Elizabeth P. Burrows

Organic Explosives and Related Compounds

For much of this century production and usage of explosives and propellants have been responsible for release to the environment of a variety of energetic organic nitro compounds. This chapter covers the compounds of greatest importance; their uses are indicated and methods for their manufacture or laboratory synthesis are summarized. Those physicochemical properties of greatest utility in environmental risk assessment are identified and listed. Analytical methods are described briefly, with references given to more detailed literature. For the more extensively studied compounds, the microbiological and chemical transformations known to take place in the laboratory and in the environment and the metabolic transformations observed in animals and man are discussed. Toxic manifestations in mammals, humans, fish and other aquatic organisms, as well as threshold levels for these effects, are summarized. While the process of utilization of available experimental data to develop criteria and standards to assure protection of human health and preservation of the biosphere is in its infancy and changing rapidly, a short summary of criteria currently accepted in the U.S. for certain of the munitions compounds is presented.

[34] Synthesis of affinity labels for steroid-receptor proteins

Publisher Summary The general considerations underlying active-site-directed irreversible enzyme inhibition (affinity labeling of enzymes) have been applied to the study of steroid-binding proteins, restricting attention to cytoplasmic androgen and progestagen receptors. There are two requisites for the affinity labeling of a steroid receptor. The steroid must bind reversibly at the active site of the receptor and possess a functional group capable of forming a covalent bond with an amino acid residue either within (endo) or adjacent to (exo) the binding site. The first requisite seems relatively easy to fulfill. The progesterone receptor of chick oviduct forms a highly stable (k d ∼ 10 -10 ) complex with progesterone and competition studies show that other steroids form complexes somewhat less stable but with k d ∼ 10 -10 . Thus, in the absence of progesterone, the progesterone-binding protein should strongly bind other steroids. The second requisite is more difficult. The amino acids in the polypeptide chain at the binding site are not known. Cysteine may be one because it has been shown for both a rat prostate 5α-dihydrotestosterone receptor and the chick oviduct progesterone receptor that sulfhydryl groups are involved either in the binding of the steroid to the receptor or in the maintenance of the active structure of the protein. It is assumed that one or both of the oxygen functions of 5α-dihydrotestosterone (C-3 and C-17) and of progesterone (C-3 and C-20) is involved in binding. A reactive substituent at a position near one of these oxygen functions would probably be closer to the polypeptide chain in the steroid–receptor complex than a more remotely positioned substituent and consequently would be more likely to undergo reaction. Four general classes of chemical reactions that are used in attempts at affinity labeling apply here such as alkylation reactions, photochemical insertion reactions, disulfide bond formation, and mercaptide bond formation.