Chemistry Reference
In-Depth Information
region of the spectrum and notable luminescent emissions - perturbations of these
spectral characteristics upon nucleic-acid binding provide a convenient means to
appraise the extent or nature of the interaction.
11.2 Mononuclear Complexes
[Ru(phen)
3
]
2+
(phen = 1,10 - phenanthroline; see Figure 11.1 d) has received particu-
lar attention as an inert metalloprobe of biological molecules. Its DNA binding
ability has been most extensively investigated by Barton and coworkers, who in the
early 1980s, elaborated upon the work of Dwyer
et al.
by investigating the
in vitro
enantioselectivity of the complex.
3
On the basis of hypochromicity measurements
it was proposed that the complex bound via intercalation of a single phenanthroline
ligand. Preferential association between the D form of the complex and right-handed
B - DNA was confi rmed. The observed enantioselectivity is believed to be due to the
unfavourable steric interactions between the nonintercalated ligands of the L enan-
tiomer with the sugar-phosphate backbone of the DNA. Alternatively, the nonin-
tercalating phenanthroline ligands of the D isomer fi t easily within the complementary
right-handed helical groove. No enantioselectivity was observed in experiments
conducted with left-handed Z-DNA, presumably due to the altered groove dimen-
sions. The intercalative model proposed by Barton
et al.
was supported by experi-
ments utilizing the analogous complex with 4,7-diphenyl-1,10-phenanthroline (DIP;
Figure 11.1o) as the ligand. As expected, the phenyl groups heightened the observed
enantioselectivity, purportedly by exaggerating the steric interactions between the
L enantiomer and the phosphate backbone, as well as enhancing the extent of
intercalation.
4
Again, both enantiomers were found to bind to Z-DNA with equal
affi nity. By contrast, [Ru(bpy)
3
]
2+
(bpy = 2,2
- bipyridine; Figure 11.1 a), lacking suf-
fi ciently elongated polyaromatic ligands to participate in intercalation, associated
with DNA only weakly in what was believed to be primarily an electrostatic
interaction.
5
However, the intercalative binding proposal has been the subject of consider-
able controversy. Viscosity measurements undertaken by Chaires
et al.
6
and scan-
ning force microscopy investigations by Williams, Bottomley
et al.
7
both suggested
a nonintercalative mode of binding. Subsequent NMR experiments of Collins
et al.
8
gave some indication that [Ru(phen)
3
]
2+
may indeed be partially intercalating, a
result confi rmed by more recent linear dichroism studies by Nordén and Lincoln:
9
they claimed that both enantiomers of the complex may bind with one phenanthro-
line ligand partially (semi- or quasi-) intercalated via the minor groove, and their
proposed binding geometry is in reasonable agreement with the available NMR
data. This partial intercalation model is commonly seen amongst complexes which
have polyaromatic ligands that either have insuffi cient span to insert fully between
stacked base pairs, or in cases where the intercalating ligand deviates from planarity,
inhibiting complete insertion.
10
Indeed, a circular and linear dichroism study by
Nordén and coworkers eventually dismissed an intercalative binding mode for
[Ru(DIP)
3
]
2+
.
11
′
