should be the same as those of the ImNN:NaOO pair. However
the thermal stability of this pair (+7.9 1C) was rather low
compared with the ImNN:NaOO pair and almost the same as
those of the ImON:NaNO and ImNO:NaON pairs. In our
previous study,4 we suggested that the ImOO exists as a
tautomeric form, represented as ImOO(t), possessing an
ADAA H-bonding pattern. This being the case, then the base
pair between ImOO(t) and NaNN should have four repulsive
and two attractive secondary interactions together with three
primary H-bonds (Fig. 2C). Accordingly, the overall strength
of interaction of the ImOO(t):NaNN pair can be estimated as
three H-bonds and ꢀ2 of secondary interactions, which was
thermally similar to those of four H-bonds and ꢀ6 of secondary
interactions. The attached ꢀDG0 data also support these
considerations. Thus, the ImNN:NaOO pair by giving rise to
a favorable contribution to the enthalpy of formation was
most thermodynamically stable, and the remaining pairs
showed similar thermodynamic parameters (see the ESIw).
The synthesis of the new 1,8-naphthyridine nucleosides NaNN
(5) and NaOO (10) and their incorporation into ODNs have
been accomplished. Comparison of the base-pairing properties
of a series of Im:Na pairs revealed that the ImNN:NaOO pair
possessing a DAAD:ADDA H-bonding pattern was most
thermally and thermodynamically stable. Our results showed
the importance of the secondary interaction, depending on the
arrangement of H-bonds, together with the number of H-bonds
and the stacking effect of the expanded aromatic surfaces in the
duplex stability.17 Application of this markedly stable
base-pairing motif toward developing alternative stable base
pairs other than the Watson–Crick base pairs is underway.
Fig. 2 Consideration of thermal and thermodynamic stability of a series
of Im:Na base-pairing motifs. The dotted line represented repulsive
secondary interaction and the bold line represented attractive secondary
interaction. The index represented the sum of both secondary interactions.
The listed DTm and ꢀDG0 values were obtained from a series of ODN
I:ODN II.
complementarity of H-bonds is one of the important factors
for duplex stability. However, the thermal stability of these
Im:Na base pairs was different. As described in the introduction,
Jorgensen and Pranata suggested the importance of secondary
interaction for the stability of the hydrogen bonded complexes.11
The validity of their consideration is well demonstrated and
evaluated in many complexes possessing a variety of H-bonding
patterns.13–16 Our results can also be understood in view of their
hypothesis. Thus, the ImON:NaNO pair has a DADA:ADAD
H-bonding pattern (Fig. 2A). In this pair, six repulsive
secondary interactions (represented by dotted lines) arising
from D–D and A–A repulsion have to be considered together
with four primary H-bonds. Accordingly, the overall strength
of interaction of the ImON:NaNO pair can be estimated as
four primary H-bonds and six repulsive secondary interactions
(ꢀ6) represented as ‘‘index’’. The ImNO:NaON pair possessing
an ADAD:DADA H-bonding pattern is expected to have the
same overall strength of interaction (Fig. 2B). This estimation
agrees well with the calculated Tm values of the ImON:NaNO
and ImNO:NaON pairs (+7.8 1C vs. +7.5 1C). Since the
ImNN:NaOO pair has a DAAD:ADDA H-bonding pattern
(Fig. 2D), this pair is expected to have four repulsive and two
attractive secondary interactions (represented by bold lines)
together with four primary H-bonds. Accordingly, the overall
strength of interactions of the ImNN:NaOO pair can be
estimated as four primary H-bonds and –2 of secondary
interactions, which was, in fact, thermally more stable than
the ImON:NaNO and ImNO:NaON pairs (+11.4 1C vs. +7.8
and +7.5 1C). For the ImOO:NaNN pair, if this pair has an
ADDA:DAAD H-bonding pattern as illustrated in Fig. 1C,
the overall strength of interaction of this pair can be estimated
as four H-bonds and ꢀ2 of secondary interactions, which
Notes and references
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2 I. Hirao, Curr. Opin. Chem. Biol., 2006, 10, 622.
3 A. T. Krueger and E. T. Kool, Chem. Biol., 2009, 16, 242.
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N. Atsumi, Y. Ueno and A. Matsuda, J. Am. Chem. Soc., 2003,
125, 9970.
5 S. Hikishima, N. Minakawa, K. Kuramoto, Y. Fujisawa,
M. Ogawa and A. Matsuda, Angew. Chem., Int. Ed., 2005, 44, 596.
6 Y. Hirama, H. Abe, N. Minakawa and A. Matsuda, Tetrahedron,
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7 Y. Hirama, N. Minakawa and A. Matsuda, Bioorg. Med. Chem.,
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8 S. Hikishima, N. Minakawa, K. Kuramoto, S. Ogata and
A. Matsuda, ChemBioChem, 2006, 7, 1970.
9 N. Minakawa, S. Ogata, M. Takahashi and A. Matusda, J. Am.
Chem. Soc., 2009, 131, 1644.
10 S. Ogata, M. Takahashi, N. Minakawa and A. Matsuda, Nucleic
Acids Res., 2009, 37, 5602.
11 W. L. Jorgensen and J. Pranata, J. Am. Chem. Soc., 1990,
112, 2008.
12 The Tm values of duplexes containing ImON:NaNO and ImNO:NaON
pairs have been already reported in our previous paper. However, all
Tms were measured again for accurate comparison.
13 T. J. Murray and S. C. Zimmerman, J. Am. Chem. Soc., 1992,
114, 4010.
14 H. C. Ong and S. C. Zimmerman, Org. Lett., 2006, 8, 1589.
15 F. H. Beijer, R. P. Sijbesma, H. Kooijman, A. L. Spek and
E. W. Meijer, J. Am. Chem. Soc., 1998, 120, 6761.
16 S. Djurdjevic, D. A. Leigh, H. McNab, S. Parsons, G. Teobaldi
and F. Zerbetto, J. Am. Chem. Soc., 2007, 129, 476.
17 The stacking abilities of a series of naphthyridine bases were
higher than those of purine bases and similar to those of the
imidazopyridopyrimidine bases (see the ESIw).
c
10820 Chem. Commun., 2011, 47, 10818–10820
This journal is The Royal Society of Chemistry 2011