DNA Structure, Bonding and Replication
The discovery by Kool and coworkers [1] that the apolar 2,4-difluorotoluene (F) mimics thymine
(T) in enzyme-catalyzed DNA replication has led to a controversy about the question if hydrogen
bonding is really so important in this process of biomolecular recognition. Instead, spatial fit
between DNA bases in the active site of DNA polymerase was proposed as the determining
factor. We show [2-4] that, proceeding from the latter, hydrogen bonding in AF is indeed
important for the experimentally observed ability of 2,4-difluorotoluene (F) to act as the
complementary base of adenine (A) in enzyme-catalyzed DNA replication. These hydrogen
bonds can be formed only if the right Watson-Crick geometry can be adopted [4]. In that case,
both stabilizing donor–acceptor orbital interactions and electrostatic attraction substantially lower
the overall barrier of the reaction. We confirm the core ideas of Kool's steric model but, at the
same time, we show that it does not rule out an important role for hydrogen bonding [4]. Thus,
we propose a new model for biocatalytic DNA replication, which is a synthesis of the traditional
and the steric model.
[1] Kool, E. T.; Morales, J. C.; Guckian, K. M. Angew. Chem. 2000, 112, 1046; Angew. Chem.
Int. Ed. 2000, 39, 990.
[2] Fonseca Guerra, C.; Bickelhaupt, F. M. Angew. Chem. 1999, 111, 3120; Angew. Chem. Int.
Ed. 1999, 38, 2942.
[3] Fonseca Guerra, C.; Bickelhaupt, F. M.; Snijders, J. G.; Baerends, E. J. Chem. Eur. J. 1999,
5, 3581.
[4] Fonseca Guerra, C.; Bickelhaupt, F. M. Angew. Chem. 2002, 114, 2194; Angew. Chem. Int.
Ed. 2002, 41, 2092.