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Stereochemical Effects During [M - H]- Dissociations of Epimeric 11-OH-17β-Estradiols and Distant Electronic Effects of Substituents at C(11) Position on Gas Phase Acidity

par Bourgoin-Voillard, Sandrine;Zins, Emilie-Laure;Fournier, Françoise;Jacquot, Yves;Afonso, Carlos;Pèpe, Claude;Leclercq, Guy ;Tabet, Jean-Claude
Référence Journal of the American Society for Mass Spectrometry, 20, 12, page (2318-2333)
Publication Publié, 2009-12

Article révisé par les pairs

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Résumé :

The affinity of estradiol derivatives for the estrogen receptor (ER) depends strongly on nature and stereochemistry of substituents in C(11) position of the 17β-estradiol (I). In this work, the stereochemistry effects of the 11α-OH-17β-estradiol (IIIα) and 11β-OH-17β-estradiol (IIIβ) were investigated using CID experiments and gas-phase acidity (ΔH°acid) determination. The CID experiments showed that the steroids decompose via different pathways involving competitive dissociations with rate constants depending upon the α/β C(11) stereochemistry. It was shown that the fragmentations of both deprotonated [IIIα-H]- and [IIIβ-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 ΔH°acid of both epimers (IIIα and IIIβ), 17β-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: (IIIβ) ≫ (II) > (I) > (IIIα). Interestingly, the α/β C(11) stereochemistry appeared to influence strongly the gas-phase acidity. This phenomenon could be explained through stereospecific proton interaction with π-orbital cloud of A ring, which was confirmed by theoretical calculation. © 2009.