Quinone-sensitized Steady-state Photolysis of Acetophenone Oximes Under Aerobic Conditions: Kinetics and Product Studies[dagger]

Photochemistry and Photobiology, Jan/Feb 2006 by Park, Adriana, Kosareff, Nicole M, Kim, Jason S, de Lijser, H J Peter

ABSTRACT

Oxidation of oximes via photosensitized electron transfer (PET) results in the formation of the corresponding ketones as the major product via oxime radical cations and iminoxyl radicals. The influence of electron-releasing and electron-accepting substituents on these reactions was studied. The observed substituent effect strongly supports formation of iminoxyl radicals from the oximes via an electron transfer-proton transfer sequence rather than direct hydrogen atom abstraction. Correlation of the relative conversion of the oximes with Hammett parameters shows that radical effects dominate for the meta-substituted acetophenone oximes (ρ^sub rad^/ρ^sub pol^ = 5.4; r^sup 2^ = 0.93), whereas the para-substituted oximes are influenced almost equally by radical and ionic effects (ρ^sub rad^/ρ^sub pol^ = -1.1; r^sup 2^ = 0.98). From these data sets we conclude that the follow-up reactions proceed through a number of intermediates with both radical and ionic character. This was confirmed by product studies with the use of an isotopically labeled nucleophile. In addition to the major oxidation product (ketone), a chlorine-containing product was often identified as well. Studies on the formation of this product show that the most likely pathway is either via a direct nucleophilic addition in a complex formed between the oxime radical cation and the chloranil radical anion or via a radical substitution (S^sub H^2) mechanism. These studies show that with the increasing use of oximes as drugs and pesticides, intake of these chemicals followed by enzymatic oxidation may result in the formation of a variety of reactive intermediates, which may lead to cell and tissue damage.

Abbreviations: BA, bromanil; CA, chloranil: CP, chlorinated product; DFT, density functional theory; ET-PT, electron transfer-proton transfer; FA, fluorunil: HAT, hydrogen atom transfer; IP, ionization potential; LFP, laser Hash photolysis; NOS, nitric oxide synthase; PET, photosensitized electron transfer; ROS, reactive oxygen species; SS, steady-state; TCHQ, 2,3,5,6-tetrachlorohydroquinone.

© 2006 American Society for Photobiology 0031-8655/06

INTRODUCTION

The use of oximes and related compounds in pesticides (1,2) and drugs (3-6) has increased in recent years, leading to a larger availability in the environment (7) and an increased risk of uptake by organisms. Detoxification of such xenobiotics typically involves oxidative pathways (8), which, in the case of oximes, can result in the formation of reactive oxygen species (ROS) such as iminoxyl radicals (9-16). Little is known about these reactive intermediates. Oxime radical cations and iminoxyl radicals are the proposed intermediates in the nitric oxide synthase (NOS) catalyzed metabolism of l-arginine to l-citrulline (17,18). Iminoxyl radicals have also been proposed as intermediates in the formation of nitric oxide from oximes (19,20). It was shown that the in vivo metabolism of cyclohexanone oxime (an intermediate in the synthesis of Nylon-6) in rats resulted in excessive nitric oxide (NO) formation, which may be responsible for the toxicity of this compound (21). A number of alkyl- and aryloximes have been shown to act as nitric oxide donors under oxidative conditions; in fact, some are commercially available and were reported to produce significant vasorelaxation in isolated dog coronary arteries and the rat aorta (22-24). However, cyclohexanone oxime and structurally related oximes were shown to be animal carcinogens (25,26). Clearly, a good understanding of the structure-reactivity relationships in different types of oximes as well as the actual intermediates involved would be very beneficial.

We recently reported on our initial photochemical studies involving a series of ortho-, meta-, and para-substituted acetophenone oximes (27). With the use of laser flash photolysis (LFP) it was shown that substituents have a significant effect on the initial electron transfer step. Triplet chloranil (^sup 3^CA) is rapidly quenched by the oxime (4 × 10^sup 7^ - 2 × 10^sup 10^M^sup -^ s^sup -1^). Correlation of the quenching rate constants with Hammett substituent coefficients suggested that steric, polar and radical effects are important for ortho-substituted acetophenone oximes, polar effects are important for para-substituted oximes, and radical stabilization is more important than polar effects for the meto-substituted substrates. Although these results seem consistent with an electron transferproton transfer sequence, it cannot be ruled out that the formation of the iminoxyl radicals proceeds via a hydrogen atom transfer (HAT) process (Fig. 1).

Free-radical processes are known to be sensitive to both radical and polar effects (28,29), which could explain the observations. One argument against a HAT process is the fact that the calculated bond dissociation energies in substituted acetophenone oximes were reported to be relatively independent of the substituent (30,31). Consequently, one would expect little effect on the HAT process by the substituent. The measured rates for quenching of triplet chloranil by the substituted acetophenone oximes showed a dramatic effect, suggesting a different process. However, the methodology that was used recently for obtaining the O-H bond strengths in substituted oximes was called into question. It was shown that as a result of these measurements significant deviations of certain bond strengths were obtained (32).