DFT Computational Study of the Methanolytic Cleavage of DNA and RNA Phosphodiester Models Promoted by the Dinuclear Zn Complex of 1,3-Bis(1,5,9-triazacyclododec-1-yl)propane.
A density functional theory study of the cleavage of a DNA model [p-nitrophenyl methyl phosphate (2)] and two RNA models [p-nitrophenyl 2-hydroxypropyl phosphate (3) and phenyl 2-hydroxypropyl phosphate (4)] promoted by the dinuclear Zn complex of 1,3-bis(1,5,9-triazacyclododec-1-yl)propane formulat...
| Publicado en: | Journal of the American Chemical Society Vol. 135; no. 45; pp. 17209 - 17223 |
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| Autores principales: | , , |
| Formato: | Artículo |
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American Chemical Society
11/13/2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=93271477&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 93271477 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: 11/13/2013 vid: 135 iid: 45 pid: 997 pub: American Chemical Society artinfo: ui: 93271477 10.1021/ja4088264 ppf: 17209 ppct: 14 formats: tig: atl: DFT Computational Study of the Methanolytic Cleavage of DNA and RNA Phosphodiester Models Promoted by the Dinuclear Zn Complex of 1,3-Bis(1,5,9-triazacyclododec-1-yl)propane. aug: au: Maxwell, Christopher I. Mosey, Nicholas J. Stan Brown, R. affil: Uppsala Biomedicinska Centrum, BMC, Husarg. 3, Box 596, 751 24 Uppsala, Sweden Department of Chemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6 su: Scission (Chemistry) Phosphodiesters Density functional theory DNA models Free energy (Thermodynamics) Lewis acids Transesterification Hydrogen bonding sug: subj: Scission (Chemistry) Phosphodiesters Density functional theory DNA models Free energy (Thermodynamics) Lewis acids Transesterification Hydrogen bonding ab: A density functional theory study of the cleavage of a DNA model [p-nitrophenyl methyl phosphate (2)] and two RNA models [p-nitrophenyl 2-hydroxypropyl phosphate (3) and phenyl 2-hydroxypropyl phosphate (4)] promoted by the dinuclear Zn complex of 1,3-bis(1,5,9-triazacyclododec-1-yl)propane formulated with a bridging methoxide (1a) was undertaken to determine possible mechanisms for the transesterification processes that are consistent with experimental data. The initial substrate-bound state of 2:1a or 3:1a has the two phosphoryl oxygens bridging Zn1 and Zn2. For each of 2 and 3, four possible mechanisms were investigated, three of which were consistent with the overall free energy for the catalytic cleavage step for each substrate. The computations revealed various roles for the metal ions in the three mechanisms. These encompass concerted or stepwise processes, where the two metal ions with associated alkoxy groups [Zn:(-OCH) and Zn:(-O-propyl)] play the role of a direct nucleophile (on 2 and 3, respectively) or where Zn:(-OCH) can act as a general base to deprotonate an attacking solvent molecule in the case of 2 or the attacking 2-hydroxypropyl group in the case of 3. The Zn ion can serve as a spectator (after exerting a Lewis acid role in binding one of the phosphates' oxygens) or play active additional roles in providing direct coordination of the departing aryloxy group or positioning a hydrogen-bonding solvent to assist the departure of the leaving group. An important finding revealed by the calculations is the flexibility of the ligand system that allows the Zn-Zn distance to expand from 3.6 Å in 1a to over 5 Å in the transforming 2:1a and 3:1a complexes during the catalytic event. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2013 holdings: @attributes: islocal: N |
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