title: Stereochemical effects during [M-H]- dissociations of epimeric 11-OH-17beta-estradiols and distant electronic effects of substituents at C(11) position on gas phase acidity.
abstract: The affinity of estradiol derivatives for the estrogen receptor (ER) depends strongly on nature and stereochemistry of substituents in C(11) position of the 17beta-estradiol (I). In this work, the stereochemistry effects of the 11alpha-OH-17beta-estradiol (III(alpha)) and 11beta-OH-17beta-estradiol (III(beta)) were investigated using CID experiments and gas-phase acidity (DeltaH degrees (acid)) determination. The CID experiments showed that the steroids decompose via different pathways involving competitive dissociations with rate constants depending upon the alpha/beta C(11) stereochemistry. It was shown that the fragmentations of both deprotonated [III(alpha)-H]- and [III(beta)-H]- epimers were initiated by the deprotonation of the most acidic site, i.e. the phenolic hydroxyl at C(3). This view was confirmed by H/D exchange and double resonance experiments. Furthermore, the DeltaH degrees (acid) of both epimers (III(alpha) and III(beta)), 17beta-estradiol (I), and 17-desoxyestradiol (II) was determined using the extended Cooks' kinetic method. The resulting values allowed us to classify steroids as a function of their gas-phase acidity as follows: (III(beta)) >> (II) > (I) > (III(alpha)). Interestingly, the alpha/beta C(11) stereochemistry appeared to influence strongly the gas-phase acidity. This phenomenon could be explained through stereospecific proton interaction with pi-orbital cloud of A ring, which was confirmed by theoretical calculation.
authors.affiliation: Université Pierre et Marie Curie, UMR 7201, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bourgoin-Voillard
authors.forename: Emilie-Laure
authors.initials: EL
authors.lastname: Zins
authors.forename: Françoise
authors.initials: F
authors.lastname: Fournier
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
authors.forename: Carlos
authors.initials: C
authors.lastname: Afonso
authors.forename: Claude
authors.initials: C
authors.lastname: Pèpe
authors.forename: Guy
authors.initials: G
authors.lastname: Leclercq
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tabet
mesh_terms: D004579:Electron Transport; D004958:Estradiol / Q000032:analysis* / Q000737:chemistry*; D005740:Gases / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D044367:Phase Transition; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D005740:Gases; D004958:Estradiol