Quantum chemical study of the complexation process of bis-β-D-glucopyranosyl diazacrown derivative with aspirin and paracetamol molecules

1,10-N,N'-bis-(beta-D-ureidoglucopyranosyl)-4,7,13-trioxa-1,10-diazacyclopentadecane is studied as a potential carrier of aspirin and paracetamol. The host:drug complexes in stoichiometry 1:1 are investigated in aqueous solution using the quantum chemical method B3LYP-GD2/6-31G(d,p) and the polarizable continuum model of solvent. Five new conformers of the host molecule, which are energetically more stable than the one found in the earlier work, [M. Adamiak, S. Porwafiski, A. Ignaczak, Tetrahedron 74 (2018) 2166-2173] are presented and their properties are compared to the previous data. For the complexes host:aspirin and host:paracetamol the energies of interaction, deformation and complexation as well as the NMR chemical shifts are analyzed in detail. It is shown that the complexes in stoichiometry 1:1 are stable, having the lowest complexation energy of -26 and -21 kcal/mol. From 1 to 3 moderate hydrogen bonds between host and guest are observed. In the energetically preferred structures neither aspirin nor paracetamol penetrates the area between the glucose units and diazacrown ring, what classifies them as non-inclusion complexes.