Modification of Estradiol at the 17-Position. Effect of Changing the OH Group for a Transition-Metal Carbonyl Cluster on the Estradiol Receptor Recognition

The reaction of [Co₂(CO)₆(17α-ethynyl-17β-estradiol)] (2a) with Fe(CO)₅ in acetone produces [FeCo(CO)₆(17α-ethynyl-17β-dehydroxyestradiol)] (3a) as the result of the dehydroxylation ability of the iron pentacarbonyl. The molecular structure of 3a has been investigated not only by NMR spectroscopy but also by use of molecular modeling techniques. The structural data for the organometallic part of the molecule are derived from a single-crystal X-ray determination of the model complex [FeCo(CO)₅(PPh₃)(H₃CC₂CH₂)], carried out at 123 K: triclinic, P1 (No. 2), a = 10.315(1) Å, b = 10.579(1) Å, c = 12.989(2) Å, α = 67.62(1)°, β = 89.44(2)°, γ = 79.30(2)°, V = 1287.1(7) ų, Z = 2, R_F = 0.063. The mixed-metal cluster [FeCo(CO)₆(HCCCH₂)] was used as a model of the cation [Co₂(CO)₆(HCCCH₂)]⁺, and its structure was rationalized by means of extended Hückel molecular orbital calculations. The biological results obtained from the incubation in vitro of the steroid–organometallic complex 3a with lamb uterine cytosol (used as a source of estradiol receptor) indicate that the absence of the 17-OH group on estradiol prevents the formation of an irreversible (covalent) bond between the metal-labeled steroid and its specific receptor. The biochemical implications of such a change in reactivity are discussed.