{"title":"Recent advances in Schiff bases and Cu(II) complexes: Applications in fluorescence imaging and anticancer therapy (2020–2024)","authors":"Alaa Shafie , Amal Adnan Ashour","doi":"10.1016/j.jinorgbio.2025.112909","DOIUrl":"10.1016/j.jinorgbio.2025.112909","url":null,"abstract":"<div><div>Schiff base derivatives have garnered significant attention for their bioimaging and anticancer potentials. In the realm of bioimaging, Schiff base derivatives have shown exceptional capabilities in detecting various metal ions, due to their strong binding affinities and fluorescence properties. Moreover, the potential Schiff bases and their Cu(II) complexes as anticancer agents is being actively explored, with studies demonstrating their ability to induce apoptosis and inhibit cell proliferation in various cancer cell lines. This review article provides a comprehensive overview of recent advancements in the field of cell imaging utilizing Schiff base derivatives for the recognition of Cu<sup>2+</sup> in living cells and organisms. From 2022 to 2024, significant progress has been made in understanding the applications of Schiff bases in cell imaging techniques, ranging from fluorescence microscopy to molecular imaging modalities. Additionally, article has focused on leveraging the unique properties of Schiff base Cu(II) complexes to expand the anticancer efficacy. The article offering insights into the mechanisms underlying enhanced anticancer activity and the development of novel anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112909"},"PeriodicalIF":3.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785777","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":"Rationalizing the structural basis of organic-platinum hybrid complexes binding towards quadruplex-duplex hybrids through all-atom simulations","authors":"Salvatore Muscarella, Irene Treccarichi, Luisa D'Anna, Angelo Spinello","doi":"10.1016/j.jinorgbio.2025.112904","DOIUrl":"10.1016/j.jinorgbio.2025.112904","url":null,"abstract":"<div><div>Guanine-rich sequences containing complementary base pairs can fold into non-canonical quadruplex-duplex hybrid (QDH) conformations. These structures possess unique structural features, leading to the presence of a peculiar binding pocket that can be distinguished from a canonical double helix or a G-quadruplex (G4) structure. Recently, two organic-metal hybrid platinum complexes, able to selectively and strongly recognize a particular type of QDH with a lateral duplex stem-loop, were reported in the literature. However, solution structures are not available for all the investigated compounds, leaving unanswered questions on the structural traits underlying the different binding affinity of these complexes. In this work, we address this gap using all-atom simulations to unravel the key features driving the high selectivity of these organic‑platinum hybrid complexes at an atomistic level. In particular, their binding affinity depends on a delicate balance between the extended π-π stacking interactions performed in the G4-duplex binding pocket and the capacity to form stable hydrogen bonds with the surrounding nucleobases. Thus, our findings provide essential insights to guide the rational design of novel compounds that selectively target QDH structures.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112904"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian Saporito-Magriña , Lila Lopez-Montañana , María Laura Facio , Guadalupe Pagano , Topp Nicole , Ariana Danzi , Juan Ignacio Bellida , Agustín Silva , Matías Albizzati , Marisa Gabriela Repetto
{"title":"Ascorbic acid potentiates the formation of IgG-enriched protein aggregates in plasma in a Cu(II)-mediated manner","authors":"Christian Saporito-Magriña , Lila Lopez-Montañana , María Laura Facio , Guadalupe Pagano , Topp Nicole , Ariana Danzi , Juan Ignacio Bellida , Agustín Silva , Matías Albizzati , Marisa Gabriela Repetto","doi":"10.1016/j.jinorgbio.2025.112905","DOIUrl":"10.1016/j.jinorgbio.2025.112905","url":null,"abstract":"<div><div>Protein aggregates have been reported in disease but also in physiological contexts in tissues as well as circulating protein aggregates in the bloodstream. Free Cu(II) induces the aggregation of serum proteins and this metal yields highly oxidant species upon reaction with hydrogen peroxide and also reacts with ascorbic acid (AA). A broad population is exposed to high doses of AA as second line therapy for different pathologies or as nutritional supplementation. This study addresses the effect of AA on the formation of plasma protein aggregates, observed by optic density, protein quantification and electrophoresis (SDS-PAGE) that, contrary to hampering the Cu(II)-induced plasma protein aggregation, AA potentiates their formation. Free Cu(II) induces the formation of IgG-enriched plasma protein aggregates but the combination with AA potentiates the incorporation of gamma-globulin (IgG) whereas other proteins such as albumin become depleted. The potentiating effect of Cu(II) and AA was corroborated employing isolated IgG. This effect of AA on Cu(II)-induced protein aggregation is not reproduced with isolated albumin. Additionally, AA does not potentiate Fe(III)-mediated aggregation of IgG, albumin or human plasma. Finally, it was shown that in healthy subjects which were administered high doses of intravenous AA, the aggregates can be obtained from the centrifuged plasma after 30 min of the administration of the antioxidant. Aggregated IgG have been shown to activate Fc receptors, involved in oxidative burst and inflammatory processes observed in neutrophils. Thus, the effect of AA on the immune system could be linked to the accumulation of protein aggregates enriched in specific proteins.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112905"},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705198","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":"Coiled coils as ligands for inclusion in the inorganic chemist's toolbox - For advances in MRI contrast agent design.","authors":"Anna F A Peacock","doi":"10.1016/j.jinorgbio.2025.112903","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2025.112903","url":null,"abstract":"<p><p>Ligands are essential tools in synthetic inorganic chemistry, enabling the fine-tuning of metal ion properties to optimize performance. Spanning from small molecules to macromolecular proteins, ligands vary widely in structure and function. De novo designed coiled coils serve as a unique bridge between these extremes, offering precise control over metal coordination. Here, we explore the application of coiled coil ligands in MRI contrast agent design, leveraging their versatility to systematically modulate the coordination chemistry and hydration state of gadolinium - the metal used in most clinical MRI contrast agents. This novel class of gadolinium-based agents demonstrates superior performance compared to existing clinical agents, highlighting the potential of coiled coil ligands. Furthermore, when coordinated to copper, these ligands form complexes that challenge the conventional notion that copper is unsuitable for MRI contrast agents. These findings establish coiled coil ligands as a powerful platform for advancing contrast agent design.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":" ","pages":"112903"},"PeriodicalIF":3.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762780","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}
Hao Wang , Guozhu Ren , Yue Xu , Ruiping Deng , Rui Wang , Liang Zhou
{"title":"Novel erbium complex with anticancer activity against radiation resistant lung adenocarcinoma cells","authors":"Hao Wang , Guozhu Ren , Yue Xu , Ruiping Deng , Rui Wang , Liang Zhou","doi":"10.1016/j.jinorgbio.2025.112902","DOIUrl":"10.1016/j.jinorgbio.2025.112902","url":null,"abstract":"<div><div>In this work, novel erbium complex with anticancer activity against radiation resistant lung adenocarcinoma cells was obtained and demonstrated. Firstly, stronger inhibitory effect of Er<sup>3+</sup> on non-small cell lung cancer (NSCLC) cells and NSCLC- radiation resistant (RR) cells was experimentally confirmed. Then, by selecting highly biocompatible porphyrins as ligands, a novel erbium complex tetraphenylporphyrin erbium acetylacetonate (Er(acac)TPP) was synthesized and purified. Compared with Cisplatin, notably, Er(acac)TPP exhibits relatively higher inhibitory efficiency on NSCLC-RR cells. Moreover, the toxicities of Er(acac)TPP to normal cells are much lower than that of cancer cells. Subsequently, cell expansion, increased apoptosis, a decline in mitochondrial membrane potential (MMP), an accumulation of intracellular reactive oxygen species (ROS), increased Caspase-9 protein level and G2/M arrest were seen. These data all pointed to Er(acac)TPP as a possible candidate for more research and development as a chemotherapeutic drug.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112902"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682899","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}
Xinyan Zou , Wenting Xiao , Xiang Zhou , Rui Shen , Aihong Yang , Xiaodi Kou
{"title":"An insight into porphyrin carbamate derivatives and a Cu(II) metalloporphyrin as G-quadruplex binder: Synthesis, single crystal characterization, binding ability and anti-tumor potential","authors":"Xinyan Zou , Wenting Xiao , Xiang Zhou , Rui Shen , Aihong Yang , Xiaodi Kou","doi":"10.1016/j.jinorgbio.2025.112901","DOIUrl":"10.1016/j.jinorgbio.2025.112901","url":null,"abstract":"<div><div>Telomere with a G-quadruplex (Gq) structure is a recognized anti-tumor target. It was found that the aromatic plane of porphyrin may form π-π interactions with the Gq structure and the coordination of metal ions to porphyrin may increase its aromatic plane. Therefore, in this work, two porphyrin carbamate derivatives (<strong>1</strong> and <strong>2</strong>) and a Cu(II) metalloporphyrin (<strong>1-Cu</strong>) were designed and synthesized. The single crystals of <strong>1</strong> and <strong>1-Cu</strong> were obtained and characteristics related to the binding interactions were analyzed at molecular level. With further Hirshfeld surface, molecular electrostatic potential, and frontier molecular orbital analyses, it was revealed that porphyrin ring, phenyl carbamate side chain and the coordinated copper ion may form synergistic binding forces with the Gq structure. Subsequently, binding ability and binding mode were tested with UV–Vis, fluorescence, and circular dichroism spectroscopies and PCR-stop method. Result showed that all three compounds selectively bound to Gq with the highest binding constant of 3.19 × 10<sup>7</sup>, which was an order of magnitude higher than those to the duplex DNA. Further molecular docking and molecular dynamics simulations supported the synergistic end stacking and groove binding modes. At last, anti-tumor potentials were evaluated with cytotoxicity, cell staining, cell apoptosis, and cell migration assays. Results showed that compared with the positive control drug, the IC<sub>50</sub> values of <strong>1</strong> and <strong>1-Cu</strong> to the tumor cells were significantly lower, and their cytotoxicities to tumor cells were much higher than those to normal cells. Therefore, this work provided important information for designing novel drugs targeting Gq telomere.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112901"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673124","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}
Tugce Boztepe , Federico Karp , Silvia Cabrera , José Aleman , Diego G. Lamas , Cristián Huck-Iriart , Germán A. Islan , Ignacio E. León
{"title":"An oral delivery approach for riboflavin-targeted platinum(II)-loaded lipid nanoparticles into alginate-gelatin matrices against 2D and 3D colorectal carcinoma models","authors":"Tugce Boztepe , Federico Karp , Silvia Cabrera , José Aleman , Diego G. Lamas , Cristián Huck-Iriart , Germán A. Islan , Ignacio E. León","doi":"10.1016/j.jinorgbio.2025.112900","DOIUrl":"10.1016/j.jinorgbio.2025.112900","url":null,"abstract":"<div><div>This study investigated the use of riboflavin-targeted Nanostructured Lipid Carriers (R-NLCs) to deliver a platinum-based anticancer drug [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) to colorectal cancer cells. Three different R-8-QO-Pt-NLC formulations were prepared via hot-homogenization by ultrasonication method. The physicochemical characterizations of NLCs were analyzed by small- and wide-angle X-ray scattering (SAXS/WAXS) and fourier transformed infrared spectroscopy (FTIR). The cytotoxic effects and IC<sub>50</sub> values of R-8-QO-Pt-NLC formulations were compared with those of the free 8-QO-Pt. Cellular uptake and apoptosis were evaluated towards HCT 116 cells in monolayer (2D). The liquid overlay technique was used to generate 3D multicellular tumor spheroids, MCTS. The anticancer and antimetastatic activities of the free 8-QO-Pt and R-8-QO-Pt-NLCs were determined in MCTS. The results revealed that R-8-QO-Pt-NLC exhibited greater cytotoxicity and lower IC<sub>50</sub> values than free 8-QO-Pt in both 2D and 3D cell cultures. Furthermore, results showed that the volumes of the spheroids were reduced in response to increasing concentrations of R-8-QO-Pt-NLC, showing higher inhibition of cell migration in colorectal cancer spheroids at concentrations of 10.0, 15.0, and 25.0 μM than free 8-QO-Pt. To provide protection against gastric acid conditions, an additional drug delivery system based on alginate (Alg) and gelatin (Gel) beads for R-8-QO-Pt-NLC oral administration was developed. While free and R-NLC encapsulated 8-QO-Pt were practically inactivated at pH 1.2 and 37 °C, it was revealed that the Alg-Gel beads retain 5.7 times the initial activity of the R-8-QO-Pt-NLC. The findings of this research indicate that R-8-QO-Pt-NLC embedded in Alg-Gel beads are promising hydrogels for targeted colorectal delivery systems.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112900"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734922","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":"Broadening the chemical diversity of oxidovanadium(V) complexes for targeting neglected tropical diseases","authors":"Gonzalo Scalese , Nicolás Pérez , Josefina Pereyra , Yasmina Sanabria , Olivier Blacque , Ignacio Machado , Leticia Pérez-Díaz , Dinorah Gambino","doi":"10.1016/j.jinorgbio.2025.112891","DOIUrl":"10.1016/j.jinorgbio.2025.112891","url":null,"abstract":"<div><div>Chagas disease and Leishmaniasis, caused by <em>Trypanosoma cruzi</em> and <em>Leishmania spp.</em>, respectively, are highly prevalent neglected tropical diseases (NTDs) that pose significant global health challenges. In our pursuit of effective vanadium-based therapeutics against these diseases, we previously developed several series of oxidovanadium(V) complexes featuring bidentate bioactive ligands and Schiff base tridentate ligands. The current study extends our previous research by incorporating in the same molecule, a tridentate bromo-substituted isonicotinyl hydrazone Schiff base ligand, BrIS, and a 8-hydroxyquinoline derivative (L), leading to the synthesis and comprehensive characterization of five new complexes, [V<sup>V</sup>O(BrIS-2H)(L-H)]. Most of new complexes exhibited activity in the micromolar range against the infective trypomastigote form of <em>T. cruzi</em> (EC<sub>50, 24h</sub>: 0.73–7.95 μM) and against <em>L. infantum</em> promastigotes (IC<sub>50, 5 days</sub>: 1.14–1.16 μM) and some of them showed good selectivity indexes towards the parasites (SI up to 52). Notably, the vanadium uptake by the parasites was higher for the new [V<sup>V</sup>O(BrIS-2H)(L-H)] compounds compared to [V<sup>V</sup>O(IN-2H)(L-H)] analogues previously developed, where IN is the structurally related 2-hydroxy-1-naphtaldehyde isonicotinoylhydrazone ligand, with accumulation in the soluble cell fraction. High-dose incubations resulted in trypanocidal effects and suggested the generation of reactive oxygen species (ROS). Further analysis revealed that [V<sup>V</sup>O(BrIS-2H)(L-H)] complexes induced a higher percentage of apoptosis, whereas the [V<sup>V</sup>O(IN-2H)(L-H)] series was associated with autophagic cell death. These findings highlight the potential of the [V<sup>V</sup>O(BrIS-2H)(L-H)] series as promising anti-<em>T. cruzi</em> agents and underscore the need for further research to optimize their therapeutic efficacy and explore their mechanisms of action.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112891"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668695","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":"Preparation of ferrocene‑iridium(III) acylhydrazone complexes and their anticancer application against A549 cell line","authors":"Wenzhi Yang , Jia Wen , Xicheng Liu , Jinfeng Liu","doi":"10.1016/j.jinorgbio.2025.112899","DOIUrl":"10.1016/j.jinorgbio.2025.112899","url":null,"abstract":"<div><div>Two ferrocene‑iridium(III) acylhydrazone complexes (<strong>Fe-Ir1</strong> and <strong>Fe-Ir2</strong>) were designed and synthesized, which showed excellent anti-proliferative activity against A549 human lung adenocarcinoma and A549/DDP (cisplatin-resistant) cell lines, especially for <strong>Fe-Ir1</strong> (IC<sub>50</sub> = 10.2 ± 0.4 μM, twice that of cisplatin). Meanwhile, <strong>Fe-Ir1</strong> showed low toxicity to BEAS-2B cells (normal dividing human bronchial epithelial cells), indicating its favorable selectivity. <strong>Fe-Ir1</strong> entered A549 cells following an non-energy-dependent pathway, targeted lysosomes, induced changes in lysosomal membrane permeability, reduced glycolytic stress, arrested cell cycle, then promoted early-stage apoptosis and effectively inhibited cell migration. Western blotting also showed that the <strong>Fe-Ir1</strong> could promote the expression of Bax protein and inhibited Bcl-2 and PARP protein in A549 cells. In vivo experiments demonstrated that <strong>Fe-Ir1</strong> had significant capabilities in inhibiting tumor growth, cancer cell metastasis and spread. In conclusion, <strong>Fe-Ir1</strong> holds promise as a potential alternative to platinum-based drugs and warrants further research, offering more hope and vitality to cancer patients.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112899"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642739","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}
Olivia R. Stiller , Bennett R. Streit , Garrett Honzay , Jennifer L. DuBois , Kenton R. Rodgers , Gudrun S. Lukat-Rodgers
{"title":"Deciphering the role of the distal pocket in Staphylococcus aureus coproheme decarboxylase","authors":"Olivia R. Stiller , Bennett R. Streit , Garrett Honzay , Jennifer L. DuBois , Kenton R. Rodgers , Gudrun S. Lukat-Rodgers","doi":"10.1016/j.jinorgbio.2025.112896","DOIUrl":"10.1016/j.jinorgbio.2025.112896","url":null,"abstract":"<div><div>Coproheme decarboxylase (ChdC) catalyzes the sequential oxidative decarboxylation of coproheme III propionate side chains at positions 2 and 4 to form heme <em>b</em> by activation of two molecules of H<sub>2</sub>O<sub>2</sub> at its substrate's iron center. The coproheme III binding pocket lacks the distal His-Arg pair that polarizes and acts as a catalytic base toward activation of coordinated H<sub>2</sub>O<sub>2</sub> in canonical heme-dependent peroxidases. Instead ChdC from <em>Staphylococcus aureus</em> has a Gln (Q185). This report presents thermodynamic, kinetic, and spectroscopic results that provide comparative insight into how wild type (WT) and Q185A and Q185R variant ChdCs activate H<sub>2</sub>O<sub>2</sub>. Reactivities with H<sub>2</sub>O<sub>2</sub> and cyanide affinities at pH 7.5 follow the trend: WT > Q185R > Q185A. Both variants exhibited greater catalase efficiency than WT ChdC. Vibrational resonance Raman signatures of ferric coproheme−CN<sup>−</sup> and ferrous coproheme−CO complexes of WT, Q185A, and Q185R <em>Sa</em>ChdCs revealed that the Arg mutation does not significantly alter the distal environment while Q185A has a more open active site. Together these data are consistent with a modest role for Q185 in promoting the decarboxylation reaction. A model for the proton transfer required for H<sub>2</sub>O<sub>2</sub> activation that involves the Gln185 iminol tautomer is presented. The three ChdCs reacted with chlorite to generate harderoheme III and heme <em>b</em> to varying extents. In reaction with chlorite, coproheme III:<em>Sa</em>ChdC was cleanly converted to harderoheme III:<em>Sa</em>ChdC, which exhibited vinyl bending and stretching modes at 423 and 1622 cm<sup>−1</sup>, respectively. Differences in <em>Sa</em>ChdC reactivity with ClO<sub>2</sub><sup>−</sup> and H<sub>2</sub>O<sub>2</sub> relative to those of chlorite dismutase and peroxidases, respectively, are discussed.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112896"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682898","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}