MOLECULAR RECOGNITION OF CYCLITOLS BY NEUTRAL POLYAZA-HYDROGEN-BONDING RECEPTORS - THE STRENGTH AND INFLUENCE OF INTRAMOLECULAR HYDROGEN-BONDS BETWEEN VICINAL ALCOHOLS

Polyaza-clefts 1, 2, and 3 were investigated as receptors for cyclohexane diols and triols (23, 24, 25) in chloroform. The receptors were designed to form hydrogen bonds to the triols from above and below the cyclohexane rings. The synthesis of the receptors was accomplished by two different routes, beginning with either the central or the peripheral pyridine rings. Binding studies performed in chloroform gave only moderate binding constants of 2-110 M(-1). For the binding of 2 with 23, Delta H = 4.5 and T Delta S at 295 K = -1.8 kcal/mol. Molecular dynamics studies suggest that binding of the triols involves the formation of four intermolecular hydrogen bonds and the cleavage of one intramolecular cyclitol hydrogen bond. IR studies confirm that the diols and triols possess intramolecular hydrogen bonds under the experimental conditions for the binding studies. The strength of the trans intramolecular hydrogen bond in trans- 1,2-cyclohexanediol is 1.93 +/- 0.08 kcal/mol, as determined by examination of the conformational equilibrium of compound 29. The strength of a cis intramolecular hydrogen bond was found to be 2.22 +/- 0.16 to 2.51 +/- 0.13 kcal/mol, as determined by measuring the equilibrium between the alpha and beta anomers of 33 and 34. When considering the strength of one intramolecular hydrogen bond, the binding constants correlate well with literature values for four hydrogen bonds in a host-guest complex. In addition, the differential strength of the cis and trans intramolecular hydrogen bonds correlates well with the selectivities of binding the triols with 1 and 2. Future saccharide receptors in nonpolar organic solvent will need to effectively compete with or complement the intramolecular hydrogen bonds to achieve large association constants.