Thiourea-based rotaxanes: anion transport across synthetic lipid bilayers and antibacterial activity against Staphylococcus aureus†

Abstract

We report the synthesis of two rotaxanes (1 and 2) whose rings have appended thiourea units for the selective recognition of Cl⁻ anions. Rotaxane 1 transports Cl⁻ across synthetic lipid bilayers more efficiently than 2, exhibiting EC₅₀ values of 0.243 mol% versus 0.736 mol%, respectively. A control rotaxane (3) without the thiourea units and the individual axle (4) also showed Cl⁻ transport, although with much lower efficiency (EC₅₀ values of 4.044 mol% and 4.986 mol%). The unthreaded ring (5) showed the lowest transport activity. This trend highlights the advantage of the interlocked system with a ring containing thiourea units. We also investigated how the membrane composition of liposomes influences the transport activity of 1 and 2, observing higher Cl⁻ transport in membranes with higher fluidity. Additionally, we demonstrated that rotaxane 1 can kill drug-resistant and osmotolerant Staphylococcus aureus when used in combination with NaCl or arachidonic acid. The latter is known to increase the fluidity of the membrane in S. aureus, highlighting cooperative behavior. This work provides new insights into how various structural features and the membrane environment influence the anion transport activity of rotaxanes, offering important design principles for optimizing future rotaxanes for biomedical and other applications.