High-affinity inclusion of sitagliptin by cucurbit[7]uril: structural insights and fluorescence-based sensing

The host-guest complexation between sitagliptin and cucurbit[7]uril (CB7) was systematically investigated using a combination of spectroscopic, calorimetric, and computational techniques. ¹H and ¹⁹F NMR studies revealed significant complexation-induced chemical shifts consistent with the inclusion of the hydrophobic moiety of sitagliptin inside the CB7 cavity, while the polar triazolopiperazine residue remained near the portal. UV-visible absorption titration indicated complex formation. A competitive fluorescence displacement assay based on berberine chloride as a fluorescent dye enabled reliable determination of the binding constant, yielding K _a of 1.41 × 10⁷ M^-1. Isothermal titration calorimetry (ITC) further confirmed strong binding with K _a ∼ 10⁶ M^-1 and revealed an enthalpy-driven interaction with favorable entropy contributions. Density functional theory (DFT) calculations supported the formation of an inclusion complex. In addition, the CB7·berberine reporter pair demonstrated a sensitive fluorescence response toward sitagliptin, with low limits of detection and quantification, indicating potential for sensing applications.