Encapsulation of Prodan in beta-cyclodextrin environments: A critical study via electronic spectroscopy and molecular mechanics

We present a detailed study on the binding of the naphthalene based fluorescence probe Prodan with two cyclic oligosachharides namely, natural beta-cyclodextrin (β-CD) and its synthetic derivative, succinyl-2-hydroxypropyl beta-cyclodextrin (SHPβ-CD) using electronic absorption and fluorescence spectroscopy along with theoretical techniques. The encapsulation of Prodan inside the β-CD cavities leads to pronounced changes in its emission characteristics, including dramatic blue shifts (27 nm in 10 mM SHPβ-CD and 19 nm in 10 mM β-CD) in the emission maximum accompanied by increase in the emission yield, fluorescence anisotropy and lifetime values. Detailed analyses of the fluorescence along with relevant absorption spectroscopic data indicate that Prodan readily enters the doughnut-shaped hydrophobic cavities of the β-CDs and forms 1:1 inclusion complexes, the binding affinity being significantly higher in case of SHPβ-CD. Furthermore, docking studies performed via molecular mechanics methods (MM+) indicate that the dimethylamino group of Prodan is most likely to be oriented towards the wider rim of the cyclodextrin cavity. Quantum mechanical calculations reveal that incorporation of Prodan into the β-CD cavities, results in the formation of a N-TICT (dimethylamino twisted intramolecular charge transfer) state.