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Biomimetics (Basel, Switzerland) Apr 2024To inhibit the deep conversion of partial oxidation products (POX-products) in C-H bonds' functionalization utilizing O,...
Efficient Inhibition of Deep Conversion of Partial Oxidation Products in C-H Bonds' Functionalization Utilizing O via Relay Catalysis of Dual Metalloporphyrins on Surface of Hybrid Silica Possessing Capacity for Product Exclusion.
To inhibit the deep conversion of partial oxidation products (POX-products) in C-H bonds' functionalization utilizing O, 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin cobalt(II) and 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin copper(II) were immobilized on the surface of hybrid silica to conduct relay catalysis on the surface. Fluorocarbons with low polarity and heterogeneous catalysis were devised to decrease the convenient accessibility of polar POX-products to catalytic centers on the lower polar surface. Relay catalysis between Co and Cu was designed to utilize the oxidation intermediates alkyl hydroperoxides to transform more C-H bonds. Systematic characterizations were conducted to investigate the structure of catalytic materials and confirm their successful syntheses. Applied to C-H bond oxidation, not only deep conversion of POX-products was inhibited but also substrate conversion and POX-product selectivity were improved simultaneously. For cyclohexane oxidation, conversion was improved from 3.87% to 5.27% with selectivity from 84.8% to 92.3%, which was mainly attributed to the relay catalysis on the surface excluding products. The effects of the catalytic materials, product exclusion, relay catalysis, kinetic study, substrate scope, and reaction mechanism were also investigated. To our knowledge, a practical and novel strategy was presented to inhibit the deep conversion of POX-products and to achieve efficient and accurate oxidative functionalization of hydrocarbons. Also, a valuable protocol was provided to avoid over-reaction in other chemical transformations requiring high selectivity.
PubMed: 38786482
DOI: 10.3390/biomimetics9050272 -
Chemical Science May 2024Artificial metalloenzymes (ArMs) are constructed by anchoring organometallic catalysts to an evolvable protein scaffold. They present the advantages of both components...
Artificial metalloenzymes (ArMs) are constructed by anchoring organometallic catalysts to an evolvable protein scaffold. They present the advantages of both components and exhibit considerable potential for the catalysis of new-to-nature reactions. Herein, surface-displayed hemoglobin (VHb) that anchored the cobalt porphyrin cofactor instead of the original heme cofactor was used as an artificial thiourea oxidase (ATOase) to synthesize 5-imino-1,2,4-thiadiazoles. After two rounds of directed evolution using combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy, the evolved six-site mutation VHb (6SM-VHb) exhibited significant improvement in catalytic activity, with a broad substrate scope (31 examples) and high yields with whole cells. This study shows the potential of using VHb ArMs in new-to-nature reactions and demonstrates the applicability of surface-displayed methods to enhance catalytic properties through the substitution of porphyrin cofactors in hemoproteins .
PubMed: 38784746
DOI: 10.1039/d4sc00005f -
RSC Advances May 2024Molecular hydrogen shows antioxidant activity and distinct efficacy towards vascular diseases, but the understanding of this is not yet satisfactory at the atomic level....
Molecular hydrogen shows antioxidant activity and distinct efficacy towards vascular diseases, but the understanding of this is not yet satisfactory at the atomic level. In this work, we study the binding properties of H to the heme group in relation with other diatomic molecules (DMs), including O, NO and CO, and their displacement reactions, using first-principles calculations. We carry out molecular modeling of the heme group, using iron-porphyrin with the imidazole ligand, , FePIm, and smaller models of Fe(CHN)NH with = 3 and 1, and of molecular complexes of heme-DM and -H. Through analysis of optimized geometries and energetics, it is found that the order of binding strength of DMs or H to the Fe of heme is NO > O > CO > H > H for FePIm-based systems, while it is H > O > NO > CO > H for model-based systems. We calculate the activation energies for displacement reactions of H and H by other DMs, revealing that the H displacements occur spontaneously while the H displacements require a large amount of energy. Finally, our calculations corroborate that the rate constants increase with increasing temperature according to the Arrhenius relation.
PubMed: 38784410
DOI: 10.1039/d4ra02091j -
Journal of the American Chemical Society Jun 2024Electrochemical steps are increasingly attractive for green chemistry. Understanding reactions at the electrode-solution interface, governed by kinetics and mass...
Electrochemical steps are increasingly attractive for green chemistry. Understanding reactions at the electrode-solution interface, governed by kinetics and mass transport, is crucial. Traditional insights into these mechanisms are limited, but our study bridges this gap through an integrated approach combining voltammetry, electrochemical impedance spectroscopy, and electrospray ionization mass spectrometry. This technique offers real-time monitoring of the chemical processes at the electrode-solution interface, tracking changes in intermediates and products during reactions. Applied to the electrochemical reduction of oxygen catalyzed by the iron(II) tetraphenyl porphyrin complex, it successfully reveals various reaction intermediates and degradation pathways under different kinetic regimes. Our findings illuminate complex electrocatalytic processes and propose new ways for studying reactions in alternating current and voltage-pulse electrosynthesis. This advancement enhances our capacity to optimize electrochemical reactions for more sustainable chemical processes.
PubMed: 38778765
DOI: 10.1021/jacs.4c04989 -
Journal of Advanced Research May 2024The combination of a photosensitizer and indoleamine-2,3 dioxygenase (IDO) inhibitor provides a promising photoimmunotherapy (PIT) strategy for melanoma treatment. A...
INTRODUCTION
The combination of a photosensitizer and indoleamine-2,3 dioxygenase (IDO) inhibitor provides a promising photoimmunotherapy (PIT) strategy for melanoma treatment. A dual drug delivery system offers a potential approach for optimizing the inhibitory effects of PIT on melanoma proliferation and metastasis.
OBJECTIVE
To develop a dual drug delivery system based on PIT and to study its efficacy in inhibiting melanoma proliferation and metastasis.
METHODS
We constructed a multifunctional nano-porphyrin material (P18-APBA-HA) using the photosensitizer-purpurin 18 (P18), hyaluronic acid (HA), and 4-(aminomethyl) phenylboronic acid (APBA). The resulting P18-APBA-HA was inserted into a phospholipid membrane and the IDO inhibitor epacadostat (EPA) was loaded into the internal phase to prepare a dual drug delivery system (Lip\EPA\P18-APBA-HA). Moreover, we also investigated its physicochemical properties, targeting, anti-tumor immunity, and anti-tumor proliferation and metastasis effects.
RESULTS
The designed system utilized the pH sensitivity of borate ester to realize an enhanced-targeting strategy to facilitate the drug distribution in tumor lesions and efficient receptor-mediated cellular endocytosis. The intracellular release of EPA from Lip\EPA\P18-APBA-HA was triggered by thermal radiation, thereby inhibiting IDO activity in the tumor microenvironment, and promoting activation of the immune response. Intravenous administration of Lip\EPA\P18-APBA-HA effectively induced anti-tumor immunity by promoting dendritic cell maturation, cytotoxic T cell activation, and regulatory T cell suppression, and regulating cytokine secretion, to inhibit the proliferation of melanoma and lung metastasis.
CONCLUSION
The proposed nano-drug delivery system holds promise as offers a promising strategy to enhance the inhibitory effects of the combination of EPA and P18 on melanoma proliferation and metastasis.
PubMed: 38768811
DOI: 10.1016/j.jare.2024.05.017 -
Redox Biology Jul 2024Activation of inflammation is tightly associated with metabolic reprogramming in macrophages. The iron-containing tetrapyrrole heme can induce pro-oxidant and...
Activation of inflammation is tightly associated with metabolic reprogramming in macrophages. The iron-containing tetrapyrrole heme can induce pro-oxidant and pro-inflammatory effects in murine macrophages, but has been associated with polarization towards an anti-inflammatory phenotype in human macrophages. In the current study, we compared the regulatory responses to heme and the prototypical Toll-like receptor (TLR)4 ligand lipopolysaccharide (LPS) in human and mouse macrophages with a particular focus on alterations of cellular bioenergetics. In human macrophages, bulk RNA-sequencing analysis indicated that heme led to an anti-inflammatory transcriptional profile, whereas LPS induced a classical pro-inflammatory gene response. Co-stimulation of heme with LPS caused opposing regulatory patterns of inflammatory activation and cellular bioenergetics in human and mouse macrophages. Specifically, in LPS-stimulated murine, but not human macrophages, heme led to a marked suppression of oxidative phosphorylation and an up-regulation of glycolysis. The species-specific alterations in cellular bioenergetics and inflammatory responses to heme were critically dependent on the availability of nitric oxide (NO) that is generated in inflammatory mouse, but not human macrophages. Accordingly, studies with an inducible nitric oxide synthase (iNOS) inhibitor in mouse, and a pharmacological NO donor in human macrophages, reveal that NO is responsible for the opposing effects of heme in these cells. Taken together, the current findings indicate that NO is critical for the immunomodulatory role of heme in macrophages.
Topics: Humans; Heme; Animals; Nitric Oxide; Mice; Macrophages; Lipopolysaccharides; Inflammation; Nitric Oxide Synthase Type II; Oxidative Phosphorylation; Energy Metabolism; Glycolysis
PubMed: 38762951
DOI: 10.1016/j.redox.2024.103191 -
RSC Advances May 2024The development of functional organic materials is crucial for the advancement of various fields, such as optoelectronics, energy storage, sensing, and biomedicine. In...
The development of functional organic materials is crucial for the advancement of various fields, such as optoelectronics, energy storage, sensing, and biomedicine. In this context, we successfully prepared a stable ambipolar perfluoroporphyrin-based polymeric film by electrochemical synthesis. Our strategy involved the synthesis of a novel tetra-pentafluorophenyl porphyrin covalently linked to four 3,4-ethylenedioxythiophene (EDOT) moieties. The resulting monomer, EDOT-TPPF, was obtained through a straightforward synthetic approach with a good overall yield. The unique molecular structure of EDOT-TPPF serves a dual function, with EDOT moieties allowing electropolymerization for polymeric film formation, while the electron-acceptor porphyrin core enables electrochemical reduction and electron transport. The electrochemical polymerization permits the polymer (PEDOT-TPPF) synthesis and film formation in a reproducible and controllable manner in one step at room temperature. Spectroelectrochemical experiments confirmed that the porphyrin retained its optoelectronic properties within the polymeric matrix after the electrochemical polymerization. The obtained polymeric material exhibited stable redox capabilities. Current charge-discharge cycles and electrochemical impedance spectroscopy of the electrochemically generated organic film demonstrated that the polymer could be applied as a promising active material in the development of supercapacitor energy storage devices.
PubMed: 38756855
DOI: 10.1039/d4ra00945b -
RSC Advances May 2024Porphyrin and porphyrinoid derivatives have been extensively studied in the assembly of catalysts and sensors, seeking biomimetic and bioinspired activity. In...
Porphyrin and porphyrinoid derivatives have been extensively studied in the assembly of catalysts and sensors, seeking biomimetic and bioinspired activity. In particular, Fe and Ni porphyrins can be used for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) by immobilization of these molecular catalysts on semiconductor materials. In this study, we designed a hybrid material containing a crystalline mesoporous TiO thin film in which the catalytic centres are Ni-porphyrin (NiP), Fe-porphyrin (FeP), and a NiP/FeP bimetallic system to assess whether the coexistence of both metalloporphyrins improves the OER activity. The obtained photoelectrodes were physicochemically and morphologically characterized through high-resolution FE-SEM images, UV-vis and Raman spectroscopies, cyclic voltammetry, and impedance measurements. The results show a differential behavior of the mono- and bimetallic porphyrin systems, where the Fe(iii) centre in FeP may increase the acidity and lower the reduction potential of the Ni couple when co-deposited with NiP leading to an improved photoelectrochemical water-oxidation performance. We have validated the cooperative effect of both metal complexes within this novel system, where the μ-peroxo-bridged interaction between Fe and Ni is integrated into a supramolecular heterometallic structure of porphyrins.
PubMed: 38756854
DOI: 10.1039/d3ra08047a -
Chemical Science May 2024Ring-contracted porphyrin analogues, such as subporphyrins and calix[3]pyrroles, have recently attracted considerable attention not only as challenging synthetic targets... (Review)
Review
Ring-contracted porphyrin analogues, such as subporphyrins and calix[3]pyrroles, have recently attracted considerable attention not only as challenging synthetic targets but also as functional macrocyclic compounds. Although canonical porphyrins and calix[4]pyrrole are selectively generated acid-catalyzed condensation reactions of pyrrole monomers, their tripyrrolic analogues are always missing under similar conditions. Recent progress in synthesis has shown that strain-controlled approaches using boron(iii)-templating, core-modification, or ring tightening provide access to various contracted porphyrins. The tripyrrolic macrocycles are a new class of functional macrocycles exhibiting unique ring-contraction effects, including strong boron chelation and strain-induced ring expansion. This Perspective reviews recent advances in synthetic strategies and the novel ring-contraction effects of subporphyrins, triphyrins(2.1.1), calix[3]pyrroles, and their analogous.
PubMed: 38756809
DOI: 10.1039/d4sc02028f -
Chemical Science May 2024Energy-efficient separation of CH/CH is a great challenge, for which adsorptive separation is very promising. CH-selective adsorption has big implications, while the...
Energy-efficient separation of CH/CH is a great challenge, for which adsorptive separation is very promising. CH-selective adsorption has big implications, while the design of CH-sorbents with ideal adsorption capability, particularly with the CH/CH-selectivity exceeded 2.0, is still challenging. Instead of the current strategies such as chemical modification or pore space modulation, we propose a new methodology for the design of CH-sorbents. With a Cu-TCPP [TCPP = 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin] framework dispersed onto a microporous carbon and a hierarchical-pore carbon, two composite sorbents are fabricated. The composite sorbents exhibit enhanced CH-selective adsorption capabilities with visible light, particularly the composite sorbent based on the hierarchical-pore carbon, whose CH and CH adsorption capacities (0 °C, 1 bar) are targetedly increased by 27% and only 1.8% with visible light, and therefore, an CH-selectivity (CH/CH = 10/90, v/v) of 4.8 can be realized. With visible light, the adsorption force of the CH molecule can be asymmetrically enhanced by the excitation enriched electron density over the adsorption sites formed the close interaction between the Cu-TCPP and the carbon layer, whereas that of the CH molecule is symmetrically altered and the forces cancelled each other out. This strategy may open up a new route for energy-efficient adsorptive separation of CH/CH with light.
PubMed: 38756801
DOI: 10.1039/d4sc00898g