Self-Assembly of Functionalized Benzene-1,3,5-tricarboxamide (BTA) Derivatives

Abstract

In order to develop novel materials, small molecules can be self-assembled into supramolecular structures. By generating non-covalent interactions, a high level of order can be achieved on the molecular scale, leading to inherently dynamic supramolecular structures. Hydrogen-bonding motifs are popular in apolar organic solvents due to their high affinity and directionality. However, hydrogen bonding in water is not a straightforward force for self-assembly due to the competition between water molecules and hydrogen bonds. In addition, hydrophobic effect act as another major driving force for aggregation. Therefore, it remains challenging to design small molecules and control their self-assembly in water. Consequently, it is essential to have a deeper understanding of self-assembly in water in order to develop functional and responsive aqueous systems and biomaterials. This thesis describes the synthesis and characterization of novel benzene-1,3,5-tricarboxamide (BTA) derivatives. By generating non-covalent interactions, a high level of order can be achieved on the molecular scale, leading to inherently dynamic supramolecular structures. A brief overview of functional supramolecular materials, and the different interactions that lead to their formation, and their properties is provided in the introduction. Several relevant advances in the literature are reviewed, particularly those relating to benzene-1,3,5-tricarboxamide-based supramolecular polymers in water. A wide variety of strategies and molecular designs are discussed in the overview. An understanding of self-assembly in water is essential to developing new functional and responsive aqueous systems and biomaterials. Understanding the role of hydrogen bonding and hydrophobic interactions are essential to shed light on BTA self-assembly in water. In chapter 2 benzene-1,3,5-tricarboxamide (BTA) derivatives in aqueous solution are shown to self-assemble into two different nanostructures. The BTA derivatives have one alkyl chain and two PEG (polyethylene glycol) chains or two alkyl chains and one polyethylene glycol chain. Small angle X-ray scattering (SAXS) and electron microscopy were used characterize two series of derivatives, revealing micelle structures for derivatives with one alkyl and two PEG chains, but nanotapes and nanoribbons for derivatives with two alkyl chains and one PEG chain. In chapter 3 BTA derivatives with different alkyl chains (C10-C18) and polyethylene glycol chains (Mn 550 g mol-1) self-assemble in aqueous solution are shown to form micelles or vi nanotapes, depending on their architecture (number of alkyl chains versus PEG chains). There is a dose-dependent increase in the cytotoxicity of breast cancer cells compared to fibroblast controls. The compounds exhibit high stability, maintaining their self-assembled structures at low pH (relevant to acidic tumour conditions) as well as in buffers and cell culture media. Chapter 4 describes the synthesis of a bola-amphiphile new BTA-PEG-BTA structure, containing two hydrophobic BTA (C16) units linked via PEG chain (Mn 4000 g mol-1). The synthesised conjugate self-assembles into micelles with 10 nm radius with cubic ordering which shows high thermal stability up to 90 °C. Chapter 5 describes the synthesis and characterization of BTA derivatives based on AA-OMe peptide with two alkyl chain with one AA-OMe peptide or two PEG chains and one AA-OMe unit. The derivative with two PEG chain with one peptide self-assembles into micelles ~3 nm size in aqueous solution whereas the analogue with two alkyl chains and one AA-OMe was not soluble in water even at low concentration. Chapter 6 provides conclusion and suggestion for future work