Stability and pKa Modulation of Aminophenoxazinones and Their Disulfide Mimics by Host-Guest Interaction with Cucurbit[7]uril. Direct Applications in Agrochemical Wheat Models

Abstract

Aqueous solubility and stability often limit the application of aminophenoxazinones and their sulfur mimics as promising agrochemicals in a sustainable agriculture inspired by allelopathy. This paper presents a solution to the problem using host-guest complexation with cucurbiturils (CBn). Computational studies show that CB7 is the most suitably sized homologue due to its strong affinity for guest molecules and its high water solubility. Complex formation has been studied by direct titrations monitored using UV-vis spectroscopy, finding a preferential interaction with protonated aminophenoxazinone species with high binding affinities (CB7 center dot APOH+ , Ka = (1.85 +/- 0.37) x 106 M-1; CB7 center dot DiS-NH3+ , Ka = (3.91 +/- 0.53) x 104 M-1; and DiS-(NH3+)2 , Ka= (1.27 +/- 0.42) x 105M-1). NMR characterization and stability analysis were also performed and revealed an interesting pKa modulation and stabilization by cucurbiturils (2-amino-3H-phenoxazin-3-one (APO), pKa = 2.94 +/- 0.30, and CB7 center dot APO, pKa = 4.12 +/- 0.15; 2,2 '-disulfanediyldianiline (DiS-NH2), pKa = 2.14 +/- 0.09, and CB7 center dot DiS-NH2 , pKa = 3.26 +/- 0.09), thus favoring applications in different kinds of crop soils. Kinetic studies have demonstrated the stability of the CB7 center dot APO complex at different pH media for more than 90 min. An in vitro bioassay with etiolated wheat coleoptiles showed that the bioactivity of APO and DiS-NH2 is enhanced upon complexation.