Major fecal metabolite of dieldrin in rat. Structure and chemistry

Abstract

The structure (C-12 jy «-hydroxy dieldrin) of the major fecal metabolite of dieldrin in the rat has been confirmed via pmr spectroscopy employing spin decoupling techniques and the new shift reagent, Eu(DPM)3. Detailed studies of the spectral and reaction properties of this metabolite have established the stereochemical structure and have shown that the system is susceptible to degradation. Evidence is presented which indicates that the major fecal metabolite in the rat cannot be converted to the major urinary metabolite but that a common intermediate hybrid ion (or radical) may exist in their formation from dieldrin. It is proposed that an activated dieldrin molecule may mimic certain male steroidal hormones or their precursors in regard to the capability of anchimeric participation of a double bond. Studiesof the metabolism and other degradative proc-I esses of dieldrin (I) continue to be complicated by difficulties in the unequivocal identification of the transformation products which generally require stereochemical structure proof. This difficulty in making positive structure assignments seems to be primarily due to the lack of substantial spectral and chemical data on related strained model systems. The only metabolite of dieldrin whose structure is unequivocal, having been confirmed by synthesis, is that of Zra«s-4,5-dihydroxy-4,5-dihydroaldrin. [The numbering system used herein for these compounds complies with that suggested by Benson (1969).] Since this metabolite was reported (Korte and Arent, 1965) to possess optical activity, it would be one of the enantiomers of this structure. Recent investigations in our laboratory (McKinney et al., 1971) employing proton magnetic resonance (pmr) spectroscopy including decoupling experiments and sample treatment with the new pmr shift reagent, tris(dipivalomethanato)europium [Eu(DPM)3], enabled the rapid and accurate stereochemical structure determination of some postulated chlorinated polycyclodiene pesticide metabolites.The purpose of this work was to test first the applicability of this pmr method for positive structure assignment of the major fecal metabolite of dieldrin in the rat for which most recent investigators (Baldwin et al., 1970a) have assigned structure II. Secondly, structure confirmation of this metabolite would render its conversion reactions more predictable, and since it is the primary metabolite excreted by the rat, its toxicological meaning in relation to the problems of environmental contamination should be carefully assessed. As a working hypothesis in the chemical studies, it was thought that if the assignment of the position of hydroxylation of dieldrin to the ostensibly aliphatic C-12 methylene group was correct and, if this hydroxyl group had a syn relationship to the epoxide group, conjugation or any other similarly activating derivatization would enable a rather facile rearrangement to occur with the formation of a bridged ketone of identical structure (III) to that proposed (Damico et al., 1968b) for the major urinary metabolite of d...

Carbon-13 Fourier transform nuclear magnetic resonance with tris(1,1,1,2,2,3,3-heptafluoro-7,7,-dimethyloctane-4,6-dionato)europium(III) for configurational confirmation of polychlorinated pesticides, endrin and dieldrin

“…For pesticides that have carbon atoms devoid of protons (such as the reactive chlorinated end of endrin or dieldrin) the pmr technique alone is clearly inadequate even though it has been widely used for this purpose (Parsons and Moore (1966), Marchand and Rose (1968), Bukowski and Cisak (1968), McCullock et al (1969), and ). Keith (1971) and McKinney et al (1972), in an effort to study degradation reactions of some pesticides, have implemented the use of pmr spectroscopy by employing additional techniques such as proton spin decoupling and a chemical-shift reagent, Eu(dpm)s, tris(dipivalomethanato)europium(III). These studies, while accurately describing the structural features of that portion of the molecule containing protons, yielded no information whatever concerning the crucial chlorinated section of the molecule.…”