A Micellar Multitasking Device: Sensing pH Windows and Gauging the Lipophilicity of Drugs with Fluorescent Signals

A multitasking fluorescent device can be obtained by forming micelles of Triton X-100, containing a lipophilic macrocyclic Cu2+ complex and the coordinating fluorophore Coumarin 343 (C343), which features a COOH moiety. At low pH the two micellised components do not interact, and the fluorescence of Courmarin 343 (C343) is intense. At intermediate pH, C343 is deprotonated and coordinates to the Cu2+ centre in its apical position, with fluorescence quenching. At higher pH the deprotonated C343 is displaced from Cu2+ by the formation of an OH- complex, and the fluorescence is revived. This allows the system to carry out its first task as it behaves as an "on-off-on" fluorescent sensor for pH windows. The "off" part of the window ranges from pH 6 to 8. In this interval, in which the carboxylate form of C343 is apically coordinated to the Cu2+ complex inside micelles, the device carries out its second task, that is, it behaves as a gauge for lipophilicity. For pHs between 6 and 8, molecules containing a COOH group are in their COO- form and distribute between bulk water and micelles proportionally to their lipophilicity. Upon entering the micelle, their COO- moiety competes for coordination with C343, displacing it from the Cu2+ centre, and this results in fluorescence revival, the intensity of which is also proportional to the lipophilicity of the examined molecule. We have chosen the physiological pH value (7.4) as the working pH, and we have examined the lipophilicity of fatty acids and of the widely used family of nonsteroidal anti-inflammatory drugs (NSAIDs). The device successfully measures their lipophilicity, expressing it with an "off-on" type fluorescent signal, as demonstrated by the correlation of the fluorescence increase with the logarithmic water/octanol partition coefficient (log P) and with the difference between the pK(a) observed in micelles and that measured in water for NSAIDs.