Interactions between Caffeine, Theophylline and Derivatives with Gold Nanoparticles and Implications for Aptamer‐Based Label‐Free Colorimetric Detection

Abstract Caffeine, theophylline, and other methylxanthines have interesting biological activities and are consumed in high quantities globally, causing health and environmental concerns. Gold nanoparticles (AuNPs) have excellent optical properties for biosensor development, although little is known about the adsorption of these xanthine derivatives to AuNPs. In this work, interactions of these compounds with AuNPs were studied. Caffeine, theophylline and theobromine are adsorbed in a manner that affords protection against salt‐induced aggregation, whereas xanthine and paraxanthine are adsorbed to destabilize and thus aggregate the AuNPs. Caffeine and theophylline are able to protect AuNPs starting at concentrations as low as 6.3 μM. Xanthine and paraxanthine induce significant AuNP aggregation at 5 μM. Adsorption was also confirmed by surface‐enhanced Raman scattering (SERS). Using two recently selected DNA aptamers for caffeine and theophylline, the label‐free colorimetric sensing method was tested; our results indicated that due to adsorption of these target molecules, this method cannot be directly used for their detection. The adsorption of these compounds to AuNPs may enable various detection methods such as SERS, but at the same time, it may complicate other detection methods.