Enthalpic Nature of the CH/π Interaction Involved in the Recognition of Carbohydrates by Aromatic Compounds, Confirmed by a Novel Interplay of NMR, Calorimetry, and Theoretical Calculations

Abstract

Specific interactions between molecules, including those produced by a given solute, and the surrounding solvent are essential to drive molecular recognition processes. A simple molecule such as benzene is capable of recognizing and differentiating among very similar entities, such as methyl 2,3,4,6-tetra-O-methyl-alpha-D-galactopyranoside (alpha-Me(5)Gal), methyl 2,3,4,6-tetra-O-methyl-beta-D-galactopyranoside (beta-Me(5)Gal), 1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose (beta-Ac(5)Gal), and methyl 2,3,4,6-tetra-O-methyl-alpha-D-mannopyranoside (alpha-Me(5)Man). In order to determine if these complexes are formed, the interaction energy between benzene and the different carbohydrates was determined, using Calvet microcalorimetry, as the enthalpy of solvation. These enthalpy values were -89.0 +/- 2.0, -88.7 +/- 5.5, -132.5 +/- 6.2, and -78.8 +/- 3.9 kJ mol(-1) for the four complexes, respectively. Characterization of the different complexes was completed by establishing the molecular region where the interaction takes place using NMR. It was determined that beta-Me(5)Gal is stabilized by the CH/pi interaction produced by the nonpolar region of the carbohydrate on the alpha face. In contrast, alpha-Me(5)Man is not specifically solvated by benzene and does not present any stacking interaction. Although alpha-Me(5)Gal has a geometry similar to that of its epimer, the obtained NMR data seem to indicate that the axial methoxy group at the anomeric position increases the distance of the benzene molecules from the pyranose ring. Substitution of the methoxy groups by acetate moieties, as in beta-Ac(5)Gal, precludes the approach of benzene to produce the CH/pi interaction. In fact, the elevated stabilization energy of beta-Ac(5)Gal is probably due to the interaction between benzene and the methyl groups of the acetyls. Therefore, methoxy and acetyl substituents have different effects on the protons of the pyranose ring.

Dynamic Peptides as Biomimetic Carbohydrate Receptors

“…The complex must result from a combination of hydrogen-bonding and C À H/p interactions. [2,5,11] Furthermore, we emphasize that the interaction is highly selective since only trehalose but not sucrose (or any of the methylglucosides) amplifies TyrTyr, and (conversely) trehalose amplifies TyrTyr but not PhePhe.…”

“…[10] These synthetic lectins are tripods of (cationic) N-heterocycles, and it is likely that HisHis binds NANA in a similar way as a result of a combination of hydrogen-bonding and CÀH/p interactions. [11] It should be emphasized that an ITC titration of HisHis with acetic acid and with the methyl ester of NANA as well as an ITC titration of l-histidine with NANA showed no significant interaction. In addition, the NMR titration of HisHis with the methyl ester of NANA showed no significant shifts.…”

“…The complex must result from hydrogen bonding and some type of hydrophobic interaction. [2,5,11] The methyl group of MFP is essential since none of the other methylglucosides (or disaccharides) amplifies ThrThr. Moreover, MFP amplifies ThrThr but not SerSer.…”

Aromatic interactions at the catalytic subsite of sucrose phosphorylase: Their roles in enzymatic glucosyl transfer probed with Phe52 → Ala and Phe52 → Asn mutants

“…Phosphate was constant at 50 mM. 2 Phosphate concentration was varied at 17 levels between 0.01 and 140 mM for the wild-type enzyme. For the mutants, phosphate was varied at 11 levels between 1 and 250 mM.…”

Dynamische Peptide als biomimetische Kohlenhydratrezeptoren

“…[10] Diese synthetischen Lektine sind Tripoden aus (kationischen) N-Heterocyclen, und wahrscheinlich bindet HisHis NANA mit einer ähnlichen Kombination aus Wasserstoffbrückenbindungen und CÀH/pWechselwirkungen. [11] Es muss betont werden, dass eine ITCTitration von HisHis mit Essigsäure und mit dem Methylester von NANA sowie eine ITC-Titation von l-Histidin mit NANA keine signifikante Wechselwirkung ergaben. Ebenso konnten bei der NMR-Titration von HisHis mit dem Methylester von NANA keine signifikanten Verschiebungen beobachtet werden.…”