Synthesis and binding affinities of new 17α-substituted estradiol-rhenium “n+1” mixed-ligand and thioether-carbonyl complexes

Abstract

The development of technetium and rhenium-based radiotracers for the steroid receptor system requires the use of suitable donor groups on the steroid to provide stable binding sites for the metal. Previous approaches have mainly exploited methods involving various N- and S-coordinating chelate systems or organometallic complexes. In this work, we have prepared several novel chelate systems attached to a series of 17α-substituted estradiol derivatives and examined their binding to the estrogen receptor (ER). The neutral “n+1” mixed-ligand and dithioether-carbonyl complexes that we prepared contain the metal in three oxidation states, +5, +3 or +1, attached to a 17α-substituted estradiol derivative through a thiol group, an isocyanide group, or a dithioether unit, respectively. In our preliminary investigations, we used rhenium as a nonradioactive analog of the radionuclide technetium. All complexes synthesized were evaluated in a competitive radiometric receptor binding assay at 0°C and 25°C to determine their relative binding affinities (RBA) to the ER (relative to 3,17β-estradiol, RBA = 100%). The complexes show binding affinities up to 23.4% at 0°C and 14.1% at 25°C.