Hidden conjugates

The results of our calculations based on both the static and dynamic theories show that most of the nonbenzenoid cyclic conjugated systems examined exhibit in a greater or lesser degree a marked double-bond fixation. The static theory indicates that even in benzene there exists a hidden tendency to distort into a skewed structure and that such a tendency is actually realized in [4n-f-2] annulenes larger than a certain critical size. In nonalternant hydrocarbons bond distortion is a rather common phenomenon. Fulvenes, fulvalenes and certain peri-condensed nonalternant hydrocarbons undergo a first-order bond distortion, and... 

MCD measurements are useful not only in purely spectroscopic investigations, for example, in the detection of hidden absorption bands or for the identification of degenerate absorptions, but also in structural organic chemistry. There is, for instance, a rule that describes the influence of the molecular environment on the MCD effect of the n- r band of a ketone (Seamans et al., 1977 Linder et al., 1977). However, the method is clearly most useful for investigating cyclic conjugated n systems. 

SMR revision and practice at judging the states of compounds at different pHs. Hidden symmetry nom conjugation. 

With few exceptions, diagrammatic presentations of metabolic pathways for xenobiotics include a number of structures that are enclosed within brackets. This is the means by which the otetabolism chemist designates a proposed intermediate, or hidden metabolite, in that particular pathway. Often, the proposed intermediate is considered so transient in nature that its isolation would be impractical, if not impossible, and its reactivity so great that its occurrence as a terminal metabolite would be virtually inconceivable. When secondary metabolic processes are involved, these transient metabolites are referred to as hidden conjugates. These intermediate, transitory metabolites have their own chemical and toxicological properties and it is reasonable to assume that they may influence, at least in part, the toxic action of the parent xenobiotic. 

One of the most intriguing facets associated with the study of xenobiotic metabolism is the occasional discovery of metabolites whose pathways of formation defy logical explanation. One of the least intriguing is the report by a colleague that a major metabolite was overlooked in one s own study. Each of these situations may arise from what might be termed "hidden" metabolites. These hidden metabolites are common to both primary and secondary biotransformation processes, but this paper deals solely with the latter where the metabolite is referred to as a hidden conjugate. 

Perhaps the most common reason for the existence of hidden conjugates, especially in the past, is the failure of the analytical methods employed to detect total xenobiotic residues present in a sample. This problem has been solved to a great extent by the use of radiotracer techniques in xenobiotic investigations. Once its existence is established, the analytical chemist can usually isolate and identify the metabolite. This, however, does not mean that... 

While there may be additional causes for Che existence of hidden conjugates, Chose mentioned above will be addressed in this paper. What we do not know can hurt us, and the author is well aware Chat the most important hidden conjugates possibly have yet to be postulated. 

When conjugates are present in a sample extract but are insensitive to the analytical methods being utilized, they are indeed hidden from the analyst. Such was Che case in one of the first scientific projects in which Che present author participated. 

Figure 9. Identification of metabolites A through D in urine of rats treated with CDA led to the proposed hidden metabolites shown here in brackets. The reactive sulfate conjugate apparently undergoes glutathione conjugation, further metabolism via the mercapturic acid pathway and, finally, C-S cleavage, methylation and sulfur oxidation of C to yield D.

Figure 14- Hidden conjugates of quercetin, a naturally-occurring mutagen, are the glucuronide and sulfate derivative of isorhamnetin. These products are not present in the excreta of mammals but are biliary metabolites.

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