Organisch Chemisches Institut, Universität Münster, Corrensstr. 40, D-48149 Münster, Germany.
Org Biomol Chem. 2012 Mar 14;10(10):2084-93. doi: 10.1039/c2ob06492h. Epub 2012 Jan 30.
Quantum chemical calculations (DFT, SCS-MP2) show that the relative energies of the four principal alanine conformations are only marginally altered by the introduction of a single fluorine substituent into the methyl group. The fluorine gauche effect and attractive interactions of fluorine to the O-H or N-H moieties (formation of hydrogen bridges) do stabilize particular conformers of 3-fluoroalanine. This is true for the neutral molecule both in the gas phase and in aqueous solution (CPCM-model), but also for the zwitterionic forms and the conformers of the related carboxylate ions and also for the respective ammonium ions in aqueous solution. In water (CPCM calculations), the zwitterion is almost equal in energy to the most stable conformer of the neutral 3-fluoroalanine. Compared to alanine the atomic charges of the amino group and the carboxyl function of 3-fluoroalanine are not significantly influenced by the fluorine at C3, which relates to the fact that both experimental pK(a) values are almost equal for alanine and 3-fluoroalanine.
量子化学计算（DFT、SCS-MP2）表明，在甲基中引入单个氟取代基仅略微改变四种主要丙氨酸构象的相对能量。氟 gauche 效应和氟与 O-H 或 N-H 部分的吸引力相互作用（形成氢键）确实稳定了 3-氟丙氨酸的特定构象。对于中性分子，无论是在气相还是在水溶液中（CPCM 模型），对于两性离子形式以及相关羧酸离子的构象以及在水溶液中的相应铵离子都是如此。在水中（CPCM 计算），两性离子的能量几乎与中性 3-氟丙氨酸最稳定的构象相等。与丙氨酸相比，3-氟丙氨酸的氨基和羧基官能团的原子电荷受 C3 上的氟的影响不大，这与实验 pK(a) 值对于丙氨酸和 3-氟丙氨酸几乎相等的事实有关。
