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Article: Dinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study
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TitleDinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study
 
AuthorsGao, H3
Ke, Z3
Deyonker, NJ2
Wang, J3
Xu, H3
Mao, ZW3
Phillips, DL1
Zhao, C3
 
Issue Date2011
 
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html
 
CitationJournal Of The American Chemical Society, 2011, v. 133 n. 9, p. 2904-2915 [How to Cite?]
DOI: http://dx.doi.org/10.1021/ja106456u
 
AbstractDensity 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 2(L 2O)). 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 18O kinetic isotope effect (KIE) and leaving 18O 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). © 2011 American Chemical Society.
 
ISSN0002-7863
2012 Impact Factor: 10.677
2012 SCImago Journal Rankings: 5.182
 
DOIhttp://dx.doi.org/10.1021/ja106456u
 
ISI Accession Number IDWOS:000289455200027
Funding AgencyGrant Number
National Natural Science Foundation of China20673149
20973204
20950110326
Guangdong Provincial Natural Science Foundation9351027501000003
Research Grants Council of Hong KongHKU 7039/07P
Sun Yat-sen University
Funding Information:

We gratefully acknowledge the National Natural Science Foundation of China (20673149, 20973204, 20950110326) and Guangdong Provincial Natural Science Foundation (9351027501000003) to C.Y.Z. and N.J.D., and the Research Grants Council of Hong Kong (HKU 7039/07P) to D.L.P. for financial support of this research. This work was partially sponsored by the high-performance grid computing platform of Sun Yat-sen University. The high performance computing facility at the University of Memphis is also acknowledged. We thank the reviewers for many insightful comments and suggestions.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorGao, H
 
dc.contributor.authorKe, Z
 
dc.contributor.authorDeyonker, NJ
 
dc.contributor.authorWang, J
 
dc.contributor.authorXu, H
 
dc.contributor.authorMao, ZW
 
dc.contributor.authorPhillips, DL
 
dc.contributor.authorZhao, C
 
dc.date.accessioned2011-09-23T05:43:40Z
 
dc.date.available2011-09-23T05:43:40Z
 
dc.date.issued2011
 
dc.description.abstractDensity 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 2(L 2O)). 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 18O kinetic isotope effect (KIE) and leaving 18O 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). © 2011 American Chemical Society.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of The American Chemical Society, 2011, v. 133 n. 9, p. 2904-2915 [How to Cite?]
DOI: http://dx.doi.org/10.1021/ja106456u
 
dc.identifier.doihttp://dx.doi.org/10.1021/ja106456u
 
dc.identifier.eissn1520-5126
 
dc.identifier.epage2915
 
dc.identifier.hkuros194564
 
dc.identifier.isiWOS:000289455200027
Funding AgencyGrant Number
National Natural Science Foundation of China20673149
20973204
20950110326
Guangdong Provincial Natural Science Foundation9351027501000003
Research Grants Council of Hong KongHKU 7039/07P
Sun Yat-sen University
Funding Information:

We gratefully acknowledge the National Natural Science Foundation of China (20673149, 20973204, 20950110326) and Guangdong Provincial Natural Science Foundation (9351027501000003) to C.Y.Z. and N.J.D., and the Research Grants Council of Hong Kong (HKU 7039/07P) to D.L.P. for financial support of this research. This work was partially sponsored by the high-performance grid computing platform of Sun Yat-sen University. The high performance computing facility at the University of Memphis is also acknowledged. We thank the reviewers for many insightful comments and suggestions.

 
dc.identifier.issn0002-7863
2012 Impact Factor: 10.677
2012 SCImago Journal Rankings: 5.182
 
dc.identifier.issue9
 
dc.identifier.pmid21319769
 
dc.identifier.scopuseid_2-s2.0-79952270966
 
dc.identifier.spage2904
 
dc.identifier.urihttp://hdl.handle.net/10722/138986
 
dc.identifier.volume133
 
dc.languageeng
 
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of the American Chemical Society
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAlanine - analogs and derivatives - chemistry - metabolism
 
dc.subject.meshHeterocyclic Compounds, 1-Ring - chemistry - metabolism
 
dc.subject.meshOrganophosphorus Compounds - chemistry - metabolism
 
dc.subject.meshRNA - chemistry - metabolism
 
dc.subject.meshZinc - chemistry - metabolism
 
dc.titleDinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study
 
dc.typeArticle
 
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<contributor.author>Xu, H</contributor.author>
<contributor.author>Mao, ZW</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. University of Memphis
  3. Sun Yat-Sen University