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 (III_α) and 11β-OH-17β-estradiol (III_β) 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 [III_α-H]⁻ and [III_β-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 (III_α and III_β), 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: (III_β)≫(II)>(I)>(III_α). 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.

雌二醇衍生物对雌激素受体 (ER) 的亲和力在很大程度上取决于17β-雌二醇 ( I ) 的C ₍₁₁₎位取代基的性质和立体化学。在这项工作中，使用 CID 实验和气相酸度 (ΔH_酸^∘ ) 测定研究了 11α-OH-17β-雌二醇 (III _α ) 和 11β-OH-17β-雌二醇 (III _β )的立体化学效应。CID 实验表明，类固醇通过不同的途径分解，包括竞争性解离，速率常数取决于 α/β C ₍₁₁₎立体化学。结果表明，两者的碎片都去质子化 [III _α -H] ^- 和 [III _β -H] ^-差向异构体由最酸性位点的去质子化引发，即 C ₍₃₎处的酚羟基。这一观点得到了 H/D 交换和双共振实验的证实。此外，ΔH_酸^∘两个差向异构体（III的_α和III _β），17β雌二醇（我），和17-desoxyestradiol（II）中的溶液使用扩展厨师动力学方法测定。结果值使我们能够将类固醇作为其气相酸度的函数进行分类，如下所示：(III _β )≫( II )>( I )>(III _α )。有趣的是，α/β C ₍₁₁₎立体化学似乎强烈影响气相酸度。这种现象可以通过立体定向质子与A环的π轨道云相互作用来解释，理论计算证实了这一点。