The competition between various groups for a proton is studied by ab initio molecular orbital methods. It is found that reorientations of the two groups involved in a H-bond can reverse the equilibrium position of the proton shared between them. Specifically, the carbonyl and hydroxyl groups were modeled by H2CO and HOH. In the H-bond between these two groups, association of the proton with the carbonyl (H2COH.OH2)+ is favored over the hydroxyl (H2CO-..HOH2)+ when the latter group is situated along a lone pair of the carbonyl oxygen. However, displacement of the water to the C=O axis between the two carbonyl lone pairs reverses the situation and (H2CO HOH2)+ is more stable. A similar reversal of stability is observed in the H-bond involving a Schiff base (modeled by CH2NH) and amine (NH3). In one arrangement where the lone pairs of the two groups point toward one another, the proton prefers the Schiff base to the amine-i.e., (H2CHNH.NH3)+ is more stable than (H2CHN..HNH3)+. On the other hand, rotation of the lone pair of the amine away from the Schiff base nitrogen results in proton transfer across to the amine. These shifts in stability correspond to reversal of relative pK of the groups involved. A fundamental principle emerging from the calculations is that ion-dipole electrostatic interactions favor transfer of a proton to the group that is positioned as closely as possible to the negative end ofthe dipole moment vector ofthe other. The ideas developed here suggest a number of means by which conformational changes may be utilized to shift protons from residue to residue within a protein molecule such as an enzyme or bacteriorhodopsin.
Results of quantum mechanical calculations are presented that suggest a number of mechanisms whereby protons may be shifted from one group to another along an H bond. The first factor to be considered is a stretching of the bond that drastically raises the energy barrier to transfer. It is possible to predict barriers for an arbitrary system based only on results for a simple system and knowledge of the relevant bond length in the isolated subsystems. Factors that increase the intrinsic basicity of the B group in A-H-B lead not only to a lowering of the energy of the A-HB state relative to AH-B but also to a reduction in the barrier to transfer of the proton from A to B. Ions in the vicinity of the H bond exert a powerful influence and can shift the proton to the less basic group across a gradient of several pK units. Rather than shielding the proton from the external ion, the H bond acts instead to amplify the effects of the electric field. Reorientation of the A and B groups relative to one another, i.e., bends of the H bond, also produce surprisingly large changes in the relative energies of the AH-B and A-HB states. Such bends are capable of pushing the proton across to the normally less basic group, providing a mechanism of coupling conformational changes to proton "pumping" activity.,tt is found that the high and low pH states of a given H bond can have dramatically different relative populations of the AH-B and A-HB configurations. These observations are explained in terms of fundamental concepts involving electrostatic interaction energies.
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