Nucleophilic Cyclopropane Ring Opening in Duocarmycin SA Derivatives by Methanol under Acid Conditions: A Quantum Mechanical Study in the Gas-Phase and in Solution (Articolo in rivista)

Type
Label
  • Nucleophilic Cyclopropane Ring Opening in Duocarmycin SA Derivatives by Methanol under Acid Conditions: A Quantum Mechanical Study in the Gas-Phase and in Solution (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Alternative label
  • P. Cimino, R. Improta , G. Bifulco, R. Riccio, L. Gomez-Paloma, V. Barone, V (2004)
    Nucleophilic Cyclopropane Ring Opening in Duocarmycin SA Derivatives by Methanol under Acid Conditions: A Quantum Mechanical Study in the Gas-Phase and in Solution
    in Journal of organic chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • P. Cimino, R. Improta , G. Bifulco, R. Riccio, L. Gomez-Paloma, V. Barone, V (literal)
Pagina inizio
  • 2816 (literal)
Pagina fine
  • 2824 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 69 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Nucleophilic Cyclopropane Ring Opening in Duocarmycin SA Derivatives by Methanol under Acid Conditions: A Quantum Mechanical Study in the Gas-Phase and in Solution (literal)
Abstract
  • We present a quantum-mechanical study of the SN2 acid-catalyzed solvolysis with methanol of seven simplified duocarmycin SA (DNA alkylating agent) derivatives characterized by spirocyclic systems of increasing complexity, all containing the cyclopropyl/cyclohexadienone substrate. The reaction has been studied at the DFT-PBE0/6-31G(d) level in the gas phase and in methanol solution, using in the latter case the polarizable continuum model (PCM) to describe solvent effects. The results delivered by this computational protocol are in full agreement with the available experimental evidences and are not modified by extension of the basis set or by using a second-order many-body treatment (MP2) in place of DFT. This allows investigation of substituent effects in terms of structure/reactivity relationships and evaluation of the role of stereoelectronic effects. Furthermore, reactivity indices (hardness, electrophilicity) have been computed and shown to correlate well with activation energies. Together with their intrinsic interest, the details of the mechanism of the acid-catalyzed nucleophilic addition to the activated cyclopropane issuing from the present study pave the route for a deeper understanding of the molecular basis for the remarkable profile of the DNA-alkylation by DSA derivatives. (literal)
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