Saccharide receptor achieves concentration dependent mannoside selectivity through two distinct cooperative binding pathways

Binding Studies on a Library of Induced‐Fit Synthetic Carbohydrate Receptors with Mannoside Selectivity

“…Upon association,d istinct shifts occurred in the peaks corresponding to all the identifiable protons of both receptor and glycan, which indicates complexation-induced changes in chemical environments. In combination with mass spectrometry data as well as our previous studies on the binding of 1, [31] we attribute these changes in d to the supramolecular association between the receptors and the variouso ctyloxy glycans. In the spectra in Figure 3A,t he largest shift of the b-Man proton peaks corresponds to the H 5 peak, which shifts 0.13 ppm upfield.…”

“…Determining K a from NMR peak shift data requires choosing an appropriate model that accountsf or all the equilibria present and fitting the peak shifts to these modelst oe xtract K a values. [31] We have previously shownt hat for the association between 1 and b-Man in CDCl 3 ,m ultiple equilibria, including 1:1, 1:2, and 2:1 b-Man:1,o ccur.W ith the exception of the binding between 1 and b-Man, we found no evidenceo ft hese higher order complexes from the peak fitting (see Supporting Information), which is consistent with the resultsf rom ESI-MS spectra.S oa1 :1 binding model was considered to fit the titration dataw ith the exception of the 1:b-Man system,w here a 1 2 :b-Man equilibrium was also considered. In the case of 1:b-Man system, the titrationd ata did not fit wellw hen only a1 :1 binding model was considered.…”

“…Based on prior work by the groups of Roelens [19] and Mazik,[20] we reasoned that receptors with different H-bond donors and acceptorsm ay differ in their specificities to the carbohydrate guests as ar esult of differences in noncovalentb ondingw ith the sugars.T he structuralv ariations exploredh ere consist of changing the heterocyclest oi nclude furan, thiophene, and Nmethyli midazole groups with amine, imine, and amide linkages of the heterocycle to the biaryl core, and increasing receptor valency by linking two biaryl cores with an oligoethylene glycol chain, the latter inspired from previouss tudies showing 1 binds b-Glc and b-Man in a2:1 host-guest stoichiometry. [31] All receptors were synthesized from the commont etraazide intermediate 11 [31] (Scheme 1). The amine-basedr eceptors 1-4 were prepared from intermediate 11 in ao ne-pot procedure involving three reactions occurring on each of the four azide sites.…”

“…The K a values increasew ith decreasing temperature, suggesting that the binding is entropically disfavored, whichi sc onsistentw ith previous studies of the binding of 1 with b-Man. [31] The obtained K a values were subjected to av an't Hoff analysis to determine DH o and DS o for the binding of 10 to b-Man, and values of À28.5 kcal mol À1 and À81.3 e.u. were determined, respectively (see Supporting Information).…”

“…To this end, we have reported previously ah ighly flexible tetrapodal synthetic carbohydrate receptor 1 ( Figure 1B)t hat possessesf our aminopyrroles organized around biaryl core that binds a-mannosides preferentially in chloroform through H-bondinga nd CÀH···p interactions in concert with multivalent and cooperative equilibria. [31] This receptor is one of only very few synthetic carbohydrate receptorss of ar reported that are selectivefor mannose. [19a,c,e,f,g,m] Like naturalg lycan-binding proteins, this receptor is promiscuousa nd forms 1:1c omplexes in CHCl 3 with all monosaccharides assayed, and selectivity as high as 16.8:1 a-Man: a-Gal and 1.5:1 a-Man:b-Glc is achieved as a result of 2:1a nd 1:2r eceptor-substratec omplexes.T hisr eceptor demonstrates the potentialo fflexible scaffolds for addressing the unmet challengeo fc reatings ynthetic carbohydrate receptors that possess non-glucosidic selectivities.…”