Chemistry Reference
In-Depth Information
Figure 11.6
Molecular model of
DD
-[{Ru(bpy)
2
}(
m
-bpm){Ru(Me
2
bpy)
2
}]
4+
bound to
d(CCGAGAATTCCGG)
2
.
98
the NOE data, showed that the adenine bulge site was intrahelical and base-stacked
with the adjacent guanine residues (see Figure 11.6). The binding model also indi-
cated that the DNA minor groove had signifi cantly widened at the bulge site to
accommodate the ruthenium complex. As the minor groove at the bulge site in the
free tridecanucleotide was not signifi cantly wider than ' canonical ' DNA, it was
concluded that the bulge site introduces an increased fl exibility into the local DNA
structure that allows the specifi c metal complex binding.
Interestingly, while the D
D - enantiomer of [{Ru(Me
2
bpy)
2
}
2
( m - bpm)]
4+
bound
relatively strongly at the bulge site of d(CCG
A
GAATTCCGG)
2
, the corresponding
L
L-isomer did not bind at the bulge site, with weak binding to the terminal nucle-
otide residues being observed. The study provided a rare example of total enanti-
oselectivity in the binding of an inert transition metal complex with DNA.
99,100
The
meso
- ( D
L)-diastereoisomer bound with an affi nity intermediate between the D
D -
and L
L - enantiomers.
While it had been demonstrated that dinuclear ruthenium complexes could
target single base bulges in DNA, it was not known if these metal complexes have
potential for the larger bulge sites (three or more bases) often found in DNA and
