The Epoxidation of the Olefins by meso-Tetraphenylporphyrinatochromium(3+) Chloride as an Electrochemical P-450 Model Compound

Takashi Michida; Takuryu Omichi

doi:10.1248/cpb.c12-00806

Abstract

An electrochemical P450 model compound consisting of meso-tetraphenylporphyrinatochromium(3+) chloride (CrTPP), imidazole, and acetic acid was used in acetonitrile containing alkenes. The corresponding epoxides were obtained in better yields compared to a similar electrochemical P450 model compound using meso-tetraphenylporphyrinatomanganese(3+) chloride. The results of cyclic voltammetry and controlled potential electrolysis suggest that electrochemically reduced CrTPP reacts with dissolved oxygen to oxidize alkenes to epoxides.

Metalloporphyrins are used in biomimetic chemistry as model compounds of cytochrome P450. P450 is not only an important drug-metabolizing compound, but is also of great interest because it catalyzes various oxygenation reactions and has a unique catalytic cycle.¹⁾ Our studies on biomimetic oxidations have utilized manganese porphyrins as electrochemical P450 model compounds. These porphyrins are effective in the oxidation of sulfides, the demethylation of dimethyl aniline, and the epoxidation of alkenes.^2–9) Other researchers, in particular Murray and co-workers have used chromium porphyrins to catalyze oxygen-atom transfer reactions or as P450 model compounds.¹⁰⁾ These researchers showed that (meso-tetraphenylporphinato)oxochromium(5+) ((TPP)Cr5+(O)(X)) reacts with norbornene to provide an epoxide and (TPP)Cr(3+)(X).^10–17) The aim of this paper is to clarify the utility of meso-tetraphenylporphinatochromium(3+) (CrTPP) as an electrochemical P450 model compound.

Results and Discussion

Cyclic Voltammetry (CV)

Cyclic voltammetry of CrTPP (1 mM) was performed in dry acetonitrile containing NaClO₄ as a supporting electrolyte. A glassy carbon electrode, an Ag/AgCl electrode, and a Pt wire were used as the working electrode, reference electrode, and counter electrode, respectively. The potential sweep range was from 1.8 to −1.6 V and the sweep rate was 50 mV/s. The cyclic voltammogram in dry acetonitrile containing CrTPP (1 mM) and NaClO₄ under atmospheric conditions was shown in Fig. 1.

Fig. 1. Cyclic Voltammogram of 1 mM CrTPP in Acetonitrile

Supporting electrolyte: 0.1 M NaClO₄; working electrode: glassy carbon; scan rate: 50 mV/s.

The start potential was 0.0 V. Two cathodic waves and one anodic wave were observed in the potential range from 0 to −1.6 V. A complicated voltammogram was obtained in the potential range from 0.3 to 1.5 V. The anodic wave at −0.58 V disappeared upon displacement of the dissolved air with N₂ gas, or when the potential range was changed (from 1.8 to −1.3 V). These results suggest that the second cathodic wave is due to the reduction of dissolved oxygen. Numerical values pertaining to the first cathodic wave was summarized in Table 1.

Table 1. First Cathodic Wave Obtained upon Cyclic Voltammetry of CrTPP in Acetonitrile Solution

Soluente	Epc (V) vs. Ag/AgCl	Ip v^−1/2, µA (mV/s)^−1/2
CrTPP (1 mM)^a)	−0.99	2.36
CrTPP (1 mM)^b)	−1.06	1.44
CrTPP (1 mM)+AcOH (1%)^a)	−1.26	14.85
CrTPP (1 mM)+AcOH (1%)^b)	−1.19	2.15
CrTPP (1 mM)+imidazole (5 mM)^a)	−1.41	14.35
CrTPP (1 mM)+imidazole (5 mM)^b)	−1.47	1.84
CrTPP (1 mM)+imidazole (5 mM)+AcOH (1%)^a)	−1.16	14.40
CrTPP (1 mM)+imidazole (5 mM)+AcOH (1%)^b)	−1.27	2.24

a) Under air. b) Under N₂.

The addition of acetic acid (1%) to the electrolyte resulted in fusion of the two cathodic waves in the potential range from 0 to −1.6 V: the first cathodic wave shifted approximately 200 mV lower and the intensity peak (ip) (peak current) of the cathodic wave increased more than sevenfold. The anodic wave at −0.58 V was not observed in this voltammogram. Displacement of dissolved air with N₂ gas reduced the cathodic wave. The results suggest that the electrochemical reduction product of CrTPP was oxidized and reduced several times in the presence of dissolved air. The addition of imidazole (5 mM) to the electrolyte resulted in the cathodic wave shifting approximately 400 mV lower, in a manner similar to that observed following the addition of acetic acid. As shown in Fig. 2, when both acetic acid (1%) and imidazole (5 mM) were added to the electrolite solution of CrTPP (1 mM), a new oxidation wave was appeared at −1.24 V, which was a counter part of the first cathodic wave.

Fig. 2. Cyclic Voltammogram of 1 mM CrTPP in Acetonitrile Containing Imidazole (5 mM) and Acetic Acid (1%)

Supporting electrolyte: 0.1 M NaClO₄; working electrode: glassy carbon; scan rate: 50 mV/s.

Cyclic voltammograms of chromium porphyrins have been published in several papers.^18,19) For example, Fuhrhop et al. measured the redox potential of 25 metalloporphyrins using cyclic voltammetry, and reported that the half-wave potentials of chromium octaethyl–porphyrin in dimethyl sulfoxide (DMSO) containing 0.01 M tetrabutyl ammonium perchlorate (TBAP) are +0.79 V (4⁺/3⁺) and −1.14 V (3⁺/2⁺) vs. saturated calomel electrode (SCE).¹⁸⁾ Cheung et al. reported the results of cyclic using a Pt electrode on CrTPP in benzonitrile and DMSO and stated that the potentials are −0.86 V vs. SCE to 3⁺/2⁺, and +0.95 V vs. SCE to 4⁺/3⁺.¹⁹⁾ Based on these literature values, the reversible cathodic wave at −1.27 V in Fig. 2 corresponds to 3⁺/2⁺.

It has been postulated that the active species of cytochrome P450 is an oxo-Fe⁴⁺-porphyrin radical cation, which is a formal Fe⁵⁺ species. Oxo(meso-tetraphenylporphinato)chromium(5+) ((CrTPP)O) has been used as a model compound of the active species of P450.²⁰⁾ Creager and Murray reported that the half wave potential of (CrTPP)O(5⁺/4⁺) in methylene chloride is +0.71 V vs. SCE.¹⁰⁾ However, no cathodic or anodic wave corresponding to (CrTPP)O(5⁺/4⁺) was observed in the cyclic voltammogram of CrTPP in acetonitrile containing imidazole (5 mM) and acetic acid (1%).

Controlled Potential Electrolysis (CPE)

CPE was performed in an undivided cell. A glassy carbon electrode and an Ag/AgCl electrode were used. The electrolytic solution was acetonitrile containing CrTPP (1 mM), alkenes (100 mM), acetic acid (1%), imidazole (5 mM) and NaClO₄ as the supporting electrolytes. The electrolytic solution was stirred during electrolysis under atmospheric conditions. At hourly intervals, 0.5 µL of electrolytic solution was withdrawn and analyzed by gas chromatography. The electrolytic experiments were stopped after 4 h, since alkene consumption had stopped. The results are summarized in Table 2.

Table 2. Results of Controlled Potential Electrolysis of CrTPP in the Presence of Alkenes

Alkene	Product	Duration of electrolysis (h)	Concentration of product (mM)	Current efficiency (%)
Cyclooctene	Cyclooctene oxide	4	8.31	14.1
Cyclohexene	Cyclohexene oxide	4	8.01	15.1
Cyclopentene	Cyclopentene oxide	4	8.02	21.1
Styrene	Styrene oxide	5.5	6.78	22.9

Calculation of the current efficiency is based on the assumption that two electrons are consumed to produce an epoxide from the corresponding alkene. This assumption is based on the fact that the catalytic cycle of cytochrome P450 consumes one oxygen molecule and two electrons during oxidization.

Epoxidation of cyclooctene was complete after 4 h. Cyclooctene oxide (8.31 mM) was detected by gas chromatography, providing a current efficiency of 14.1%. Replacement of the substrate did not provide any drastic variation in the CPE results.

In earlier electrochemical P450 model compound studies, we reported the results of CPE of meso-tetraphenylporphyrinatomanganese(3+) chloride in the presence of alkenes.⁶⁾ When styrene was used as the alkene and MnTPP was used as the electrochemical P450 model compound, the epoxide concentration was 5.4 mM and the current efficiency was 89.5%. CrTPP improved the yield of strene oxide, but the current efficiency was reduced remarkably. Garrison et al. studied the epoxidation of a series of alkenes by oxo-porphinato chromium(5+), and reported one-electron oxidation of alkenes by the oxo-chromium complex as well as epoxidation.²¹⁾ One-electron oxidation of alkenes by (CrTPP)O in our electrochemical P450 model compound could explain the decreased current efficiency.

Chromiumporphyrins catalyze epoxidation and another oxidations using oxidants such as iodosobenzene, per carboxylic acid, hydro peroxides, pentafluoroiodobenzene, and 4-cyano-N,N-dimethylaniline N-oxide.^{12,17,20,22–25)} In most papers dealing with these oxidations, the generation of an oxo chromium(5+) porphyrin complex is proposed in the reaction scheme. This paper is the first report of the oxidation of an alkene using chromium porphyrin, electron transfer, and molecular oxygen.

The reaction mechanism for these reactions, based on the CV and CPE results, were shown in Chart 1. CrTPP is electrochemically reduced to the corresponding 2+ complex (A) by the cathode. A reacts with a dissolved oxygen molecule immediately, then a second electron transfer occurs. Cleavage of water from the reduced complex gives the oxo chromium(5+) porphyrin complex (B). A two-electron oxidation of the alkene provides an epoxide and CrTPP. The details of this mechanism are currently being investigated in our laboratory.

Chart 1

Experimental

Materials

Acetonitrile was purified as described previously.²⁶⁾ Other chemicals were reagent grade and used without purification. CrTPP, imidazole, acetic acid, sodium perchlorate, cyclooctene, cyclohexene, cyclopentene were purchased from Nacalai Tesque, Kyoto, Japan and styren was purchased from Wako Pure Chemical Industries, Ltd., Osaka, Japan.

Apparatus

A BAS ALS/DY2323 Bi-potentiostat equipped with a Cib cell stand and EPSON DIRECT Endeavor AT-900C were used for cyclic voltammetry. A Hokutodenko HF-102 coulometer and HA-501 potentiostat were used for controlled potential electrolysis. Gas chromatography was carried out with a Shimadzu GC-14A equipped with a C-R6A Chromatopac.

Controlled Potential Electrolysis (CPE)

A representative procedure is as follows. Acetonitrile (30 mL) containing CrTPP (20.0 mg), cyclooctene (331 mg), imidazole (102 mg), acetic acid (0.3 mL) and NaClO₄ (3.67 g) were used as the supporting electrolyte and placed in an undivided cell. A glassy carbon plate, a Pt plate, and an Ag/AgCl electrode were used as the working electrode, counter electrode, and reference electrode, respectively. Aliquots (0.5 µL) were analyzed and products were determined by GC (capillary column, GL Sciences Inert Cap (0.25 mm×30 m, df 0.25 µm)).

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