Fluorescent Artificial Receptor for Dopamine based on Molecular Recognition-driven Dynamic Covalent Chemistry in a Lipid Nanoreactor

Abstract

Molecular recognition and detection of small bioactive molecules, like neurotransmitters, remain a challenge for chemists, whereas nature found an elegant solution in form of protein receptors. Here, we introduce a concept of a dynamic artificial receptor that synergically combines molecular recognition with dynamic imine bond formation inside a lipid nanoreactor, inducing a fluorescence response. The designed supramolecular system combines a lipophilic recognition ligand derived from a boronic acid, a fluorescent aldehyde based on push-pull styryl pyridine and a phenol-based catalyst. The recognition ligand specifically captures dopamine inside lipid nanodroplets and thus triggers imine bond formation with the aldehyde, producing the emission color change. The rational design of the fluorescent aldehyde, the catalyst and the recognition ligand allows dramatic acceleration of the imine bond formation required for rapid sensing of dopamine. The nanoprobe enables dopamine detection with micromolar sensitivity and singe-nanoprobe imaging of dopamine gradients through its robust two-color ratiometric response. It displays remarkable selectivity without interference of competing biogenic primary amines and biological media: blood serum, plasma, urine and cell lysate. The proposed concept of a dynamic artificial receptor offers a solution to the long-standing problem of molecular recognition and sensing of small molecules in complex biological media.