Structure searching rationale

Our goal in this discussion is to present the types of structural variations that have been studied in the various classes of hallucinogens and to explain how these changes affect biologic activity. Where possible, reasonable explanations for these differences are offered. Since we are just beginning to scratch the surface in our search for useful structure-activity relationships, the reader will soon note that most of the correlations are empirical, with no readily apparent biochemical or pharmacologic rationale. 

It is time to reflect on how well VSEPR satisfies the criteria for a successful bonding theory. Since it combines the features of Lewis dot structures (molecular formula) with a geometric prediction, we fulfill two of the three requirements, but we still have not answered the major question, that is, What is the rationale for bonding Our search must continue. 

In this chapter, a rationale of the structure-activity relationships of various series of bioactive secondary metabolites from Indo-Pacific marine invertebrates is reviewed. These include alkaloids, terpenes and polybrominated diphenyl ethers which were subjected to a series of bioassays in search for insecticidal, antibacterial, fungicidal, and cytotoxic lead compounds. From these various biotests, it was observed that the bioactivity of an analogue is not due to general toxicity but rather possesses a degree of specificity on a particular target biomolecule. The relationship between chemical structures and biological activity is related to the specific action of a compound. 

Obviously, the search for the active sites of a reaction is a very involved task requiring the concerted application of various techniques to well-selected catalytic materials, desirably under reaction conditions. Even then progress toward reliable identification of the responsible structures may be slow due to the complexity of the catalytic surfaces. There is, however, an additional rationale for such research, because the data generated are often of considerable value for practical catalyst development. Therefore, the literature is full of opinions about active sites on catalysts for various reactions, which may be everything from well-supported proposals down to mere speculation. 

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