Azacrown-calixpyrrole isosteres: receptors and sensors for anions

Abstract

Calix[4]pyrroles (CPs) and polyammonium azacrowns (ACs) are well-known receptors for anions. CPs bind anions by directional hydrogen bonds that do not always work well for aqueous analytes. The positive charge in polyammonium ACs allows for a stronger but non-directional anion-ammonium electrostatic attraction but lack selectivity. Bridging the gap between CPs and ACs could increase affinity and potentially preserve the selectivity of anion binding. We have synthesized a flexible calixpyrrole-azacrown near isosteric receptor and incorporated an environmentally sensitive dansyl fluorophore to enable fluorescence measurements. Anion binding was evaluated using NMR and fluorescence titrations. The isosteric receptor shows a strong affinity for aqueous phosphates and phosphonates (Na⁺ salts) in the order HAsO₄²⁻ > H₂PO₄⁻ > H₂P₂O₇²⁻ > glyphosate²⁻ > AMP⁻ > methylphosphonate⁻ ≫ ADP²⁻ or ATP³⁻ but does not bind halides. This is in stark contrast to CP which shows a strong preference for halides over oxyanions. The anion binding by the new receptor was accompanied by analyte-specific changes in fluorescence intensity and spectral width and by a wavelength shift. These parameters were used in qualitative and quantitative sensing of aqueous anions. By applying machine-learning algorithms, such as linear discriminant analysis and support vector machine linear regression, this one sensor can differentiate between 10 different analytes and accurately quantify herbicide glyphosate and methylphosphonate, a product of sarin, soman or cyclosarin hydrolysis. In fact, glyphosate can be quantified even in the presence of competing anions such as orthophosphate (LODs were ≤ 1 μM).