Chemistry Reference
In-Depth Information
Despite universal support for the intercalative binding mode of dppz-based
complexes, the groove via which the complexes intercalated became a point of
contention, but present understanding is that it binds from the minor groove.
NMR studies have suggested that both D - [Ru(phen)
2
(dpq)]
2+
(dpq =
-
f
] quinoxaline; Figure 11.1i) and D - [Ru(phen)
2
(dpqC)]
2+
(dpqC =
dipyrido[3,2 -
d
:2
′
,3
′
dipyrido[3,2 -
a
:2
-
c
](6,7,8,9 - tetrahydro)phenazine; Figure 11.1 k) bind via the
minor groove.
8,32
The dpq and dpqC complexes do not bind to DNA as strongly as
do their dppz or dppx analogues (dppx = 7,8-dimethyldipyridophenazine; Figure
11.1l), presumably as they cannot intercalate as effectively as dppz or dppx, which
possess larger aromatic areas that may potentially stack between DNA bases. Addi-
tional NMR experiments conducted by Collins
et al.
on [Ru(Me
2
phen)
2
(dpq)]
2+
and
[Ru(Me
2
phen)
2
(dppz)]
2+
(2,9 - Me
2
phen = 2,9 - dimethyl - 1,10 - phenanthroline; Figure
11.1e) also suggested intercalation via the minor groove (methylated phenanthro-
line ligands were used to simplify the NMR spectra and to provide strong NOE
signals in NOESY spectra).
17,18
Recently, Nordén and coworkers conceded the pos-
sibility of intercalation from either groove when the other is blocked; this concession
was based in part on spectroscopic investigations into the properties of DNA-bound
[Ru(phen)
2
(dppz)]
2+
in the presence and absence of the minor-groove binder 4
′
,3
′
′
,6 -
diamidino - 2 - phenylindole (DAPI).
33,34
Negligible enantioselectivity is observed in the DNA-binding of [Ru(phen)
2
-
(dppz)]
2+
17,28
and its 2,2
- bipyridine analogue [Ru(bpy)
2
(dppz)]
2+
,
34
although in each
case differential luminescence and binding rates were observed between the D and
L isomers of each complex, suggesting different binding geometries for each
enantiomer.
The bulk of studies conducted into polypyridyl complex-nucleic acid interac-
tions have concerned themselves with intercalating mononuclear complexes, typi-
cally of the form [Ru(ancillary)
2
(intercalator)]
2+
, where there is a single dedicated
intercalating ligand and a pair of ancillary ligands that occupy the groove (to a vari-
able extent). Due to the three-dimensional nature of the association between these
octahedral complexes and their chiral polynucleotide targets, the nature of all the
ligands
′
infl uences the binding affi nity of the complex
although a larger intercalative surface area generally correlates with a greater
binding affi nity.
35
Molecular modelling suggests that increasing the
length
of the intercalating
ligand favours binding via the minor groove, whereas increases to the
width
of this
ligand promote binding from the major groove.
36
These fi ndings are corroborated
by experimental results obtained with Ru(II) and Rh(III) complexes featuring the
relatively wide intercalating ligand phi (phenanthrenequinone diimine; Figure
11.1p). NMR experiments suggest that D - cis - a - [Ru(RR - picchxnMe
2
)(dpq)]
2+
(pic-
chxnMe
2
=
N,N
−
ancillary or intercalating
−
- di(2 - picolyl) - 1,2 - diaminocyclohexane; Figure 11.1 q)
intercalates via the minor groove of DNA, whereas the analogous complex with a
phi intercalator, D -
cis
- a - [Ru(RR - picchxnMe
2
)(phi)]
2+
, binds via the major groove.
37
The phi ligand has seen particularly extensive use in octahedral rhodium complexes,
and such species almost invariably intercalate via the major groove.
38
Rhodium
complexes containing phi, or derivatives thereof, have demonstrated an impressive
degree of selectivity for features such as base sequences,
38,39
sequence - dependent
′
- dimethyl -
N,N
′
