Electron-paramagnetic-resonance studies of the chlopromazine free radical formed during enzymic oxidation by peroxidase-hydrogen peroxide

Biochimica et Biophysica Acta (BBA) - Specialized Section on Biophysical Subjects Pub Date : 1964-07-29 DOI:10.1016/0926-6577(64)90160-3

L.H. Piette, G. Bulow, Isao Yamazaki

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引用次数: 110

Abstract

1.
1. The tranquilizing drug chlorpromazine was enxymically oxidized to the freeradical intermadiate which was identical with the red intermediate observed optically at 530 mμ.
2.
2. The stiochiometry for the peroxidaseH₂O₂ reaction was detemrined to be
3.
3. The dismutation reaction rate constant, k_d, at pH 4.8 was measured to be 15.0 M⁻¹·sec⁻. This extreme stability of the free radical allowed further oxidation of the free radical by the enzyme in the substrate-limited case; the rate constant for this reaction was found to be 3.9·10⁻¹, approx. 10 times slower than k₄, the first oxidation.
4.
4. It is suggested that the stability of the free radical may be responsible for the psychotropic activity of the drug.

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氯丙嗪自由基在过氧化物酶-过氧化氢酶氧化过程中形成的电子顺磁共振研究

1.1. 安定药氯丙嗪在530 μ m .2.2下被酶氧化为与光学观察到的红色中间体相同的游离中间体。测定过氧化物酶H2O2反应的化学计量为3.3。pH值为4.8时，裂解反应速率常数kd为15.0 M−1·sec−。自由基的这种极端稳定性允许酶在底物受限的情况下进一步氧化自由基;该反应的速率常数约为3.9·10−1。第一次氧化比k4慢10倍。这表明，自由基的稳定性可能是负责的精神药物的活性。

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Biochimica et Biophysica Acta (BBA) - Specialized Section on Biophysical Subjects

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