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On the significance of the trigger reaction in the action of the calicheamicin γI 1 anti-cancer drug

Lindh, Roland LU ; Ryde, Ulf LU and Schütz, Martin (1997) In Theoretical Chemistry Accounts 97(1). p.203-210
Abstract

The significance of the so-called trigger reaction in the reaction mechanism of the calicheamicin γI 1 anti-cancer drug has been studied with ab initio quantum chemical methods. The structures of four fragments of calicheamicin γI 1, consisting of either 39 or 41 atoms, have been fully optimized using the Becke-Perdew86 density functional method and the 6-31G* basis sets. The four structures constitute members of an isodesmic reaction for which the reaction energy is a direct measure of the change in activation energy of the Bergman reaction, caused by the structural rearrangements of the preceding trigger reaction. This difference in activation energy has been calculated with density... (More)

The significance of the so-called trigger reaction in the reaction mechanism of the calicheamicin γI 1 anti-cancer drug has been studied with ab initio quantum chemical methods. The structures of four fragments of calicheamicin γI 1, consisting of either 39 or 41 atoms, have been fully optimized using the Becke-Perdew86 density functional method and the 6-31G* basis sets. The four structures constitute members of an isodesmic reaction for which the reaction energy is a direct measure of the change in activation energy of the Bergman reaction, caused by the structural rearrangements of the preceding trigger reaction. This difference in activation energy has been calculated with density functional theory, using the exchange-correlation functional mentioned above, and with second-order Møller-Plesset perturbation theory (MP2), employing an ANO-type basis set. In both cases a value of 12 kcal/ mol is obtained. The study firmly supports the hypothesis that the significance of the trigger reaction is to saturate a double bond in the vicinity of the enediyne group, which counteracts the formation of the biradical state of the drug. The MP2 computations became feasible by a novel implementation of an integral-direct, distributed-data, parallel MP2 algorithm.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bergman reaction, Calicheamicin, Integral-direct MP2, Parallel MP2, Trigger reaction
in
Theoretical Chemistry Accounts
volume
97
issue
1
pages
8 pages
publisher
Springer
external identifiers
  • scopus:0031285827
ISSN
1432-881X
DOI
10.1007/s002140050254
language
English
LU publication?
yes
id
1288e736-d9a5-4b94-9b2e-9c2ccbf1ed8d
date added to LUP
2017-02-04 11:35:33
date last changed
2017-06-19 16:44:29
@article{1288e736-d9a5-4b94-9b2e-9c2ccbf1ed8d,
  abstract     = {<p>The significance of the so-called trigger reaction in the reaction mechanism of the calicheamicin γ<sup>I</sup> <sub>1</sub> anti-cancer drug has been studied with ab initio quantum chemical methods. The structures of four fragments of calicheamicin γ<sup>I</sup> <sub>1</sub>, consisting of either 39 or 41 atoms, have been fully optimized using the Becke-Perdew86 density functional method and the 6-31G* basis sets. The four structures constitute members of an isodesmic reaction for which the reaction energy is a direct measure of the change in activation energy of the Bergman reaction, caused by the structural rearrangements of the preceding trigger reaction. This difference in activation energy has been calculated with density functional theory, using the exchange-correlation functional mentioned above, and with second-order Møller-Plesset perturbation theory (MP2), employing an ANO-type basis set. In both cases a value of 12 kcal/ mol is obtained. The study firmly supports the hypothesis that the significance of the trigger reaction is to saturate a double bond in the vicinity of the enediyne group, which counteracts the formation of the biradical state of the drug. The MP2 computations became feasible by a novel implementation of an integral-direct, distributed-data, parallel MP2 algorithm.</p>},
  author       = {Lindh, Roland and Ryde, Ulf and Schütz, Martin},
  issn         = {1432-881X},
  keyword      = {Bergman reaction,Calicheamicin,Integral-direct MP2,Parallel MP2,Trigger reaction},
  language     = {eng},
  number       = {1},
  pages        = {203--210},
  publisher    = {Springer},
  series       = {Theoretical Chemistry Accounts},
  title        = {On the significance of the trigger reaction in the action of the calicheamicin γ<sup>I</sup> <sub>1</sub> anti-cancer drug},
  url          = {http://dx.doi.org/10.1007/s002140050254},
  volume       = {97},
  year         = {1997},
}