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Chemical Reviews Mar 2018As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive... (Review)
Review
As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these proteins, they share common mechanistic grounds. An open-shell transition metal like iron or copper is employed to interact with O and its derived intermediates such as hydrogen peroxide to afford a variety of metal-oxygen intermediates. These reactive intermediates, including metal-superoxo, -(hydro)peroxo, and high-valent metal-oxo species, are the basis for the various biological functions of O-utilizing metalloproteins. Collectively, these processes are called oxygen activation. Much of our understanding of the reactivity of these reactive intermediates has come from the study of heme-containing proteins and related metalloporphyrin compounds. These studies not only have deepened our understanding of various functions of heme proteins, such as O storage and transport, degradation of reactive oxygen species, redox signaling, and biological oxygenation, etc., but also have driven the development of bioinorganic chemistry and biomimetic catalysis. In this review, we survey the range of O activation processes mediated by heme proteins and model compounds with a focus on recent progress in the characterization and reactivity of important iron-oxygen intermediates. Representative reactions initiated by these reactive intermediates as well as some context from prior decades will also be presented. We will discuss the fundamental mechanistic features of these transformations and delineate the underlying structural and electronic factors that contribute to the spectrum of reactivities that has been observed in nature as well as those that have been invented using these paradigms. Given the recent developments in biocatalysis for non-natural chemistries and the renaissance of radical chemistry in organic synthesis, we envision that new enzymatic and synthetic transformations will emerge based on the radical processes mediated by metalloproteins and their synthetic analogs.
Topics: Hemeproteins; Iron; Metalloporphyrins; Models, Molecular; Oxygen; Quantum Theory; Reactive Oxygen Species
PubMed: 29286645
DOI: 10.1021/acs.chemrev.7b00373 -
Biosensors Oct 2018In recent years, scientific advancements have constantly increased at a significant rate in the field of biomedical science. Keeping this in view, the application of... (Review)
Review
In recent years, scientific advancements have constantly increased at a significant rate in the field of biomedical science. Keeping this in view, the application of porphyrins and metalloporphyrins in the field of biomedical science is gaining substantial importance. Porphyrins are the most widely studied tetrapyrrole-based compounds because of their important roles in vital biological processes. The cavity of porphyrins containing four pyrrolic nitrogens is well suited for the binding majority of metal ions to form metalloporphyrins. Porphyrins and metalloporphyrins possess peculiar photochemical, photophysical, and photoredox properties which are tunable through structural modifications. Their beneficial photophysical properties, such as the long wavelength of emission and absorption, high singlet oxygen quantum yield, and low in vivo toxicity, have drawn scientists' interest to discover new dimensions in the biomedical field. Applications of porphyrins and metalloporphyrins have been pursued in the perspective of contrast agents for magnetic resonance imaging (MRI), photodynamic therapy (PDT) of cancer, bio-imaging, and other biomedical applications. This review discusses photophysics and the photochemistry of porphyrins and their metal complexes. Secondly, it explains the current developments and mode of action for contrast agents for MRI. Moreover, the application of porphyrin and metalloporphyrin-based molecules as a photosensitizer in PDT of cancer, the mechanism of the generation of reactive oxygen species (ROS), factors that determine the efficiency of PDT, and the developments to improve this technology are delineated. The last part explores the most recent research and developments on metalloporphyrin-based materials in bio-imaging, drug delivery, and the determination of ferrochelatase in bone marrow indicating their prospective clinical applications.
Topics: Humans; Magnetic Resonance Imaging; Metalloporphyrins; Photochemistry; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 30347683
DOI: 10.3390/bios8040095 -
International Journal of Molecular... Apr 2023Renal immune injury is a frequent cause of end-stage renal disease, and, despite the progress made in understanding underlying pathogenetic mechanisms, current... (Review)
Review
Renal immune injury is a frequent cause of end-stage renal disease, and, despite the progress made in understanding underlying pathogenetic mechanisms, current treatments to preserve renal function continue to be based mainly on systemic immunosuppression. Small molecules, naturally occurring biologic agents, show considerable promise in acting as disease modifiers and may provide novel therapeutic leads. Certain naturally occurring or synthetic Metalloporphyrins (Mps) can act as disease modifiers by increasing heme oxygenase (HO) enzymatic activity and/or synthesis of the inducible HO isoform (HO-1). Depending on the metal moiety of the Mp employed, these effects may occur in tandem or can be discordant (increased HO-1 synthesis but inhibition of enzyme activity). This review discusses effects of Mps, with varying redox-active transitional metals and cyclic porphyrin cores, on mechanisms underlying pathogenesis and outcomes of renal immune injury.
Topics: Heme Oxygenase (Decyclizing); Metalloporphyrins; Heme Oxygenase-1; Kidney
PubMed: 37047787
DOI: 10.3390/ijms24076815 -
Molecules (Basel, Switzerland) Mar 2016Catalysis is a topic of continuous interest since it was discovered in chemistry centuries ago. Aiming at the advance of reactions for efficient processes, a number of... (Review)
Review
Catalysis is a topic of continuous interest since it was discovered in chemistry centuries ago. Aiming at the advance of reactions for efficient processes, a number of approaches have been developed over the last 180 years, and more recently, porphyrins occupy an important role in this field. Porphyrins and metalloporphyrins are fascinating compounds which are involved in a number of synthetic transformations of great interest for industry and academy. The aim of this review is to cover the most recent progress in reactions catalysed by porphyrins in scalable procedures, thus presenting the state of the art in reactions of epoxidation, sulfoxidation, oxidation of alcohols to carbonyl compounds and C-H functionalization. In addition, the use of porphyrins as photocatalysts in continuous flow processes is covered.
Topics: Alcohols; Catalysis; Metalloporphyrins; Molecular Structure; Organic Chemicals; Oxidation-Reduction; Porphyrins
PubMed: 27005601
DOI: 10.3390/molecules21030310 -
Molecules (Basel, Switzerland) Aug 2022The emergence of metal-organic frameworks (MOFs) in recent years has stimulated the interest of scientists working in this area as one of the most applicable archetypes... (Review)
Review
The emergence of metal-organic frameworks (MOFs) in recent years has stimulated the interest of scientists working in this area as one of the most applicable archetypes of three-dimensional structures that can be used as promising materials in several applications including but not limited to (photo-)catalysis, sensing, separation, adsorption, biological and electrochemical efficiencies and so on. Not only do MOFs have their own specific versatile structures, tunable cavities, and remarkably high surface areas, but they also present many alternative procedures to overcome emerging obstacles. Since the discovery of such highly effective materials, they have been employed for multiple uses; additionally, the efforts towards the synthesis of MOFs with specific properties based on planned (template) synthesis have led to the construction of several promising types of MOFs possessing large biological or bioinspired ligands. Specifically, metalloporphyrin-based MOFs have been created where the porphyrin moieties are either incorporated as struts within the framework to form porphyrinic MOFs or encapsulated inside the cavities to construct porphyrin@MOFs which can combine the peerless properties of porphyrins and porous MOFs simultaneously. In this context, the main aim of this review was to highlight their structure, characteristics, and some of their prominent present-day applications.
Topics: Adsorption; Catalysis; Metal-Organic Frameworks; Metalloporphyrins; Porphyrins
PubMed: 35956867
DOI: 10.3390/molecules27154917 -
Military Medical Research Sep 2018AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has... (Review)
Review
AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard (SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM, chlorine gas and radiation exposure studies.
Topics: Animals; Antioxidants; Chemical Warfare Agents; Humans; Lung Injury; Metalloporphyrins; Mice; Mustard Gas; Oxidative Stress; Radiation Injuries, Experimental; Radiation Pneumonitis
PubMed: 30185231
DOI: 10.1186/s40779-018-0176-3 -
Chemistry (Weinheim An Der Bergstrasse,... Apr 2022Metal complexes of multi-porphyrins and multi-corroles are unique systems that display a host of extremely interesting properties. Availability of free meso and β... (Review)
Review
Metal complexes of multi-porphyrins and multi-corroles are unique systems that display a host of extremely interesting properties. Availability of free meso and β positions allow formation of different types of directly linked bis-porphyrins giving rise to intriguing optical and electronic properties. While the fields of metalloporphyrin and corroles monomer have seen exponential growth in the last decades, the chemistry of metal complexes of bis-porphyrins and bis-corroles remain rather underexplored. Therefore, the impact of covalent linkages on the optical, electronic, (spectro)electrochemical, magnetic and electrocatalytic activities of metal complexes of bis-porphyrins and -corroles has been summarized in this review article. This article shows that despite the (still) somewhat difficult synthetic access to these molecules, their extremely exciting properties do make a strong case for pursuing research on these classes of compounds.
Topics: Coordination Complexes; Metalloporphyrins; Porphyrins
PubMed: 35088477
DOI: 10.1002/chem.202104550 -
Molecules (Basel, Switzerland) Mar 2018Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed... (Review)
Review
Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si-H insertion, and olefination of carbonyl compounds. In particular, chiral and achiral metalloporphyrins have been successfully explored as biomimetic catalysts for these carbene transfer reactions under both homogeneous and heterogeneous conditions. In this work the use of synthetic metalloporphyrins (MPorph, M = Fe, Ru, Os, Co, Rh, Ir, Sn) as homogeneous or heterogeneous catalysts for carbene transfer reactions in the last years is reviewed, almost exclusively focused on the literature since the year 2010, except when reference to older publications was deemed to be crucial.
Topics: Metalloporphyrins; Methane
PubMed: 29596367
DOI: 10.3390/molecules23040792 -
Molecules (Basel, Switzerland) Jul 2016Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and... (Review)
Review
Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and peroxygenases. Their ability to perform oxidation and degradation of recalcitrant compounds, including aliphatic hydrocarbons, phenolic and non-phenolic aromatic compounds, sulfides, and nitroso-compounds, has been deeply investigated. Such a broad substrate specificity has suggested their use also in the bleaching of textile plant wastewaters. In fact, industrial dyes belong to very different chemical classes, being their effective and inexpensive oxidation an important challenge from both economic and environmental perspective. Accordingly, we review here the most widespread synthetic metalloporphyrins, and the most promising formulations for large-scale applications. In particular, we focus on the most convenient approaches for immobilization to conceive economical affordable processes. Then, the molecular routes of catalysis and the reported substrate specificity on the treatment of the most diffused textile dyes are encompassed, including the use of redox mediators and the comparison with the most common biological and enzymatic alternative, in order to depict an updated picture of a very promising field for large-scale applications.
Topics: Adsorption; Catalysis; Coloring Agents; Cytochrome P-450 Enzyme System; Enzymes, Immobilized; Heme; Metalloporphyrins; Molecular Structure; Oxidation-Reduction; Peroxidases; Sorption Detoxification; Substrate Specificity; Textiles; Wastewater
PubMed: 27455229
DOI: 10.3390/molecules21070964 -
Antioxidants & Redox Signaling May 2014Half a century of research provided unambiguous proof that superoxide and species derived from it-reactive oxygen species (ROS)-play a central role in many diseases and... (Review)
Review
SIGNIFICANCE
Half a century of research provided unambiguous proof that superoxide and species derived from it-reactive oxygen species (ROS)-play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential.
RECENT ADVANCES
The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials.
CRITICAL ISSUES AND FUTURE DIRECTIONS
Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution.
Topics: Animals; Catalysis; Enzyme Activation; Humans; Hydrophobic and Hydrophilic Interactions; Metalloporphyrins; Molecular Mimicry; Mutation; Superoxide Dismutase
PubMed: 23964890
DOI: 10.1089/ars.2013.5576