Chemistry Reference
In-Depth Information
Groove binding of transition metal polyazine complexes to DNA is controlled
by complex lipophilicity and molecular shape. Also known as surface binding, groove
binding is association of a species with the hydrophobic pocket formed between the
sugar-phosphate backbones of each strand. The complex [Ru(Me
4
phen)
3
]
2+
is a well-
known groove binder.
57
The methyl substituents on the phen ligand contribute to
the complex's overall lipophilicity, but provide steric bulk that prevents more inti-
mate interactions with the DNA.
Extended, planar polyazine ligands that can intercalate into the base stack of
DNA have been shown to enhance metal complex-DNA electronic interactions
prior to photolysis.
5,51
Two ligands often included in a metal complex' s architecture
that promote intercalation are dppz and 9,10-phenanthrenequinone diimine (phi).
Complexes with bulky planar ligands have been reported to bind by an alternative
mechanism. The complex [(phen)
2
Rh(chrysi)]
3+
reported by Barton and coworkers
inserts its a-chrysenequinone diimine (chrysi) ligand into the bases stack accompa-
nied by displacement of a base pair. Photocleavage of DNA by metalloinsertor
complexes was shown to be an effective method of identifying base mismatches in
the DNA.
61
It is important to note that the mode of DNA-metal complex interaction prior
to photolysis is not always clear. The reader is referred to a review by Kirsch De-
Mesmeaker, Lecompte and Kelly for a historical account of 'The controversial case
of [Ru(phen)
3
]
2+
.
2
Hexacoordinate transition metal complexes with two or three bidentate ligands
tend to have strongly enantioselective binding interactions with DNA.
59
DNA in its
most common B form is a right-handed double helix (Figure 8.2), interacting more
strongly with
∆
enantiomers of tris(chelate) metal complexes. Barton has shown that
- [Ru(Ph
2
phen)
3
]
2+
binds strongly in the major groove of the double-
helix, intercalating the base pairs. The other enantiomer
the complex
∆
- [Ru(Ph
2
phen)
3
]
2+
does
not bind as strongly, owing to the steric repulsion of the bulky ancillary ligands with
the sugar-phosphate backbone of DNA provided by the stereochemistry around the
metal centre.
Λ
8.4.2 Mechanisms of DNA Photochemical Degradation
Photochemical degradation of DNA has been pursued in recent years toward appli-
cations in PDT, and DNAase and RNAase biomimetics. The mechanisms of DNA
degradation under photolytic or oxidative stress have been thoroughly reviewed, so
minimal explanation of these pathways is given below.
52,53,62
Photoinitiated binding
of metal complexes has been studied, coined ' photo - cisplatin ' agents. Photobinding
through an ancillary ligand also leads to DNA covalent modifi cation. Oxidation of
the DNA bases by ES electron transfer reaction and hydrogen atoms abstraction
are important to the photochemical function of some transition metal polyazine
complexes. Photocleavage of DNA by the transition metal polyazine ES in the pres-
ence or absence of dissolved
3
O
2
refl ects separate mechanisms of action. Many of
the transition metal polyazine complexes studied for their photochemical interac-
tion with DNA exhibit multiple ES reactions with DNA.
