Flexibility at the Fringes: Conformations of the Steroid Hormone β-Estradiol

We present the accurate experimental structure of the steroid hormone β-estradiol obtained with high-resolution rotational spectroscopy under the solvent free, isolated, and cold conditions of a molecular jet. This is the first time that the rotational signature of a steroid hormone is reported. β-Estradiol is a primary female sex hormone and features a rigid steroidal ring system. Three conformers could be identified in the cold environment of a supersonic molecular jet, which only differ in the orientation of the two hydroxy groups attached to the steroidal backbone. The conformers are almost isoenergetic and have very similar rotational constants but still could be clearly resolved and assigned. The high sensitivity of the technique allowed us to record and identify all singly substituted ¹³ C isotopologues in natural abundance for the dominant conformer. The additional spectroscopic constants led to an accurate determination of its experimental molecular structure. Along with a previous comparison of β-estradiol structures in the solid state and the liquid phase, this study completes the investigations in all three main phases by providing the interaction free gas-phase structure.