Chemistry Reference
In-Depth Information
The concept of 'photochemically' activated Rh(III) cisplatin analogues has
been investigated for complexes of the type
cis
- [RhCl
2
(polypyridyl)
2
]
+
.
50,51
For
example, c
is
- [RhCl
2
(phen)
2
]
+
(phen 1,-10-phenanthroline) was found to undergo
light-induced covalent binding to DNA.
52
Although kinetically inert under thermal
conditions, irradiation of the complexes results in d-electron promotion into ligand-
fi eld bands, thus increasing the rate of ligand exchange by orders of magnitude rela-
tive to thermal conditions. The reaction with N7 of guanine residues occurred owing
to reductive quenching of the excited state by nucleobase-metal charge transfer,
although with minimal biological effects.
50
Such promising preliminary results led
to the investigation of other complexes that demonstrated oxidative DNA strand
scission.
51
In particular, work by Barton and coworkers have led to many promising
developments in this fi eld.
10.3.5 Site - Specifi c Rhodium - DNA Interactions
Barton and coworkers have produced a large body of work investigating the site-
specifi c interaction of Rh(III) intercalating complexes with DNA, with a view to
introducing selective cleavage of the DNA strand in specifi c regions towards ' site -
directed' photodynamic therapy. Such work has also led to insights into the func-
tions of nucleic acids in biological processes, and the complexes developed have
been used both as photoactivated chemotherapeutic agents,
51
and as probes for
charge transport processes in DNA.
53
The pairing of nucleobases in healthy cells occurs through combination of GC
and AT residues. DNA base mismatches (i.e. CC, CA or CT combinations) arise
owing to enzymatic errors or DNA damage during the process of genetic recombi-
nation or DNA replication.
54,55
The inability of cells to repair mismatches is associ-
ated with cancerous transformations.
56
Early work by Barton and coworkers involved
the development of phenanthrenequinone diimine (phi) complexes of rhodium, that
may intercalate into the major groove of DNA, and subsequently promote photoac-
tivated strand scission.
57 - 59
In an extension of this work, bulky heterocyclic aromatic
imine ligands were introduced in complexes such as [Rh(bpy)
2
(chrysi)
3+
] (chrysi = 5,6 -
chrysenequinonediimine, Figure 10.3 ).
60
The bulky four-ring chrysene ligand, being
too large to intercalate into standard DNA grooves, instead intercalated pre-
ferentially into the larger, perturbed site of the thermodynamically destabilized
Figure 10.3
[Rh(bpy)
2
(chrysi)
3+
] (chrysi = 5,6-chrysenequinonediimine)
