Inhibition of the prototropic tautomerism in chrysazine by p-sulfonatocalixarene hosts

This study explores the interesting effect of p-sulfonatocalix[n]arene hosts (SCXn) on the excited-state tautomeric equilibrium of Chrysazine (CZ), a model antitumour drug molecule. Detailed photophysical investigations reveal that conversion of CZ from its more dipolar, excited normal form (N*) to the less dipolar, tautomeric form (T*) is hindered in SCXn-CZ host–guest complexes, which is quite unexpected considering the nonpolar cavity of the hosts. The atypical effect of SCXn is proposed to arise due to the partial inclusion or external binding of CZ with the hosts, which facilitates H-bonding interactions between CZ and the sulfonate groups present at the portals of the hosts. The intermolecular H-bonding subsequently leads to weakening of the pre-existing intramolecular H-bond network within CZ, and thus hinders the tautomerizaion process. Our results suggest that rather than the binding affinity, it is the orientation of CZ in the SCXn-CZ complexes, and its proximity to the portals of the host that plays a predominant role in influencing the tautomeric equilibrium. These observations are supported by quantum chemical calculations. Thermodynamic studies validate that SCXn-CZ interaction is essentially enthalpy driven and accompanied by small entropy loss, which is consistent with the binding mechanisms.