Chemistry Reference
In-Depth Information
tation, changes to spectroscopy and viscosity measurements. Each form of DNA has
specifi c advantages and disadvantages toward use in photochemical experiments
and multiple types are required to get a more complete understanding of the metal
complex- DNA photochemical mechanism.
8.4 Designing Transition Metal Polyazines for DNA Photomodifi cation
Photomodifi cation of DNA by transition metal polyazine complexes is attractive
because of the structural diversity of this class of complexes.
18,19
Two major design
considerations for chromophores applicable as DNA photomodifi cation agents are:
the impact of structural changes on the interaction of the chromophore with DNA,
and the impact of chromophore structure on the effi ciency and mechanism of their
DNA photochemistry. Recent reports present photochemical mechanisms that help
elaborate previously described photochemistry (Table 8.1) and have prompted cell
studies to explore application in PDT.
8.4.1 Ground State Interactions of Transition Metal Polyazine Complexes
and DNA
The mechanism of DNA modifi cation by photosensitizers is often multistep with
the fi rst step involving some form of metal complex- DNA association.
2,50,51
Smaller,
compact polyazine transition metal complexes tend to have an electrostatic interac-
tion with DNA.
56
Lipophilic substituents on the polyazine ligands give complexes
that bind in the hydrophobic minor or major groove of the DNA double helix.
57
Ligands with extended, planar aromatic substituents favour intercalation between
DNA bases.
5,51
More recently, metal complexes have been shown to insert between
strands of the double helix, a behaviour that is previously not described.
51
Binding
of transition metal polyazine complexes to DNA is enantioselective, a refl ection of
the chiral nature of DNA and the often chiral nature of polyazine chelated metal
complexes. Barton has pioneered exploiting the different binding modes as shape-
selective probes of DNA and RNA structure.
5,51,58,59
The strength of the DNA- metal
complex interaction has a direct impact on the photosensitizer function as a DNA
modifi cation tool.
Electrostatic interaction of cationic transition metal polyazine complexes with
DNA can be described by the polyelectrolyte approximation of counterion conden-
sation theory.
60
DNA is polyanionic with a single negative charge per nucleotide in
aqueous solution. Usually Na
+
acts as the counterion to the DNA negative charge.
Transition metal polyazine complexes studied for DNA photomodifi cation can have
large negative to large positive charges. Exchange effi ciency of Na
+
at the DNA
surface by an incoming complex ion is a factor of the charge of the complex, the
concentration of free metal complex and Na
+
concentration (ionic strength). Com-
plexes with large positive charges that are structurally compact have stronger elec-
trostatic interactions with DNA. The prototypical transition metal polyazine complex
[Ru(bpy)
3
]
2+
exhibits ionic binding to DNA.
56
