The molecular structure of 16α-iodo-17β-estradiol, a high affinity ligand for the estrogen receptor

16α-Iodoestradiol is an estrogenic steroid with high affinity for the estrogen receptor. When labelled with a gamma emitting isotope, such as ¹²⁵I, the resulting radioactive steroid is an excellent ligand for the sensitive analysis of the estrogen receptor. The X-ray study of the crystal structure of 16α-iodoestradiol reveals that the bond distances and angles of the iodinated estrogen are similar to those of estradiol and estriol. The substitution of iodine for the 16α-hydroxyl group has little effect on geometric and electronic properties of the molecule and does not interfere with the hydrogen bonding ability of the 17β-hydroxyl group. The difference in receptor binding affinity between 16α-estradiol and estriol may be due to competition for intermolecular hydrogen bond formation between the hydroxyls at C(16) and C(17) on estriol. X-Ray data indicate that the 16-hydroxyl can form significantly shorter and presumably stronger hydrogen bonds.