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Article: Dinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study

TitleDinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study
Authors
Issue Date2011
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html
Citation
Journal Of The American Chemical Society, 2011, v. 133 n. 9, p. 2904-2915 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/138986
ISSN
2015 Impact Factor: 13.038
2015 SCImago Journal Rankings: 7.123
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorGao, Hen_HK
dc.contributor.authorKe, Zen_HK
dc.contributor.authorDeyonker, NJen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorXu, Hen_HK
dc.contributor.authorMao, ZWen_HK
dc.contributor.authorPhillips, DLen_HK
dc.contributor.authorZhao, Cen_HK
dc.date.accessioned2011-09-23T05:43:40Z-
dc.date.available2011-09-23T05:43:40Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of The American Chemical Society, 2011, v. 133 n. 9, p. 2904-2915en_HK
dc.identifier.issn0002-7863en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138986-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.htmlen_HK
dc.relation.ispartofJournal of the American Chemical Societyen_HK
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 studyen_HK
dc.typeArticleen_HK
dc.identifier.emailPhillips, DL:phillips@hku.hken_HK
dc.identifier.authorityPhillips, DL=rp00770en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/ja106456uen_HK
dc.identifier.pmid21319769-
dc.identifier.scopuseid_2-s2.0-79952270966en_HK
dc.identifier.hkuros194564en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952270966&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume133en_HK
dc.identifier.issue9en_HK
dc.identifier.spage2904en_HK
dc.identifier.epage2915en_HK
dc.identifier.eissn1520-5126-
dc.identifier.isiWOS:000289455200027-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridGao, H=36666205500en_HK
dc.identifier.scopusauthoridKe, Z=14048262500en_HK
dc.identifier.scopusauthoridDeyonker, NJ=12791651400en_HK
dc.identifier.scopusauthoridWang, J=35328272400en_HK
dc.identifier.scopusauthoridXu, H=35328606500en_HK
dc.identifier.scopusauthoridMao, ZW=23989068600en_HK
dc.identifier.scopusauthoridPhillips, DL=7404519365en_HK
dc.identifier.scopusauthoridZhao, C=7403563836en_HK

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