Chemistry Reference
In-Depth Information
and RNA structures, it is generally only possible for one metal centre to bind deeply
within the minor groove. The rigid ruthenium complex cannot follow the curvature
of the groove in nonduplex structures that are not dramatically altered from the
standard duplex, and hence the second metal centre must project out of the groove.
It was proposed that dinuclear ruthenium complexes linked by a fl exible chain could
overcome this limitation, and potentially allow both metal centres to bind optimally
in the minor groove.
The stereoisomers of a series of dinuclear ruthenium(II) complexes
[{Ru(phen)
2
}
2
( m - bb
n
)]
4+
with fl exible bridging ligands (bb
n
; Figure 11.2 k) - bb2 (1,2 -
bis[4(4
′
- methyl - 2,2
′
- bipyridyl)]ethane), bb5 (1,5 - bis[4(4
′
- methyl - 2,2
′
- bipyridyl)]pentane),
bb7 (1,7-bis[4(4
′
- methyl - 2,2
′
- bipyridyl)]heptane) and bb10 (1,10 - bis[4(4
′
- methyl -
2,2
-bipyridyl)]decane} - were synthesized and their binding to the single adenine
bulge - containing tridecanucleotide, d(CCG
A
GAATTCCGG)
2
, studied.
119
Based on
the results from a fl uorescent DAPI - displacement assay (DAPI = 4
′
,6 - diamidino - 2 -
phenylindole; see Section 11.3.7), equilibrium dialysis and affi nity binding chroma-
tography experiments it was determined that the D
D - enantiomer of the bb7 - bridged
complex bound the bulge-containing oligonucleotide with the highest affi nity. NMR
experiments demonstrated that the D
D - bb7 - bridged complex still selectively tar-
geted the bulge site, while molecular modelling showed the ability of the fl exibly
linked complex to follow the curvature of the DNA minor groove, as shown in
Figure 11.10. It was concluded that fl exibly linked dinuclear complexes will still
exhibit the selectivity for nonduplex DNA sites observed for the rigid complexes,
′
Figure 11.10
Comparison of the binding of
DD
-[{Ru(phen)
2
}
2
(
m
-bb7)]
4+
(left) and
DD
-
[{Ru(phen)
2
}
2
(
m
-bpm)]
4+
(right) to the adenine-bulged tridecanucleotide duplex. The com-
plexes are coloured black, and the arrows indicate the location of the second of the ruthenium
metals centres (after the fi rst one has positioned itself in the bulge region) showing how in
the fl exibly linked complex the linker follows the curve in the groove
119
