RESUMO
Chains of hydrogen bonds such as those found in water and proteins are often presumed to be more stable than the sum of the individual Hâ bonds. However, the energetics of cooperativity are complicated by solvent effects and the dynamics of intermolecular interactions, meaning that information on cooperativity typically is derived from theory or indirect structural data. Herein, we present direct measurements of energetic cooperativity in an experimental system in which the geometry and the number of Hâ bonds in a chain were systematically controlled. Strikingly, we found that adding a second H-bond donor to form a chain can almost double the strength of the terminal Hâ bond, while further extensions have little effect. The experimental observations add weight to computations which have suggested that strong, but short-range cooperative effects may occur in H-bond chains.
RESUMO
Hydrogen bonds are ubiquitous interactions in molecular recognition. The energetics of such processes are governed by the competing influences of pre-organization and flexibility that are often hard to predict. Here we have measured the strength of intramolecular interactions between H-bond donor and acceptor sites separated by a variable linker. A striking distance-dependent threshold was observed in the intramolecular interaction energies. H-bonds were worth less than -1 kJ mol-1 when the interacting groups were separated by ≥6 rotating bonds, but ranged between -5 and -9 kJ mol-1 for ≤5 rotors. Thus, only very strong external H-bond acceptors were able to compete with the stronger internal H-bonds. In addition, a constant energetic penalty per rotor of â¼5-6 kJ mol-1 was observed in less strained situations where the molecule contained ≥4 rotatable bonds.