Development of a Cone Homooxacalix[3]arene-Based Fluorescent Chemosensor for the Selective Detection of Biogenic Ammonium Ions in Protic Solvents

We report here on the development of a fluorescent cone homooxacalix[3]arene-based receptor with a pyrene unit on the wide rim of the macrocycle (<b>Ox3F</b>) for the selective detection of primary ammonium ions, including those of biological importance. <b>Ox3F</b> was synthesized efficiently via an innovative strategy that enables the regio- and iteroselective wide rim functionalization of the readily available <i>p</i>-<i>t</i>Bu-substituted homooxacalix[3]arene precursor. Nuclear magnetic resonance studies and <i>in silico</i> methods highlighted the <i>endo</i>-complexation of primary ammonium ions, including the protonated form of biogenic dopamine, tryptamine, serotonin, mexamine, and 3-iodothyronamine. The binding mode is similar for all guests with the ion deeply inserted into the polyaromatic cavity, enabling the NH₃⁺ head to establish three hydrogen bonds with the ethereal oxygens of the macrocycle. Fluorescence quenching of the pyrene unit was observed following the π–π interaction between the pyrene moiety and the aromatic groups of serotonin, mexamine, and 3-iodothyronamine. No quenching was observed upon complexation of the smaller aromatic neurotransmitter dopamine as well as aliphatic amines and polyamines. This study presents a novel approach for biologically relevant ammonium ion chemosensing with ongoing efforts focused on translating these systems for aqueous environment applications.