Distal conformation of thyroid hormones. The crystal structure of 3,5,3′-triiodothyroacetic acid N-diethanolamine (1:1) complex

In the crystal structure of a complex of the hypocholesteremic thyromimetic agent, 3,5,3′-triiodothyroacetic acid and N-diethanolamine (1:1), the 3′-iodine is observed for the first time in the distal position, away from the α-ring of the diphenyl ether portion of a thyroactive analogue of thyroxine. This result was anticipated from stereochemical and biological activity studies. However, previous observations of structures in which the 3′-iodine was proximal had cast some doubt on the stability of the 3′-distal conformation. The present evidence now suggests that the relative energies of the two conformers are similar and that both conformers are readily accessible in solution.