Modulation in the acidity constant of acridine dye with cucurbiturils: stimuli-responsive pKa tuning and dye relocation into live cells

Abstract

The noncovalent host–guest interactions of the cationic (AcH⁺) and neutral (Ac) forms of an acridine dye with macrocyclic hosts such as cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) have been investigated to evaluate the effect of cavity size on the photophysical properties and the protolytic equilibrium of the acridine dye. The cationic form undergoes significant complexation with CB7 (K_eq = 10⁶ M⁻¹), causing a sharp decrease in the fluorescence intensity, whereas the neutral Ac form of the dye undergoes weak complexation with CB7 (K_eq = 10³ M⁻¹) and the binding constant is lowered by three orders of magnitude compared to that of the CB7–AcH⁺ system. The Job plot revealed that both forms form a 1 : 1 complex with CB7. On the other hand, the AcH⁺ form shows strong emission quenching on interaction with CB8 and the formation of the 1 : 2 CB8 : AcH⁺ complex has been confirmed from the Job plot. The strong affinity of CB7 and CB8 to the protonated form resulted in a large upward pK_a shift (ΔpK_a ∼ 3.4 units for CB7 and ∼1.3 units for CB8) in the dye. Taking advantage of the above modulations in the fluorescence and pK_a values, adamantylamine-induced fluorescence regeneration, controlled pK_a tuning and dye relocation from the CB7 cavity to cell lines have been established for the first time, which find potential applications in fluorescence off–on sensing and drug delivery.