The Relevance of Carbohydrate Hydrogen-Bonding Cooperativity Effects: A Cooperative 1,2-trans-Diaxial Diol and Amido Alcohol Hydrogen-Bonding Array as an Efficient Carbohydrate-Phosphate Binding Motif in Nonpolar Media

• Published in: Chemistry : a European journal 2002-04, Vol.8 (8), p.1908-1914
• Main Authors: Muñoz, Eva Maria, López de la Paz, Manuela, Jiménez-Barbero, Jesús, Ellis, Gary, Pérez, Marta, Vicent, Cristina
• Format: Article
• Language: English
• Subjects: carbohydrates; Carbohydrates - chemistry; Chemical Phenomena; Chemistry, Physical; cooperative phenomena; Hydrogen Bonding; hydrogen bonds; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Monosaccharides - chemistry; Phosphates - chemistry; Spectroscopy, Fourier Transform Infrared; sugar-phosphate binding; supramolecular chemistry; Thermodynamics
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/1521-3765(20020415)8:8<1908::AID-CHEM1908>3.0.CO;2-J

Carbohydrates with suitably positioned intramolecularly hydrogen‐bonded hydroxyl and amide groups have the potential to act as efficient bidentate phosphate binders by taking advantage of σ‐ and/or σ,π‐H‐bonding cooperativity in nonpolar solvents. Donor–donor 1,2‐trans‐diaxial amido alcohol (1) and diol (3), in which one of the donor centres is cooperative, are very efficient carbohydrate–phosphate binding motifs. We have proven and quantified the key role of hydrogen‐bonding centres indirectly involved in complexation, which serve to generate an intramolecular H‐bond (six‐membered cis H‐bond) in 1 and 3. This motif enhances the donor nature of the H‐bonding centres that are directly involved in complexation. A comparison of the thermodynamic parameters of the complexes formed between phosphate and a cooperative (1‐Phos) or anti‐cooperative (2‐Phos) bidentate H‐bonded motif of a carbohydrate has allowed us to quantify the energetic advantage of H‐bonding cooperativity in CDCl3 and CDCl3/CCl4 (1:1.3) (ΔΔG °=−2.2 and −2.0 kcal mol−1, respectively). The solvent dependences of the entropy and enthalpy contributions to binding provide a valuable example of the delicate balance between entropy and enthalpy that can arise for a single process, providing effective cooperative binding in terms of ΔG °. The use of cooperativity to achieve efficient binding of the hydrogen‐bonding centres of sugar derivatives to the phosphate H‐bonding motif has been studied (see figure). The energetic contribution to binding in nonpolar solvents has been evaluated.