Journal of Inorganic Biochemistry最新文献

{"title":"Synthesis and evaluation of the combined chemotherapeutic and photodynamic action of new Pt-complexes of natural chlorins","authors":"Petr V. Ostroverkhov ,&nbsp;Anna D. Plutinskaya ,&nbsp;Ksenia V. Luneva ,&nbsp;Evgeniya O. Borzhitskaya ,&nbsp;Polina E. Lavrinova ,&nbsp;Nikolay D. Govorov ,&nbsp;Aleksey B. Golovanov ,&nbsp;Ekaterina S. Neryabova ,&nbsp;Leonid Y. Martinov ,&nbsp;Maxim N. Usachev ,&nbsp;Elena V. Filonenko ,&nbsp;Olga A. Bezborodova ,&nbsp;Mikhail A. Grin","doi":"10.1016/j.jinorgbio.2026.113240","DOIUrl":"10.1016/j.jinorgbio.2026.113240","url":null,"abstract":"<div><div>The combination of multiple therapeutic methods or drugs in the treatment of oncological diseases is a well-established strategy commonly referred to as combination therapy. This approach allows to reduce the adverse effects and enhance treatment efficacy by overcoming resistance to one of the agents within the combination. In the present study, novel Pt(II) complexes of natural chlorins bearing carboxyl and pyridine substituents were synthesized as potential agents for combination therapy. The structures of the synthesized complexes were confirmed by various physicochemical methods, including ¹H and ¹³C NMR spectroscopy, mass spectrometry, high-resolution chromatography-mass spectrometry and Fourier-transform infrared (FTIR) spectroscopy. <em>In vitro</em> evaluation of the compounds demonstrated an increase in both photoinduced and dark cytotoxicity of the Pt complexes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113240"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023365","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":"Substituent size versus metal binding of inhibitors with variants of influenza endonuclease","authors":"Alysia J. Kohlbrand ,&nbsp;Ryjul W. Stokes ,&nbsp;Banumathi Sankaran ,&nbsp;Seth M. Cohen","doi":"10.1016/j.jinorgbio.2025.113210","DOIUrl":"10.1016/j.jinorgbio.2025.113210","url":null,"abstract":"<div><div>The influenza virus causes a significant burden of illness each year. Although vaccination is the most effective method to prevent seasonal influenza infection, viral escape mechanisms make vaccine composition difficult to predict. Antivirals are crucial for decreasing rates of morbidity and mortality from influenza viral infection. The newest anti-influenza drugs target the RNA-dependent RNA polymerase acidic N-terminal (PA_N) endonuclease, a critical component of influenza viral replication machinery. This study examines the structure of inhibitors of PA_N that utilize a hydroxypyridinone-based metal-binding pharmacophore (MBP). Specifically, this report explores how the size of substituent groups impacts the binding conformation and affinity of a series of compounds against both wild-type (WT) and resistance mutant strains, I38T and E23K. Co-crystal structures revealed that the distance between compounds and enzyme residue 38 was conserved to maintain strong interactions, resulting in deviations from ideal coordination geometries at the active site metal centers. This suggests the interactions with residue 38 with each compound is important and can impact inhibitor potency as a consequence of distortions in the metal binding geometry of the compounds.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113210"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921996","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":"Mechanistic and spectroscopic characterization of human CYP17A1 in Nanodiscs","authors":"Ilia G. Denisov ,&nbsp;Yilin Liu ,&nbsp;Piotr J. Mak ,&nbsp;Stephen G. Sligar","doi":"10.1016/j.jinorgbio.2025.113211","DOIUrl":"10.1016/j.jinorgbio.2025.113211","url":null,"abstract":"<div><div>The human cytochrome P450 CYP17A1 plays a critical role in the production of steroid hormones, converting pregnenolone to dehydroepiandrosterone and progesterone to androstenedione. Sequential reactions catalyzed by CYP17A1 are hydroxylation at C17 position, followed by C17 – C20 carbon‑carbon bond scission. The mechanism of the lyase reaction is still debated, with two proposed reaction pathways favoring either a peroxo- (Compond 0) or iron-oxo (Compound 1) driven catalysis. In this review we summarize the results obtained through collaboration between the Sligar laboratory at University of Illinois and the Kincaid laboratory at Marquette University over the last 15 years. We used a combination of spectroscopic and functional studies of human CYP17A1 incorporated in lipid Nanodiscs, mimicking the native membrane environment, to dissect the elementary steps of P450 reaction cycle and characterize the iron‑oxygen intermediates in the presence of substrates for both reactions catalyzed by CYP17A1. In addition, we used the mutations E305G and T306A to probe the effect of perturbing the proton delivery required for the formation of Compound 1, but not for Compound 0, and the mutation N202S involved in substrate positioning at the active site. Resonance Raman spectra, in combination with cryo-radiolytic reduction of the oxy-complex of CYP17A1, provided a detailed picture of hydrogen bonding and protonation of peroxo- and hydroperoxo- intermediates and identified a new transient hemiketal complex on the peroxo-driven pathway of lyase reaction. These results consistently demonstrated the predominant role of the peroxo-driven catalysis for the lyase reaction in CYP17A1 incorporated in lipid Nanodiscs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113211"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921999","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":"Cyclometalated iridium complex as a PD-L1 inhibitor: Suppressing expression via COX-2 blockade","authors":"Yating Zhang ,&nbsp;Jingyue Zhao ,&nbsp;Zhengqi Shen ,&nbsp;Xiangyu Dai ,&nbsp;Peisen Wang ,&nbsp;Zhi Su ,&nbsp;Suxing Jin ,&nbsp;Xuling Xue ,&nbsp;Hong-Ke Liu","doi":"10.1016/j.jinorgbio.2025.113198","DOIUrl":"10.1016/j.jinorgbio.2025.113198","url":null,"abstract":"<div><div>Metal-based Programmed Cell Death Ligand 1 (PD-L1) inhibitors partially overcome the limitations of small-molecule inhibitors, such as ambiguous targeting and complex synthetic processes. This study explores a cyclometalated iridium(III) complex Ir-FA by incorporating bioactive natural product trans-ferulic acid (FA), which could be a promising metal-based PD-L1 inhibitor. Ir-FA demonstrated selective cytotoxicity against A549 cells while exhibiting no toxicity toward normal HLF cell line. Mechanistic studies revealed that Ir-FA induces mitochondrial dysfunction via reactive oxygen species (ROS) overproduction and membrane potential collapse. Concurrently, Ir-FA effectively suppressed the expression and activity of key inflammatory mediators, cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2). Crucially, this combined action, mitochondrial impairment and COX-2/PGE2 inhibition, resulted in the marked downregulation of intracellular PD-L1 expression, which might help suppress the tumor immune evasion. These findings highlight the potential of exploiting the synergistic effects of iridium coordination chemistry and anti-inflammatory activity to develop innovative metal-based agents targeting the Programmed Cell Death Protein 1/PD-L1 immune checkpoint pathway. This work created a transformative platform for developing multifunctional metallodrugs with synergizing chemotherapy and immune activation, holding significant value for cancer treatment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113198"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839080","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 evaluation of dinuclear ruthenium p-cymene complex with the mononuclear counterpart: A structural perspective","authors":"Anushka Verma ,&nbsp;Arabinda Muley ,&nbsp;Nafeesa Shahnaz ,&nbsp;Sharan Shanmuga Vuppaladadium Rathnam ,&nbsp;Roy Anindya ,&nbsp;Somnath Maji","doi":"10.1016/j.jinorgbio.2026.113217","DOIUrl":"10.1016/j.jinorgbio.2026.113217","url":null,"abstract":"<div><div>Human cancer is a complex and highly diverse disease based on multiple aetiologies, multiple cell targets and distinct developmental stages. Notably, ruthenium-based complexes have emerged as good alternatives to traditional platinum-based drugs for cancer therapy. In this context, a mono and a dinuclear novel ruthenium(II) <em>p</em>-cymene complex formulated as [(<em>p</em>-cymene)Ru(<strong>L</strong>)Cl](PF₆) and [(<em>p</em>-cymene)₂Ru₂(<strong>L</strong>)Cl₂](PF₆)₂ (<strong>L</strong> = N-(3,5-di(pyridin-2-yl)-4<em>H</em>-1,2,4-triazol-4-yl)-1,8-naphthalimide) respectively have been synthesized and characterized by different spectroscopic techniques <em>i.e.</em>, UV–vis, ¹H NMR, ¹³C NMR, COSY, FT-IR and mass spectrometry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cyclic voltammetry has also been performed. In addition, cytotoxicity against cancer cell growth was examined using two human breast cancer cell lines, MDA-MB-231 and MCF-7. Both the complex exhibited strong DNA cleavage activity <em>in vitro</em>. However, cytotoxicity, cell viability and ROS production ability of [(<em>p</em>-cymene)₂Ru₂(<strong>L</strong>)Cl₂](PF₆)₂ was found to be comparatively higher against triple negative breast cancer cell line MDA-MB-231.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113217"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964736","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":"Persulfidation of the zinc finger protein ZRANB2 modulates its RNA binding and alternative splicing function","authors":"Matthew S. Hursey ,&nbsp;Abigail D. Reitz ,&nbsp;Samuel E. Fidler,&nbsp;Sarah L.J. Michel","doi":"10.1016/j.jinorgbio.2026.113213","DOIUrl":"10.1016/j.jinorgbio.2026.113213","url":null,"abstract":"<div><div>Zinc finger Ran-binding domain-containing protein 2 (ZRANB2) is an RNA-binding protein that plays a key role in alternative splicing. It contains two N-terminal RanBP2-type ZF domains in which four cysteine residues coordinate Zn(II) in a tetrahedral geometry to afford proper folding and function. Persulfidation, a post-translational modification in which cysteine thiols (-SH) are converted to persulfides (-SSH) by hydrogen sulfide (H₂S), has emerged as a means for regulating ZF activity. ZRANB2 is frequently identified as persulfidated in chemoselective proteomics screens, and here, we evaluate the direct modification of ZRANB2 by H₂S. Using a recombinantly expressed two-domain construct (ZRANB2-2D), we report that Zn(II)-bound ZRANB2-2D undergoes persulfidation when exposed to H₂S and oxygen with superoxide generated as an intermediate. This modification induces a loss of Zn(II)-dependent structure and abrogates binding to an RNA oligonucleotide from exon 3 of the transformer-2 protein homolog beta (TRA2B) RNA, a splicing target of ZRANB2, as well as to an optimized RNA oligonucleotide. Consistent with impaired RNA binding, cellular treatment with H₂S leads to decreased formation of a TRA2B splice product, suggesting a connection to persulfidation of ZRANB2 in cells. Notably, addition of a reductant restores ZRANB2-2D RNA-binding activity in vitro. These results position persulfidation as a rheostat for modulating ZF protein function, exemplified here by its role in regulating ZRANB2 RNA binding and splicing.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113213"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008309","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":"Carbon monoxide chemistry of α-V70I Mo-nitrogenase: Evidence from EPR- and IR-monitored photolysis – or, what a difference a methyl makes","authors":"Simon J. George ,&nbsp;Aubrey D. Scott ,&nbsp;Leland B. Gee ,&nbsp;Lance C. Seefeldt ,&nbsp;Stephen P. Cramer","doi":"10.1016/j.jinorgbio.2025.113203","DOIUrl":"10.1016/j.jinorgbio.2025.113203","url":null,"abstract":"<div><div>A critical step in the global nitrogen cycle is the conversion of dinitrogen into biologically accessible ammonia. In Nature this is accomplished by the nitrogenase (N₂ase) family of enzymes. Carbon monoxide (CO) has long been known as an inhibitor of dinitrogen reduction by N₂ase, but it can also be a substrate of the enzyme, when it is catalytically reduced to hydrocarbons. Understanding the CO interactions with N₂ases are thus relevant to both dinitrogen fixation and Fischer-Tropsch-like chemistry. Here, the interaction of CO with the α-V70I variant of <em>Azotobacter vinelandii</em> MoFe N₂ase was investigated using electron paramagnetic resonance (EPR) and infrared (IR) monitored photolysis of bound CO under cryogenic conditions. This was supplemented by further analysis of stopped-flow Fourier transform IR (SF-FT-IR) data under turnover conditions. The α-V70I variant adds a single methyl group close to the FeMo-cofactor active site, and the results show that this inhibits and slows, but does not substantially chemically change, the binding of CO to the FeMo-cofactor. The EPR spectra of both the hi-CO and lo-CO states closely resemble those from the wild-type enzyme. Similarly, the SF-FT-IR spectra of CO inhibited α-V70I and wild-type enzyme are strikingly similar, showing only small shifts in band energies which allow better interpretation of the published wild-type spectra. The extra carbon does, however, impact and inhibit the photochemical release and migration of CO at cryogenic temperatures, resulting in novel CO-bound species. These include a product species, termed Lo-1*, which may involve CO photochemically migrating on the FeMo-cofactor.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113203"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921994","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":"Conjugation-driven modulation of excited-state dynamics and photobiological activity in Ru(II) bis-terpyridyl oligothienyl complexes","authors":"Alisher Talgatov ,&nbsp;Ge Shi ,&nbsp;Gurleen Kaur ,&nbsp;Xinyang Sun ,&nbsp;Kalara D. Gamage ,&nbsp;Habiba Afrin ,&nbsp;Joshua Rahmon ,&nbsp;Elamparuthi Ramasamy ,&nbsp;Houston D. Cole ,&nbsp;Colin G. Cameron ,&nbsp;Wenfang Sun ,&nbsp;Sherri A. McFarland","doi":"10.1016/j.jinorgbio.2025.113190","DOIUrl":"10.1016/j.jinorgbio.2025.113190","url":null,"abstract":"<div><div>To elucidate how ligand conjugation modulates photophysical behavior and photobiological activity, a new family of bis-terpyridyl Ru(II) complexes bearing oligothienyl-substituted ligands, <strong>[Ru(tpy)(tpy-<em>n</em>T)]</strong>^{<strong>2+</strong>} (<em>n</em> = 0–4; <strong>Ru-</strong><em><strong>n</strong></em><strong>T</strong>), were synthesized and comprehensively characterized. Progressive thiophene extension produced predictable bathochromic shifts and enhanced intensity of intraligand (ILCT) and metal-to-ligand charge-transfer (MLCT) absorption bands, accompanied by red-shifted phosphorescence (673–818 nm), microsecond excited-state lifetimes, and singlet‑oxygen generation (Φ_Δ = 0.46–0.86). The transition from <strong>Ru-1T</strong> to <strong>Ru-2T</strong> marked a sharp increase in triplet-state lifetime and Φ_Δ, signifying a shift from predominantly MLCT to mixed MLCT/ILCT character. Photocytotoxicity toward SK-MEL-28 melanoma cells revealed wavelength- and oxygen-dependent structure–activity relationships: <strong>Ru-2T</strong> exhibited exceptional potency under normoxia (EC₅₀ ≈ 0.5 nM, PI &gt;10³), whereas <strong>Ru-4T</strong> retained sub-micromolar activity and high phototoxic indices under hypoxia and red-light irradiation. Increasing thiophene length also enhanced lipophilicity (log <em>D</em>_o/w ≈ −1.8 → +0.2), correlating with diminished photocytotoxicity but sustained activity under oxygen limitation. Extension of these studies to microbial models revealed parallel trends – <strong>Ru-2T</strong> was most effective against Gram-positive <em>E. faecalis</em> V587 (EC₅₀ = 0.17 μM, PI = 216), while <strong>Ru-4T</strong> showed selective photoactivity toward Gram-negative <em>E. coli</em> W3110 (EC₅₀ = 6.5 μM, PI ≈ 21). Collectively, these results demonstrate that systematic control of conjugation and polarity in Ru(II) bis-terpyridyl frameworks enables tuning of excited-state character, wavelength responsiveness, and biological activity, establishing design principles for oxygen-adaptive photoactive metallodrugs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113190"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909785","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":"When the wrong metal stops the cycle: Dynamics and specificity in plant copper-dependent peptide cyclases","authors":"Courtney M. Petersen,&nbsp;Winston C. Pitts,&nbsp;Shabnam Hematian","doi":"10.1016/j.jinorgbio.2025.113201","DOIUrl":"10.1016/j.jinorgbio.2025.113201","url":null,"abstract":"<div><div>Herein, we report the expression of split BURP domain peptide cyclases (BpCs), primarily CamB1 from <em>Ceanothus americanus</em>, in <em>Escherichia coli</em> using the pET22b vector without a fusion partner while retaining their disordered N-terminal region. To our knowledge, this represents the first full-length split BpC expressed and isolated without reliance on a stabilizing fusion tag (<em>e.g.</em>, maltose binding protein, MBP). Both CamB1 and ArbB2, from <em>Coffea arabica</em>, were purified and refolded from inclusion bodies, and displayed robust catalytic turnover on a minimal peptide substrate. Copper titrations revealed that catalytic assays using glutathione as the reducing agent require copper far in excess of the stoichiometric number of active sites, with activity plateauing at ∼50-fold excess, likely reflecting competition with nonspecific copper binding or solution speciation. Using ascorbic acid in place of glutathione not only restores but also increases maximal activity, requiring only near-stochiometric copper. Metal impact studies demonstrated that noncognate metals inhibit activity. Zn(II) most severely inhibited BpC function at low micromolar concentrations in enzyme-initiated assays containing Cu(II), Zn(II), and glutathione, but this effect was markedly alleviated in reducing agent-initiated assays and instead resembled the modest inhibition by Ag(I), which fully suppressed activity only near 1 mM. These results highlight how assay order influences metal competition at the active site. Given that BURP-domain proteins are implicated in plant stress responses, including tolerance to metal exposure, these findings suggest that Zn(II) and Ag(I) inhibition may represent a biochemical mechanism by which environmental metal stress modulates BpC activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113201"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881775","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":"Cytotoxicity of metal-containing carbon monoxide-releasing molecules: A current assessment","authors":"M. Kubeil ,&nbsp;H. Stephan","doi":"10.1016/j.jinorgbio.2026.113235","DOIUrl":"10.1016/j.jinorgbio.2026.113235","url":null,"abstract":"<div><div>Carbon monoxide-releasing molecules (CORMs) have drawn attention since the beginning of the century. Since then, many publications have been devoted to optimizing the physicochemical properties of CORMs, with a focus on the release kinetics of CO as a function of external stimuli such as light, enzyme, and redox triggering, as well as ligand exchange and pH changes. This was followed by studies on the use of CORMs and later carbon monoxide-releasing nanomaterials (CORNMs) as pharmaceutical active compounds/materials in biological systems. In this context, there is an ongoing debate as to whether the pharmacological efficacy can be clearly attributed to CO alone or whether CO-free metal fragments or both mechanisms contribute to biological efficacy. This review focuses in particular on CORMs and CORNMs that exhibit cell toxicity and on corresponding characterization methods that allow biological efficacy to be assigned. The methods to be used to obtain reliable information on biodistribution and pharmacokinetic properties, as well as the characterization of the kinetics of controlled CO release in living organisms, are outlined.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113235"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008281","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}