A multifunctional lactose-containing molecule: Structural characterization, biocompatibility and host-guest...

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 H₂O 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.