Synthesis and receptor binding of polynuclear organometallic estradiol derivatives

Abstract

Twelve novel organometallic derivatives of estradiol were synthesized with the aim of utilizing organometallic cold bioprobes as radioisotopic labels substitutes for steroid hormone receptor assays. For this purpose, we envisaged the attachment of several stable cobalt, molybdenum, osmium carbonyl clusters (tetra- and pentanuclear species) at estradiol 17α-, 16α-, 2- or 4- positions. The binding affinity of these new complexes for uterine estradiol receptor has been measured by the competitive binding method. The results show that the 17α- position can tolerate substitution by bulky organometallic groups (especially in the case of cobalt and molybdenum carbonyl clusters). Estradiol derivatives which are functionalized at C-4 and C-16α bind estradiol receptor with reasonable affinity and the RBA values are the same for the complexed and uncomplexed hormones. The 2-position is more sensitive to organometallic substitution and the complexation at the 2-alkyne results in a dramatic decrease of the RBA values. These results show that the attachment of polynuclear moieties in estradiol 17α-, 4- and 16α-, positions gives rise to compounds which are of potential utility in a new non-radioisotopic receptor assay since the metal-carbonyl markers are readily detected by high-sensitivity Fourier-transform infra-red spectroscopy.