以硫酸鹽衍生化環糊精為對掌選擇劑對 硫利達嗪藥物分離之毛細管電泳動態學

Enantiomerization of Thioridazine in Dynamic Capillary Electrophoresis Using Sulfated Cyclodextrins as Chiral Selectors

柯廷璋(Ting-Chang Ko)

指導教授 ： 林萬寅

國立臺灣大學/理學院/化學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.01285

摘要

本篇論文以毛細管區帶電泳法探討抗精神病藥物硫利達嗪(thioridazine)對掌異構物間的動態學。
第一部分為在反向電壓、低pH值緩衝液環境下，以含有7~11個硫酸根取代基的硫酸鹽衍生化環糊精(MI-S-b-CD)為對掌選擇劑分離分析物對掌異構物。結果顯示，在對掌異構物的波峰之間出現一個不尋常的平台。此平台為對掌異構物之間的轉換所形成。藉由測量不同溫度的平台高度、對掌異構物訊號的半高寬以及相對高度，經由軟體ChromWin2005與DCXplore的應用，可以計算出不同溫度下的反應速率常數，進而求得ΔH ≠、ΔS≠、ΔG≠298K等活化參數。在15 oC~25 oC間，平台的高度隨溫度增加而上升，但在27 oC~33 oC間平台的高度已不再增加，甚至在33 oC以後，平台的高度反而隨著溫度的上升而下降，此現象顯示分析物的對掌異構轉換過程中，會隨著溫度的升高而涉及其他化學反應的參與。
第二部分則以其他種類的環糊精等對掌選擇劑來分離分析物的對掌異構物，探討不同對掌選擇劑對分析物對掌異構化動態學的影響，與MI-S-b-CD分離的結果做比較。而除了S-b-CD (18)之外，其他的對掌選擇劑進行分離時，則沒有平台的訊號產生。此結果顯示對掌異構物間的轉換，與所使用特定的對掌選擇劑有關，也意謂S-b-CD的硫酸根取代基位置與取代基數目在thioridazine的對掌異構化扮演著重要的角色。

關鍵字

對掌異構化 ； 毛細管電泳動態學 ； 硫利達嗪硫酸鹽衍生化環糊精

並列摘要

In this study, we investigated the enationmerization reaction of thioridazine, a commonly prescribed phenothiazine neuroleptic drug, in dynamic capillary zone electrophoresis.
In the first part, the reversed voltage was applied with citrate buffer at low pH using randomly (degree of substitution: 7~11) sulfated -substituted beta-cyclodextrin (MI-S-b-CD) as chiral selectors and the enantiomers of thioridazine could be well-resolved. Interestingly, an unusual plateau signal was observed between the two enantiomeric peaks. The plateau height which depends on the temperature is an indication of a rapid interconversion of the enantiomers. With the plateau height, relative peak height and the peak widths at half height of each individual enatiomeric peak at different temperatures as parameters, the rate constants and dynamic parameters (ΔH≠, ΔS≠, and ΔG≠298K) of enationmerization can be evaluated using software ChromWin2005 and DcXplore. In the temperature range between 15 oC and 25 oC, the plateau height increases with increasing temperature. However, in the temperature range between 33 oC and 45 oC, the plateau height decreases with increasing temperature. The results reveal that additional chemical reactions other than the enantiomerization of thioridazine are involved.
In the second part, other types of chiral selectors were used for enantioseperation of thioridazine in order to compare with the MI-S-b-CD system. We found that, with the use of other chiral selectors, except for the S-b-CD (18) system, the formation of plateau in the enantioseperation of thioridazine could not be observed. The results reveal that the position, as well as the number, of sulfate substituent of S-b-CD plays an important role in the enantiomerization reaction of thioridazine.

並列關鍵字

enantiomerization ； dynamic capillary electrophoresis ； thioridazine ； sulfated cyclodextrin ； chiral selectors ； activation parameters ； plateau

參考文獻

7. Lin, C. E.; Chen, K. H.; Liao, W. S.; Lin, W. Y.; Hsiao, Y. Y. J. Chromatogr. A 2002, 979, 399.

10. Liao, W. S.; Lin, C. H.; Chen, C. Y.; Kuo, C. M.; Liu, Y. C.; Wu, J. C.; Lin, C. E. Electrophoresis 2007, 28, 3922.

2. A. Tiselus, Trans. Faraday. Soc. 1937, 33, 524.

3. J. Knox, Chromatographia 1988, 26, 329.

4. S. Hjerten, Chromatogr. Rev. 1967, 9, 122.