Semiempirical Study of the Bergman Reaction: Towards a Computationally Efficient and Accurate Method for Modeling Enediyne Anticancer Antibiotics

ACS Citation

Brummel, H. A.; Shields, G. C. Semiempirical Study of the Bergman Reaction: Towards a Computationally Efficient and Accurate Method for Modeling Enediyne Anticancer Antibiotics. Int. J. Quantum Chem. 1995, No. 22, 51-€“59.

Abstract

Over the past 7 years, the enediyne anticancer antibiotics have been widely studied due to their DNA cleaving ability. The focus of these antibiotics, represented by kedarcidin chromophore, neocarzinostatin chromophore, calicheamicin, esperamicin A, and dynemicin A, is on the enediyne moiety contained within each of these antibiotics. In its inactive form, the moiety is benign to its environment. Upon suitable activation, the system undergoes a Bergman cycloaromatization proceeding through a 1,4-dehydrobenzene diradical intermediate. It is this diradical intermediate that is thought to cleave double-stranded DNA through hydrogen atom abstraction. Semiempirical, semiempirical CI, Hartree-Fock ab initio, and MP2 electron correlation methods have been used to investigate the inactive hex-3-ene-1,5-diyne reactant, the 1,4-dehydrobenzene diradical, and a transition state structure of the Bergman reaction. Geometries calculated with different basis sets and by semiempirical methods have been used for single-point calculations using electron correlation methods. These results are compared with the best experimental and theoretical results reported in the literature. Implications of these results for computational studies of the enediyne anticancer antibiotics are discussed.

Source Name

International Journal of Quantum Chemistry

Publication Date

1995

Issue

22

Page(s)

51-59

Document Type

Citation

Citation Type

Article

Share

COinS