Zhou L, Thompson R A, Ellison D K, Locke D C
Analytical Research Department, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA.
J Capillary Electrophor. 1997 Nov-Dec;4(6):279-85.
Aminoindanol poses an interesting separation problem because it contains two chiral centers and exists as four stereoisomers. The capillary electrophoretic separation of the cis- and the larger trans-diastereomers of aminoindanol is simply achieved by pH control of the tris buffer background electrolyte. In accordance with theory, maximum separation occurs at the pH equal to the mean value of the pKA values of the isomers. The separation of the enantiomers of both the cis- and trans-diastereomers is effected using the chiral selector alpha-cyclodextrin (alpha-CD). The cis-enantiomeric pair is better separated than the trans-pair, as reflected by the larger difference in the binding constants, K, for the cis-enantiomers with the alpha-CD, K values were measured from the change in electrophoretic mobility with selector concentration, over the temperature range 15 degrees C-35 degrees C. The associated delta H degrees and delta S degrees values were determined for the transfer of each enantiomer from the aqueous buffer phase to the alpha-CD phase. The corresponding K values and associated thermodynamic quantities were also measured for the aminoindan enantiomers, which lack the hydroxyl group of aminoindanol. The effect of chiral selector size was evaluated for the aminoindanols by measuring K and the associated values using beta-CD, which has a larger cavity than the alpha-CD. The better fit of the larger trans-isomers leads to larger K values for the trans-isomers but reduced Ks for the cis-. The gamma-CD cavity is too large to produce chiral discrimination. The low solubility of the beta-CD requires the addition of high concentrations of urea to the tris buffer. Urea has little effect on the K values of the trans-aminoindanols with alpha-CD, but leads to larger values for the cis-isomers.
氨基茚满带来了一个有趣的分离问题，因为它含有两个手性中心，以四种立体异构体的形式存在。通过控制三羟甲基氨基甲烷（Tris）缓冲背景电解质的pH值，可轻松实现氨基茚满顺式和较大的反式非对映异构体的毛细管电泳分离。根据理论，在pH值等于异构体pKA值的平均值时，分离效果最佳。使用手性选择剂α-环糊精（α-CD）对顺式和反式非对映异构体的对映体进行分离。顺式对映体对的分离效果优于反式对映体对，这反映在顺式对映体与α-CD的结合常数K的差异更大上，K值是通过在15℃至35℃的温度范围内，随着选择剂浓度变化的电泳迁移率变化来测量的。测定了每种对映体从水缓冲相转移到α-CD相时的相关焓变（ΔH°）和熵变（ΔS°）值。还测量了缺少氨基茚满羟基的氨基茚对映体的相应K值和相关的热力学量。通过使用比α-CD具有更大空腔的β-环糊精测量K及其相关值，评估了手性选择剂大小对氨基茚醇的影响。较大的反式异构体的更好匹配导致反式异构体的K值更大，但顺式异构体的K值降低。γ-环糊精的空腔太大，无法产生手性识别。β-环糊精的低溶解度要求在Tris缓冲液中加入高浓度的尿素。尿素对反式氨基茚醇与α-CD的K值影响不大，但会导致顺式异构体的K值更大。
