Metalloporphyrins as chemical mimics of cytochrome P-450 systems

Chorghade, Mukund S.; Dezaro, Derek A.; Hill, David R.; Lee, Elaine C.; Pariza, R. J.; Andersen, Jan Vanggaard; Hansen, Kristian T.; Dolphin, David

doi:10.1016/s0960-894x(01)80830-1

Cited by 9 publications

(5 citation statements)

References 10 publications

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“…Metalloporphyrins have long been employed as models of heme proteins, − and the use of nitrogenous bases as axial ligands in these metalloporphyrin systems has extensive historic precedent. Originally, these ligands were applied in biomimetic chemistry as substitutes for the axial cysteine thiolate (P-450) or histidine imidazole (horseradish peroxidase, hemoglobin, myoglobin, cytochrome c oxidase) in the natural metalloproteins.…”

Section: Introductionmentioning

confidence: 99%

Competitive Reaction of Axial Ligands during Biomimetic Oxygenations

et al. 2000

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Nitrogenous bases have commonly been employed as axial ligands for metalloporphyrins in biomimetic model compounds and catalytic oxygenation chemistry. The addition of bases such as pyridines or imidazoles to metalloporphyrin-catalyzed hydrocarbon oxidation reactions is known to affect catalyst selectivity and turnover rate; this effect has been correlated with the electron-donor ability of the ligand. We have found that the role of pyridine in these reactions is far more involved than that of a simple axial ligand: pyridine is a competitive substrate and is converted in high yield to the N-oxide. Subsequently, both of these species act as ligands to the metal center. Thus, catalytic systems containing oxidizable pyridines involve complex equilibria with multiple forms of ligated catalyst, and kinetic results should be interpreted with caution. Alternatives to free pyridine were tested, including a pyridine “tail” which is covalently attached to the porphyrin.

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Section: Introductionmentioning

confidence: 99%

Competitive Reaction of Axial Ligands during Biomimetic Oxygenations

et al. 2000

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“…Hydroxylation and epoxidation reactions catalyzed by tetraphenylporphinatoiron(III) chloride (FeTPPCl) with iodosylbenzene as the oxygen donor were reported in 1979 13. Numerous studies of metalloporhyrin/porphine‐catalyzed oxidation reactions have been performed more recently 14–17. Typical systems consist of porphyrin/porphine complexes with metal ions like manganese, iron and chromium, together with oxygen‐donating compounds such as iodosylbenzene, NaClO, amine N ‐oxides and periodate 4.…”

mentioning

confidence: 99%

Mimicry of phase I drug metabolism – novel methods for metabolite characterization and synthesis

Johansson

Weidolf

Jurva

2007

Rapid Comm Mass Spectrometry

122

125

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The extent to which electrochemical oxidation, electrochemically assisted Fenton chemistry and synthetic metalloporphines can be used to mimic cytochrome P450 catalyzed oxidations has been investigated for a large range of metabolic reactions. Most relevant metabolic oxidations can be mimicked by at least one of the three investigated systems. The EC oxidation system successfully mimics benzylic hydroxylation, hydroxylation of aromatic rings containing electron-donating groups, N-dealkylation, S-oxidation, dehydrogenation and less efficiently N-oxidation and O-dealkylation. The EC-Fenton system is able to mimic aliphatic hydroxylation, benzylic hydroxylation, aromatic hydroxylation, N-dealkylation, N-oxidation, O-dealkylation, S-oxidation and dehydrogenation. The porphine system mimics all types of reactions although the yields are low for some reactions. In conclusion, these three complementary systems can be used during the drug discovery and development of new drugs to elucidate the structure of metabolites that are difficult to characterize in biological matrices. Moreover, such techniques can replace the classical chemistry strategy, especially when synthesis is complicated or too time-consuming in order to access metabolites for further testing.

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“…Therefore, metalloporphyrins have been utilized to mimic the in vivo metabolism of some pharmaceuticals. [23] For example, the anti-inflammatory drug, 2-[2-(2,6-dichlorophenylamino)phenyl]acetic acid (diclofenac), is metabolized to two hydroxylated products, 4¢-hydroxylated product 7 and 5-hydroxylated product 8 (Scheme 6). The major 4¢-hydroxylated product is synthesized by cytochrome P450 2C9, [24,25] while the minor 5-hydroxylated metabolite 8 is produced by several cytochrome P450s, including P450 3A4, 2C8, and 2C19.…”

Section: Reaction With Iron-and Manganese-porphyrinsmentioning

confidence: 99%

2.10 C—O Bond Formation by Arene C—H Activation via Biomimetic and Organocatalytic Oxidation

Wang¹

2015

Catalytic Transformations via C-H Activation Vol. 2

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Metalloporphyrins as chemical mimics of cytochrome P-450 systems

Cited by 9 publications

References 10 publications

Competitive Reaction of Axial Ligands during Biomimetic Oxygenations

Competitive Reaction of Axial Ligands during Biomimetic Oxygenations

Mimicry of phase I drug metabolism – novel methods for metabolite characterization and synthesis

2.10 C—O Bond Formation by Arene C—H Activation via Biomimetic and Organocatalytic Oxidation

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