Intramolecular Oxidative O‐Demethylation of an Oxoferryl Porphyrin Complexed with a Per‐O‐methylated β‐Cyclodextrin Dimer

Abstract

The intramolecular oxidation of ROCH to ROCH OH, where the latter compound spontaneously decomposed to ROH and HCHO, was observed during the reaction of the supramolecular complex (met-hemoCD3) with cumene hydroperoxide in aqueous solution. Met-hemoCD3 is composed of meso-tetrakis(4-sulfonatophenyl)porphinatoiron(III) (Fe TPPS) and a per-O-methylated β-cyclodextrin dimer having an -OCH PyCH O- linker (Py=pyridine-3,5-diyl). The O=Fe TPPS complex was formed by the reaction of met-hemoCD3 with cumene hydroperoxide, and isolated by gel-filtration chromatography. Although the isolated O=Fe TPPS complex in the cyclodextrin cage was stable in aqueous solution at 25 °C, it was gradually converted to Fe TPPS (t =7.6 h). This conversion was accompanied by oxidative O-demethylation of an OCH group in the cyclodextrin dimer. The results indicated that hydrogen abstraction by O=Fe TPPS from ROCH yields HO-Fe TPPS and ROCH . This was followed by radical coupling to afford Fe TPPS and ROCH OH. The hemiacetal (ROCH OH) immediately decomposed to ROH and HCHO. This study revealed the ability of oxoferryl porphyrin to induce two-electron oxidation.

Stereoselective Metabolism of Omeprazole by Cytochrome P450 2C19 and 3A4: Mechanistic Insights from DFT Study

“…The intermolecular oxidation of R′-OCH 3 ( S -omeprazole) to R′-OCH 2 OH is catalyzed by CYP2C19, and R′-OCH 2 OH disintegrates to R-OH and HCHO in the presence of a water molecule. The oxidation of R′-OCH 3 to R′-OCH 2 OH is rare in an organic reaction; however, a recent report supports our predicted mechanism . In the metabolic process of S -omeprazole, the hydrogen abstraction process is the rate-determining step and the activation free energy barriers for this step are 17.5 and 19.3 kcal/mol for doublet and quartet species, respectively (Figures and S5).…”

“…The oxidation of R′-OCH 3 to R′-OCH 2 OH is rare in an organic reaction; however, a recent report supports our predicted mechanism. 47 In the metabolic process of S-omeprazole, the hydrogen abstraction process is the rate-determining step and the activation free energy barriers for this step are 17.5 and 19.3 kcal/mol for doublet and quartet species, respectively (Figures 4 and S5).…”

A water-soluble supramolecular complex that mimics the heme/copper hetero-binuclear site of cytochromecoxidase

“…This system takes advantage of the very stable formation of a self-assembling 1 : 2 complex of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron (FeTPPS) with per- O -methylated β-cyclodextrins (CDs). 19 We have previously studied the porphyrin/cyclodextrin complexes as simple biomimetic models of heme proteins that function under aqueous conditions, 20 – 23 where the molecular cage of per- O -methylated β-CDs provided a microscopic hydrophobic environment for FeTPPS similar to the heme pocket of heme proteins. 24 Here, we have synthesised a per- O -methylated β-CD dimer linked by a Cu II –terpyridine complex (Cu II TerpyCD 2 , Scheme 1 ) to replicate the distal tridentate Cu B site of C c O.…”

Heterocomponent ternary supramolecular complexes of porphyrins: A review

“…As a result, formation of stable complexes with Fe III TPPS occurred (Fig. 23) [120][121][122][123][124][125][126][127][128][129][130][131][132][133]. Such CD-porphyrin complexes were shown to form ternary complexes with various small molecules (e.g.…”