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ChemComm
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COMMUNICATION
Journal Name
Both T·T mismatched base pairs and kinking by phen and TAP
ligands may be important components of the binding of
ruthenium polypyridyl complexes to higher-order DNA
structures containing loop regions. Octahedral complexes have
an inherently greater potential for specific interactions than
square planar ones but not much is known about their binding
modes.17 So far the only structural evidence is provided by the
work of the Thomas group as already stated.5 In that work (in
which the ancillary ligands were bpy) the diruthenium cation
References
DOI: 10.1039/C9CC04316K
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G. Biffi, D. Tannahill, J. McCafferty and S. Balasubramanian,
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threaded through
a diagonal loop, with the principal
4
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interactions being with the central thymine residue of the loop.
We have previously shown that, of the well-known ancillary
ligands in these systems, bpy is less likely to cause kinking and
stacking than either phen or TAP.18 More recently the TAP
analogue of this diruthenium compound has been shown to
have a range of useful properties in cell systems.19 It was
studied as an enantiomeric mixture and gave spectroscopic
results clearly indicative of several binding modes. The
specificity of these complexes does not just arise from end-
stacking to the G-quadruplex chromophore but plausibly also
includes the sort of thymine interactions revealed by the
present work. There are several examples of ruthenium
polypyridyl complexes which are luminescent when bound to
what may well be thymine-adenine loop regions of G-
quadruplexes, but there is no structural data for any of these.
The binding modes seen in this work, which have no
counterpart in duplex DNA, and would not be predictable from
any modelling calculation, provide a useful springboard for
understanding luminescence and other spectroscopic
behaviour. Each of the binding modes shown in figure 4 would
have different luminescence behaviour if it were the phen
analogue, based on our previous work. Ru3, being almost
enclosed, would be most luminescent, with Ru1 and Ru4
expected to be similar, and Ru2 the most exposed to quenching
of the excited state via non-radiative pathways. A previous
paper from our laboratory has considered the delta
enantiomer/duplex DNA case in detail.14
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14
15
In future we aim to provide a comparable interpretation of the
binding of lambda complexes to G-quadruplex loop regions. We
would also like to understand the crucial factor which
determines whether the G-quadruplex is parallel, or antiparallel
as in ref 10. It is not clear how much of the switch can be
ascribed to the modification of the dppz ligand and how much
the crystallisation is sequence dependent.
16
17
18
Acknowledgements
We thank Diamond Light Source and EPSRC for a studentship
(to K. McQ.) and the BBSRC for support from grant nos.
BB/019250/1 and BB/M004635/1 (To CJC, JAB, JPH and DJC).
We gratefully acknowledge the provision of beamtime on
beamline I03 at Diamond Light Source Ltd. (MX18745-1).
19
S. A. Archer, A. Raza, F. Dröge, C. Robertson, A. J. Auty, D.
Chekulaev, J. A. Weinstein, T. Keane, A. J. H. M. Meijer, J.
W. Haycock, S. MacNeil and J. A. Thomas, Chem. Sci., 2019,
2, 3502–3513.
Conflicts of interest
There are no conflicts to declare.
4 | J. Name., 2012, 00, 1-3
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