5-甲基胞嘧啶质子转移及脱氨反应机理的理论研究
|
摘要
作为异构平衡和氧化还原反应中最简单和最基本的现象之一,分子内或分子间质子转移在很多化学过程中起着重要的作用。质子转移可以沿着有机分子之间形成的氢键进行传递,这种转移与分子体系的能量传递和电子转移同样重要,几乎所有的有机化学反应中都包含了全部或者部分质子转移过程,质子转移在分子间信息传递具有重要作用,氢键的形成和质子转移现象在众多化学过程中很常见而且很重要,因为许多化学,物理和生物过程都包括这种键的形成和断裂。
本论文中采用密度泛函理论在B3LYP/6-31+G*基组水平研究了5-甲基胞嘧啶在水分子和六种氨基酸残基辅助下的质子转移异构化反应及水解脱氨反应。论文主要包括以下三个方面的内容:
1、对于水分子辅助的5-甲基胞嘧啶异构化反应,由于反应的环境中均存在水,因此水分子可能参与分子内的质子转移过程,当水分子参与质子转移时可以形成六元或八元环的结构,水分子参与了过渡态的形成,改变了质子转移的反应途径,质子转移由分子内的直接转移过程变为通过水分子的质子交换传递过程,反应势垒小于直接质子转移过程,因此水在5-甲基胞嘧啶异构化反应中起到非常重要的作用。
2、我们用醋酸,乙酰胺,甲基亚氧基甲二胺,甲醇,甲胺,p-甲酚等六种模拟氨基酸残基化合物辅助5-甲基胞嘧啶异构化反应,得出结论,形成八元环状结构的异构化过程的辅助效果好于形成六元环状结构的异构化过程的辅助效果,其中乙酸中的羧基作辅助基团,质子转移所跨越正向反应能垒最低,其正向反应能垒为16.39KJ.mol~(-1)。
3、研究结果表明,5-甲基胞嘧啶可以通过水解方式脱去环外氨基生成胸腺嘧啶,水解脱氨过程分三步完成,反应的第一步,5-甲基胞嘧啶在水分子作用下异构化生成亚氨式结构,第二步为碱基与水分子加成反应形成中间体的过程,水分子中带负电荷的O进攻碱基骨架上与氨基相连的C=N双键中带正电荷的C,水分子中带正电荷的H进攻C=N双键中带负电荷的N,形成四元环结构的过渡态,该过程属于偶极加成反应。在过渡态中O-H键和C=N键部分断裂,H...N键和O...C之间的键部分形成,形成的四元环平面基本垂直于5-甲基胞嘧啶骨架。第三步为中间体脱氨形成产物的过程。这一步中,羟基O-H中的H进攻氨基上的N,同样形成一个四元环的过渡态,随着N-H键的形成和N-C键的彻底断裂,NH_3基本形成,随着原羟基中的O逐渐靠近碱基骨架平面,氨基的逐渐远离,生成了水解脱氨产物胸腺嘧啶。
总之,通过对5-甲基胞嘧啶异构化、水解脱氨等过程的理论研究,初步阐明了上述过程的分子机制和热力学行为。
As one of the simplest and most basic phenomenons in the isomerization balance and redox reaction,proton transfer(PT)in intra- and inter- molecule plays an important role in many chemical processes,proton transfer can passed through hydrogen bonds formed between organic molecules.Such transfer is as important as energy transfer and electronic transfer which are in molecular system,almost all organic reactions have included all or part of the proton transfer process.Proton transfer plays an important role in the transmission of information between molecules.Hydrogen bond formation and proton transfer phenomena in many chemical processes are very important and common,because many chemical, physical and biological processes involve the forming and breaking of this kind of bonds.
In this paper,we investigate the intramolecular or intermolecular proton transfers(PTs)isomerization under the assistant of water molecular or the six simulated acid residues compounds and the hydrolysis deamination using the density functional theory at 6-31+G~* bases set level.The main contents of the paper contain 3 parts,just as follows:
1.water-catalyzed pathways of the 5—methylcytosine isomerization.Because these processes can occur in the water solution,maybe the water molecule participate in the proton transfer.When water is involved in the proton transfer,the transition state has a structure of six-member or eight-member ring.The results show that the water molecule takes part in the forming of transition state.The reaction path or mechanism is changed due to the participating of water,the proton transfer is one kind of exchange process between water and another molecule,the barrier of exchange process is much smaller than direct proton transfer.So the water plays an important role in the proton transfer of the 5—methylcytosine isomerization.
2.We have chosen six kinds of compounds(CH_3COOH,CH_3CONH_2, CH_3-NH-C(NH)-NH_2,CH_3NH_2,CH_3OH,and CH_3-C_6H_4-OH)to simulate amino acid catalyzed pathways for the 5-methylcytosine isomerization.In the six compounds,the combining of the carboxyl of the CH_3COOH is most favorable for the proton transfer of 5-methylcytosine.In this proton transfer process,it must surmount a energy barrier of 16.39 KJ.mol~(-1)for this proton transfer process.
3.5—methylcytosine have amino out of ring can be changed by hydrolysis.The products of amino hydrolysis are thymine.The hydrolysis deamination includes three steps,In the first step,5—methylcytosine isomerization with water molecules, In the second steps,the O(negative charge)of water attack the C(positive charge) of C=N and the H(positive charge)of water attack the N(negative charge)of C=N linked directly with amino,and the transition state with a new-formed four-member ring is produced.This process belongs to dipole addition reaction.In the transition state of this step,the bond of O-H and the bond of C=N are broken partly,and the bond H...N and bond O...C are formed partly.The new-formed four-member ring has a structure of plane,but it is not coplanar with base skeleton.In the third steps, the H of OH attacks the N of amino.The transition states also have a four-member ring.Accompany with the forming N-H a single bond and the bond between N of amino and C of base is weaken greatly,the skeleton of NH_3 is formed in the rough. Along with the leaving of amino,the O of hydroxyl is more and more closed to the plane of base skeleton,the products of amino hydrolysis are thymine.
In summary,the research of the isomerization,the hydrolysis deamination of 5—methylcytosine unveil the information of molecule mechanism,the thermodynamic characters of these processes.
本论文中采用密度泛函理论在B3LYP/6-31+G*基组水平研究了5-甲基胞嘧啶在水分子和六种氨基酸残基辅助下的质子转移异构化反应及水解脱氨反应。论文主要包括以下三个方面的内容:
1、对于水分子辅助的5-甲基胞嘧啶异构化反应,由于反应的环境中均存在水,因此水分子可能参与分子内的质子转移过程,当水分子参与质子转移时可以形成六元或八元环的结构,水分子参与了过渡态的形成,改变了质子转移的反应途径,质子转移由分子内的直接转移过程变为通过水分子的质子交换传递过程,反应势垒小于直接质子转移过程,因此水在5-甲基胞嘧啶异构化反应中起到非常重要的作用。
2、我们用醋酸,乙酰胺,甲基亚氧基甲二胺,甲醇,甲胺,p-甲酚等六种模拟氨基酸残基化合物辅助5-甲基胞嘧啶异构化反应,得出结论,形成八元环状结构的异构化过程的辅助效果好于形成六元环状结构的异构化过程的辅助效果,其中乙酸中的羧基作辅助基团,质子转移所跨越正向反应能垒最低,其正向反应能垒为16.39KJ.mol~(-1)。
3、研究结果表明,5-甲基胞嘧啶可以通过水解方式脱去环外氨基生成胸腺嘧啶,水解脱氨过程分三步完成,反应的第一步,5-甲基胞嘧啶在水分子作用下异构化生成亚氨式结构,第二步为碱基与水分子加成反应形成中间体的过程,水分子中带负电荷的O进攻碱基骨架上与氨基相连的C=N双键中带正电荷的C,水分子中带正电荷的H进攻C=N双键中带负电荷的N,形成四元环结构的过渡态,该过程属于偶极加成反应。在过渡态中O-H键和C=N键部分断裂,H...N键和O...C之间的键部分形成,形成的四元环平面基本垂直于5-甲基胞嘧啶骨架。第三步为中间体脱氨形成产物的过程。这一步中,羟基O-H中的H进攻氨基上的N,同样形成一个四元环的过渡态,随着N-H键的形成和N-C键的彻底断裂,NH_3基本形成,随着原羟基中的O逐渐靠近碱基骨架平面,氨基的逐渐远离,生成了水解脱氨产物胸腺嘧啶。
总之,通过对5-甲基胞嘧啶异构化、水解脱氨等过程的理论研究,初步阐明了上述过程的分子机制和热力学行为。
As one of the simplest and most basic phenomenons in the isomerization balance and redox reaction,proton transfer(PT)in intra- and inter- molecule plays an important role in many chemical processes,proton transfer can passed through hydrogen bonds formed between organic molecules.Such transfer is as important as energy transfer and electronic transfer which are in molecular system,almost all organic reactions have included all or part of the proton transfer process.Proton transfer plays an important role in the transmission of information between molecules.Hydrogen bond formation and proton transfer phenomena in many chemical processes are very important and common,because many chemical, physical and biological processes involve the forming and breaking of this kind of bonds.
In this paper,we investigate the intramolecular or intermolecular proton transfers(PTs)isomerization under the assistant of water molecular or the six simulated acid residues compounds and the hydrolysis deamination using the density functional theory at 6-31+G~* bases set level.The main contents of the paper contain 3 parts,just as follows:
1.water-catalyzed pathways of the 5—methylcytosine isomerization.Because these processes can occur in the water solution,maybe the water molecule participate in the proton transfer.When water is involved in the proton transfer,the transition state has a structure of six-member or eight-member ring.The results show that the water molecule takes part in the forming of transition state.The reaction path or mechanism is changed due to the participating of water,the proton transfer is one kind of exchange process between water and another molecule,the barrier of exchange process is much smaller than direct proton transfer.So the water plays an important role in the proton transfer of the 5—methylcytosine isomerization.
2.We have chosen six kinds of compounds(CH_3COOH,CH_3CONH_2, CH_3-NH-C(NH)-NH_2,CH_3NH_2,CH_3OH,and CH_3-C_6H_4-OH)to simulate amino acid catalyzed pathways for the 5-methylcytosine isomerization.In the six compounds,the combining of the carboxyl of the CH_3COOH is most favorable for the proton transfer of 5-methylcytosine.In this proton transfer process,it must surmount a energy barrier of 16.39 KJ.mol~(-1)for this proton transfer process.
3.5—methylcytosine have amino out of ring can be changed by hydrolysis.The products of amino hydrolysis are thymine.The hydrolysis deamination includes three steps,In the first step,5—methylcytosine isomerization with water molecules, In the second steps,the O(negative charge)of water attack the C(positive charge) of C=N and the H(positive charge)of water attack the N(negative charge)of C=N linked directly with amino,and the transition state with a new-formed four-member ring is produced.This process belongs to dipole addition reaction.In the transition state of this step,the bond of O-H and the bond of C=N are broken partly,and the bond H...N and bond O...C are formed partly.The new-formed four-member ring has a structure of plane,but it is not coplanar with base skeleton.In the third steps, the H of OH attacks the N of amino.The transition states also have a four-member ring.Accompany with the forming N-H a single bond and the bond between N of amino and C of base is weaken greatly,the skeleton of NH_3 is formed in the rough. Along with the leaving of amino,the O of hydroxyl is more and more closed to the plane of base skeleton,the products of amino hydrolysis are thymine.
In summary,the research of the isomerization,the hydrolysis deamination of 5—methylcytosine unveil the information of molecule mechanism,the thermodynamic characters of these processes.
引文
[1]Kabir,M.;Mookerjee,A.;Datta,R.P.;et al.lnt J.Mod.Phys.B,2003,17:2061.
[2]Massobrio,C.;Pasquarello,A.;Car,R.Chem Phys Lett,1995,238:215.
[3]Baaden,M.;Burgard,M.;Wipff,G.J.Phys.Chem.B,2001,105:11131.
[4]Da,Rocha,S.R.P.;Johnstom,K.P.;Rossky,P.J.JPhys Chem B.2002,106:13250.
[5]Ahuja,R.;Belonoshko,A.B.;Johansson;B.Phys Rev E.1998,57:1673.
[6]Gupta,P.;Hall,C.K.AIChE Journal.1995,41:985.
[7]Gupta,P.;Hall,C.K.;Voegler,A.C.Protein Science.1998,7:2642.
[8]董程林,成曙,肖晨静,传感器与微系统,2006,25:12.
[9]Srinivas M,Patnaik L M.Adaptive Probabilities of Crossover and Mutation in Genetic Algorithms[J].IEEE Transactions on System,Man,and Cybernetics,1994,24:656.
[10]陈华宝,王保林,淮阴师范学院学报(自然科学版),2003,2:192.
[11]崔秀君,苏忠民,计算机与应用化学,2005,22:1038
[12]Xu L and Shao X G,Methods of Chemometrics,2nd ed.Beijing:Science Press,2004.
[13]刘雪松,程翼宇,化学学报,2005,63:2216.
[14]林梦海,量子化学计算方法与应用。第一版,北京,科学出版社,2004年.
[15]C.Reochardt,Solvents and Solvent Effects in Organic Chemistry.VCH,(1990)13
[16]Q.Zhang,Anqing Normal College Transaction(Natural Science Edition).1(1995)8
[17]J.Olejnik,B.Brzezinski,G.Zundel,J.Mol.Struct.1992,271:157
[18]G.Zundel,M.Eckert,.J.Mol.Struct(Theochem).1989,200:73
[19]X.F.Pang,Acta.Physical.Sinica.1997,46:625
[20]J.Bian,Z.D.Chen,J.G.Wu,Chin.Chem.Bulletin.1997,4:12
[21]J.Mavri,D.Hadzi,J.Mol.Struct.1992,270:247
[22]D.Borgis,J.Phy.Chem.1992,96:3188
[23]R.Desiraju,Acc.Chem.Res.1991,24:290.
[24]F.Hibbert,Adv.Phys.Org.Chem.1986,22:113
[25]R.W.Beeman and F.Matsumura,Nature London 1973,242:274.
[26]C.Fockenberg,G.E.HalI,J.M.Press,T.J.Sears,J.T.Mucherman,J.Phys.Chem.A,1999,103:5722.
[27]Sergei Skokov,Ralph A.Wheeler;J.Phys.Chem.A;2000,104:6314.
[28]P.Hohenberg and W.Kohn,Phys.Rev.B 1964,136:864.
[29]Kohn W.,Sham L.J.,Phys.Rev.A 1965,140:1133.
[30]L.H.Thomas,Proc.Camb.Phil.Soc.1927,23:542.
[31]E.Fermi,Rend.Accad.Lincei.1927,6:602.
[32]P.A.M.Dirac,Proc.Cam.Phil.Soc.1930,26:2;76.
[33]J.C.Slater Phys.Rev.1951,81:385.
[34]J.C.Slater Adv.Quant.Chem.1972,6:1.
[35]J.P.Perdew Y.Wang,Phys.Rev.B 1986,33:8800.
[36]J.P.Perdew Phys.Rev.B 1986,33:8822.
[37]A.D.Becke Phys.Rev.A 1988,38:3098.
[38]J.P.Perdew,J.A.Chevary,K.Hackson,S.H.Vosko,M.R.Pederson,D.J.Singh,C.Fiolhais,Phys.Rev.B 1992,46:6671.
[39]J.P.Perdew,K.Burke,M.Ernzerhof,Phys.Rev.Lett.1996,77:1396.
[40]F.A.Hamprecht,A.J.Cohen,D.J.Tozer,N.C.Handy,J.Chem.Phys.1998,109:6264.
[41]A.D.Becke,J.Chem.Phys.1993,98:5648.
[42]J.B.Foresman and A.Frisch,Exploring Chemistry with Electronic Structure Methods(Gaussian,Inc.,Pittsburgh,PA,1996).
[43]徐光宪,黎乐民,王德明,《量子化学基本原理和从头计算法》(中册,1985), 科学出版社。
[44]张瑞勤、步宇翔等,中国科学(B辑),2000,30：419．
[45] Partha Pratim Bera and Henry F. Schaefer, PNAS 2005, 102: 6698.
[46] C. von Sonntag, The Chemistry of Free-Radical-Mediated DNA Damage, Physical and Chemical Mechanisms in Molecular Radiation Biology, (W. A. Glass and M. N. Varma, NewYork, 1991, 287.
[47] Jean Cadet, Thienry Delatour, T. Douki, D. Gasparutto, J. P. Pouget, J.L. Ravanat, S. Sauvaigo, Mutation Research 1999, 424: 9.
[48] M. J.Frisch; G. W.Trucks; H. B. Schlegel; G. E. Scuseria; M. A. Robb; J. R. Cheeseman; V. G. Zakrzewski; J. A. Jr. Montgomery; R. E. Stratmann; J. C. Burant; S. Dapprich; J. M. Millam; A.D.Daniels; K. N. Kudin; M. C. Strain;O. Farkas; J. Tomasi; V. Barone; M. Cossi; R. Cammi; B. Mennucci; C. Pomelli; C. Adamo; S. Clifford; J. Ochterski; G. A. Petersson; P. Y. Ayala; Q.Cui; K. Morokuma; D. K. Malick; A. D. Rabuck; K. Raghavachari; J. B. Foresman; J.Cioslowski; J. V.Ortiz; B. B. Stefanov; G. Liu; A. Liashenko; P. Piskorz; I. Komaromi; R. Gomperts; R. L. Martin; D. J. Fox; T. Keith; M. A. Al-Laham; C. Y.Peng; A. Nanayakkara; C. Gonzalez; M.Challacombe; P. M. W. Gill; B. Johnson; W. Chen; M. W. Wong; J. L. Andres; C. Gonzalez;M.Head-Gordon; E. S. Replogle; J. A. Pople, Gaussian, Inc. ; Pittsburgh, PA, 2003.
[49] Singh N. P., et al.Experira.Cell Res., 1988,175:184-191.
[50] Vigreus C.,et al, Muta. Res., 1998, 419:79-90.
[51] D. P. Lane, Br. J. Cancer, 1999, 80:1
[52] R. Shapiro, V Difate, M. Welcher, Am. J. Chem. Soc. 1974, 6:906
[53] N. Korzheva, et al., Science 2000,289: 619-625.
[54] X. J. Lin, DFT Study on the Mechanism of DNA Damage Caused by the Isomerization of DNA Purine Base. Biophysical Chemistry 2006
[55] S.E.Bennett, Prog. Nucleic. Acid Res. Molec. Biol., 1994,48:315-317.
[2]Massobrio,C.;Pasquarello,A.;Car,R.Chem Phys Lett,1995,238:215.
[3]Baaden,M.;Burgard,M.;Wipff,G.J.Phys.Chem.B,2001,105:11131.
[4]Da,Rocha,S.R.P.;Johnstom,K.P.;Rossky,P.J.JPhys Chem B.2002,106:13250.
[5]Ahuja,R.;Belonoshko,A.B.;Johansson;B.Phys Rev E.1998,57:1673.
[6]Gupta,P.;Hall,C.K.AIChE Journal.1995,41:985.
[7]Gupta,P.;Hall,C.K.;Voegler,A.C.Protein Science.1998,7:2642.
[8]董程林,成曙,肖晨静,传感器与微系统,2006,25:12.
[9]Srinivas M,Patnaik L M.Adaptive Probabilities of Crossover and Mutation in Genetic Algorithms[J].IEEE Transactions on System,Man,and Cybernetics,1994,24:656.
[10]陈华宝,王保林,淮阴师范学院学报(自然科学版),2003,2:192.
[11]崔秀君,苏忠民,计算机与应用化学,2005,22:1038
[12]Xu L and Shao X G,Methods of Chemometrics,2nd ed.Beijing:Science Press,2004.
[13]刘雪松,程翼宇,化学学报,2005,63:2216.
[14]林梦海,量子化学计算方法与应用。第一版,北京,科学出版社,2004年.
[15]C.Reochardt,Solvents and Solvent Effects in Organic Chemistry.VCH,(1990)13
[16]Q.Zhang,Anqing Normal College Transaction(Natural Science Edition).1(1995)8
[17]J.Olejnik,B.Brzezinski,G.Zundel,J.Mol.Struct.1992,271:157
[18]G.Zundel,M.Eckert,.J.Mol.Struct(Theochem).1989,200:73
[19]X.F.Pang,Acta.Physical.Sinica.1997,46:625
[20]J.Bian,Z.D.Chen,J.G.Wu,Chin.Chem.Bulletin.1997,4:12
[21]J.Mavri,D.Hadzi,J.Mol.Struct.1992,270:247
[22]D.Borgis,J.Phy.Chem.1992,96:3188
[23]R.Desiraju,Acc.Chem.Res.1991,24:290.
[24]F.Hibbert,Adv.Phys.Org.Chem.1986,22:113
[25]R.W.Beeman and F.Matsumura,Nature London 1973,242:274.
[26]C.Fockenberg,G.E.HalI,J.M.Press,T.J.Sears,J.T.Mucherman,J.Phys.Chem.A,1999,103:5722.
[27]Sergei Skokov,Ralph A.Wheeler;J.Phys.Chem.A;2000,104:6314.
[28]P.Hohenberg and W.Kohn,Phys.Rev.B 1964,136:864.
[29]Kohn W.,Sham L.J.,Phys.Rev.A 1965,140:1133.
[30]L.H.Thomas,Proc.Camb.Phil.Soc.1927,23:542.
[31]E.Fermi,Rend.Accad.Lincei.1927,6:602.
[32]P.A.M.Dirac,Proc.Cam.Phil.Soc.1930,26:2;76.
[33]J.C.Slater Phys.Rev.1951,81:385.
[34]J.C.Slater Adv.Quant.Chem.1972,6:1.
[35]J.P.Perdew Y.Wang,Phys.Rev.B 1986,33:8800.
[36]J.P.Perdew Phys.Rev.B 1986,33:8822.
[37]A.D.Becke Phys.Rev.A 1988,38:3098.
[38]J.P.Perdew,J.A.Chevary,K.Hackson,S.H.Vosko,M.R.Pederson,D.J.Singh,C.Fiolhais,Phys.Rev.B 1992,46:6671.
[39]J.P.Perdew,K.Burke,M.Ernzerhof,Phys.Rev.Lett.1996,77:1396.
[40]F.A.Hamprecht,A.J.Cohen,D.J.Tozer,N.C.Handy,J.Chem.Phys.1998,109:6264.
[41]A.D.Becke,J.Chem.Phys.1993,98:5648.
[42]J.B.Foresman and A.Frisch,Exploring Chemistry with Electronic Structure Methods(Gaussian,Inc.,Pittsburgh,PA,1996).
[43]徐光宪,黎乐民,王德明,《量子化学基本原理和从头计算法》(中册,1985), 科学出版社。
[44]张瑞勤、步宇翔等,中国科学(B辑),2000,30：419．
[45] Partha Pratim Bera and Henry F. Schaefer, PNAS 2005, 102: 6698.
[46] C. von Sonntag, The Chemistry of Free-Radical-Mediated DNA Damage, Physical and Chemical Mechanisms in Molecular Radiation Biology, (W. A. Glass and M. N. Varma, NewYork, 1991, 287.
[47] Jean Cadet, Thienry Delatour, T. Douki, D. Gasparutto, J. P. Pouget, J.L. Ravanat, S. Sauvaigo, Mutation Research 1999, 424: 9.
[48] M. J.Frisch; G. W.Trucks; H. B. Schlegel; G. E. Scuseria; M. A. Robb; J. R. Cheeseman; V. G. Zakrzewski; J. A. Jr. Montgomery; R. E. Stratmann; J. C. Burant; S. Dapprich; J. M. Millam; A.D.Daniels; K. N. Kudin; M. C. Strain;O. Farkas; J. Tomasi; V. Barone; M. Cossi; R. Cammi; B. Mennucci; C. Pomelli; C. Adamo; S. Clifford; J. Ochterski; G. A. Petersson; P. Y. Ayala; Q.Cui; K. Morokuma; D. K. Malick; A. D. Rabuck; K. Raghavachari; J. B. Foresman; J.Cioslowski; J. V.Ortiz; B. B. Stefanov; G. Liu; A. Liashenko; P. Piskorz; I. Komaromi; R. Gomperts; R. L. Martin; D. J. Fox; T. Keith; M. A. Al-Laham; C. Y.Peng; A. Nanayakkara; C. Gonzalez; M.Challacombe; P. M. W. Gill; B. Johnson; W. Chen; M. W. Wong; J. L. Andres; C. Gonzalez;M.Head-Gordon; E. S. Replogle; J. A. Pople, Gaussian, Inc. ; Pittsburgh, PA, 2003.
[49] Singh N. P., et al.Experira.Cell Res., 1988,175:184-191.
[50] Vigreus C.,et al, Muta. Res., 1998, 419:79-90.
[51] D. P. Lane, Br. J. Cancer, 1999, 80:1
[52] R. Shapiro, V Difate, M. Welcher, Am. J. Chem. Soc. 1974, 6:906
[53] N. Korzheva, et al., Science 2000,289: 619-625.
[54] X. J. Lin, DFT Study on the Mechanism of DNA Damage Caused by the Isomerization of DNA Purine Base. Biophysical Chemistry 2006
[55] S.E.Bennett, Prog. Nucleic. Acid Res. Molec. Biol., 1994,48:315-317.