The three-dimensional structure of 0,0',-N-trimethyl-d-tubocurarine, a neuromuscular blocking agent, has been determined by x-ray crystallography. This may help to provide insight into its pharmacologic action.d-Tubocurarine is a curare alkaloid that has been used for centuries by South American Indians to prepare poison arrows for hunting wild animals for food. Death results from respiratory paralysis and subsequent asphyxiation. Its major action is the interruption of transmission of a nerve impulse at the neuromuscular junction. This is thought to reflect complex formation between the drug and cholinergic receptors located at the postjunctional membrane, competitively blocking the transmitter action of acetylcholine (1). The bis-quaternary ammonium structure of d-tubocurarine and its more potent derivative, O,O',N-trimethyl-dtubocurarine (see Fig. 1), suggests that coulombic interaction occurs between the cationic centers of the drug and certain anionic groups of the receptor site, and that these, as well as stereo-specific van der Waals interactions, probably account for its binding specificity and biological activity.We report here the crystal and molecular structure of 0,0',-
The presence of four iodine atoms in the molecule of thyroxine directed our attention to the problem of determining its crystal structure.Samples of thyroxine and sodium thyroxine were kindly supplied by Dr A. B. Hems of Glaxo Laboratories, Greenford, Middlesex. As the DL-sodium salt was found to crystallize more readily and to form better crystals, it was decided to start work on that compound. Its chemical formula is I I I HO--~O-~,-CH2-CH(NH~)COONa • 5H~O.
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