Use of halogenated units for the construction of artificial carbohydrate receptors

To investigate the potential of halogen-containing building blocks in the development of artificial carbohydrate receptors, the 1,3,5-trisubstituted 2,4,6-triethylbenzene scaffold with halogenated subunits and classical hydrogen bonding sites was used as a model system. In the first studies, the influence of the presence of halogens on the binding properties of compounds bearing benzamidomethyl units was investigated, whereby the type of halogen and its ring position were varied. The question was whether the presence of halogens could lead to an increase in binding effectivity and whether this increase can be attributed to the formation of halogen bonds (especially for X = Br and I in ortho position) with the sugar substrate or to other effects. The binding studies revealed some interesting relationships between structure and binding affinity for the tested compounds 1-9. For those bearing the halogen substituent in the ortho position to the amide functionality, the binding affinity increases in the expected order 4 (o-F) < 3 (o-Cl) < 2 (o-Br) < 1 (o-I). In the presence of small amounts of water in CDCl3, an increase in binding strength was observed in comparison to experiments conducted in dry CDCl3. The present studies aim to provide impulses for the use of halogenated building blocks in the design of artificial carbohydrate receptors. Optimizing the type of halogenated units and the receptor architecture should result in more effective carbohydrate receptors capable of functioning effectively in aqueous media through a combination of different noncovalent interactions.