Adamantane appended antimicrobial supramolecular self-associating amphiphiles

Herein, we present the synthesis of two novel adamantane appended supramolecular self-associating amphiphiles. The antimicrobial efficacy of these compounds is determined against both clinically relevant Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli. We also explore the self-associative properties of these amphiphiles in both polar organic DMSO-d(6) 0.5% H2O and H2O (D2O)/EtOH 19:1 solutions, confirming aggregate stability through the determination of zeta potential values, aggregate size through a combination of H-1 NMR DOSY and dynamic light scattering studies as appropriate, and critical aggregate concentration through the derivation of concentration-dependent surface tension values. We also perform a variety of H-1 NMR dilution studies and in-silico modelling to further explore the roles of intermolecular hydrogen bonding and lipophilicity within aggregate formation and antimicrobial efficacy. Finally, we perform haemolysis and Galleria mellonella toxicity assays to establish the potential of these compounds to undergo further development as antibiotic agents.