Calorimetric Measurement of the CH/π Interaction Involved in the Molecular Recognition of Saccharides by Aromatic Compounds

Abstract

Can a benzene molecule differentiate between two isomeric carbohydrates? It is generally accepted that two factors govern molecular recognition: complementarity and preorganization. Preorganization requires the presence of cavities for positioning the host's groups of complementary nature to those of the guest. This study shows that, in fact, groups should be complementary to recognize each other (for the case presented here, it is controlled by the CH/pi interaction) but preorganization is not essential. Since weak interactions have their origin in dispersion forces, they also have impact on the enthalpic term of the free energy, so it was considered that their participation can be demonstrated by measuring the energy involved. For recognition to happen, two conditions must be satisfied: specificity and associated stabilizing energy. In this study we evaluated the heat of dissolution of different carbohydrates such as methyl 2,3,4,6-tetra-O-methyl-alpha-d-mannopyranoside and methyl 2,3,4,6-tetra-O-methyl-beta-d-galactopyranoside using different aromatic solvents. The solvation enthalpies in benzene were -78.8 +/- 3.9 and -88.7 +/- 5.5 kJ mol(-1) for each carbohydrate, respectively; and these values yielded a CH/pi energy of interaction of 9.9 kJ mol(-1). In addition, NMR studies of the effect of the addition of benzene to chloroform solutions of the two carbohydrates showed that benzene specifically interacts with the hydrogen atoms of the pyranose ring at positions 3, 4, and 5 located on the alpha face of the methyl-beta-galactoside, so it is, in fact, able to recognize it. Thus, the interactions between carbohydrates and the aromatic residues of proteins occur in the absence of the confinement generated by the protein structure. By experimentally measuring the energy associated with this interaction and comparing it to theoretical calculations, it was also possible to unequivocally determine the existence of CH/pi interactions between carbohydrates and proteins.

Three‐Dimensional Potential Energy Surface of Selected Carbohydrates’ CH/π Dispersion Interactions Calculated by High‐Level Quantum Mechanical Methods

“…A similar interaction energy value for the CH/p interaction has been observed by Bautista-Ibanes et al using calorimetric experiments. [21] They have also shown, using 1 H NMR experiments, that all three hydrogen atoms of the apolar face of the mannopyranose derivate, namely H1, H3, H5, are involved in the interaction. The inclusion of all apolar CH hydrogen atoms in the CH/p interaction in solution have also been suggested by the IR experiments.…”

“…[18] This shows that these interactions are not simply hydrophobic but they can exist without solvent effects and physical attractive forces play an important role. These complexes were also studied by IR experiments in gas phase and in solution, [19,20] calorimetric experiments in solution [21] and NMR experiments. [17,[22][23][24][25] These interactions are also often considered examples of CH/p interactions.…”

An evaluation of the GLYCAM06 and MM3 force fields, and the PM3-D* molecular orbital method for modelling prototype carbohydrate–aromatic interactions

“…In these structures, the aromatic group interacts with either the upper or the lower face of the sugar. The most stable group of complexes (8,9,10) involves the interaction of the arene with one O-H and one C-H group of the upper face of the sugar. The next group of complexes (1, 2, 3, 5, and 6) is higher in energy by 1-3 kcal mol −1 , and, except for (3), involve the interaction of only C-H groups of the lower face of the sugar.…”

“…Amino acids having aromatic side chains (tryptophan, tyrosine and phenylalanine) are frequently found in protein active sites which recognize carbohydrates, and the importance of the associated arene-carbohydrate interactions is well recognized [6][7][8][9]. A number of experimental [10,11] and theoretical [12][13][14][15] studies have shown that there are major contributions to these intermolecular interactions involving the aliphatic C-H and O-H groups which point towards the aromatic system. The corresponding protein crystal structures display mainly C-H-interactions, but in the binary complexes, fucose-toluene and ␣-methyl glucose-toluene, the most stable structures involve O-H-interactions, which are reflected in their infrared spectra [11].…”

Magnitude of CH/O interactions between carbohydrate and water

“…The carbohydrate-aromatic interactions, which are sometimes denoted as CH/p interactions, were used for recognition of carbohydrates by artificial receptors [11][12][13][14]. The carbohydrate-aromatic interactions have been studied extensively both by experimental [15][16][17][18][19][20][21][22][23] and by theoretical [24][25][26][27][28][29][30][31][32][33][34][35] methods. The carbohydrate recognition processes involve desolvation of water molecules from the carbohydrate molecule.…”