Encapsulation and modulation of protolytic equilibrium of beta-carboline-based norharmane drug by cucurbit[7]uril and micellar environments for enhanced cellular uptake

The effect of supramolecular nanocavity on photophysical and acid-dissociation properties of Norharmane (NHM), a physiologically important, anxiety control and memory-enhancing beta-carboline-based drug, has been investigated using steady-state absorption and fluorescence spectroscopy. Self-assembled organization derived from surfactants and rigid water-soluble macrocyclic host Cucurbit[7]uril (CB7) have been selected for this investigation. The confined-space offered by the supramolecular assemblies modulates the pK(a) value of NHM (up to 3 units) as it can exist in two protolytic forms at near neutral pH. Therefore, the pH-dependent binding properties, modulation of pK(a) value and its consequences on the photophysical, chemical and solubility properties are investigated in detail. This investigation shows a large shift in the protolytic equilibrium which in turn causes ca. 15 times solubility-enhancement at near neutral pH. Moreover, the effect of enhanced solubility has been further investigated by the augmentation in the cellular uptake of NHM entrapped inside CB7. Thus, the modulation of the acid-base properties and solubility of beta-carboline-based drugs will have immense potential for their formulation, cellular uptake and bioavailability.