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

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TitleStereochemical Effects During M-H (-) Dissociations of Epimeric 11-OH-17 beta-Estradiols and Distant Electronic Effects of Substituents at C-(11) Position on Gas Phase Acidity
Publication TypeJournal Article
Year of Publication2009
AuthorsBourgoin-Voillard, S, Zins EL, Fournier F, Jacquot Y, Afonso C, Pepe C, Leclercq G, Tabet JC
JournalJournal of the American Society for Mass Spectrometry
Volume20
Issue12
Pagination2318-2333
Date PublishedDec
ISBN Number1044-0305
Accession NumberISI:000272628200018
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 17 beta-estradiol (I). In this work, the stereochemistry effects of the 11 alpha-OH-17 beta-estradiol (III alpha) and 11 beta-OH-17 beta-estradiol (III beta) were investigated using CID experiments and gas-phase acidity (Delta H 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 Delta H degrees(acid) of both epimers (III alpha and III beta), 17 beta-estradiol (I), and 17-desoxyestradiol (11) 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. (J Am Soc Mass Spectrom 2009, 20, 2318-2333) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry

URL<Go to ISI>://000272628200018
DOI10.1016/j.jasms.2009.08.017
Short TitleStereochemical Effects During M-H (-) Dissociations of Epimeric 11-OH-17 beta-Estradiols and Distant Electronic Effects of Substituents at C-(11) Position on Gas Phase Acidity
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