水液相环境下氢氧根水分子簇催化布洛芬旋光异构及质子的作用
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摘要
采用基于密度泛函理论的B3LYP方法和从头算的MP2方法,结合自洽反应场理论的SMD模型,研究了布洛芬(Ibu)分子2种稳定构象的旋光异构反应。研究发现:Ibu的旋光异构有氢氧根拔α-氢和氢氧根水分子簇联合拔α-氢两种机理。势能面计算表明:对于构象1,氢氧根拔α-氢时旋光异构的决速步骤能垒为42.69kJ·mol~(-1),氢氧根水分子簇联合拔α-氢时旋光异构的决速步骤能垒为48.83kJ·mol~(-1);对于构象2,氢氧根拔α-氢时旋光异构的决速步骤能垒为38.73kJ·mol~(-1),氢氧根水分子簇联合拔α-氢时旋光异构的决速步骤能垒为50.72kJ·mol~(-1)。质子的存在会使Ibu旋光异构反应的后半程变成无势垒放热反应。结果表明,水液相碱性环境下布洛芬分子可以较快地旋光异构,质子与氢氧根离子共存会使Ibu旋光异构的反应速度更快。
The hybrid density functional B3 LYP and ab initio MP2 methods combined with SMD solvation model of self-consistent reaction field theory were used to study the optical isomerism reactions of two stable conformations of ibuprofen(Ibu)molecules.It is found that there are two mechanisms of the optical isomerism of ibuprofen.One isα-H eliminated by hydroxyl ion,and the other isα-H eliminated by hydroxyl ion and water molecule cluster.The calculation of potential energy surface shows that,for conformation 1,the rate-determining step energy barrier of optical isomerism is 42.69kJ·mol~(-1) forα-H eliminated by hydroxyl and that is 48.83kJ·mol~(-1) forα-H eliminated by hydroxyl ion and water molecule cluster;for conformation 2,the corresponding rate-determining step energy barriers are38.73kJ·mol~(-1) and 50.72kJ·mol~(-1),respectively.The existence of protons makes the late half stage of optical isomerism reaction become a barrier-free exothermic reaction.The results indicate that the optical isomerism of ibuprofen molecules can become very quick in the water alkaline liquid phase environment,and the coexistence of protons and hydroxide ions makes the reaction of ibuprofen optical isomerization faster.
The hybrid density functional B3 LYP and ab initio MP2 methods combined with SMD solvation model of self-consistent reaction field theory were used to study the optical isomerism reactions of two stable conformations of ibuprofen(Ibu)molecules.It is found that there are two mechanisms of the optical isomerism of ibuprofen.One isα-H eliminated by hydroxyl ion,and the other isα-H eliminated by hydroxyl ion and water molecule cluster.The calculation of potential energy surface shows that,for conformation 1,the rate-determining step energy barrier of optical isomerism is 42.69kJ·mol~(-1) forα-H eliminated by hydroxyl and that is 48.83kJ·mol~(-1) forα-H eliminated by hydroxyl ion and water molecule cluster;for conformation 2,the corresponding rate-determining step energy barriers are38.73kJ·mol~(-1) and 50.72kJ·mol~(-1),respectively.The existence of protons makes the late half stage of optical isomerism reaction become a barrier-free exothermic reaction.The results indicate that the optical isomerism of ibuprofen molecules can become very quick in the water alkaline liquid phase environment,and the coexistence of protons and hydroxide ions makes the reaction of ibuprofen optical isomerization faster.
引文
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[2] CHENG H,ROGERS J D,DEMETRIADES J L,et al.Pharmacokinetics and bioinversion of Ibuprofen enantiomers in humans[J].Pharmaceutical Research,1994,11(6):824-830.DOI:10.1023/A:1018969506143.
[3]代卫国,何丹农.手性布洛芬对映体的选择性光电化学氧化[J].物理化学学报,2017,33(5):960-967.DOI:10.3866/PKU.WHXB201702086.DAI W G,HE D N.Selective photoelectrochemical oxidation of chiral Ibuprofen enantiomers[J].Acta Physico-Chimica Sinica,2017,33(5),960-967.DOI:10.3866/PKU.WHXB201702086(Ch).
[4]郭慧卿,成日青,陈建平,等.布洛芬热分解及其动力学研究[J].广州化工,2015,43(7):100-102.GUO H Q,CHENG R Q,CHEN J P,et al.Thermal behavior and decomposition kinetics of Ibuprofen[J].Guangzhou Chemical Industry,2015,43(7):100-102(Ch).
[5]邹晓威,梅泽民,王丽萍,等.孤立条件下布洛芬分子手性转变过程的理论研究[J].原子与分子物理学报,2015,32(2):173-180.DOI:103969/j.issn.1000-0364.2015.02.001.ZOU X W,MEI Z M,WANG L P,et al.The theoretical research on the chiral transition of Ibuprofen molecules under isolated conditions[J].Journal of Atomic and Molecular Physics,2015,32(2):173-180.DOI:103969/j.issn.1000-0364.2015.02.001(Ch).
[6]梅泽民,王佐成,赵衍辉,等.水环境下布洛芬分子的手性转变机理[J].吉林大学学报(理学版),2015,53(2):331-339.DOI:10.13413/j.cnki.jdxblxb.2015.02.34.MEI Z M,WANG Z C,ZHAO Y H,et al.Theoretical research of chiral shift mechanism of Ibuprofen molecule under water environment[J].Journal of Jilin University(Science Edition),2015,53(2):331-339.DOI:10.13413/j.cnki.jdxblxb.2015.02.34(Ch).
[7]高峰,王佐成,闫红彦,等.布洛芬分子手性转变裸反应机理及水分子的催化作用——基于羰基和苯环作H迁移桥梁[J].中山大学学报(自然科学版),2016,55(6):115-124.DOI:10.13471/j.cnki.acta.snus.2016.06.018.GAO F,WANG Z C,YAN H Y,et al.Bare reaction mechanism of chiral transition of ibuprofen molecules and the catalysis of water molecules using carbonyl and benzene ring as H transfer bridge[J].Acta Scientiarum Naturalium Universitatis Sunyatsen,2016,55(6):115-124.DOI:10.13471/j.cnki.acta.snus.2016.06.018(Ch).
[8]王佐成,梅泽民,吕洋,等.扶手椅型单壁碳纳米管的尺寸对布洛芬分子手性转变的限域影响[J].复旦学报(自然科学版),2015,54(2):234-244.DOI:10.15943/j.cnki.fdxb-jns.2015.02.013.WANG Z C,MEI Z M,LY,et al.The confined affect of the size of armchair single-walled carbon nanotubes(SWCNT)on the chiral transition of Ibuprofen molecule[J].Journal of Fudan University(Natural Science),2015,54(2):234-244.DOI:10.15943/j.cnki.fdxb-jns.2015.02.013(Ch).
[9]孙永清,王佐成,高峰,等.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[J].复旦学报(自然科学版),2016,55(6):739-749.DOI:10.15943/j.cnki.fdxb-jns.2016.06.012.SUN Y Q,WANG Z C,GAO F,et al.Theoretical research on the co-catalysis of water and MOR zeolite combined environment on the chiral transition of Ibuprofen molecules[J].Journal of Fudan University(Natural Science),2016,55(6):739-749.DOI:10.15943/j.cnki.fdxb-jns.2016.06.012(Ch).
[10]TIAN C J,PENG X,WANG Z G,et al.Enantiomerization mechanism of thalidomide and the role of water and hydroxide ions[J].Chemistry-A European Journal,2012,18(45):14305-14313.DOI:10.1002/chem.201202651.
[11]赵晓波,佟华,杨晓翠,等.水环境下氢氧根水分子团簇催化赖氨酸旋光异构及羟自由基致损伤的机理[J].中山大学学报(自然科学版),2018,57(5):88-97.DOI:10.13471/j.cnki.acta.snus.2018.05.011.ZHAO X B,TONG H,YANG X C,et al.Mechanism of optical isomerism of lysine catalyzed by hydroxide ion-water clusters and the damage induced by hydroxyl radicals in water environment[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2018,57(5):88-97.DOI:10.13471/j.cnki.acta.snus.2018.05.011(Ch).
[12]杨晓翠,高峰,佟华,等.水液相环境下α-丙氨酸分子的旋光异构及氢氧根和羟基自由基的作用[J].武汉大学学报(理学版),2019,65(1):19-29.DOI:10.14188/j.1671-8836.2019.01.003.YANG X C,GAO FENG,TONG H,et al.Optical isomerization ofα-Alanine molecules and roles of hydroxyl ions and hydroxyl radicals in water liquid phase environment[J].Journal of Wuhan University(Natural Science Edition),2019,65(1):19-29.DOI:10.14188/j.1671-8836.2019.01.003(Ch).
[13]MARENICH A V,CRAMER C J,TRUHLAR D G,et al.Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions[J].The Journal of Physical Chemistry B,2009,113(18):6378-6396.DOI:10.1021/jp810292n.
[14]BECKE A D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].Chemistry Physics,1993,98(7):5648-5652.DOI:10.1063/1.464913.
[15]BINKLEY J S,POPLE J A.Moller-Plesset theory for atomic ground state energies[J].International Journal of Quantum Chemistry,1975,9(2):229-236.DOI:10.1002/qua.560090204.
[16]GARRETT B C,TRUHLAR D G.Criterion of minimum state density in the transition state theory of bimolecular reactions[J].The Journal of Chemical Physics,1979,70(4):1593-1598.DOI:10.1063/1.437698.
[17]GONZALEZ C,SCHLEGEL H B.Reaction path following in mass-weighted internal coordinates[J].Journal of Physical Chemistry,1990,94(14):5523-5527.DOI:10.1021/j100377a021.
[18]FRISCH M J,TRUCKS G W,SCHLEGEL H B,et al.Gaussian09.Revision E.01[CP].Pittsburgh:Gaussian Inc,2013.
[19]AND L G,LESZCZYNSKI J.Intramolecular proton transfer in mono-and dihydrated tautomers of guanine:An ab initio post Hartree-Fock study[J].Journal of the American Chemical Society,1998,120(20):5024-5032.DOI:10.1021/ja972017w.