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Molecules (Basel, Switzerland) Dec 2023Only a single enzyme system-nitrogenase-carries out the conversion of atmospheric N into bioavailable ammonium, an essential prerequisite for all organismic life. The... (Review)
Review
Only a single enzyme system-nitrogenase-carries out the conversion of atmospheric N into bioavailable ammonium, an essential prerequisite for all organismic life. The reduction of this inert substrate at ambient conditions poses unique catalytic challenges that strain our mechanistic understanding even after decades of intense research. Structural biology has added its part to this greater tapestry, and in this review, I provide a personal (and highly biased) summary of the parts of the story to which I had the privilege to contribute. It focuses on the crystallographic analysis of the three isoforms of nitrogenases at high resolution and the binding of ligands and inhibitors to the active-site cofactors of the enzyme. In conjunction with the wealth of available biochemical, biophysical, and spectroscopic data on the protein, this has led us to a mechanistic hypothesis based on an elementary mechanism of repetitive hydride formation and insertion.
Topics: Nitrogenase; Nitrogen Fixation; Catalysis; Molybdenum; Nitrogen
PubMed: 38138449
DOI: 10.3390/molecules28247959 -
ACS Nano Dec 2023Acute respiratory disease syndrome (ARDS) is a common critical disease with high morbidity and mortality rates, yet specific and effective treatments for it are...
Acute respiratory disease syndrome (ARDS) is a common critical disease with high morbidity and mortality rates, yet specific and effective treatments for it are currently lacking. ARDS was especially apparent and rampant during the COVID-19 pandemic. Excess reactive oxygen species (ROS) production and an uncontrolled inflammatory response play a critical role in the disease progression of ARDS. Herein, we developed molybdenum nanodots (MNDs) as a functional nanomaterial with ultrasmall size, good biocompatibility, and excellent ROS scavenging ability for the treatment of acute lung injury (ALI). MNDs, which were administered intratracheally, significantly ameliorated lung oxidative stress, inflammatory response, protein permeability, and histological severity in ALI mice without inducing any safety issues. Importantly, transcriptomics analysis indicated that MNDs protected lung tissues by inhibiting the activation of the Nod-like receptor protein 3 (NLRP3)-dependent pyroptotic pathway. This work presents a promising therapeutic agent for patients suffering from ARDS.
Topics: Humans; Mice; Animals; Reactive Oxygen Species; Molybdenum; Pandemics; Acute Lung Injury; Lung; Respiratory Distress Syndrome; Lipopolysaccharides
PubMed: 38084420
DOI: 10.1021/acsnano.3c08147 -
Molecules (Basel, Switzerland) Jul 2023Mo/W-containing formate dehydrogenases (FDH) catalyzes the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active sites. The... (Review)
Review
Mo/W-containing formate dehydrogenases (FDH) catalyzes the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active sites. The metal-containing FDHs are members of the dimethylsulfoxide reductase family of mononuclear molybdenum cofactor (Moco)- or tungsten cofactor (Wco)-containing enzymes. In these enzymes, the active site in the oxidized state comprises a Mo or W atom present in the bis-Moco, which is coordinated by the two dithiolene groups from the two MGD moieties, a protein-derived SeCys or Cys, and a sixth ligand that is now accepted as being a sulfido group. SeCys-containing enzymes have a generally higher turnover number than Cys-containing enzymes. The analogous chemical properties of W and Mo, the similar active sites of W- and Mo-containing enzymes, and the fact that W can replace Mo in some enzymes have led to the conclusion that Mo- and W-containing FDHs have the same reaction mechanism. Details of the catalytic mechanism of metal-containing formate dehydrogenases are still not completely understood and have been discussed here.
Topics: Formate Dehydrogenases; Oxidation-Reduction; Metalloproteins; Molybdenum; Catalytic Domain; Pteridines; Coenzymes
PubMed: 37513211
DOI: 10.3390/molecules28145338 -
Journal of Biological Inorganic... Mar 2015The prokaryotic formate metabolism is considerably diversified. Prokaryotes use formate in the C1 metabolism, but also evolved to exploit the low reduction potential of... (Review)
Review
The prokaryotic formate metabolism is considerably diversified. Prokaryotes use formate in the C1 metabolism, but also evolved to exploit the low reduction potential of formate to derive energy, by coupling its oxidation to the reduction of numerous electron acceptors. To fulfil these varied physiological roles, different types of formate dehydrogenase (FDH) enzymes have evolved to catalyse the reversible 2-electron oxidation of formate to carbon dioxide. This review will highlight our present knowledge about the diverse physiological roles of FDH in prokaryotes, their modular structural organisation and active site structures and the mechanistic strategies followed to accomplish the formate oxidation. In addition, the ability of FDH to catalyse the reverse reaction of carbon dioxide reduction, a potentially relevant reaction for carbon dioxide sequestration, will also be addressed.
Topics: Carbon Dioxide; Energy Metabolism; Formate Dehydrogenases; Formates; Molybdenum; Prokaryotic Cells; Tungsten
PubMed: 25476858
DOI: 10.1007/s00775-014-1218-2 -
Journal of Inorganic Biochemistry Oct 2022In this work four vanadium complexes (compounds 1, 2, 3 and 4) and one molybdenum complex (compound 5) with hydrazone ligands derived from pyridoxal were synthesized and...
In this work four vanadium complexes (compounds 1, 2, 3 and 4) and one molybdenum complex (compound 5) with hydrazone ligands derived from pyridoxal were synthesized and characterized. All compounds are mononuclear species, two of them (compounds 3 and 5) are dioxide complexes and the other three (compounds 1, 2 and 4) monoxide complexes. The vanadium atom of the compound 3 is five-coordinated and all the other compounds have a six coordinated environment polyhedron. The poses for the potential intercalation of the compounds 2 and 3 with DNA were obtained by using AutoDock software. Optimizations were also performed at PM6-D3H4 semi-empirical level whereas the study of the nature of the interaction was carried out by means of the Energy Decomposition Analysis and the Non-Covalent Interaction index by using in both cases Density Functional Theory computations. The cytotoxicity in lung cancer cells (A549 cell line) of all the compounds was also evaluated. After 24 h of treatment, vanadium complexes showed high values of IC, between 419.93 ± 22.58 and 685.88 ± 46.55 μM. After 48 h, the results showed that the compound 3 had the lowest IC value, 65.32 ± 9.95 μM, and the compound 2 the highest value, 375.28 ± 32.09 μM. The molybdenum complex showed the lowest IC value at 48 h (11.22 ± 1.34 μM). The toxicity of the compounds 3, 4 and 5 was tested in vivo, using zebrafish model, and the molybdenum complex showed higher toxic effects than the studied vanadium complexes.
Topics: Animals; Ligands; Molybdenum; Pyridoxal; Vanadium; Zebrafish
PubMed: 35870443
DOI: 10.1016/j.jinorgbio.2022.111937 -
Molecules (Basel, Switzerland) Jun 2022Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build active site analogues. These... (Review)
Review
Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build active site analogues. These studies not only led to an ever more detailed mechanistic understanding of the biological template, but also paved the way to atypical selectivity and activity, such as catalytic hydrogen evolution. This review is aimed at representing the last decade's progress in the research of and with molybdenum and tungsten functional model compounds. The portrayed systems, organized according to their ability to facilitate typical and artificial enzyme reactions, comprise complexes with dithiolene ligands, resembling molybdopterin, as well as entirely non-natural nitrogen, oxygen, and/or sulfur bearing chelating donor ligands. All model compounds receive individual attention, highlighting the specific novelty that each provides for our understanding of the enzymatic mechanisms, such as oxygen atom transfer and proton-coupled electron transfer, or that each presents for exploiting new and useful catalytic capability. Overall, a shift in the application of these model compounds towards uncommon reactions is noted, the latter are comprehensively discussed.
Topics: Iron-Sulfur Proteins; Ligands; Molybdenum; Organometallic Compounds; Oxidoreductases; Oxygen; Tungsten
PubMed: 35744820
DOI: 10.3390/molecules27123695 -
Molecules (Basel, Switzerland) May 2022Pterins are bicyclic heterocycles that are found widely across Nature and are involved in a variety of biological functions. Notably, pterins are found at the core of... (Review)
Review
Pterins are bicyclic heterocycles that are found widely across Nature and are involved in a variety of biological functions. Notably, pterins are found at the core of molybdenum cofactor (Moco) containing enzymes in the molybdopterin (MPT) ligand that coordinates molybdenum and facilitates cofactor activity. Pterins are diverse and can be widely functionalized to tune their properties. Herein, the general methods of synthesis, redox and spectroscopic properties of pterin are discussed to provide more insight into pterin chemistry and their importance to biological systems.
Topics: Molybdenum; Molybdenum Cofactors; Oxidation-Reduction; Pterins; Spectrum Analysis
PubMed: 35630801
DOI: 10.3390/molecules27103324 -
Advanced Healthcare Materials Jul 2022Bacterial infections have seriously threatened human health and the abuse of natural or artificial antibiotics leads to bacterial resistance, so development of a new... (Review)
Review
Bacterial infections have seriously threatened human health and the abuse of natural or artificial antibiotics leads to bacterial resistance, so development of a new generation of antibacterial agents and treatment methods is urgent. 2D molybdenum sulfide (MoS ) has good biocompatibility, high specific surface area to facilitate surface modification and drug loading, adjustable energy bandgap, and high near-infrared photothermal conversion efficiency (PCE), so it is often used for antibacterial application through its photothermal or photodynamic effects. This review comprehensively summarizes and discusses the fabrication processes, structural characteristics, antibacterial performance, and the corresponding mechanisms of MoS -based materials as well as their representative antibacterial applications. In addition, the outlooks on the remaining challenges that should be addressed in the field of MoS are also proposed.
Topics: Anti-Bacterial Agents; Disulfides; Escherichia coli; Humans; Molybdenum; Phototherapy
PubMed: 35385610
DOI: 10.1002/adhm.202200360 -
Molecules (Basel, Switzerland) Sep 2022This article gives an overview of the research activity of the LAC2 team at LCC developed at Castres in the field of sustainable chemistry with an emphasis on the... (Review)
Review
This article gives an overview of the research activity of the LAC2 team at LCC developed at Castres in the field of sustainable chemistry with an emphasis on the collaboration with a research team from the University of Zagreb, Faculty of Science, Croatia. The work is situated within the context of sustainable chemistry for the development of catalytic processes. Those processes imply molecular complexes containing oxido-molybdenum, -vanadium, -tungsten or simple polyoxometalates (POMs) as catalysts for organic solvent-free epoxidation. The studies considered first the influence of the nature of complexes (and related ligands) on the reactivity (assessing mechanisms through DFT calculations) with model substrates. From those model processes, the work has been enlarged to the valorization of biomass resources. A part concerns the activity on vanadium chemistry and the final part concerns the use of POMs as catalysts, from molecular to grafted catalysts, (ep)oxidizing substrates from fossil and biomass resources.
Topics: Catalysis; Molybdenum; Oxidation-Reduction; Tungsten; Vanadium
PubMed: 36144747
DOI: 10.3390/molecules27186011 -
Molecules (Basel, Switzerland) Nov 2023The pyranopterin dithiolene ligand is remarkable in terms of its geometric and electronic structure and is uniquely found in mononuclear molybdenum and tungsten enzymes.... (Review)
Review
The pyranopterin dithiolene ligand is remarkable in terms of its geometric and electronic structure and is uniquely found in mononuclear molybdenum and tungsten enzymes. The pyranopterin dithiolene is found coordinated to the metal ion, deeply buried within the protein, and non-covalently attached to the protein via an extensive hydrogen bonding network that is enzyme-specific. However, the function of pyranopterin dithiolene in enzymatic catalysis has been difficult to determine. This focused account aims to provide an overview of what has been learned from the study of pyranopterin dithiolene model complexes of molybdenum and how these results relate to the enzyme systems. This work begins with a summary of what is known about the pyranopterin dithiolene ligand in the enzymes. We then introduce the development of inorganic small molecule complexes that model aspects of a coordinated pyranopterin dithiolene and discuss the results of detailed physical studies of the models by electronic absorption, resonance Raman, X-ray absorption and NMR spectroscopies, cyclic voltammetry, X-ray crystallography, and chemical reactivity.
Topics: Models, Molecular; Molybdenum; Ligands; Metalloproteins; Catalysis; Coenzymes
PubMed: 38005178
DOI: 10.3390/molecules28227456