Azacrown-calixpyrrole isosteres: receptors and sensors for anions

• Published in: Chemical science (Cambridge) Vol. 14; no. 27; pp. 7545 - 7552
• Main Authors: Sartori, Austin R, Radujevi, Aco, George, Sandra M, Anzenbacher, Pavel
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 12.07.2023; The Royal Society of Chemistry
• Subjects: Affinity; Algorithms; Anions; Binding; Chemistry; Discriminant analysis; Fluorescence; Halides; Herbicides; Hydrogen bonds; Ions; Machine learning; NMR; Nuclear magnetic resonance; Phosphates; Phosphonates; Pyrroles; Receptors; Sarin; Support vector machines
• ISSN: 2041-6520; 2041-6539; 2041-6539
• DOI: 10.1039/d3sc01970e

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 HAsO 4 2− > H 2 PO 4 − > H 2 P 2 O 7 2− > glyphosate 2− > AMP − > methylphosphonate − > ADP 2− or ATP 3− 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). Hybrid isosteres display different selectivities and affinities for anions.