Piperine Encapsulation within Cucurbit[n]uril (n=6,7): A Combined Experimental and Density Functional Study

Abstract

AbstractThe formation of host‐guest between piperine and cucurbit[n]uril (n=6,7) molecules were studied using experimental and density functional theory (DFT) calculations. The host‐guest complexation was monitored using UV‐Visible and isothermal calorimetric (ITC) methods. The obtained Jobs plot indicate the formation of 1:1 complex. ITC analysis shows a moderate binding of the guest to the host molecules. The enthalpy of binding and the free energy of formation were negative indicating the facile formation of inclusion complex at room temperature. DFT studies confirm the formation of stable inclusion complexes. In stable inclusion complex of piperine with cucurbit[6]uril, the aromatic moiety was found to be inside the cucurbituril cavity, while in the cucurbit[7]uril inclusion complex, the piperidine moiety was inside the cavity, which was further confirmed by time dependent‐DFT study. The global reactivity descriptors analysis, indicate the formation of piperine inclusion complex with cucurbit[7]uril, could prevent the isomerization reaction of piperine. Atoms‐in‐molecules analysis shows the presence of extra inter and intramolecular bond critical points in the piperine inclusion complex with cucurbit[7]uril, which accounts for its extra stability. The computed intermolecular bond parameters confirm the existence of a non‐covalent with partial electrostatic interactions between the guest and host molecules. Energy decomposition analysis, suggest the Pauli repulsion to be higher for the cucurbit[6]uril inclusion complex, while the dispersion plays a major role in stabilizing the cucurbit[7]uril inclusion complex, which was further corroborated by noncovalent index analysis.