Molecular structure of thyroxine analogs. Crystal structure of 3,5,3'-triiodothyroacetic and 3,5,3'.5'-tetraiodothyroacetic acid N-diethanolamine (1:1) complexes

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Abstract
Crystallographic data demonstrate that conformations of thyroid hormones and their derivatives in which the phenyl rings are skewed (.vphi. .vphi.''; .+-. 90,0.degree.) or twist-skewed (.vphi..vphi.''; .+-. 108, .+-. 28.degree.) are energetically favored. Acetic acid metabolites are consistently observed in the skewed conformation, whereas their parent hormones are observed in the twist-skewed conformation. These preferences are manifestations of long-range conformational transmission and together with plasma protein binding data may indicate a site-specific preference for the skewed vs. twist-skewed conformation. These findings result in part from crystal structure determinations of the N-diethanolamine (1:1) complexes of the active thyroxine metabolites 3,5,3''-triiodothyroacetic acid (T3AA) 3,5,3'',5''-tetraiodothyroacetic acid (T4AA) which are reported here. The conformation of the 3''-iodine in the hypocholesteremic agent T3AA is distal, the biologically preferred conformation, and the overall conformation of T3AA is transoid, while that of T4AA is cisoid.