水液相下两性组氨酸分子对映异构的密度泛函理论

DFT study on the enantiotropy of amphoteric His molecule in water-liquid phase environment

采用DFT的M06-2X和MN15杂化泛函方法,结合处理溶剂效应的SMD模型方法,对标题反应进行研究。研究发现:His分子可在α-H质子以羧基(质子化的)下面的O为桥迁移;H质子从氨基(质子化的)N迁移到质子化羧基上面的O后,α-H再以N和羧基(质子化的)下面的O分别为桥迁移;质子从氨基(质子化的)N迁移到咪唑环上的N后,α-H再以氨基(质子化的)N和羧基(质子化的)下面的O分别为桥迁移5个反应通道实现对映异构。势能面计算表明:隐性溶剂效应下5个通道决速步的自由能垒分别是245.6、238.1、297.3、270.9和257.7 kJ/mol;显性溶剂效应下这些能垒分别降到139.9、120.7、161.7、142.7和157.3 kJ/mol。结果表明,水液相下His只能少量的消旋,生命体补充His比较安全。

The title reaction was performed using the M06-2X and MN15 methods of DFT combined with the Slovation Model Density(SMD)model method based on self-consistent reaction field theory.The results showed that,His molecule can be transferred when the carbonyl O atom as the only bridge ofα-H proton,andα-H transfers with amino group N and carbonyl O atom as bridges after the proton of protonated amino group N transfers to carbonyl O atom,respectively;Also,α-H achieves enantiotropy in five channels using amino group N and carbonyl group O as bridges after the proton transfers from the protonated amino group N to the N of the imidazole ring,respectively.Investigation on the potential energy surface showed that the free energy barriers of rate-determining step for each of the five channels are 245.6,238.1,297.3,270.9 and 257.7 kJ/mol under the effect of recessive solvent;the energy barriers are reduced to about 139.9,120.7,161.7,142.7 and 157.3 kJ/mol under the effect of dominant solvent.The results show that His can racemize with a small amount in the water-liquid environment,and it is relatively safe to be used to supply His for life.