以X光繞射的方法研究物質的結構: 從結晶的予體-受體單體、半結晶的共聚物到共組裝的單一顆粒

Abstract

在本論文中，分別以X光二維纖維繞射與同調繞射成像研究予體-受體共聚高分子(PTh4FBT)和共組裝的單一顆粒(脂質囊)的結構。首先，為了引導結構建立的概念，超過四十種的予體-受體共軛分子的單晶結構被用來訂定其組成單元對其結晶形態的影響。這些單晶結構不只是顯示了其堆疊的傾向還顯示出了其分子構向的不定性。在緩慢生長的晶體中存在的分子構向的不定性顯示出要達到大範圍構向的一致是很有挑戰性的，因為其分子結構複雜而且分子是很容易扭曲的。 Th2FBT單晶結構確認了具FBT單元分子其分子構向的不定性。因為結晶的過程中Th2FBT的構向並不能統一，所以 PTh4FBT結晶態中分子內部之構向與分子之間的c方向上的滑移必須被審視。透過PTh4FBT的X光二維繞射的圖譜與由Cerius2模擬的二維圖譜可以得到PTh4FBT反式構向與分子在c方向上滑移程度的分子模型。在X光同調繞射成像研究上，利用X光自由電子雷射：SACLA，成功取得單一脂質囊在水中之同調共軛繞射成像，而脂質囊可分為包埋與未包埋阿黴素奈米顆粒的樣品，兩者都可以做結構的重建與取得定量結構的資訊，因此了解到包埋之阿黴素奈米顆粒的大小尺寸。最後以單一DNA分子的模擬同調共軛繞射成像，就目前的光源SACLA來說光通量仍要提高至108 倍與克服水的對比性差的問題，才可能實現原子級解析度的成像。

The thesis consists of two major parts: the first deals with the structure of semi-crystalline donor (D) - acceptor (A) conjugated copolymer (PTh4FBT) by X-ray 2D-fiber diffraction and the second deals with X-ray coherent diffraction imaging (XCDI) of single particle assembly (liposome) using X-ray free electron laser. In order to develop the sense for structure model building, first more than 40 crystal lattices of conjugated oligomers to identify the morphological influence of each building block on the D-A molecules are summarized. These lattice structures reveal not only the packing preferences of the conjugated oligomers but also the conformational disorder in the lattices. The presence of this disorder in slowly grown crystals implies that attaining total long-range conformational order is challenging for D-A oligomers, which are structurally complicated and readily distorted. The single crystal structure of Th2FBT confirms the low conformational preference of the FBT containing molecule. Since crystallization process does not assist to unify the conformation of Th2FBT, both intrachain conformation and interchain c-shifts in the crystalline state of PTh4FBT have to be scrutinized. Through comparing the X-ray 2D-fiber diffraction pattern of PTh4FBT, and the simulated patterns generated from Cerius2 molecular modeling, it was found that the diffration pattern generated from the lattice containing PTh4FBT with anti-conformation and limited interchain c-shift matches best with the experimental one. In the XCDI experiments, individual liposome particles in water, with or without inserted doxorubicin nanorods were studied at SACLA. In spite of the low X-ray scattering cross section, the diffracted intensity of blank (drug-free) liposomes was sufficient for spatial reconstruction to yield quantitative structural information. When the particles contained doxorubicin, the complex structural parameters of the nanorods can be clearly revealed. Finally, the simulation of single molecule DNA is performed. We show that the current photon flux at SACLA needs to be increased by 108 time in order to reach atomic resolution of the XCDI image.