Potentiometric Sensing of Nonsteroidal Painkillers by Acyclic Squaramide Ionophores

[Image: see text] We report here a small library of a new type of acyclic squaramide receptors (L1–L5) as selective ionophores for the detection of ketoprofen and naproxen anions (KF(–) and NS(–), respectively) in aqueous media. (1)H NMR binding studies show a high affinity of these squaramide receptors toward KF(–) and NS(–), suggesting the formation of H-bonds between the two guests and the receptors through indole and −NH groups. Compounds L1–L5 have been tested as ionophores for the detection of KF(–) and NS(–) inside solvent PVC-based polymeric membranes. The optimal membrane compositions were established through the careful variation of the ligand/tridodecylmethylammonium chloride (TDMACl) anion-exchanger ratio. All of the tested acyclic squaramide receptors L1–L5 have high affinity toward KF(–) and NS(–) and anti-Hofmeister selectivity, with L4 and L5 showing the highest sensitivity and selectivity to NS(–). The utility of the developed sensors for a high precision detection of KF(–) in pharmaceutical compositions with low relative errors of analysis (RSD, 0.99–1.4%) and recoveries, R%, in the range 95.1–111.8% has been demonstrated. Additionally, the chemometric approach has been involved to effectively discriminate between the structurally very similar KF(–) and NS(–), and the possibility of detecting these analytes at concentrations as low as 0.07 μM with R(2) of 0.947 and at 0.15 μM with R(2) of 0.919 for NS(–) and KF(–), respectively, was shown.