Scheiner S, Hillenbrand E A
Proc Natl Acad Sci U S A. 1985 May;82(9):2741-5. doi: 10.1073/pnas.82.9.2741.
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 of the dipole moment vector of the 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.
采用从头算分子轨道方法研究了不同基团对质子的竞争。研究发现，参与氢键的两个基团的重新取向可以改变它们之间共享质子的平衡位置。具体而言，用H₂CO和HOH分别模拟羰基和羟基。在这两个基团之间的氢键中，当羟基沿着羰基氧的孤对电子排列时，质子与羰基结合形成(H₂COH…OH₂)⁺比与羟基结合形成(H₂CO…HOH₂)⁺更有利。然而，当水向两个羰基孤对电子之间的C = O轴位移时，情况会发生逆转，(H₂CO…HOH₂)⁺更稳定。在涉及席夫碱（用CH₂NH模拟）和胺（NH₃）的氢键中也观察到了类似的稳定性逆转。在一种排列中，两个基团的孤对电子相互指向，质子更倾向于与席夫碱结合而不是胺——即(H₂CHNH…NH₃)⁺比(H₂CHN…HNH₃)⁺更稳定。另一方面，胺的孤对电子从席夫碱氮原子处旋转离开会导致质子转移到胺上。这些稳定性的变化对应于相关基团相对pK值的逆转。计算得出的一个基本原理是，离子 - 偶极静电相互作用有利于质子转移到与另一个偶极矩矢量负端尽可能靠近的基团上。这里提出的观点表明了许多方法，通过这些方法，构象变化可用于在蛋白质分子（如酶或细菌视紫红质）内将质子从一个残基转移到另一个残基。
