Chemistry Reference
In-Depth Information
twisting,
40,41
base mismatches
42,43
and base triples.
44
The usual enantioselectivity
favouring the D form is observed in DNA-binding experiments with these complexes.
45
The role of ancillary ligands is therefore important, as the steric bulk of the
nonintercalating ligands directly infl uences how deeply the complex may intercalate.
In addition, hydrophobic interactions, van der Waals contacts, and hydrogen bonding
brought about by the ancillary ligands are believed to be the major driving forces
behind many DNA-complex associations.
18,27
A good illustration of this is the
complex [Ru(IP)
2
(dppz)]
2+
(IP = imidazole[4,5 -
f
][1,10]phenanthroline; Figure
11.1n), which, with its bulkier aromatic ancillary ligands, binds to DNA with an
affi nity several times that of its parent complex [Ru(bpy)
2
(dppz)]
2+
.
46
Increased
hydrophobicity in the form of strategically placed methyl groups can also strengthen
the DNA - complex interaction: [Ru(5,6 - Me
2
phen)
2
(dppz)]
2+
(5,6 - Me
2
phen = 5,6 -
dimethyl - 1,10 - phenanthroline; Figure 11.1 f) binds more strongly than does
[Ru(phen)
2
(dppz)]
2+
.
47
Ultimately, how well the ancillary ligands complement the
shape of the groove in which they are binding (which itself depends on the nature
of the target nucleic acid) may be the most signifi cant factor governing binding.
48
A detailed survey of DNA recognition by metallointercalators is beyond the
scope of this review; however, an excellent review from the Barton laboratory has
recently been published.
49
Furthermore, rhodium(III) - based metallointercalators
have been more extensively utilized for DNA recognition than ruthenium(II) com-
plexes. However, the modifi cation of the intercalating and ancillary ligands in
[Ru(ancillary)
2
(intercalator)]
2+
complexes has allowed some modulation of the
binding selectivity to achieve specifi c DNA recognition. At the most basic level,
ruthenium complexes can be used to distinguish between the A, B and Z-forms of
DNA. For example, both the D and L enantiomers of [Ru(DIP)
3
]
2+
bind to Z - form
(left-handed) DNA, whereas only the D isomer binds to B-DNA;
50
however, this
was subsequently disputed by Norden and coworkers.
11
Alternatively, [Ru(TMP)
3
]
2+
(TMP = 3,4,7,8 - tetramethyl - 1,10 - phenanthroline; Figure 11.1 h) has been shown to
specifi cally bind A - form DNA.
51
More recently, it has been demonstrated that ruthe-
nium-based metallointercalators can be used to target DNA mismatch sequences.
These noncomplementary base pairs can occur naturally, or through the interaction
of genotoxic chemicals or ionizing radiation, and can lead to a range of diseases.
52
Barton and coworkers have reported that [Ru(bpy)
2
(tactp)]
2+
(tactp = 4,5,9,18 -
tetraazachrysenol(9,10 - b) - triphenylene; Figure 11.1 u) preferentially binds a CC
mismatch.
49
The tactp intercalating ligand combines the DNA light-switch effect of
dppz-based complexes with the chrysi (5,6-chrysene quinone diimine; Figure 11.1v)
ligand that is selective for mismatch sites. The sterically bulky chrysi ligand is too
wide to intercalate at matched DNA sites, but is suited to thermodynamically desta-
bilized sites.
49
11.3 Dinuclear Complexes
The utility of mononuclear metal complexes as probes for structural recognition in
polynucleotides is limited by their relatively small size, as a typical mononuclear
