| 摘要: | 在材料科學中，對掌性質在材料的開發上是被忽略的。但最近利用光導及電激方法在手性分子形狀控制和機構上的進展，對於開發新穎材料在於分子辨認、光學及機械性質方面上，提供可能性。單一手性分子的持續研究和藥物市場是同等重要的，延長那些已被開發的外消旋化合物中的單一手性分子之產品生命週期，對於藥廠的是一個很重要的策略。而這個策略將會變成藥廠抵制製作非專利藥公司的重要工具。因此，我們的研究目標是在於如何利用單一手性分子來產生單一手性化合物時，所伴隨的化學方法來操作結晶動力學，打破對掌性的障礙。關於外消旋分子一些基本的結晶動力學參數例如像：誘導時間(τ)、表面能(γ)、吉布士能障(ΔGcr)、成核速率(J)、穩定晶核的臨界大小(rc)、結晶質量的成長速率(RG)、能量係數(g)、同質異構、晶貌及被用來估計終點的不同之起始超飽和比例(S0)等，在不同單一手性的情況下被互相比較。結晶的過程能夠藉由程序分析技術，像是電導或者是聚焦光束反射測量儀來追蹤；對掌異構物的分離可以藉由高效能液相層析儀來達成；同質異構物可藉由差示掃描量熱法來分析，藉由光學顯微鏡和晶體結構預測軟體來分析晶貌。目前我們主要研究的系統，是著重在依普和它的鹽類，但是類似這種非對稱性結晶動力學的研究將會被延伸到胺基酸和糖類，也許針對生物界裡極具爭議性的「為何生物體內只有單一手性分子存在？」之議題，可以提供新的觀點。而膽固醇的結晶動力學之研究，可以為抑制膽結石的形成、動脈硬化，提供一個新預防方法。 ; In material science, chirality has been ignored or avoided in the development of new materials. But recent advances in the development of mechanisms to control the shape and properties of chiral molecules by photo-induction and electrical-trigger offer the potential for development of novel materials in molecular recognition, optical or mechanical properties. On an equal footing is the constant growth of single-enantiomer drugs at a similar rate as the pharmaceutical market. One important strategy to improve the bottom lines of drug companies is to extend the profitable life of products by re-developing single-enantiomer forms of drugs that had been approved as racemates. This strategy has become one of the major defensive tools of pharmaceutical companies against generic drug-makers. Therefore, our immediate research goal is to break the chiral barrier by chemically manipulating crystallization kinetics with the use of homochiral molecules to yield enantiopure products. Fundamental parameters of the crystallization kinetics of racemic species, such as the induction time, , the interfacial energy, , the Gibbs energetic barrier, ΔGcr, the nucleation rate, J, the critical size of stable nuclei, rc, the crystal mass growth rate, RG, the power number, g, polymorphism, crystal habit and the end-point will be evaluated with different initial supersaturation ratio, S0, and compared under the effects of different kinds of homochiral molecules. The crystallization event will be followed by process analytical techniques such as electrical conductance or focused beam reflectance measurements (FBRM). Chiral resolution will analyzed by high performance liquid chromatography, polymorphism by differential scanning calorimetry, crystal habit by optical microscopy and crystal morphology predictor such as Cerius2. For the time being, our model system is ibuprofen and its salts. But, similar study in asymmetric crystallization kinetics will be extended to amino acid building blocks and sugar which may provide new insight into the much debated origin of the homochirality of the biological world. Crystallization kinetics study on cholesterol may even point to the ways for preventing the formation of gallstones and atherosclerotic plaques. 表 ; 研究期間 9708 ~ 9807 |
