JBIC Journal of Biological Inorganic Chemistry最新文献

{"title":"Anticancer potential of benzo[b]thiophene functionalized thiosemicarbazone ligands and their organoruthenium complexes.","authors":"Emine Öztürk, Elif Subaşı, Gizem Kurşunluoğlu, Betül Şen Yüksel, Hülya Ayar Kayalı","doi":"10.1007/s00775-024-02090-w","DOIUrl":"https://doi.org/10.1007/s00775-024-02090-w","url":null,"abstract":"<p><p>As novel promising anticancer candidates, the piano-stool type complexes of ruthenium, [RuCl(η⁶-p-cymene)(N,S-L_n)]PF₆, K₁-₄, were synthesized from the reaction of the substituted benzo[b]thiophene based thiosemicarbazone ligands (L_1-4) with [{RuCl(η⁶-p-cymene)}₂(μ-Cl)₂]. All complexes were fully characterized using elemental analysis, and spectroscopic methods such as FT-IR and ¹H NMR. The molecular masses of the complexes were proved by MALDI-TOF analysis. Single crystal X-ray diffraction study was employed in the structural elucidation of complex K₁ which shows a distorted octahedral geometry around the Ru(II) ion. Furthermore, spectroscopic methods revealed that in all complexes the ligands are coordinated to the metal center in neutral thione form via N, S donors. In this study, the effect of all ligands, complexes and commercial drugs with a different concentration on the viability of OVCAR-3, A2780 and OSE cells were compared. In this comparison, the cytotoxicity of ruthenium (II) complexes on two ovarian cancer cell lines (human A2780 and human OVCAR-3) was evaluated. For this purpose, the resazurin assay was performed. Based on our studies, complex K₂ showed the highest toxicity against OVCAR-3 and A2780 cells. The cytotoxic effect of K₂ was found to be higher than that of the commercial anticancer agents Oxalpin and Carbodex, 1.8-34.7-fold for OVCAR-3 cells and 1.9-11.8-fold for A2780 cells, respectively. These results provide insight into the potential of ruthenium (II) complexes as a cytotoxic agent for the treatment of ovarian cancer, particularly for primary tumors.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-sulfur cluster redox chemistry and dimer dissociation in the outer mitochondrial membrane protein, mitoNEET.","authors":"Kanita A Chaudhry, Krishani K Rajanayake, Richard T Carroll, Dragan Isailovic, Max O Funk","doi":"10.1007/s00775-024-02093-7","DOIUrl":"https://doi.org/10.1007/s00775-024-02093-7","url":null,"abstract":"<p><p>The outer mitochondrial membrane protein known as mitoNEET was discovered when it was labeled by a photoaffinity derivative of the anti-diabetes medication, pioglitazone. The biological role for mitoNEET and its specific mechanism for achieving this remains an active subject for research. There is accumulating evidence suggesting that mitoNEET could be a component of mitochondrial FeS cofactor biogenesis. The protein was composed of an N-terminal membrane associated domain and a C-terminal domain oriented to the cytosol. The cytosolic domain was an iron-sulfur (2Fe-2S) metalloprotein with a rare 3Cys/1His coordination environment. It was previously reported that mitoNEET formed dimers that were remarkably sensitive to pH, likely a consequence of the protonation of the single His-iron ligand. The hypothesis pursued in the research reported here was that perhaps the dissociation of mitoNEET was also sensitive to the redox state of the iron sulfur cluster. To use native electrospray ionization mass spectrometry (ESI-MS) to monitor the reduction reaction ammonium dithionite was envisioned as the appropriate reagent to avoid sodium ion adduct formation from sodium dithionite. The preparation of ammonium dithionite was updated and the compound had the same properties as the sodium salt with redox dyes and the oxidized form of glutathione. The dissociation of mitoNEET treated with ammonium dithionite anaerobically was readily evident as ammonium dithionite was found to be compatible with redox chemistry evaluated by native ESI-MS.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The nitrogenase mechanism: new roles for the dangler?","authors":"Rebeccah A Warmack, Douglas C Rees","doi":"10.1007/s00775-024-02085-7","DOIUrl":"https://doi.org/10.1007/s00775-024-02085-7","url":null,"abstract":"<p><p>Dangler sites protruding from a core metallocluster were introduced into the bioinorganic lexicon in 2000 by R.D. Britt and co-workers in an analysis of the tetramanganese oxygen-evolving cluster in photosystem II. In this perspective, we consider whether analogous dangler sites could participate in the mechanism of dinitrogen reduction by nitrogenase. Two possible roles for dynamic danglers in the active site FeMo cofactor are highlighted that might occur transiently during turnover. The first role for a dangler involves the S2B belt sulfur associated with displacement by carbon monoxide and other ligands, while the second dangler role could involve the entire cluster upon displacement of the His-  <math><mi>α</mi></math>  442 side chain to the molybdenum by a free carboxyl group of the homocitrate ligand. To assess whether waters might be able to interact with the cofactor, a survey of small ligands (water and alkali metal ions) contacting [4Fe4S] clusters in synthetic compounds and proteins was conducted. This survey reveals a preference for these sites to pack over the centers of 2Fe2S rhombs. Waters are excluded from the S2B site in the resting state of nitrogenase, suggesting it is unlikely that water molecules coordinate to the FeMo cofactor during catalysis. While alkali metal ions are found to generally influence the properties of catalysts for dinitrogen reduction, no convincing evidence was found that any of the waters near the FeMo cofactor could instead be sodium or potassium ions. Dangler sites, if they exist in the nitrogenase mechanism, are likely formed transiently by localized changes to the resting-state FeMo cofactor structure.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Globin ferryl species: what is the nature of the protonation event at pH < 5?","authors":"Cezara Zagrean-Tuza, Lavinia Padurean, Maria Lehene, Adrian M V Branzanic, Radu Silaghi-Dumitrescu","doi":"10.1007/s00775-024-02089-3","DOIUrl":"https://doi.org/10.1007/s00775-024-02089-3","url":null,"abstract":"<p><p>The ferryl state in globins has previously been reported to undergo a protonation event below pH 5, as assessed using pH jump experiments with stopped-flow UV-Vis spectroscopy. This protonation entails hypsochromic shifts in the α and β bands (~ 20 to 40 nm) and an ~ 10 nm reduction in the energy difference between these two bands. We now report that in Mb this event is also characterized by a hypsochromic shift in the Soret band (~ 5 nm). No similar shifts in Soret, α, and β bands are seen upon the denaturation of ferryl Mb with guanidine-suggesting that the spectroscopic changes in ferryl Mb at pH < 5 are not caused by changes in the solvent exposure or in hydrogen bonding around the ferryl unit. Under the same denaturing conditions (pH jump below pH 5, and/or guanidine), ferric-aqua and ferrous-oxy Mb show no spectral changes of the order seen in the ferryl pH jump experiments. Together, these observations suggest that the protonation event is localized on the iron-bound oxygen atom, as opposed to somewhere on a hydrogen-bonding partner. Time-dependent density functional theory (TD-DFT) calculations were not able to systematically predict the UV-Vis spectra of the heme to the level of detail needed to interpret the experimental findings in this study.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shift of cell-death mechanisms in primary human neutrophils with a ruthenium photosensitizer.","authors":"Nicolás Montesdeoca, Jennifer M Mohr, Sebastian Kruss, Johannes Karges","doi":"10.1007/s00775-024-02088-4","DOIUrl":"https://doi.org/10.1007/s00775-024-02088-4","url":null,"abstract":"<p><p>Primary human neutrophils are the most abundant human white blood cells and are central for innate immunity. They act as early responders at inflammation sites, guided by chemotactic gradients to find infection or inflammation sites. Neutrophils can undergo both apoptosis as well as NETosis. NETosis is a form of neutrophil cell death that releases chromatin-based extracellular traps (NETs) to capture and neutralize pathogens. Understanding or controlling the balance between these cell-death mechanisms is crucial. In this study, the chemical synthesis and biologic assessment of a ruthenium complex as a light-activated photosensitizer that creates reactive oxygen species (ROS) in primary human neutrophils is reported. The ruthenium complex remains non-toxic in the dark. However, upon exposure to blue light at 450 nm, it exhibits potent cytotoxic effects in both cancerous and non-cancerous cell lines. Interestingly, the metal complex shifts the cell-death mechanism of primary human neutrophils from NETosis to apoptosis. Cells irradiated directly by the light source immediately undergo apoptosis, whereas those further away from the light source perform NETosis at a slower rate. This indicates that high ROS levels trigger apoptosis and lower ROS levels NETosis. The ability to control the type of cell death undergone in primary human neutrophils could have implications in managing acute and chronic infectious diseases.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NifEN: a versatile player in nitrogenase assembly, catalysis and evolution.","authors":"Yilin Hu, Markus W Ribbe","doi":"10.1007/s00775-024-02086-6","DOIUrl":"https://doi.org/10.1007/s00775-024-02086-6","url":null,"abstract":"<p><p>The Mo-nitrogenase catalyzes the reduction of N₂ to NH₃ at the cofactor of its catalytic NifDK component. NifEN shares considerable homology with NifDK in primary sequence, tertiary structure and associated metallocenters. Better known for its biosynthetic function to convert an all-iron precursor (L-cluster; [Fe₈S₉C]) to a mature cofactor (M-cluster; [(R-homocitrate) MoFe₇S₉C]), NifEN also mimics NifDK in catalyzing substrate reduction at ambient conditions. The recently discovered ability of NifEN to reduce N₂ to NH₃ is particularly interesting, as it points to NifEN as a plausible, prototype ancient nitrogenase during evolution. Moreover, the dual function of NifEN in assembly and catalysis makes it a great template to reconstruct the functional variants or equivalents of NifDK, which could facilitate the mechanistic investigation and heterologous synthesis of nitrogenase. This perspective provides an overview of our recent studies of NifEN, with a focus on the implications of its functional versatility for nitrogenase assembly, catalysis and evolution.</p>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into periplasmic nitrate reductase function under single turnover","authors":"Jennifer McGarry,&nbsp;Breeanna Mintmier,&nbsp;Mikayla C. Metzger,&nbsp;Nitai C. Giri,&nbsp;Nicholas Britt,&nbsp;Partha Basu,&nbsp;Jarett Wilcoxen","doi":"10.1007/s00775-024-02087-5","DOIUrl":"10.1007/s00775-024-02087-5","url":null,"abstract":"<div><p>Nitrate reductases play pivotal roles in nitrogen metabolism by leveraging the molybdopterin cofactor to facilitate the reduction of nitrate to nitrite. Periplasmic nitrate reductases (NapA) utilize nitrate as a terminal electron acceptor when oxygen is limiting, helping to drive anaerobic metabolism in bacteria. Despite extensive research into NapA homologs, open questions about the mechanism remain especially at the molecular level. More broadly, little is understood of how the molybdopterin cofactor is tuned for catalysis in these enzymes enabling broad substrate scope and reactivity observed in molybdenum-containing enzymes. Here, we have prepared NapA from <i>Campylobacter jejuni</i> under single turnover conditions to generate a singly reduced enzyme that can be further examined by electron paramagnetic resonance (EPR) spectroscopy. Our results provide new context into the known spectra and related structures of NapA and related enzymes. These insights open new avenues for understanding nitrate reductase mechanisms, molybdenum coordination dynamics, and the role of pyranopterin ligands in catalysis.</p></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"811 - 819"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ detection of ferric reductase activity in the intestinal lumen of an insect","authors":"Anna Karen Hernández-Gallardo,&nbsp;Trinidad Arcos-López,&nbsp;Jahir Marceliano Bahena-Lopez,&nbsp;Carlos Tejeda-Guzmán,&nbsp;Salvador Gallardo-Hernández,&nbsp;Samuel M. Webb,&nbsp;Thomas Kroll,&nbsp;Pier Lorenzo Solari,&nbsp;Carolina Sánchez-López,&nbsp;Christophe Den Auwer,&nbsp;Liliana Quintanar,&nbsp;Fanis Missirlis","doi":"10.1007/s00775-024-02080-y","DOIUrl":"10.1007/s00775-024-02080-y","url":null,"abstract":"<div><p>The rise of atmospheric oxygen as a result of photosynthesis in cyanobacteria and chloroplasts has transformed most environmental iron into the ferric state. In contrast, cells within organisms maintain a reducing internal milieu and utilize predominantly ferrous iron. Ferric reductases are enzymes that transfer electrons to ferric ions, either extracellularly or within endocytic vesicles, enabling cellular ferrous iron uptake through Divalent Metal Transporter 1. In mammals, duodenal cytochrome b is a ferric reductase of the intestinal epithelium, but how insects reduce and absorb dietary iron remains unknown. Here we provide indirect evidence of extracellular ferric reductase activity in a small subset of <i>Drosophila melanogaster</i> intestinal epithelial cells, positioned at the neck of the midgut’s anterior region. Dietary-supplemented bathophenanthroline sulphate (BPS) captures locally generated ferrous iron and precipitates into pink granules, whose chemical identity was probed combining in situ X-ray absorption near edge structure and electron paramagnetic resonance spectroscopies. An increased presence of manganese ions upon BPS feeding was also found. Control animals were fed with ferric ammonium citrate, which is accumulated into ferritin iron in distinct intestinal subregions suggesting iron trafficking between different cells inside the animal. Spectroscopic signals from the biological samples were compared to purified <i>Drosophila</i> and horse spleen ferritin and to chemically synthesized BPS-iron and BPS-manganese complexes. The results corroborated the presence of BPS-iron in a newly identified ferric iron reductase region of the intestine, which we propose constitutes the major site of iron absorption in this organism.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"773 - 784"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-024-02080-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective binding and removal of copper from biological fluids—why are PSP ligands so efficient?","authors":"Peter Faller","doi":"10.1007/s00775-024-02082-w","DOIUrl":"10.1007/s00775-024-02082-w","url":null,"abstract":"<div><p>The following comment tries to answer why the reported removal of copper from buffer, cell culture medium, and cell extract by a supported chelator called phenPS is so selective and efficient. It is further argued that the family of PSP (phosphine sulfide-stabilized phosphines) chelators, due to their unique properties, have various potential future application in biology and medicine such as chelation therapy, copper-sensors, or tools to understand copper metabolism.</p></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"639 - 640"},"PeriodicalIF":2.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vanadium complexes as potential metal-based antimicrobial drugs","authors":"Meena Kumari,&nbsp;Maridula Thakur,&nbsp;Sonika Sharma,&nbsp;Mala Sharma,&nbsp;Vineet Kumar Choudhary,&nbsp;Reena Sharma,&nbsp;Shubham Sharma,&nbsp;Shalima Kumari,&nbsp;Sachin Kumar","doi":"10.1007/s00775-024-02084-8","DOIUrl":"10.1007/s00775-024-02084-8","url":null,"abstract":"<div><p>Radical increase of antibiotic resistance among microbes has become a serious problem for clinics all over the world that has led to the need for search of novel types of antimicrobial drugs. Each year, researchers synthesize a multitude of compounds in pursuit of identifying potential chemotherapeutic agents through diverse methodological evaluations. Among the vast array of biologically significant compounds, coordination compounds exhibit a broad range of activities within biological systems. Chelation, in particular, induces significant alterations in the biological properties of ligands and the metal component, contributing to their efficacy. Chelation increases the lipophilicity of metal complexes as a result of which they are easily absorbed by the microorganisms, thus leading to their easy passage across cell membrane. The research and development in the field of metallodrugs can be advantageous to overcome the problem encountered in antibiotic resistance. The multifaceted involvement of vanadium relative to other biometals within biological systems, coupled with its comparatively lower toxicity, underscores its utility in the advancement of novel metal-based therapeutic agents. This review aims to delineate the biological significance of V(V/IV/III) complexes as antimicrobial agents. The amassed data indicate a correlation between the potency of vanadium complexes as antimicrobial agents and the oxidation state of the metal, with III being the least toxic and V representing the most toxic oxidation state of vanadium.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 7-8","pages":"685 - 706"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}