Title

Efficient and Accurate Characterization of the Bergman Cyclization for Several Enediynes Including an Expanded Substructure of Esperamicin A(1)

ACS Citation

Sherer, E. C.; Kirschner, K. N.; Pickard, F. C.; Rein, C.; Feldgus, S.; Shields, G. C. Efficient and Accurate Characterization of the Bergman Cyclization for Several Enediynes Including an Expanded Substructure of Esperamicin A(1). J. Phys. Chem. B 2008, 112 (51), 16917-€“16934.

Abstract

Incorporation of enediynes into anticancer drugs remains an intriguing yet elusive strategy for the design of therapeutically active agents. Density functional theory was used to locate reactants, products, and transition states along the Bergman cyclization pathways connecting enediynes to reactive para-biradicals. Sum method correction to low-level calculations confirmed B3LYP/6-31G(d,p) as the method of choice in investigating enediynes. Herein described as M1:Sum, calculated reaction enthalpies differed from experiment by an average of 2.1 kcal . mol(-1) (mean unsigned error). A combination of strain energy released across the reaction coordinate and the critical intramolecular distance between reacting diynes explains reactivity differences. Where experimental and calculated barrier heights are in disagreement, higher level multireference treatment of the enediynes confirms lower level estimates. Previous work concerning the chemically reactive fragment of esperamcin, MTC, is expanded to our model system MTC2.

Source Name

Journal of Physical Chemistry B

Publication Date

2008

Volume

112

Issue

51

Page(s)

16917-16934

Document Type

Citation

Citation Type

Article