Abstract
The recognition of carboxylate-containing molecules is essential to a myriad of important biological processes, such as the mode of action of the antibiotic vancomycin. However, using charge-neutral synthetic receptors to bind carboxylates in the 100 % aqueous environment remains challenging, not only because of difficulties in solubilising the hosts in water, but also due to the hydrophilicity of the carboxylate guests.This project aimed to investigate a new class of carboxylate receptors employing tetralactam units as the carboxylate binding motif. Derived from sp3 CH on the tetralactam linkage, the receptors were substituted to generate cleft-type architectures which could further provide H-bond donation, acceptance and hydrophobic effects for the substrate. There were several variables (X, Y, Z and n) on the receptor. The pincer molecules could either be isophthalamide (X = CH) or 2,6-bis(carbamoyl)pyridine (X = N), in order to study the pre-organisation effect. Architecture Y was specifically tailored for different substrates from simplest carboxylates to dipeptides. The peripheral Z engendered water solubility. The tetralactam ring sizes (n = 1 or 2) were varied to achieve different flexibilities.
In this thesis, five types of receptors (A2 to A6) based on the above design strategies were pursued and discussed in corresponding chapters (Chapter 2 to Chapter 6). Among them, studies on receptor A5 suggested strong binding constants towards simple carboxylates with Ka ~300 M-1. This represented the highest affinity recorded for charge-neutral synthetic receptors in water.
In addition, to engender the best aqueous solubility for receptors, Z groups (A7 to A10) with different sizes and charges were used throughout the thesis and were mainly discussed in Chapter 7.
| Date of Award | 1 Oct 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Anthony P Davis (Supervisor) |
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