ORGANIC
LETTERS
2008
Vol. 10, No. 6
1091-1094
Two Watson
Base-Pairs
−Crick-Like Metallo
Benjamin D. Heuberger, Dongwon Shin, and Christopher Switzer*
Department of Chemistry, UniVersity of California, RiVerside, California 92521
Received December 17, 2007
ABSTRACT
Two Watson−Crick-like metallo base-pairs are described with mutually independent geometries that have similar dimensions and stabilities to
their natural, hydrogen-bonded counterparts.
Among biomolecules, nucleic acids have unique physical
properties that render them highly adapted to their role of
information storage and transfer. Nevertheless, etiological
deconstruction of nucleic acids has shown that considerable
latitude exists for replacement of component features,
including both the backbone and nucleobases.1 Natural
nucleobases encode genetic information by presenting comple-
mentary arrays of hydrogen-bond donors and acceptors,
leading to Watson-Crick base-pairs incorporating (large)
purine and (small) pyrimidine components. A goal of
synthetic biology is to generalize the function of biomol-
ecules in a way that extends their behaviors to new molecular
systems. Efforts to extend the information-encoding capabili-
ties of nucleobases have utilized altered hydrogen-bonding
patterns,1b hydrophobic interactions,2 and metal coordination.3
However, the construction of metallo base-pairs that closely
resemble natural Watson-Crick base-pairssand mirror their
properties in all respectssremains a challenge. Toward
thisend, we report the synthesis and characterization of two
Watson-Crick-like metallo pairs, Pur2,6-py‚Ag(I)‚3-Py and
Pur6-bipy‚Ag(I)‚4-Py (Figure 1).
The metallo base-pairs Pur2,6-py‚Ag(I)‚3-Py and Pur6-bipy
‚
Ag(I)‚4-Py shown in Figure 1 incorporate large and small
heterocyclic components (purine and pyridine cores, respec-
tively) that resemble natural Watson-Crick pairs. Dif-
ferentiation of the core purine‚pyridine motif was accom-
plished geometrically by appending pyridyl groups to the
purine component symmetrically and asymmetrically, yield-
ing Pur2,6-py and Pur6-bipy. The resultant di-pyridyl purines
are complemented with a cognate 3-pyridyl or 4-pyridyl base.
Density functional calculations were used to initially validate
metallo pair design. The resulting geometries, displayed at
the bottom of Figure 1, show that the closest correspondence
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10.1021/ol703029d CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/27/2008