Cucurbit[8]uril-mediated SERS plasmonic nanostructures with sub-nanometer gap for the identification and determination of estrogens.

The SERS intensity of analytes is primarily influenced by the density and distribution of hotspots, which are often difficult to manipulate or regulate. In this study, cucurbit[8]uril (CB[8]), a kind of rigid macrocyclic molecule, was introduced to achieve ~ 1-nm nanogap between gold nanoparticles to increase the density of SERS hotspots. Three kinds of estrogens (estrone (E1), bisphenol A (BPA), and hexestrol (DES)) which are molecules with weak SERS signals were targeted in the hotspots by CB[8] to further improve the sensitivity and selectivity of SERS. It was demonstrated that CB[8] can link gold nanoparticles together through carbonyl groups. In addition, the host-guest interaction of CB[8] and estrogens was proved from the nuclear magnetic resonance hydrogen and infrared spectra. In the presence of CB[8], the SERS intensities of E1, BPA, and DES were increased to 19-fold, 74-fold, and 4-fold, respectively, and the LOD is 3.75 µM, 1.19 µM, and 8.26 µM, respectively. Furthermore, the proposed SERS method was applied to actual milk sample analysis with recoveries of E1 (85.0 ~ 112.8%), BPA (83.0 ~ 103.7%), and DES (62.6 ~ 132.0%). It is expected that the proposed signal enlarging strategy can be applied to  other analytes after further development.