Chemistry Reference
In-Depth Information
icosanucleotide, with the HAT ligand positioned at the stem-loop interface with one
set of terminal phenanthroline ligands projecting into the groove of the stem, and
the other projecting into the loop region. The groove at the stem-loop interface is
wider, or more fl exible, than the duplex stem of the icosanucleotide. It was suggested
that the binding was stabilized by energetically favourable van der Waals and hydro-
phobic interactions with the bulky dinuclear complexes.
Of the two metal complexes,
meso -
[{Ru(4,7 - Me
2
phen)
2
}
2
( m - HAT)]
4+
was found
to bind the six-base hairpin-containing icosanucleotide more strongly; however, it
also bound the control duplex sequences with signifi cant affi nity. Secretion of the
hydrophobic methyl groups away in the minor groove, and the subsequent displace-
ment of solvent, was proposed as the driving force behind this greater binding ability
of the methylated species. Alternatively, while
meso -
[{Ru(phen)
2
}
2
( m - HAT)]
4+
bound
the six-base hairpin sequence less strongly than the corresponding methyl analogue,
it showed greater selectivity in its binding when comparing the affi nity to the hairpin
sequence and control duplex structures.
Metal complexes possessing phen or 4,7-Me
2
phen terminal ligands bound the
icosanucleotide hairpin structure with greater affi nity than the ruthenium com-
plexes containing corresponding bpy and Me
2
bpy terminal ligands.
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Presumably,
the larger surface areas of the phenanthroline ligand compared to bipyridine results
in better van der Waals contacts with the walls of the minor groove, or more favour-
able hydrophobic interactions, or allows a semi-intercalative association with DNA
bases, or a combination of all three. With regards to bridging ligands, the various
studies demonstrated that ruthenium complexes containing a bpm bridge are gener-
ally selective for bulge sites, while a HAT bridging ligand is preferable for targeting
hairpin structures. It was also noted that the
meso
diastereoisomer gives the strong-
est binding, particularly in those complexes possessing phenanthroline ligands.
Simple computer models illustrated that the terminal ligands of a
meso
isomer are
able to follow the contours of the minor groove, whereas the D
D - and L
L - enantio-
meric forms of the complex encounter steric clashes at either end of the complex.
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11.3.5 Interaction of Dinuclear Complexes with RNA Sequences
Although it has been clearly established that inert dinuclear ruthenium(II) com-
plexes preferentially bind to nonduplex DNA structures, little is know about their
interaction with RNA. Nonduplex structures occur in both DNA and RNA, but are
much more prevalent in the latter. The formation of such structures is generally
transient and/or disadvantageous in DNA. Alternatively, RNA exhibits a large
diversity of nonduplex structures, which have an important role for recognition sites
for proteins, RNA splicing and RNA folding, making them promising targets for
potential diagnostic and therapeutic agents. Given the differences in the conforma-
tions of DNA and RNA, it is not possible to extrapolate the results obtained for
DNA to RNA. Standard form DNA adopts a B-type helix, whereas RNA adopts
an A-type structure. This results in signifi cant differences in the groove dimensions
- DNA contains a wide major groove and relatively narrow minor groove, whereas,
RNA has a deep and very narrow major groove and a wide shallow minor groove
(see Figure 11.9).
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