Exceptional stability of a Gd-free extracellular fluid MRI contrast agent based on manganese porphyrin","authors":"Keith Tang ,&nbsp;Henry Tieu ,&nbsp;Hanlin Liu ,&nbsp;Naixin Zhao ,&nbsp;Xiao-An Zhang","doi":"10.1016/j.jinorgbio.2025.113175","DOIUrl":"10.1016/j.jinorgbio.2025.113175","url":null,"abstract":"<div><div>Metal-ligand stability plays a central role in medicinal bioinorganic chemistry, as it impacts not only the efficacy but also the safety profiles of metal-based therapeutic and diagnostic agents. Gadolinium-based contrast agents (GBCAs) have been widely applied in clinical magnetic resonance imaging (MRI) scans for decades to enhance the detection of otherwise hardly visible diseases. However, evidence of metal dissociation from Gd chelates <em>in vivo</em> have raised safety concerns and led to the withdrawals of several clinically approved GBCAs in recent years. Here we report an exceptionally high stability of Mn(III)tetracarboxylporphyrin (MnTCP), a Gd-free extracellular fluid CA with high MRI contrast enhancement efficiency at clinic magnetic fields. The stability of MnTCP was systematically investigated under challenging conditions known to cause metal dissociation or transmetallation of GBCAs, as well as most other chelated metal complexes. The kinetic inertness of MnTCP was demonstrated at low pH and high temperature, and no sign of metal dissociation was observed. Incubation of MnTCP with excess of various endogenous metal ions, as well as metal chelators also did not cause any observable transmetalation under neutral or acidic conditions up to 50 days. Moreover, MnTCP is highly stable against reduction by endogenous species, preventing the formation of labile Mn(II)-complex. These findings are consistent with <em>in vivo</em> and intracellular behaviors of MnTCP observed in previous studies. The abnormally high stability of this tetradentate coordination complex can be attributed to structural rigidity, aromaticity and strong metal-ligand orbital interactions.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113175"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733865","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, and anticancer activity of acylthiourea-ruthenium(II) p-cymene complexes","authors":"Raúl Ramos ,&nbsp;Ana María Plutín ,&nbsp;Raúl Oscar Mocelo ,&nbsp;Jean-Pierre DJukic ,&nbsp;Camila Batista Pinto ,&nbsp;Eduardo E. Castellano ,&nbsp;Gustavo A. Echeverría ,&nbsp;Oscar E. Piro ,&nbsp;Mauricio F. Erben ,&nbsp;Legna Colina-Vegas ,&nbsp;Beatriz N. Cunha ,&nbsp;Alzir A. Batista","doi":"10.1016/j.jinorgbio.2025.113180","DOIUrl":"10.1016/j.jinorgbio.2025.113180","url":null,"abstract":"<div><div>In this work, we report the synthesis and characterization of three novel ruthenium(II) <em>p</em>-cymene complexes coordinated with acylthiourea ligands (<strong>L1−L3</strong>), of general formula [Ru(η⁶-<em>p</em>-cymene)(PPh₃)(<strong>L1–L3</strong>)Cl]PF₆ (<strong>1–3</strong>). Single-crystal X-ray crystallography of the free ligands and their complexes [Ru(η⁶-<em>p</em>-cymene)(PPh₃) (κ¹-S)-(<em>N</em>-benzoyl-<em>N</em>´-cyclopropylthiourea)Cl]PF₆ (<strong>1</strong>), Ru(η⁶-<em>p</em>-cymene)(PPh₃) (κ¹-S)<em>-(N</em>-2-furoyl-<em>N</em>´-cyclopropylthiourea)Cl]PF₆ (<strong>2</strong>), [Ru(η⁶-<em>p</em>-cymene)(PPh₃)] (κ¹-S)-(<em>N</em>-thiophene-2-carbonyl-<em>N</em>´-cyclopropyl thiourea)Cl]PF₆ (<strong>3</strong>) revealed that the acylthiourea ligands act as neutral monodentate donors, coordinating through the sulfur atom (κ¹-S). Application of the Extended Transition State–Natural Orbitals for Chemical Valence method demonstrated that the dominant interaction in complexes <strong>1–3</strong> originates from the overlap between the sulfur lone pair of the ligands and a Ru <em>d</em>-orbital, which plays a decisive role in their stability. The Interacting Quantum Atom analysis showed that both the free and coordinated acylthiourea ligands stabilize their structure through an intramolecular N–H···O=C hydrogen bond. The cytotoxicity of complexes <strong>1–3</strong> was evaluated against the A549 (lung) and MDA-MB-231 (breast) human cancer cell lines. To assess their selectivity, the compounds were also tested against two non-cancerous cell models: MRC-5 (lung fibroblasts) and MCF-10 A (breast epithelial cells). The study revealed high cytotoxicity against the MDA-MB-231 cell line, with IC₅₀ values of 0.62 ± 0.05 μM (<strong>1</strong>), 0.66 ± 0.12 μM (<strong>2</strong>), and 0.53 ± 0.12 μM (<strong>3</strong>). Activity against the A549 cell line was also significant, with IC₅₀ values of 1.05 ± 0.11 μM (<strong>1</strong>), 2.60 ± 0.25 μM (<strong>2</strong>), and 1.04 ± 0.21 μM (<strong>3</strong>). The combination of phosphine and acylthiourea ligands appears critical for achieving high cytotoxic activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113180"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712838","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":"Differences in functional cross-talk between loops C and D in two mitochondrial cytochromes","authors":"Dong-Woo Shin ,&nbsp;Fangfang Zhong,&nbsp;Ekaterina V. Pletneva","doi":"10.1016/j.jinorgbio.2025.113182","DOIUrl":"10.1016/j.jinorgbio.2025.113182","url":null,"abstract":"<div><div>The heme in the protein cytochrome (cyt) <em>c</em> is surrounded by loops C and D that differ in their sequences across species. Mutations G41S and Y48H in human (hu) cyt <em>c</em> are associated with thrombocytopenia and have been extensively studied. Herein, we describe effects of the same mutations in horse heart (hh) cyt <em>c</em> and make comparisons to those in the hu protein. While wild-type (WT) hu and hh cyt <em>c</em> proteins have similar global stabilities, unfolding of the hh protein is less cooperative. The differences are further amplified in the mutants. Loop dynamics were probed computationally through MD simulations and experimentally by characterizing the alkaline transition. With G41S and Y48H mutations in hh cyt <em>c</em>, loop C made fewer contacts with loop D and the dynamics of loop D were enhanced. Only the Y48H mutation decreased the reduction potential in hh cyt <em>c</em>, but both G41S and Y48H mutations increased the intrinsic peroxidase activity. The rate constant <em>k</em>_f for the Met-to-Lys ligand switch in the alkaline transition differed in the hu and hh cyt <em>c</em> mutational series: this rate constant decreased upon mutations in the hu protein but increased with analogous mutations in the hh protein. The observed trends are rationalized based on the sequence variation in the two proteins, particularly the identity of residue 46 and differences in interactions it makes with loop D. Functional implications of the sequence difference for electron transfer and peroxidase activity are discussed.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113182"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779744","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":"From single step hops to emergent biological phenomena","authors":"Andrew J. Smith ,&nbsp;Cadmus D. Chen ,&nbsp;Bochu Wang ,&nbsp;Xiao Huang ,&nbsp;Chenfengtao Zheng ,&nbsp;Youhyun Nam ,&nbsp;David N. Beratan","doi":"10.1016/j.jinorgbio.2025.113191","DOIUrl":"10.1016/j.jinorgbio.2025.113191","url":null,"abstract":"<div><div>Charge transfer and transport are fundamental to chemistry and biochemistry. Since the 1950s, theorists and experimentalists have advanced the field to develop a molecular-level understanding of single-electron/one-step electron transfer, and ongoing studies explore multi-step, multi-electron, and multi-particle transfer and transport. This review highlights studies from our group on electron transfer beyond the one-electron/one-step regime. In particular, we review progress on electron bifurcation reactions, ultra-long range hopping transport in cable bacteria and bacterial nanowires, oxidative damage pathways, and charge transport pathways in nucleic acids. We highlight emerging themes and mechanisms across biological structures, including the roles being discovered for electron-electron correlations, rapid long-range multi-step biological electron transport, unconventional charge transport pathways, and competing charge transfer mechanisms.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113191"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786844","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":"A cyclometalated iridium(III) complex with 2-acetylpyridine-N(4)-ortho-chlorophenyl thiosemicarbazone: Potent antiproliferative and antibacterial activities","authors":"Bruna V. Paes ,&nbsp;Davi N. Costa ,&nbsp;Igor V. Esarev ,&nbsp;Susanne Boschuk ,&nbsp;Petra Lippmann ,&nbsp;Sarah Sant'Anna Maranhão ,&nbsp;Claudia Pessoa ,&nbsp;Ingo Ott ,&nbsp;Heloisa Beraldo","doi":"10.1016/j.jinorgbio.2025.113179","DOIUrl":"10.1016/j.jinorgbio.2025.113179","url":null,"abstract":"<div><div>The cyclometalated [Ir(C<img>N)₂(H2Ac4<em>o</em>ClPh)]Cl·2H₂O complex, hereafter named <strong>Ir(III) complex</strong>, was obtained from the reaction of dichlorotetrakis(2-(2-pyridinyl)phenyl)diiridium(III), [Ir₂(N<img>C)₄Cl₂] (<strong>P1</strong>) with 2-acetylpyridine <em>N</em>(4)-ortho-chlorophenyl thiosemicarbazone (H2Ac4<em>o</em>ClPh). The <strong>Ir(III) complex</strong> and H2Ac4<em>o</em>ClPh exhibited cytotoxic effects against A549 lung and PC3 prostate cancer cells, with IC₅₀ values below 5 μM. Although the <strong>Ir(III) complex</strong> showed a higher IC₅₀ value against PC3 prostate cancer cells than H2Ac4<em>o</em>ClPh, it exhibited a higher selectivity index (SI = IC_{50 L929}/IC_{50 PC3} L929: non-malignant fibroblast cells). The <strong>Ir(III) complex</strong> did not strongly inhibit thioredoxin reductase (TrxR) activity, suggesting that its mode of action does not involve TrxR inhibition. Hoechst 33342 staining revealed that A549 cells treated with the <strong>Ir(III) complex</strong> underwent nuclear fragmentation and chromatin condensation, indicating the occurrence of cell death. After 6 h treatment with <strong>Ir(III) complex</strong>, the iridium levels in A549 tumor cells were almost 75-fold higher than after treatment with the synthesis precursor <strong>P1</strong>, which probably could explain the potent cytotoxic effects of <strong>Ir(III) complex</strong> and the low activity of <strong>P1</strong>. The antibacterial activity of <strong>Ir(III) complex</strong> against <em>Gram</em>-positive <em>Bacillus subtillis</em> bacteria was comparable to that of ciprofloxacin used as a control. The results of the present work represent a significant contribution to the investigations on the pharmacological profile of iridium(III) complexes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113179"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733823","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}