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Glassy carbon electrodes functionalised with two redox centres have been prepared by using electrochemical and solid-phase synthetic methodologies. Initially the individual coupling of anthraquinone, nitrobenzene and dihydroxybenzene to a glassy carbon electrode bearing an ethylenediamine linker was optimised by using different coupling agents and conditions. Bifunctionalisation was then carried out, either simultaneously, with a mixture of nitrobenzene and dihydroxybenzene, or sequentially, with anthraquinone then nitrobenzene and with anthraquinone then dihydroxybenzene. Characterisation of these electrodes by cyclic voltammetry and differential pulse voltammetry clearly proved the attachment of the pairs of redox centres to the glassy carbon electrode. Their partial surface coverages can be controlled by varying the coupling agent or by controlling the substrate concentration during the solid-phase coupling process. Trifunctionalisation was also realised according to this methodology.

A new macrocyclic receptor incorporating a thiourea moiety has been synthesised. Crystal structures of the macrocycle showed that the receptor has a rigid backbone but the thiourea moiety can orientate itself to bind to a DMSO solvent molecule. Force-field (MMFFs) calculations were performed to model the macrocycle and its binding properties with respect to N-protected amino acids, which were measured experimentally by NMR titration. Binding free energies were calculated by using the mode integration algorithm (MINTA) or free-energy perturbation (FEP). Excellent qualitative agreement with experiment was obtained. To further exploit the accuracy of the free-energy predictions for this system, the faster free-energy algorithm MINTA was used as a prediction tool to test the binding affinity of the macrocycle towards a series of several other amino acid derivatives, which speeded up considerably the screening process and reduced laboratory costs.

Libraries of "unsymmetrical" tweezer receptors, featuring a guanidinium head group as a carboxylate binding site and two independently synthesized peptidic arms, have been prepared and screened to identify receptors for the N-Ac-Lys-D-Ala-D-Ala tripeptide sequence. The binding properties of one such receptor structure, with dye-labeled N-Ac-Lys-D-Ala-D-Ala, were investigated. These studies demonstrated that when attached to the solid-phase, the receptor binds dye-labeled N-Ac-Lys-D-Ala-D-Ala, in buffered aqueous media, with mM binding affinity.

A series of chiral bisthiourea macrocycles 1-4 have been prepared and their binding properties with various dicarboxylate salts have been examined by using NMR titration and isothermal calorimetry experiments. Macrocycle 1, in particular, favours the 1:1 binding of N-protected L-glutamate and aspartate, but favours 1:2 binding of the corresponding D-amino acids in polar solvents (dimethyl sulfoxide and acetonitrile). The macrocycles, however, do not bind carboxylates at all in the less competitive solvent chloroform. The binding properties of these macrocyles are sensitive to small structural changes as demonstrated by the altered binding properties of macrocycles 2-4 compared with 1.

A library of “tweezer” receptors, incorporating a guanidinium “head group” and two peptide derived side arms has been prepared on the solid-phase using an orthogonally protected guanidinium scaffold 12. The library was screened with various tripeptide derivatives in an aqueous solvent system. A tweezer receptor 25 for the side chain protected tripeptide 19 was identified from the screening experiments. Receptor 25 was resynthesised and solution binding studies were carried out, which revealed that 25 binds to tripeptide 19 with Ka=8.2×104±2.5×104 (15 % DMSO/H2O, pH 8.75) and with appreciable selectivity over the tripeptide enantiomer 22 and the side chain deprotected tripeptide 20.

Synthetic receptors for peptides and amino acid derivatives are of considerable interest because of their direct relevance to many biological peptide–protein complexes, and may also lead, for example, to new biosensors, therapeutics and catalysts for peptide hydrolysis. Macrocycle 1 is a selective receptor for various dipeptide derivatives in chloroform, and most notably shows a strong preference for N-Cbz-β-alanyl amino acids over N-Cbz-β-alanyl lactic acids.