藉由互補性核甘酸鹼基對作用力製備超分子型高分子

Abstract

近年來，超分子作用力己拓展至形成配位型高分子結構，最好的例子即是生物體中的DNA核甘酸鹼基對之互補性作用力有效操控奈米生物分子自組裝（self-assembly）的型態；無庸置疑的“探索自然，學習自然”嚴然成為下世代的研究主軸，現今唯有徹底探討生物體之間有序排列的機制，由分子等級的尺度去影響更高階層的結構，才能有助於現今奈米技術的突破及成長。 本研究中，我們合成出三種新型以核甘酸為主之超分子型高分子，並且加以研究這些高分子在固態的自組裝行為及結構： (1) 生物互補性作用力行為於DNA-like 及RNA-like 高分子中之研究 DNA-Like Polymer與互補性分子進行氫鍵自組裝，可有效操控層間之大小，且皆呈現有序規則之層狀(lamellar)結構排列，這是一藉由生物官能基控制高分子奈米型態之技術。此外，我們也進一步設計相關分子結構並深入探討DNA-Like與RNA-Like Polymers氫鍵作用力的強弱。由實驗結果發現，不管是在DNA或RNA的錯合系統中，高分子的物理性質皆明顯提升，且RNA作用力會微高於DNA作用力，此結果是首度探討於高分子系統中，藉由RNA及DNA生物官能基控制高分子物理特性之重要實例。 (2) 有機/無機超分子材料 將自身互補性氫鍵作用力對之生物鹼基對導入POSS奈米結構中，形成星狀結構的有機/無機奈米複合材料，由實驗過程發現，生物鹼基對之間的自身氫鍵作用力會形成網狀物理交聯的結構，因此有效提升成膜之特性；我們進一步探討機械性質時發現，不僅優於傳統高分子(如Polyurethane及Polyethylene)，且具有更好之加工特質。藉由此精準結構之Macromer與多點氫鍵作用力結合的概念，製備出具有Polymer-like性質的超分子膜，極有潛力應用於高分子相關領域上。 (3) 具有互補型六點氫鍵作用力之新穎生物型超分子材料 杜邦工程師 Dr. Carothers 發表縮合聚合理論至今己79年，超分子科學與縮合聚合理論結合極有可能是建立下一世代的新高分子材料，藉由近年來本實驗室在生物互補性氫鍵作用力的基礎，我們也發展出一個生物自身互補型六點氫鍵作用力的官能基，作用力常數(association constant, Ka)超過10-7 M-1，且此互補性作用力幾乎不受溫度變化而影響，這是一個高Ka且易控制的作用力官能基。我們正積極開發在不同高分子上，藉此操控高分子的特性，並積極探索超分子聚合反應(supramolecular polymerization)的基礎理論，以迎合下一世代材料與技術的接軌。

In recent years, a number of supramolecular interactions have been developed and explored for the formation of complex macromolecular architectures. A perfect example can be found in nature with the nucleobase pairs of DNA. It has attracted great attention recently because novel structural organizations can be formed through highly complementary nucleobase recognition. For example, self-assembly mediated by hydrogen bonding allows DNA-like polymer chains to rapidly form functionalizable materials exhibiting unique physical properties, such as high specificity, controlled affinity, and reversibility. Nevertheless, controlling the secondary (and higher) structures of synthetic polymers remains a challenging task. Indeed, the synthesis of well-defined polymer architectures is currently quite inefficient when compared to the level of control found in biomaterials, which efficiently program the formation of higher structures at the molecular level. In this thesis, we synthesized three kinds of novel nucleobase-based supramolecular polymers and investigated their self-assembled arrays and nanostructures in sold-states: (1) Biocomplementary Interaction Behavior in DNA-like and RNA-like Polymers We synthesized poly[1-(4-vinylbenzyl)thymine] (PVBT) and 9-hexadecyladenine (A-C16) through atom transfer radical polymerization (ATRP) and alkylation, respectively. Bio-complementary PVBT/A-C16 hierarchical supramolecular complexes formed in dilute DMSO solution through nucleobase recognition—i.e., hydrogen bonding interactions between the thymine (T) groups of PVBT and the adenine (A) group of A-C16. In the bulk state, these complexes self-assemble into well-ordered lamellar structures; the changing d-spacing distance (ranging from 4.98 to 2.32 nm) at different A-C16 loadings reveals that the molecular structures of the PVBT/A-C16 complexes are readily tailored. In addition, a series of nucleobased polymers and copolymers were synthesized through atom transfer radical polymerization (ATRP). Biocomplementary DNA-like and RNA-like supramolecular complexes are formed through nucleobase recognition. This study is of discussion on the difference in the hydrogen bond strength between T-A and U-A base pairs within polymer systems, indicating that the strength of hydrogen bonds in RNA U-A pairs is stronger than that in DNA T-A base pairs. (2) Organic/Inorganic Supramolecular Materials A new polyhedral oligimeric silsesquioxane macromer octakis[N-(6-aminopyridin-2- yl)undecanamide-10-dimethyl- siloxy]silsesquioxane (POSS-C11-Py), containing eight diaminopyridine arms, has been synthesized. This POSS-C11-Py macromer is able to self-assemble to form a physically crosslinked polymer-like structure with good mechanical properties (tensile strength= 46.1 MPa, tensile modulus= 0.58 GPa, elongation= 49.3%) through quadruple hydrogen bonding interactions between these diaminopyridine terminal groups. POSS-C11-Py is the first organic/inorganic supermolecule possessing enhanced film-forming and mechanical properties as a result of self-supporting interactions, providing a potential route toward design and fabrication of supramolecular materials. (3) A New Supramolecular Material Containing Self-complementary Sextuple Hydrogen-bonding interaction This study describes an exceptionally array formed through self-assembly of a new material containing self-complementary sextuple hydrogen-bonding interaction. The new (U-DPy) derivative, N-(6-(3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)- propanamido)pyridin-2-yl)undec-10-enamide, was successfully synthesized through a three-step process with excellent yields. 1H NMR titration studies in CDCl3 showed that the self-complementary complexes formed rapidly on the NMR time scale with extremely high association constants (Kdimer >107 M-1). More surprisingly, the strength of hydrogen bonding formed through dimerization was over the fluorescence time scale. The U-DPy possessing extremely high association constant far exceeding those of existing systems provides a new strategy for designing and manipulating polymers with distinctive properties.