Dinuclear Zn(II) Complex Catalyzed Phosphodiester Cleavage Proceeds via a Concerted Mechanism: A Density Functional Theory Study.
Density functional theory (DFT) calculations were used to study the mechanism for the cleavage reaction of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl-4-nitrophenyl phosphate) catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(LO)). We present a...
| Published in: | Journal of the American Chemical Society Vol. 133; no. 9; pp. 2904 - 2916 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
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American Chemical Society
3/9/2011
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| Subjects: | |
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=62251575&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 62251575 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 3/9/2011 vid: 133 iid: 9 pid: 997 pub: American Chemical Society artinfo: ui: 62251575 10.1021/ja106456u ppf: 2904 ppct: 12 formats: tig: atl: Dinuclear Zn(II) Complex Catalyzed Phosphodiester Cleavage Proceeds via a Concerted Mechanism: A Density Functional Theory Study. aug: au: Hui Gao Zhuofeng Ke DeYonker, Nathan J. Juping Wang Huiying Xu Zong-Wan Mao Lee Phillips, David Cunyuan Zhao affil: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry/KLGHEI of Environment and Energy Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China Department of Chemistry, University of Memphis, Memphis, Tennessee 38152-3550, United States Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China su: Zinc Catalysis Density functionals Nucleic acids Electronic structure Reaction mechanisms (Chemistry) Solution (Chemistry) sug: subj: Zinc Catalysis Density functionals Nucleic acids Electronic structure Reaction mechanisms (Chemistry) Solution (Chemistry) ab: Density functional theory (DFT) calculations were used to study the mechanism for the cleavage reaction of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl-4-nitrophenyl phosphate) catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(LO)). We present a binding mode in which each terminal phosphoryl oxygen atom binds to one zinc center, respectively, and the nucleophilic 2-hydroxypropyl group coordinates to one of the zinc ions, while the hydroxide from deprotonation of a water molecule coordinates to the other zinc ion. Our calculations found a concerted mechanism for the HpPNP cleavage with a 16.5 kcal/mol reaction barrier. An alternative proposed stepwise mechanism through a pentavalent oxyphosphorane dianion reaction intermediate for the HpPNP cleavage was found to be less feasible with a significantly higher energy barrier. In this stepwise mechanism, the deprotonation of the nucleophilic 2-hydroxypropyl group is accompanied with nucleophilic attack in the rate-determining step. Calculations of the nucleophile O kinetic isotope effect (KIE) and leaving O KIE for the concerted mechanism are in reasonably good agreement with the experimental values. Our results indicate a specific-base catalysis mechanism takes place in which the deprotonation of the nucleophilic 2-hydroxypropyl group occurs in a pre-equilibrium step followed by a nucleophilic attack on the phosphorus center. Detailed comparison of the geometric and electronic structure for the HpPNP cleavage reaction mechanisms in the presence/absence of catalyst revealed that the catalyst significantly altered the determining-step transition state to become far more associative or tight, that is, bond formation to the nucleophile was remarkably more advanced than leaving group bond fission in the catalyzed mechanism. Our results are consistent with and provide a reliable interpretation for the experimental observations that suggest the reaction occurs by a concerted mechanism (see Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth, P.; Hengge, A. C. J. Am. Chem. Soc.2008, 130, 17858-17866) and has a specific-base catalysis character (see Yang, M.-Y.; Iranzo, O.; Richard, J. P.; Morrow, J. R. J. Am. Chem. Soc.2005, 127, 1064-1065). pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2011 holdings: @attributes: islocal: N |
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