水与MOR分子筛复合环境对布洛芬分子手性转变反应共催化的理论研究

Theoretical Research on the Co-catalysis of Water and MOR Zeolite Combined Environment on the Chiral Transition of Ibuprofen Molecules

采用量子力学与分子力学组合的ONIOM方法,研究布洛芬限域在水与MOR分子筛复合环境的手性转变.结构研究表明:1,2个和3个水分子助氢迁移反应的过渡态分子氢键键角不断增大,3个水分子助氢迁移反应的10元环过渡态结构明显偏离平面.反应通道研究发现:标题反应有a1,a2和b三个通道.a1和a2是经过水助羧基内质子迁移和质子以新羰基氧为桥从手性碳向苯环迁移的共同历程后,再分别直接迁移到手性碳的另一侧和以新羰基氧为桥迁移到手性碳的另一侧;b是水助质子以羰基氧为桥从手性碳的一侧迁移到另一侧.势能面计算表明,a2是主反应通道,在2个水分子助质子迁移反应时,决速步吉布斯自由能垒被降到最低值124.3kJ·mol-1,与裸反应、限域在MOR分子筛和限域在水环境的此通道决速步能垒287.1,263.4kJ·mol-1和152.2kJ·mol-1相比较,均有明显降低.结果表明:水与MOR分子筛复合环境对布洛芬手性转变具有较好的共催化作用,可作为理想的实现布洛芬手性转变的纳米反应器.

The chiral transition of ibuprofen molecules confined in water and MOR zeolite combined environment was studied by introducing the ONIOM methods using combination of quantum mechanics and molecular mechanics.The molecular structure researches show that hydrogen bond angles of the transition state molecules increases constantly in the hydrogen transfer reactions with the help of one water molecule,two and three molecules,respectively,and the 10-ring transition state structures in the hydrogen transfer reactions with the help of three water molecules significantly deviates from the plane.The study of reaction channels shows there are three channels a1,a2 and b in the title reaction.The protons transfer with the help of water molecules in carboxyl and from the chiral C to the benzene ring using the carboxyl O as the bridge,and then transfer to the other side of the chiral carbon directly or with new carbonyl O as a bridge in the channels a1 and a2,respectively.In channel b,the protons transfer with the help of water molecules transfer from one side to the other of the chiral C with carbonyl O as a bridge.Calculations of potential energy surface show a2 channel is the dominant reaction path,where the rate determined step of Gibbs free energy barrier of two water-assisted proton transfers reaction is reduced to the minimum value 124.3 kJ · mol^-1, which is significantly lower than the Gibbs free energy barrier287.1kJ·mol^-1,263.4kJ·mol^-1 and 152.2kJ·mol^-1 respectively corresponding to the bare reaction,confined in MOR zeolite and confined in water environment.The results show that water and MOR zeolite combined environment has a good co-catalysis on the chiral transition of ibuprofen molecules and can be used as an ideal nano reactor for the realization of ibuprofen molecules chiral transition.