| Abstract
| - The hydrogen-bond acceptor properties of progesterone have been investigated in vacuo with theoreticalcalculations, in solution by FTIR spectrometry and with octanol−water partition coefficients, and in the solidstate through the Cambridge Structural Database. When progesterone is in vacuo, the electrostatic potentialspreads more widely than that of O20 and is more negative by 6.8 kcal mol-1 around O3; the O3 lone-pairelectron ionization energy is lower by 0.11 eV, and consequently, the hydrogen-bonded water−O3 complexis more stable by 2.8 kJ mol-1 at 0 K. In CCl4 at 298 K, the hydrogen bonding of a phenol to O3 is morefavorable than hydrogen bonding of a phenol to O20 by 3.1 and 3.6 kJ mol-1 on the Gibbs energy and enthalpyscales, respectively. In pure hexafluoro-2-propanol, higher basicity and lower steric hindrance allows O3 tobe a triple-hydrogen-bond acceptor, while O20 is at most a double acceptor. The higher hydrogen-bond basicityand coordination number of O3 compared to those of O20 explain the octanol−water partition of progesterone.In the solid state, O3-bonded water molecules exhibit a characteristic network of hydrogen bonds, and wefind (i) more frequent hydrogen-bonded contacts to O3, (ii) longer C3O bonds in the complexes, and (iii)shorter and more linear OH···O3 hydrogen bonds. These in vitro geometric and thermodynamic hydrogenbonding parameters agree well with the hydrogen bonding of progesterone to its human receptor.
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