Contrasting pKa shift and fluorescence modulation of 6-cyano-2-naphthol within α- and β-cyclodextrin

[Display omitted] •The pKa and pKa* of a photoacid 6-cyano-2-naphthol increases within α-CD while decreases within β-CD.•The ESPT dynamics is suppressed significantly within α-CD but almost unaltered within β-CD complex.•The photoacid forms 1:2 inclusion complex with α-CD, whereas 1:1 inclusion complex with β-CD.•The hydroxyl group of the photoacid has much lesser access to water inside the α-CD complex compared to the β-CD complex. Herein, we investigate the interaction between a strong photoacid 6-cyano-2-naphthol (6CN-2OH) and a macrocyclic host α- cyclodextrin (α-CD) with a combination of molecular fluorescence and molecular dynamics simulations. Interestingly, we observe very different pKa shift and fluorescence modulation within α-CD compared to β- cyclodextrin (β-CD). While β-CD inclusion lowers pKa and pKa* of 6CN-2OH, α-CD inclusion raises them. Moreover, in contrast to negligible fluorescence change in the β-CD inclusion case, we observe a remarkable fluorescence modulation for the α-CD-inclusion case. Fluorescence transient measurements confirm significant suppression of excited-state proton transfer (ESPT) dynamics in the presence of α-CD but almost none for the β-CD complex. Isothermal calorimetry (ITC) measurements reveal that 6CN-2OH forms a 1:1 inclusion complex with β-CD with a moderate binding constant of 580 M−1; whereas it forms a 1:2 inclusion complex with α-CD with a high binding constant of 5.0 × 104 M−2. Fluorescence anisotropy decay measurements also support the different binding stoichiometry of the photoacid with the two CDs; the rotational relaxation is significantly slower in the α-CD complex than in the β-CD. Molecular dynamics simulation shows that 6CN-2OH remains entirely trapped inside the hydrophobic cavity formed by two α -CD molecules, which results in the severe depletion of water molecules from the proton-donating hydroxyl site of the 6CN-2OH molecule in the 6CN-2OH:(α-CD)2 complex than in the 6CN-2OH:β-CD complex.