ISSN:
1432-2234
Keywords:
Key words: Bergman reaction
;
Calicheamicin
;
Integral-direct MP2
;
Parallel MP2
;
Trigger reaction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract. The significance of the so-called trigger reaction in the reaction mechanism of the calicheamicin γ1 I anti-cancer drug has been studied with ab initio quantum chemical methods. The structures of four fragments of calicheamicin γ1 I , 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002140050254
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