Structural characterization of the Brooker’s merocyanine/β-cyclodextrin complex using NMR spectroscopy and molecular modeling

Brooker’s merocyanine (4-[(1-methyl-4(1H)-pyridinylidene)ethylidene]-2,5-cyclohexadien-1-one) is a dye molecule that has a unique photochemical/protolytic isomerization cycle. The cis to trans isomerization of the neutral molecule occurs only in one direction with the addition of photochemical energy. When the dye molecule is complexed with β-cyclodextrin, however, the isomerization occurs spontaneously without further energy required. To understand the difference between the native dye molecule and the complex, the molecular structures of the cis and trans isomers of Brooker’s merocyanine in β-cyclodextrin were optimized using the semi-empirical PM3 method as well as the hybrid ONIOM method which models the cyclodextrin at the PM3 level and the dye molecule using B3LYP/6-31g(d). The most stable complexes were similar in binding energy, although the molecular structures were quite different. The ONIOM optimized structures resulted in an increase in the planarity of the conjugated dye molecule when compared to the PM3 model. The trans isomer in the β-cyclodextrin cavity was also characterized experimentally using 1H-NMR complexation-induced shifts, and the results were found to be in good agreement with the proposed structure from the molecular modeling. Finally, the calculated thermodynamic properties of the trans isomer complex were compared to experimental results, and it became clear that water within the cavity must be included in the analysis to obtain accurate theoretical values.