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ACS Central Science Jun 2024Metalloporphyrins are widely used as homogeneous electrocatalysts for transformations relevant to clean energy and sustainable organic synthesis. Metalloporphyrins are...
Metalloporphyrins are widely used as homogeneous electrocatalysts for transformations relevant to clean energy and sustainable organic synthesis. Metalloporphyrins are well-known to aggregate due to π-π stacking, but surprisingly, the influence of aggregation on homogeneous electrocatalytic performance has not been investigated previously. Herein, we present three structurally related iron -phenylporphyrins whose aggregation properties are different in commonly used ,-dimethylformamide (DMF) electrolyte. Both spectroscopy and light scattering provide evidence of extensive porphyrin aggregation under conventional electrocatalytic conditions. Using the electrocatalytic reduction of CO to CO as a test reaction, cyclic voltammetry reveals an inverse dependence of the kinetics on the catalyst concentration. The inhibition extends to bulk performance, where up to 75% of the catalyst at 1 mM is inactive compared to at 0.25 mM. We additionally report how aggregation is perturbed by organic additives, axial ligands, and redox state. Periodic boundary calculations provide additional insights into aggregate stability as a function of metalloporphyrin structure. Finally, we generalize the aggregation phenomenon by surveying metalloporphyrins with different metals and substituents. This study demonstrates that homogeneous metalloporphyrins can aggregate severely in well-solubilizing organic electrolytes, that aggregation can be easily modulated through experimental conditions, and that the extent of aggregation must be considered for accurate catalytic benchmarking.
PubMed: 38947202
DOI: 10.1021/acscentsci.4c00121 -
Journal of Physics. Condensed Matter :... Jun 2024The application of half-metallic materials in single-molecule optoelectronic devices opens a promising way in advancing device performance and functionality, thus...
The application of half-metallic materials in single-molecule optoelectronic devices opens a promising way in advancing device performance and functionality, thus addressing a research question of significance. Here we propose a series of single-molecule devices with half-metallic FeN4-doped armchair graphene nanoribbon as electrodes and metalloporphyrin (MPr) molecules as photoresponsive materials for photon harvesting, which are driven by photogalvanic effects (PGEs). Through the quantum transport simulations, we systematically investigated the spin-polarized photocurrents under the linearly polarized light illumination in these devices. Since the exclusive opening only exists in the spin-up channel of the half-metallic nanoribbons, these devices can generate a large photocurrent in the spin-up direction whereas suppressing the spin-down photocurrent. Consequently, they exhibit an effective spin-filtering effect at numerous photon energies. Our study unveils the excellent spin-filtering effect achieved in single-molecule optoelectronic devices with half-metallic electrodes, showing instructive significance for the future design of new optoelectronic devices. .
PubMed: 38941993
DOI: 10.1088/1361-648X/ad5d37 -
Inorganic Chemistry Jun 2024Both metalloporphyrins and heterometallic {CrNi} rings are of significant research interest due to their proposed roles in quantum information processing devices. In...
Both metalloporphyrins and heterometallic {CrNi} rings are of significant research interest due to their proposed roles in quantum information processing devices. In this study, we present a series of complexes in which [CrNiF(Etglu)(OCBu)] (-EtgluH = -ethyl-dglucamine) heterometallic rings are coordinated to metalloporphyrin linkers: the symmetric [M(TPyP)] for M = Cu, VO, and HTPyP = 5,10,15,20-tetra(4-pyridyl)porphyrin; and the asymmetric [{VO}(TrPPyP)] for H(TrPPyP) = 5,10,15-(triphenyl)-20-(4-pyridyl)porphyrin. The magnetic interactions present in these complexes are unraveled using the continuous wave (CW) electron paramagnetic resonance (EPR) technique. The nature of the coupling between the {CrNi} rings and the central metalloporphyrin is assessed by numerical simulations of CW EPR spectra and determined to be on the order of 0.01 cm, larger than the dipolar ones and suitable for individual spin addressability in multiqubit architectures.
PubMed: 38941532
DOI: 10.1021/acs.inorgchem.4c01248 -
Frontiers in Cellular and Infection... 2024and belong to the Bacteroidota phylum. Both species inhabit the oral cavity and can be associated with periodontal diseases. To survive, they must uptake heme from the...
INTRODUCTION
and belong to the Bacteroidota phylum. Both species inhabit the oral cavity and can be associated with periodontal diseases. To survive, they must uptake heme from the host as an iron and protoporphyrin IX source. Among the best-characterized heme acquisition systems identified in members of the Bacteroidota phylum is the Hmu system, with a leading role played by the hemophore-like HmuY (HmuY) protein.
METHODS
Theoretical analysis of selected HmuY proteins and spectrophotometric methods were employed to determine the heme-binding mode of the HmuY homolog (HmuY) and its ability to sequester heme. Growth phenotype and gene expression analysis of were employed to reveal the importance of the HmuY and Hmu system for this bacterium.
RESULTS
Unlike in , where HmuY uses two histidines for heme-iron coordination, other known HmuY homologs use two methionines in this process. HmuY is the first characterized representative of the HmuY family that binds heme using a histidine-methionine pair. It allows HmuY to sequester heme directly from serum albumin and HmuY, the HmuY homolog which uses two methionines for heme-iron coordination. In contrast to HmuY, which sequesters heme directly from methemoglobin, HmuY may bind heme only after the proteolytic digestion of hemoglobin.
CONCLUSIONS
We hypothesize that differences in components of the Hmu system and structure-based properties of HmuY proteins may evolved allowing different adaptations of species to the changing host environment. This may add to the superior virulence potential of over other members of the Bacteroidota phylum.
Topics: Heme; Porphyromonas gingivalis; Tannerella forsythia; Bacterial Proteins; Porphyromonas endodontalis; Humans; Gene Expression Regulation, Bacterial; Protein Binding; Iron
PubMed: 38938884
DOI: 10.3389/fcimb.2024.1421018 -
Angewandte Chemie (International Ed. in... Jun 2024Herein we have evidenced the formation of favorable π-hole Br···metal noncovalent interactions (NCIs) involving elements from groups 9, 11 and 12. More in detail, M...
Herein we have evidenced the formation of favorable π-hole Br···metal noncovalent interactions (NCIs) involving elements from groups 9, 11 and 12. More in detail, M (M = Co2+, Ni2+, Cu2+ and Zn2+) containing porphyrins have been synthesized and their supramolecular assemblies structurally characterized by means of single crystal X-ray diffraction and Hirshfeld surface analyses, revealing the formation of directional Br···M contacts in addition to ancillary hydrogen bond and lone pair-π bonds. Computations at the PBE0-D3/def2-TZVP level of theory revealed the π-hole nature of the Br···M interaction. In addition, the physical nature of these NCIs was studied using Quantum Chemistry methodologies, providing evidence of π-hole Spodium and Regium bonds in Zn2+ and Cu2+ porphyrins, in addition to unveiling the presence of a π-hole for group 9 (Co2+). On the other hand, group 10 (Ni2+) acted as both electron donor and acceptor moiety without showing an electropositive π-hole. Owing to the underexplored potential of π-hole interactions in transition metal chemistry, we believe the results reported herein will be useful in supramolecular chemistry, organometallics, and solid-state chemistry by i) putting under the spotlight the π-hole chemistry involving first row transition metals and ii) unlocking a new tool to direct the self-assembly of metalloporphyrins.
PubMed: 38934220
DOI: 10.1002/anie.202409963 -
International Journal of Molecular... Jun 2024Hell's Gate globin-I (HGb-I) is a thermally stable globin from the aerobic methanotroph . Here we report that HGb-I interacts with lipids stoichiometrically to induce...
Hell's Gate globin-I (HGb-I) is a thermally stable globin from the aerobic methanotroph . Here we report that HGb-I interacts with lipids stoichiometrically to induce structural changes in the heme pocket, changing the heme iron distal ligation coordination from hexacoordinate to pentacoordinate. Such changes in heme geometry have only been previously reported for cytochrome c and cytoglobin, linked to apoptosis regulation and enhanced lipid peroxidation activity, respectively. However, unlike cytoglobin and cytochrome c, the heme iron of HGb-I is altered by lipids in ferrous as well as ferric oxidation states. The apparent affinity for lipids in this thermally stable globin is highly pH-dependent but essentially temperature-independent within the range of 20-60 °C. We propose a mechanism to explain these observations, in which lipid binding and stability of the distal endogenous ligand are juxtaposed as a function of temperature. Additionally, we propose that these coupled equilibria may constitute a mechanism through which this acidophilic thermophile senses the pH of its environment.
Topics: Hydrogen-Ion Concentration; Temperature; Globins; Lipids; Heme; Protein Conformation; Models, Molecular; Bacterial Proteins
PubMed: 38928500
DOI: 10.3390/ijms25126794 -
International Journal of Molecular... Jun 2024Ferrochelatase (FECH) is the terminal enzyme in human heme biosynthesis, catalyzing the insertion of ferrous iron into protoporphyrin IX (PPIX) to form protoheme IX...
Ferrochelatase (FECH) is the terminal enzyme in human heme biosynthesis, catalyzing the insertion of ferrous iron into protoporphyrin IX (PPIX) to form protoheme IX (Heme). Phosphorylation increases the activity of FECH, and it has been confirmed that the activity of FECH phosphorylated at T116 increases. However, it remains unclear whether the T116 site and other potential phosphorylation modification sites collaboratively regulate the activity of FECH. In this study, we identified a new phosphorylation site, T218, and explored the allosteric effects of unphosphorylated (UP), PT116, PT218, and PT116 + PT218 states on FECH in the presence and absence of substrates (PPIX and Heme) using molecular dynamics (MD) simulations. Binding free energies were evaluated with the MM/PBSA method. Our findings indicate that the PT116 + PT218 state exhibits the lowest binding free energy with PPIX, suggesting the strongest binding affinity. Additionally, this state showed a higher binding free energy with Heme compared to UP, which facilitates Heme release. Moreover, employing multiple analysis methods, including free energy landscape (FEL), principal component analysis (PCA), dynamic cross-correlation matrix (DCCM), and hydrogen bond interaction analysis, we demonstrated that phosphorylation significantly affects the dynamic behavior and binding patterns of substrates to FECH. Insights from this study provide valuable theoretical guidance for treating conditions related to disrupted heme metabolism, such as various porphyrias and iron-related disorders.
Topics: Ferrochelatase; Humans; Phosphorylation; Molecular Dynamics Simulation; Heme; Protoporphyrins; Catalytic Domain; Protein Binding; Binding Sites; Thermodynamics
PubMed: 38928065
DOI: 10.3390/ijms25126360 -
Genes May 2024LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the... (Review)
Review
Knockout Mouse Studies Show That Mitochondrial CLPP Peptidase and CLPX Unfoldase Act in Matrix Condensates near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production.
LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, especially during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING-activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to humans, despite their secondary role in proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules and CLPX on multi-enzyme condensates as first-aid systems near the inner mitochondrial membrane. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, mitochondrial RNA granules and nucleoids, and the D-foci-mediated degradation of toxic double-stranded mtRNA/mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, as other mitochondrial peptidases: MPPs at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.
Topics: Endopeptidase Clp; Animals; Mice; Mitochondria; Mitochondrial Proteins; Mice, Knockout; Heme; Protein Biosynthesis; Humans; Mitochondrial Membranes; Stress, Physiological
PubMed: 38927630
DOI: 10.3390/genes15060694 -
Pharmacology Research & Perspectives Aug 2024Drug repurposing has gained significant interest in recent years due to the high costs associated with de novo drug development; however, comprehensive pharmacological... (Review)
Review
Drug repurposing has gained significant interest in recent years due to the high costs associated with de novo drug development; however, comprehensive pharmacological information is needed for the translation of pre-existing drugs across clinical applications. In the present study, we explore the current pharmacological understanding of the orphan drug, hemin, and identify remaining knowledge gaps with regard to hemin repurposing for the treatment of cardiovascular disease. Originally approved by the United States Food and Drug Administration in 1983 for the treatment of porphyria, hemin has attracted significant interest for therapeutic repurposing across a variety of pathophysiological conditions. Yet, the clinical translation of hemin remains limited to porphyria. Understanding hemin's pharmacological profile in health and disease strengthens our ability to treat patients effectively, identify therapeutic opportunities or limitations, and predict and prevent adverse side effects. However, requirements for the pre-clinical and clinical characterization of biologics approved under the U.S. FDA's Orphan Drug Act in 1983 (such as hemin) differed significantly from current standards, presenting fundamental gaps in our collective understanding of hemin pharmacology as well as knowledge barriers to clinical translation for future applications. Using information extracted from the primary and regulatory literature (including documents submitted to Health Canada in support of hemin's approval for the Canadian market in 2018), we present a comprehensive case study of current knowledge related to hemin's biopharmaceutical properties, pre-clinical/clinical pharmacokinetics, pharmacodynamics, dosing, and safety, focusing specifically on the drug's effects on heme regulation and in the context of acute myocardial infarction.
Topics: Drug Repositioning; Humans; Hemin; Cardiovascular Diseases; United States; United States Food and Drug Administration; Animals; Orphan Drug Production; Drug Approval
PubMed: 38923404
DOI: 10.1002/prp2.1225 -
Biosensors & Bioelectronics Oct 2024An electrochemical (EC) sensor based on metalloporphyrin metal-organic framework (MOF) for the detection of parathion-methyl (PM) has been developed. The prepared...
An electrochemical (EC) sensor based on metalloporphyrin metal-organic framework (MOF) for the detection of parathion-methyl (PM) has been developed. The prepared MOF-525(Fe) exhibits great signal enhancement toward the electrochemical detection of PM owing to its unique structural properties and electrochemical activities. Under optimal experimental conditions, the as-prepared MOF-525(Fe) based EC sensor exhibited excellent PM sensing performance with a wide linear detection range (0.1 μM-100 μM) and low limit of detection (LOD, 1.4 nM). Compared to its corresponding Fe metalloporphyrin (linker), MOF-525(Fe) exhibited a superior sensitivity (28.31 μA cm·μM), which is 3.7 times higher than the sensitivity of FeTCPP linker (7.56 μA cm·μM) towards PM. The improved performance is associated with the high specific surface area and the large pore channels of MOF-525(Fe) facilitating a better interaction between PM and the Fe metalloporphyrin active sites, especially in the lower concentration range. Moreover, a possible affinity of the PM molecules toward Zr clusters may also contribute to the selective enrichment of PM on MOF-525(Fe). This EC sensor further demonstrated high selectivity in the presence of interfering molecules. The recovery results further confirm accurate PM sensing in actual samples, which suggests promising applications for the rapid detection of environmental organophosphates by metalloporphyrin MOFs.
Topics: Metal-Organic Frameworks; Electrochemical Techniques; Biosensing Techniques; Metalloporphyrins; Limit of Detection; Zirconium; Methyl Parathion
PubMed: 38909444
DOI: 10.1016/j.bios.2024.116515