Stability and pKa Modulation
of Aminophenoxazinones and Their Disulfide Mimics by Host–Guest
Interaction with Cucurbit[7]uril. Direct Applications in Agrochemical
Wheat Models
posted on 2022-12-22, 20:34authored byFrancisco
J. R. Mejías, Suhang He, Rosa M. Varela, José M.
G. Molinillo, Andrea Barba-Bon, Werner M. Nau, Francisco A. Macías
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·APOH+, Ka = (1.85 ± 0.37) × 106 M–1; CB7·DiS-NH3+, Ka = (3.91 ± 0.53)
× 104 M–1; and DiS-(NH3+)2, Ka= (1.27 ±
0.42) × 105 M–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·APO, pKa = 4.12 ± 0.15; 2,2′-disulfanediyldianiline
(DiS-NH2), pKa = 2.14 ± 0.09, and CB7·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·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.