A threading receptor for polysaccharides

Abstract

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms A threading receptor for polysaccharides Polysaccharides are the dominant organic molecules in the biosphere 1 , and thus key renewable resources 2,3 . However the most abundant, including cellulose and chitin, are generally the most difficult to utilise due to extreme insolubility. At present there is no method for mobilising these materials in water under mild conditions, so that modifications involve chemical transformations in aggressive media [4][5][6] or the slow action of enzymes on undissolved solids 7 . Dissolution in aqueous media at biological pH would allow new paths to exploitation. In particular, the polysaccharides could be exposed to enzymes, either natural or engineered, to which they would be far more vulnerable. The rapid conversion of cellulose to glucose is just one prospective outcome.Here we adumbrate a strategy for the dissolution of cellulose, and related polysaccharides, through the application of synthetic receptors. The approach employs cage molecules with amphiphilic interiors, complementary to the carbohydrate targets. Critically the receptors are able to thread onto the polysaccharides, forming polypseudorotaxanes 8,9 . Because of the threaded topology, many receptor molecules can bind to one polysaccharide chain, surrounding the polymer with hydrophilic groups. If binding is sufficiently strong to counteract crystal packing forces, dissolution should be feasible. We report the design and synthesis of a threading receptor for polysaccharides, and show that it forms pseudorotaxanes with water-soluble oligosaccharides.We also describe evidence for polypseudorotaxane formation from polysaccharides under certain conditions. The results demonstrate the feasibility of polysaccharide threading in water, and could point the way to systems capable of solubilisation.A defining feature of cellulose 1 and chitin 2 (Fig. 1a) is the all-equatorial disposition of intra-chain linkages and polar substituents and (consequently) the axial positioning of apolar CH groups. In the extended conformation of the polymer, this creates two parallel strips of hydrophobic surface separated by lines of hydrogen-bonding functional groups. Our strategy for complementing these supramolecular valencies is illustrated in Fig. 1b. We sought a cage-like receptor structure in which two aromatic surfaces would be held parallel to each other, separated by rigid, polar spacers. The portals of the cage would be large enough to allow threading by the polysaccharide substrates. The aromatic surfaces would be capable of forming hydrophobic and CH-π interactions with axial CH groups in the substrates, while polar groups would hydrogen bond to equatorial substituents.We had previously used a related approach to bind all-equatorial mono-and di-saccharides in water 10-13 .However, these earlier designs e...

How Does Solvation Affect the Binding of Hydrophilic Amino Saccharides to Cucurbit[7]uril with Exceptional Anomeric Selectivity?

“…Such an analysis can indeed be informative, as it has been often reported that carbohydrate binding in water with inflexible cages is driven substantially by entropy. [17,18] For the specific case of amino saccharides with CB [7], our earlier experiment [25] suggested that entropy participated importantly (ÀTDS/DG % 35 %) in the binding of GalN and GluN, for which the anomer discrimination is more dramatic than for ManN. This substantial entropic contribution is also consistent with recent experimental binding data for polysaccharides with synthetic lectins, [18] for which it was reported that entropy sometimes contributed more to the binding than enthalpy.…”

Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives

“…To the best of our knowledge, this is the highest affinity that has been measured for a biomimetic receptor binding a small, electrically neutral monosaccharide derivative in water. Receptor 9 also showed good affinities for GlcNAc 14 (10 times higher than 4 )4e and methyl β‐ d ‐glucoside ( 15 ; 5 times higher than the previous record) 4a. Surprisingly, α‐GlcNAc derivative 13 , with an axial OMe group, was also bound fairly strongly.…”

“…In 4 , the hydrophobic surfaces are provided by biphenyls, which are readily introduced and provide adequate CH–π interactions. However, biphenyls are prone to twisting, which disrupts contact with axial CH groups, while condensed aromatic compounds are planar 4a,4b. A 1,3,6,8‐tetrasubstituted pyrene is geometrically equivalent to the biphenyls in 4 , so tricyclic cage 5 was identified as a promising design.…”

“…A 1,3,6,8‐tetrasubstituted pyrene is geometrically equivalent to the biphenyls in 4 , so tricyclic cage 5 was identified as a promising design. Based on recent work,3a, 4a receptor 5 was provided with more powerful water‐solubilizing groups than 4 ; pyrenes are strongly inclined to self‐associate in water, and this needed to be countered for reliable binding characterization.…”

Platform Synthetic Lectins for Divalent Carbohydrate Recognition in Water

“…2 ), and have yielded encouraging results. Selectivities are good, and some affinities are above 10 4   m −1 , even for uncharged substrates 9a,9b. However, the selectivity for all‐equatorial carbohydrates is a constraint on potential applications, as many substrates of interest do not belong to this family.…”