Exceedingly Fast Oxygen Atom Transfer to Olefins via a Catalytically Competent Nonheme Iron Species

The reaction of [Fe(CF3SO3)2(PyNMe3)] with excess peracetic acid at ¢40 8C leads to the accumulation of a metastable compound that exists as a pair of electromeric species, [FeIII(OOAc)(PyNMe3)]2+ and [FeV(O)(OAc)(PyNMe3)]2+, in fast equilibrium. Stopped-flow UV/Vis analysis confirmed that oxygen atom transfer (OAT) from these electromeric species to olefinic substrates is exceedingly fast, forming epoxides with stereoretention. The impact of the electronic and steric properties of the substrate on the reaction rate could be elucidated, and the relative reactivities determined for the catalytic oxidations could be reproduced by kinetic studies. The observed fast reaction rates and high selectivities demonstrate that this metastable compound is a truly competent OAT intermediate of relevance for nonheme iron catalyzed epoxidations

Aktivierung von Peroxiden durch biologische und Modell-Eisen(III)-Komplexe

In summary, the results demonstrate very well how important the choice of the reaction conditions is in kinetic and mechanistic studies of particular synthetic P450 enzyme mimics. The rate of the oxo-iron(IV) porphyrin -cation radical formation, as well as the stability/reactivity of the created high valent iron species appear to be controlled by the electronic nature of the porphyrin rings and the properties of the solvent used. From the solvents studied, acetonitrile turns out to be the best choice, not only due to the highest rate constants for the formation of the oxo-iron(IV) porphyrin -cation radicals, but also due to extending the stability of the high valent iron intermediates formed in this solvent. Importantly, methanol which is commonly used as a “good protic solvent”, especially in the low-temperature studies of reactive intermediates, can show an unusual effect in which methanol molecules serve as efficient reducing agents for the oxo-iron(IV) cation radicals formed in the “peroxo shunt” reactions. Therefore, care should be taken with the interpretation of results originating from kinetic measurements carried out in pure methanol. Spectroscopic and mechanistic studies on the peroxo-shunt oxidation of the synthetic enzyme mimic of P450 carrying a thiolate proximal ligand, the SR complex, have revealed a significant effect of sulfur coordination on the formation and reactivity/stability of the oxo-iron(IV) porphyrin cation radical derived from SR. The presented results clearly show that the SR complex, in contrast to other P450 models bearing weak donor ligands, tends to cleave organic peroxo acids heterolytically independent of the polarity of the used solvent. Interestingly, studies on oxygenation reactions catalyzed by native P450 enzymes show that these natural systems, although they also carry a thiolate proximal ligand, display a different reactivity behavior than that observed for synthetic thiolate-ligated iron(III) porphyrin models. It means that the much higher ability of P450 enzymes to retain the thiolate proximal coordination during the overall catalytic cycle is associated with the fact that the electron donor capability of the thiolate ligand in the natural systems is significantly reduced by the presence of NH-S- hydrogen bonds present in the proximal protein pocket. Thus, the interaction of the protein environment with the thiolate proximal ligand substantially affects the Fe-S bond and therefore modulates the reactivity of the enzymes according to their biological function.Die Ergebnisse zeigen sehr gut wie wichtig die Wahl der richtigen Reaktionsbedingungen für kinetische und mechanistische Untersuchungen mit synthetischen P450 Enzymen ist. Die Geschwindigkeitskonstante der Porphyrineisen(IV)--Kationradikal-Bildung, sowie auch Stabilität/Reaktivität dieser hochvalenten Spezies, kann durch die elektronische Natur des Porphyrinringes und Eigenschaften der verwendeten Lösungsmitteln kontrolliert werden. An Hand der Ergebnisse aus den Studien mit unterschiedlichen Lösungsmitteln wurde sichtbar, dass Acetonitril das geeignetste Lösungsmittel für die oben erwähnten Untersuchungen ist. Dies aber nicht nur, weil der Porphyrineisen(IV)--Kationradikal in Acetonitril am schnellsten gebildet wird, sondern auch, weil diese hochvalente Eisenzwischenstufe in Acetonitril am stabilsten ist. Ein sehr wichtiger Befund dieser Studie ist, dass Methanol, welches als „gutes protisches Lösungsmittel“ verwendet wurde, auch die Rolle des Reduktanten in der Reaktion mit Porphyrineisen(IV)--Kationradikal übernehmen und “peroxo shunt”-Richtung des Cytochrom P450 katalytischen Zyklus folgen kann. Diese Überlegungen wurden durch Ergebnisse aus den kinetischen Studien in reinem Methanol belegt. Spektroskopische und mechanistische Untersuchungen der Oxidationsreaktionen mit einem Modellkomplex (SR Komplex) des Cytochrom P450, welcher eine Thiolatgruppe als axialer Ligand besitzt, zeigten, dass die Koordinierung des Thiolatliganden am Porphyrin durch Schwefel eine entscheidende Rolle für Reaktivität/Stabilität des gebildeten Porphyrineisen(IV)--Kationradikal spielt. Die Ergebnisse zeigten klar und deutlich, dass SR Komplex, im Vergleich zu P450 Modellkomplexen mit anderen Elektronendonoren als axiale Liganden, unabhängig von der Polarität des verwendeten Lösungsmittels, zur heterolytischen Spaltung der O-O-Bindung bei Peroxosäuren tendiert. Interessanterweise wurden bei den Studien über Oxygenierungsreaktionen, welche von den naturellen P450 Enzymen (mit den Thiolatliganden in der proximalen Position) katalysiert werden, festgestellt, dass die Reaktivität der synthetischen Eisen(III) Porphyrinen, mit Thiolatliganden, sich sehr oft von den naturellen Enzymen unterscheiden kann. Dies bedeutet, dass die hohe Fähigkeit der P450 Enzymen den proximalen Thiolatliganden nach dem katalytischen Zyklus behalten zu können, mit der Tatsache zusammenhängt, dass die Fähigkeit des Thiolatliganden die Elektronen abzugeben von den in der proximalen Proteintasche vorhandenen NH-S- Wasserstoffbindungen vermindert wird. Somit hat die Wechselwirkung des proximalen Thiolatliganden mit der Umgebung auf die Fe-S Bindung einen großen Einfluss. Dadurch werden die Reaktivität des Enzyms und seine biologische Funktion moduliert

Low-temperature rapid-scan detection of reactive intermediates in epoxidation reactions catalyzed by a new enzyme mimic of cytochrome p450

The use of synthetic iron(III) porphyrins as models for heme-type catalysts in biomimetic cytochrome P 450 research has provided valuable information on the nature and reactivity of intermediates produced in the "peroxide shunt" pathway.  This article reports spectroscopic detection of reactive intermediates formed in the epoxidn. reaction of cis-stilbene with m-chloroperoxybenzoic acid catalyzed by a new mimic of cytochrome P 450 with a substituted RSO3- group (1).  The application of low-temp. rapid-scan stopped-flow techniques enabled the detn. of equil. and rate consts. for the formation and decay of all intermediates in the catalytic cycle of 1, including the rate const. for the formation (1.bul.+)FeIV:O and for oxygen transfer to the substrate.  Noteworthy, the reaction of (1.bul.+)FeIV:O with cis-stilbene leads to an almost complete re-formation (95%) of the starting complex 1.  The results show that complex 1 is a valuable catalyst with promising properties for further applications in a biomimetic approach toward mimicking oxygenation reactions of cytochrome P 450

Mechanistic insight into formation of oxo-iron (IV) porphyrin pi -cation radicals from enzyme mimics of cytochrome P450 in organic solvents

Two new models for cytochrome P 450 in which the thiolate axial ligand is replaced by a RSO3- group, form oxo-iron (IV) porphyrin pi-cation radicals as sole oxidn. products in "peroxo shunt" reactions independent of the nature of the employed solvent (polar or non-polar) and electronic nature of the porphyrin rings.  Although the properties of the solvent and push-pull effects from the porphyrin rings do not affect the mode of the O-O bond cleavage (heterolytic or homolytic) in these models, they strongly affect the rate and mechanism of each reaction step leading to the formation of the high-valent iron intermediates.  This article reports the results of mechanistic studies involving the measurements of the rate of oxo-iron (IV) porphyrin pi-cation radical formation from the enzyme mimics of P 450 for different oxidant concn., temp. and pressure in selected org. solvents.  Extn. of the appropriate rate consts. and activation parameters for the reactions studied enable a detailed discussion of the effects of solvent and electronic nature of the porphyrin rings on the position of the first pre-equil. involving formation of the acylperoxo-iron (III) porphyrin intermediate, as well as on the rate of heterolytic O-O bond cleavage leading to the formation of the high-valent iron species.  Furthermore, an unusual effect of solvent on the kinetics of oxo-iron (IV) porphyrin pi-cation radical formation in methanol is demonstrated and discussed in the present work

Thermodynamic and kinetic studies on the binding of nitric oxide to a new enzyme mimic of cytochrome p450

A new model for the P450 enzyme carrying a SO3- ligand coordinated to iron(III) (complex 2) reversibly binds NO to yield the nitrosyl adduct. The rate constant for NO binding to 2 in toluene is of the same order of magnitude as that found for the nitrosylation of the native, substrate-bound form of P450cam (E·S-P450cam). Large and negative activation entropy and activation volume values for the binding of NO to complex 2 support a mechanism that is dominated by bond formation with concomitant iron spin change from S = 5/2 to S = 0, as proposed for the reaction between NO and E·S-P450cam. In contrast, the dissociation of NO from 2(NO) was found to be several orders of magnitude faster than the corresponding reaction for the E·S-P450cam/NO system. In a coordinating solvent such as methanol, the alcohol coordinates to iron(III) of 2 at the distal position, generating a six-coordinate, high-spin species 5. The reaction of NO with 5 in methanol was found to be much slower in comparison to the nitrosylation reaction of 2 in toluene. This behavior can be explained in terms of a mechanism in which methanol must be displaced during Fe−NO bond formation. The thermodynamic and kinetic data for NO binding to the new model complexes of P450 (2 and 5) are discussed in reference to earlier results obtained for closely related nitrosylation reactions of cytochrome P450cam (in the presence and in the absence of the substrate) and a thiolate-ligated iron(III) model complex