Recognition and Sensing of Creatinine

Current methods for creatinine quantification suffer from significant drawbacks when aiming to combine accuracy, simplicity, and affordability. Here, an unprecedented synthetic receptor, an aryl‐substituted calix[4]pyrrole with a monophosphonate bridge, is reported that displays remarkable affinity for creatinine and the creatininium cation. The receptor works by including the guest in its deep and polar aromatic cavity and establishing directional interactions in three dimensions. When incorporated into a suitable polymeric membrane, this molecule acts as an ionophore. A highly sensitive and selective potentiometric sensor suitable for the determination of creatinine levels in biological fluids, such as urine or plasma, in an accurate, fast, simple, and cost‐effective way has thus been developed. Creatinine quantification: A monophosphonate‐bridge calix[4]pyrrole cavitand traps creatinine and the creatininium cation in its deep and polar aromatic cavity. The receptor offers complementary hydrogen‐bonding sites to the polar functional groups of the guest. Its use as an ionophore enhances the analytical performance of ion‐selective electrodes and enables the determination of creatinine levels in biological samples.