Efficient and Accurate Characterization of the Bergman Cyclization for an Expanded Substructure of Esperamicin A1
Publication Date
2008
Description
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 MI: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.
Journal
The Journal of Physical Chemistry B
Volume
112
Issue
51
First Page
16917
Last Page
16934
Department
Chemistry
Link to Published Version
Recommended Citation
Shields, George C.; Sherer, Edward C.; Kirschner, Karl N.; Pickard, Frank C. IV; Rein, Chantelle; and Feldgus, Steven. "Efficient and Accurate Characterization of the Bergman Cyclization for an Expanded Substructure of Esperamicin A1." The Journal of Physical Chemistry B (2008) : 16917-16934.