Thiourea-linked upper rim calix[4]arene neoglycoconjugates: synthesis, conformations and binding properties

Abstract

The thiourea group has been exploited to link two or four carbohydrate units at the upper rim of tetrapropoxycalix[4]arene derivatives in the cone conformation. Two synthetic methodologies were used, the first one consisting of the condensation of di- and tetraminocalix[4]arenes with the isothiocyanate of monosaccharides in dry CH₂Cl₂ at room temperature and the second one exploiting the condensation of an aminolactoside with a calixarene isothiocyanate. The first method allows the glycoconjugates to be obtained in 75–80% overall yields. The difunctionalised derivatives exist in a closed flattened cone conformation in CDCl₃ and CD₃OD due to the formation of intramolecular hydrogen bonds involving the thiourea groups which are broken in DMSO-d₆ to give an open flattened cone conformation. The thiourea groups act not only as linkers but also as binding units for anionic substrates as evidenced by solution ¹H NMR and ESI-MS experiments. Turbidimetric analysis indicates that the tetraglucoside and tetragalactoside clusters give specific interactions with Concanavalin A (Con A) and peanut lectin (PNA), respectively. Both features show that the neoglycoconjugates could also be used as site specific molecular delivery systems.