Conformational analysis of erythrosine B (FD&C Red No. 3) and its comparison with thyroid hormone structures

Erythrosine B, also known as FD&C Red No. 3, is a tetraiodofluorescein dye that is widely used as a biological stain and color additive in food and drugs. Recent data show that erythrosine B and Rose Bengal, its polychlorophenyl derivative, are potent inhibitors of both 5'-T4 and 5-T4 monoiododeiodinase activity. However, fluorescein, the nonhalogenated parent compound, has no effect on deiodinase activity. The X-ray crystal structure of erythrosine B was determined to elucidate the structural basis for its competition with T4 for its hormone protein binding sites. These structural results show that the dye crystallizes as a free acid-ethanol solvate. The relative orientation of the benzoic acid and xanthine moieties is nearly perpendicular, similar to that observed in the structure of fluorescein. As frequently noted in thyroid hormone structures, there are short I...I and I...O contact distances in this structure. Because of the symmetric iodophenolic substitution pattern of the xanthine ring, there will always be one iodophenolic ring that is not homologous with the thyroid hormone structure. Therefore, this analysis suggests that the best conformational homology is achieved when the dye phenolic ring is matched with that of a skewed thyroid hormone structure.