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Journal of the American Chemical Society Jul 2024The development of efficient, selective, and durable CO photoreduction systems presents a long-standing challenge in full aqueous solutions owing to the presence of...
The development of efficient, selective, and durable CO photoreduction systems presents a long-standing challenge in full aqueous solutions owing to the presence of scarce CO and the fierce competition against H evolution, which is even more challenging when noble metals are not utilized. Herein, we present the facile decorations of four phosphonic acid groups on a donor-acceptor-type organic dye to obtain a water-soluble photosensitizer (), which succeeds the excellent photophysical and photoredox properties of its prototype, exhibiting long-lived delayed fluorescence (>10 μs) in aqueous solutions. Combining with a cationic cobalt porphyrin catalyst has accomplished record-high apparent quantum yields of 9.4-17.4% at 450 nm for CO-to-CO photoconversion among the precedented systems (maximum 13%) in fully aqueous solutions. Remarkable selectivity of 82-93% and turnover number of 2700 for CO production can also be achieved with this noble-metal-free system, outperforming a benchmarking ruthenium photosensitizer and a commercial organic dye under parallel conditions. Such high performances of can be well maintained under real sunlight. More impressively, no significant decomposition of was detected during the long-term photocatalysis. Eventually, the photoinduced electron transfer pathways were proposed.
PubMed: 38888951
DOI: 10.1021/jacs.4c03128 -
Biochemistry Jul 2024The conserved enzyme aminolevulinic acid synthase (ALAS) initiates heme biosynthesis in certain bacteria and eukaryotes by catalyzing the condensation of glycine and...
The conserved enzyme aminolevulinic acid synthase (ALAS) initiates heme biosynthesis in certain bacteria and eukaryotes by catalyzing the condensation of glycine and succinyl-CoA to yield aminolevulinic acid. In humans, the ALAS isoform responsible for heme production during red blood cell development is the erythroid-specific ALAS2 isoform. Owing to its essential role in erythropoiesis, changes in human ALAS2 (hALAS2) function can lead to two different blood disorders. X-linked sideroblastic anemia results from loss of ALAS2 function, while X-linked protoporphyria results from gain of ALAS2 function. Interestingly, mutations in the ALAS2 C-terminal extension can be implicated in both diseases. Here, we investigate the molecular basis for enzyme dysfunction mediated by two previously reported C-terminal loss-of-function variants, hALAS2 V562A and M567I. We show that the mutations do not result in gross structural perturbations, but the enzyme stability for V562A is decreased. Additionally, we show that enzyme stability moderately increases with the addition of the pyridoxal 5'-phosphate (PLP) cofactor for both variants. The variants display differential binding to PLP and the individual substrates compared to wild-type hALAS2. Although hALAS2 V562A is a more active enzyme , it is less efficient concerning succinyl-CoA binding. In contrast, the M567I mutation significantly alters the cooperativity of substrate binding. In combination with previously reported cell-based studies, our work reveals the molecular basis by which hALAS2 C-terminal mutations negatively affect ALA production necessary for proper heme biosynthesis.
Topics: Humans; 5-Aminolevulinate Synthetase; Anemia, Sideroblastic; Genetic Diseases, X-Linked; Loss of Function Mutation; Enzyme Stability; Heme; Porphyrias; Models, Molecular; Mutation; Protoporphyria, Erythropoietic
PubMed: 38888931
DOI: 10.1021/acs.biochem.4c00066 -
Physical Chemistry Chemical Physics :... Jun 2024Controlling spectral properties to achieve desired characteristics is an attractive goal in application-oriented research, , in the design of fluorescence sensors....
Controlling spectral properties to achieve desired characteristics is an attractive goal in application-oriented research, , in the design of fluorescence sensors. "Soft" chromophores, molecules with strong spectral responses to internal or external perturbations are good candidates for such studies. In this work, absorption, fluorescence, and magnetic circular dichroism (MCD) spectra were obtained for a series of porphyrins, substituted at the meso-positions with -hexyl groups. As the number of substituents increases from 1 to 4, significant changes are observed. The intensity of the S-S transition () in the 0-0 region strongly decreases in mono-substituted porphyrin, but upon additional substitutions it increases to values larger than in the parent, unsubstituted molecule. Such behavior can be explained, using the perimeter model, by changes in the energy splittings between the two highest (HOMO) and two lowest (LUMO) frontier molecular orbitals. Single substitution makes porphyrin a nearly perfect soft chromophore, but upon introduction of a larger number of -hexyl groups it is transformed into a hard one. DFT simulations incorrectly predict a continuous transition from a soft to hard chromophore, because the calculated ordering of two HOMO orbitals is opposite to that obtained by experiment. On the other hand, for those porphyrins that can be classified as hard chromophores, the calculations nicely reproduce contributions of Franck-Condon and Herzberg-Teller terms to absorption and fluorescence spectra.
PubMed: 38888633
DOI: 10.1039/d4cp01502a -
The Journal of Physical Chemistry... Jun 2024Metal-organic frameworks (MOFs) exhibit high adsorption and catalytic activities for various gas species. Because gas adsorption can cause a temperature increase in the...
Metal-organic frameworks (MOFs) exhibit high adsorption and catalytic activities for various gas species. Because gas adsorption can cause a temperature increase in the MOF, which decreases the capacity and adsorption rate, a strict evaluation of its effect on the thermal conductivity of MOFs is essential. In this study, the thermal conductivity measurement of the MOF under water vapor adsorption was performed using an oriented film of copper tetrakis(4-carboxyphenyl)porphyrin (Cu-TCPP) MOF. A recently developed bidirectional 3ω method enabled the anisotropic thermal conductivity measurement of layered Cu-TCPP while maintaining its ordered structure. The water adsorption was found to increase the thermal conductivity in both in-plane and cross-plane directions with different trends and magnitudes, owing to the structural anisotropy. Molecular dynamics simulations suggest that additional vibrational modes provided by the adsorbed water molecules were the reason for the thermal conductivity enhancement.
PubMed: 38888265
DOI: 10.1021/acs.jpclett.4c01244 -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024Interactions between gold-based materials and dioxygen (O2) have motivated researchers to understand reaction mechanisms for O2 activation by homo- and heterogeneous...
Interactions between gold-based materials and dioxygen (O2) have motivated researchers to understand reaction mechanisms for O2 activation by homo- and heterogeneous gold catalysts. In this work, gold(I) porphyrin dinuclear complexes were synthesized with a saddle-distorted porphyrin ligand. The gold(I) porphyrin complexes showed unprecedented O2 activation in the presence of protic solvents to form gold(III) tetradentate porphyrin complexes. Mechanistic insights into the O2 activation by the gold(I) center were elucidated by spectroscopic measurements and theoretical calculations, revealing that dissociation of halides on the gold(I) center by alcohol solvents and hydrogen bonding of an N-H proton in the distorted porphyrin with dioxygen played important roles in establishing the unique reactivities of gold(I) complexes.
PubMed: 38888030
DOI: 10.1002/chem.202401242 -
ACS Omega Jun 2024Antibiotic resistance is one of the biggest challenges that causes incurable diseases and endangers public health. Metal-porphyrin-modified nanoarchitectonics can...
Antibiotic resistance is one of the biggest challenges that causes incurable diseases and endangers public health. Metal-porphyrin-modified nanoarchitectonics can enhance the bacterial affinity and destruction of cell walls. Herein, a new photoresponsive nanoarchitectonics (BPGa@COF-Cu) was synthesized by doping Ga(III) on the surface of black phosphorus (BP) and subsequently loaded into a Cu(II)-based covalent-organic framework (COF-Cu). The COF-Cu was induced by the coupling reaction of terephthalic chloride with amino-substituted porphyrin derivatives (THPP), followed by the coordination of the Cu(II) ion. The material BPGa@COF-Cu is a nanoball, and the mean radius is ca. 250 nm. The photochemical properties of BPGa@COF-Cu show that it efficiently catalyzes HO into ·OH. BPGa@COF-Cu can also produce both singlet oxygen and heat upon 808 nm irradiation. Further, BPGa@COF-Cu was employed to inhibit bacteria, and the results showed that it can destroy the membrane of . The MIC (minimal inhibition concentration) of BPGa@COF-Cu against was 1 μg/mL. All the data suggest that BPGa@COF-Cu is a multiple nanoarchitectonics for bacterial treatment.
PubMed: 38882152
DOI: 10.1021/acsomega.4c00496 -
Frontiers in Microbiology 2024causes listeriosis, an infectious and potentially fatal disease of animals and humans. A diverse network of transcriptional regulators, including LysR-type catabolite...
causes listeriosis, an infectious and potentially fatal disease of animals and humans. A diverse network of transcriptional regulators, including LysR-type catabolite control protein C (CcpC), is critical for the survival of and its ability to transition into the host environment. In this study, we explored the physiological and genetic consequences of deleting and the effects of such deletion on the ability of to cause disease. We found that deletion did not impact hemolytic activity, whereas it resulted in significant reductions in phospholipase activities. Western blotting revealed that the Δ strain produced significantly reduced levels of the cholesterol-dependent cytolysin LLO relative to the wildtype F2365 strain. However, the Δ mutant displayed no significant intracellular growth defect in macrophages. Furthermore, Δ strain exhibited reduction in plaque numbers in fibroblasts compared to F2365, but plaque size was not significantly affected by deletion. In a murine model system, the Δ strain exhibited a significantly reduced bacterial burden in the liver and spleen compared to the wildtype F2365 strain. Interestingly, the deletion of this gene also enhanced the survival of under conditions of HO-induced oxidative stress. Transcriptomic analyses performed under HO-induced oxidative stress conditions revealed that DNA repair, cellular responses to DNA damage and stress, metalloregulatory proteins, and genes involved in the biosynthesis of peptidoglycan and teichoic acids were significantly induced in the deletion strain relative to F2365. In contrast, genes encoding internalin, 1-phosphatidylinositol phosphodiesterase, and genes associated with sugar-specific phosphotransferase system components, porphyrin, branched-chain amino acids, and pentose phosphate pathway were significantly downregulated in the deletion strain relative to F2365. This finding highlights CcpC as a key factor that regulates physiology and responses to oxidative stress by controlling the expression of important metabolic pathways.
PubMed: 38881664
DOI: 10.3389/fmicb.2024.1403694 -
Biochemistry. Biokhimiia May 2024Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel...
Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.
Topics: Verteporfin; Humans; Collagen; Fibroblasts; Animals; Wound Healing; Antifibrotic Agents; Cells, Cultured; Tissue Scaffolds; Cicatrix; Male; Fibrosis; Skin
PubMed: 38880654
DOI: 10.1134/S0006297924050146 -
European Journal of Pharmacology Aug 2024The transcription factor nuclear factor κB (NF-κB) is activated by proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and Toll-like receptor (TLR)...
Porphyrin derivatives inhibit tumor necrosis factor α-induced gene expression and reduce the expression and increase the cross-linked forms of cellular components of the nuclear factor κB signaling pathway.
The transcription factor nuclear factor κB (NF-κB) is activated by proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and Toll-like receptor (TLR) ligands. Screening of NPDepo chemical libraries identified porphyrin derivatives as anti-inflammatory compounds that strongly inhibited the up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression induced by TNF-α, interleukin-1α, the TLR3 ligand, and TLR4 ligand in human umbilical vein endothelial cells. In the present study, the mechanisms of action of porphyrin derivatives were further elucidated using human lung adenocarcinoma A549 cells. Porphyrin derivatives, i.e., dimethyl-2,7,12,18-tetramethyl-3,8-di(1-methoxyethyl)-21H,23H-porphine-13,17-dipropionate (1) and pheophorbide a (2), inhibited TNF-α-induced ICAM-1 expression and decreased the TNF-α-induced transcription of ICAM-1, vascular cell adhesion molecule-1, and E-selectin genes. 1 and 2 reduced the expression of the NF-κB subunit RelA protein for 1 h, which was not rescued by the inhibition of proteasome- and lysosome-dependent protein degradation. In addition, 1 and 2 decreased the expression of multiple components of the TNF receptor 1 complex, and this was accompanied by the appearance of their cross-linked forms. As common components of the NF-κB signaling pathway, 1 and 2 also cross-linked the α, β, and γ subunits of the inhibitor of NF-κB kinase complex and the NF-κB subunits RelA and p50. Cellular protein synthesis was prevented by 2, but not by 1. Therefore, the present results indicate that porphyrin derivative 1 reduced the expression and increased the cross-linked forms of cellular components required for the NF-κB signaling pathway without affecting global protein synthesis.
Topics: Humans; Signal Transduction; Tumor Necrosis Factor-alpha; Intercellular Adhesion Molecule-1; NF-kappa B; Porphyrins; A549 Cells; E-Selectin; Gene Expression Regulation
PubMed: 38880218
DOI: 10.1016/j.ejphar.2024.176747 -
Analytica Chimica Acta Aug 2024Non-invasive indirect blood glucose monitoring can be realized by detecting low concentrations of glucose (0.05-5 mM) in tears, but sensitive optical indicators are...
BACKGROUND
Non-invasive indirect blood glucose monitoring can be realized by detecting low concentrations of glucose (0.05-5 mM) in tears, but sensitive optical indicators are required. The intensity of the phosphorescence of a candidate optical indicator, palladium hematoporphyrin monomethyl ether (Pd-HMME), is increased by oxygen consumption under sealed conditions in the presence of glucose and glucose oxidase. However, the glucose detection limit based on this mechanism is high (800 μM) because the phosphorescence is completely quenched under ambient oxygen conditions and hence a large amount of glucose is required to reduce the oxygen levels such that the phosphorescence signal is detectable.
RESULTS
To improve the glucose detection limit of Pd-HMME phosphorescence-based methods, the triplet protector imidazole was introduced, and strong phosphorescence was observed under ambient oxygen conditions. Detectable phosphorescence enhancement occurred at low glucose concentrations (<200 μM). Linear correlation between the phosphorescence intensity and glucose concentration was observed in the range of 30-727 μM (R = 99.9 %), and the detection limit was ∼10 μM. The glucose sensor has a fast response time (∼90 s) and excellent selectivity for glucose.
SIGNIFICANCE AND NOVELTY
These results indicate the potential of the developed optical indicator for fast, selective, and reliable low-concentration glucose sensing.
Topics: Limit of Detection; Luminescent Measurements; Hematoporphyrins; Palladium; Glucose; Glucose Oxidase; Blood Glucose; Imidazoles; Biosensing Techniques; Oxygen; Humans
PubMed: 38879210
DOI: 10.1016/j.aca.2024.342825