以萘二甲醯亞胺為基礎之自組裝奈米結構及 其發光特性

Abstract

近年來，透過胜肽分子自組裝形成奈米結構之新型材料成為蓬勃發展的熱門研究題材。迄今為止，在胜肽奈米管柱的研究中，多數以雙胜肽為基底的奈米管柱被廣為探討，乃因其合成成本低，製備方法簡易且穩定性高，應用端廣泛。於本研究中我們導入一系列低分子量短鏈的雙肽胜肽分子，探討其自組裝結構以及基本物理特性。研究主題分成兩個部分進行，各別為調控奈米結構形貌表現和觀察分子聚集導致的發光表現。 在第一部分的研究主題中，設計具有聚集誘導發光特性之萘二甲醯亞胺(NI)連接雙肽的組合，第一個胺基酸為苯丙胺酸，提供部分疏水作用力，改變第二個胺基酸，使整個系統具有不同程度的雙親性，合成的材料為NI-FA、NI-FD、NI-FE和NI-FS，對以上材料進行不同濃度、酸鹼與時間變異的研究，NI-FD與NI-FE於特定條件下並無特定奈米結構形成；而NI-FA及NI-FS除了可在中性條件下，可分別形成大小為104 nm ± 3 nm 與118 nm ± 6 nm的大型胜肽奈米管柱外，在一定的濃度與酸鹼值範圍內，也都為奈米管柱的表現。與NI-FS相較下，NI-FA可於短時間內、極鹼且濃度高的環境依舊為成形的奈米管柱，形貌穩定性較高，在所觀察的環境中無任何奈米結構共存的現象，形貌一致性高，管柱尺寸較小。此外，我們也推論其形成管柱機制較目前文獻上更為完備，此機制的理解，有助於小分子自組裝胜肽奈米管柱的探討與發展。另外，NI-FA與NI-FS於人類纖維母細胞(WS1)的細胞存活度測試表現良好，預期兩者於生物應用上具相當的應用價值及發展潛力。 在第二部分的研究主題，探討萘二甲醯亞胺(NI)在4號位置連接上不同環數的環烷基作為推電子基團，依環烷尺寸小到大分別是5RNI、6RNI、7RNI和8RNI，並連接相同的短鏈胜肽分子(FDD)之螢光特性表現。材料分別為5RNI-FDD、6RNI-FDD、7RNI-FDD和8RNI-FDD，透過許多光學測試的結果，顯示只有6RNI-FDD表現出聚集誘導發光的特性，推測在六環的萘二甲醯亞胺系統(6RNI)中，位於4號位置的六環環胺與萘二甲醯亞胺(NI)的苯環平面結構可能存有較大的旋轉角度，故只有6RNI-FDD表現出聚集誘導發光的特性，其餘三者的螢光表現皆為聚集導致粹滅。並以成膠條件下做細胞培養，6RNI-FDD於子宮頸癌細胞(HeLa)及前列腺癌細胞(PC3)之細胞存活率與其他三者衍生物相較下，皆有生物相容性最高的表現，推測具有生物顯影應用的潛力。

In recent years, self-assembled peptide nanostructures have become a popular research field in material science. To date, dipeptide-based nanotubes were widely discussed because of low cost, easy preparation, high stability and diverse applications. In this study, we introduce a series of low-molecular-weight short dipeptide molecules to explore the self-assembled structure and their (photo)physical properties. There are two topics in this thesis, the first topic is to modulate the nanostructure morphology, and the other one is to study the properties of aggregation-induce emission. In the first topic, we design four 1,8-Naphthalimide (NI)/dipeptide conjugates. The first amino acid at the N-terminus of the peptide is phenylaniline, providing part of hydrophobicity and different tail peptides with various amphiphilics. They are NI-FA, NI-FD, NI-FE and NI-FS. We studied these materials with different concentrations, pH value and time evolution. We found the self-assembled nanostructure of NI-FD and NI-FE formed no specific nanostructures under certain conditions, while NI-FA and NI-FS appear large-scale well-defined peptide nanotubes with the width of 104 nm ± 3 nm and 118 nm ± 6 nm, respectively. The self-assembled structures of NI-FA and NI-FS are also nanotubes in a range of pH values and concentrations. In comparison of NI-FS and NI-FA, NI-FA can form nanotubes in shorter time and extreme pH environments, pointing to higher stability of morphology. There is no coexistence of nanostructures possessing higher uniformity of morphology and smaller size. Besides, we studied the formation of nanotubes is more detail than that in the literature. Thus, it is beneficial to the development of small molecular of self-assembled peptide nanotubes. Furthermore, we also observed NI-FA and NI-FS possess excellent cell-compatibility toward WS1 cell line. As a result, we recognized both of them are new type of nanotube-based biomaterials. In the second part of the research, we demonstrated a series of 1,8-Naphthalimide (NI) derivatives through combining different cyclic amine groups as donating electronic groups, then conjugate the same peptide sequences FDD in N terminus. They are 5RNI-FDD、6RNI-FDD、7RNI-FDD and 8RNI-FDD. Only 6RNI-FDD showed AIE effect through many photophysical studies. We speculated that there is the larger dihedral angle existed between NI and the six-membered ring at 4 position of NI. Additionally, we found 6RNI-FDD holds better cell-compatibility toward HeLa and PC3 cells via MTT assay that is very promising in application on bio-imaging.