“…The presence of 2,5-pyridinedicarboxylate (2) and 2,6-naphthalenedicarboxylate (22) have less pronounced, but still signi cant, stabilising interactions with TphC, displaying ΔT m s of 1.4 ± 1.1°C and 1.4 ± 0.7°C, respectively. The other para-substituted dicarboxylate analogues (3,(5)(6)(8)(9)(10)(11) regioisomers (12)(13), hetero-aromatics (14)(15)(16)(17)(18)(19), bicyclic aromatics (20,23), the mono-carboxylate and carboxylate isosteres , unsaturated phenylpropanoates (45)(46)(47)(48)(49)(50), phenols (51)(52), aromatic esters (53)(54)(55)(56) and aliphatic dicarboxylates (57-61) had either negligible effect on ΔT m s or their interactions with TphC were found to be slightly destabilising under the assay conditions. This indicates that for optimal interaction a six-membered para-substituted aromatic dicarboxylate is required, that limited additional substitution with hydroxyl groups around the ring and minor heteroaromatic modi cations are tolerated, and that extended aromatic systems are partially tolerated.…”