A multifunctional lactose-containing molecule: Structural characterization, biocompatibility and host–guest complexation studies toward drug delivery applications

This work presents a novel carbohydrate-based molecule, 1,10- N,N′- bis-(β-D-ureidolactosyl)-4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (TL), which was synthesised via a multistep synthetic route, with the final deprotection of the carbohydrate moieties achieved through Zemplén deacetylation. In TL, lactose units are linked to a diazacrown ether through urea bridges. The incorporation of lactose moieties is responsible for the favorable physicochemical properties of TL, including its solubility, cytotoxicity profile, and complexation ability. The host–guest complexation properties were investigated using the recently synthesised compound butane-1,4-diyl bis(2,2,2-trifluoroethane-1-sulfonate) (BFS), which has demonstrated cytotoxic activity against leukemia cell lines. The formation of TL and its complex was confirmed by advanced multidimensional NMR techniques, FT-IR spectroscopy, and conductometric analysis. Biological assays indicated that TL is non-toxic toward healthy human keratinocytes (HaCaT), while complex formation with BFS reduces its cytotoxicity. The water solubility of TL was determined to be 25.74 g/100 mL H 2 O at 298.15 K. Theoretical calculations further revealed that TL adopts a conformation stabilised by intramolecular hydrogen bonding in aqueous solution, with up to ten hydrogen bonds identified in the most stable conformer, significantly influencing its structural geometry. Moreover, TL forms a stable complex with BFS, with a calculated complexation energy of −79.94 kJ/mol.