The catalytic activity of the guanidinium units toward the cleavage of phosphoric diesters is deeply investigated both with kinetic experiments and DFT calculations. The first part of the investigation aims to determine how the structure of the substrate (phenyl or alkyl esters) is able to influence the guanidinium catalyzed hydrolysis changing the mechanism from A(N)D(N) to A(N)+D-N. In the cleavage of the DNA model bis(4-nitrophenyl)phospate (BNPP), experimental kinetic data high-light the operation of a guanidine-guanidinium catalytic dyad that can act both intermolecularly and intramolecularly on different molecular scaffolds exhibiting notable values of effective molarity. P-31 NMR spectra and DFT investigation provide indication that the deprotonated guanidine involved in such a catalysis acts as a general base in the deprotonation of a water molecule involved in the cleavage, and not as nudeophilic unit. Moreover, DFT calculations were carried out to determine the guanidinium promoted activation energy of pseudorotation. The results indicate a remarkable drop in the activation energy of this process for dialkylphosphate esters explaining, in part, the higher sensitivity of diribonucleoside to the presence of guanidinium-based catalysts compared to the more activated RNA model HPNP.

Salvio, R., Casnati, A. (2017). Guanidinium promoted cleavage of phosphoric diesters: Kinetic investigations and calculations provide indications on the operating mechanism. JOURNAL OF ORGANIC CHEMISTRY, 82(19), 10461-10469 [10.1021/acs.joc.7b01925].

Guanidinium promoted cleavage of phosphoric diesters: Kinetic investigations and calculations provide indications on the operating mechanism

Salvio R.;
2017-01-01

Abstract

The catalytic activity of the guanidinium units toward the cleavage of phosphoric diesters is deeply investigated both with kinetic experiments and DFT calculations. The first part of the investigation aims to determine how the structure of the substrate (phenyl or alkyl esters) is able to influence the guanidinium catalyzed hydrolysis changing the mechanism from A(N)D(N) to A(N)+D-N. In the cleavage of the DNA model bis(4-nitrophenyl)phospate (BNPP), experimental kinetic data high-light the operation of a guanidine-guanidinium catalytic dyad that can act both intermolecularly and intramolecularly on different molecular scaffolds exhibiting notable values of effective molarity. P-31 NMR spectra and DFT investigation provide indication that the deprotonated guanidine involved in such a catalysis acts as a general base in the deprotonation of a water molecule involved in the cleavage, and not as nudeophilic unit. Moreover, DFT calculations were carried out to determine the guanidinium promoted activation energy of pseudorotation. The results indicate a remarkable drop in the activation energy of this process for dialkylphosphate esters explaining, in part, the higher sensitivity of diribonucleoside to the presence of guanidinium-based catalysts compared to the more activated RNA model HPNP.
2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/06 - CHIMICA ORGANICA
English
Salvio, R., Casnati, A. (2017). Guanidinium promoted cleavage of phosphoric diesters: Kinetic investigations and calculations provide indications on the operating mechanism. JOURNAL OF ORGANIC CHEMISTRY, 82(19), 10461-10469 [10.1021/acs.joc.7b01925].
Salvio, R; Casnati, A
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
SalvioPhospMechanisms.pdf

solo utenti autorizzati

Tipologia: Versione Editoriale (PDF)
Licenza: Copyright dell'editore
Dimensione 1.5 MB
Formato Adobe PDF
1.5 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/247678
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 20
social impact