Chemistry Reference
In-Depth Information
Crosslinking results in inhibition of transcription and DNA replication, eventually
leading to cell death.
Following the success of cisplatin, a catalogue of research has accumulated,
investigating the interactions of other transition metals with DNA.
1,2,5 - 9
Much
research has focused on the development of novel therapeutic protocols that may
circumvent the toxicity issues associated with cisplatin chemotherapy, and to probe
the nature of nucleic acid structure and function in biological processes. To this end,
investigations have been performed on metal-DNA interactions covering a large
majority of the periodic table, many of which are reviewed in this publication.
Herein we describe recent developments focusing on the interactions of rhodium
and tin with DNA, and how such work has contributed to our understanding of the
role of nucleic acids in biological processes and facilitated the development of novel
antitumour agents.
10.2 Metal - DNA Interactions
There are three principle interactions that occur between metal complexes and oli-
gonucleotides such as DNA. The fi rst involves covalent interactions between the
Lewis acidic metal and nucleic acid Lewis bases, such as nucleophilic guanine N7
residues. The second interaction occurs through intercalation of a small molecule
between stacked base pairs of the double helix structure. Both such interactions
cause disruption of base stacking in the double helix through interference with van
der Waals or hydrogen-bonding interactions, and thus result in destabilization of
double-helix conformation. The third interaction is electrostatic, occurring between
a cationic complex and the anionic phosphate backbone.
2,8,10
Neutralization of this
negative charge reduces repulsive forces between adjacent phosphate groups, thus
stabilizing the double helix.
11,12
Of note is the fact that the former two interactions
are often selective, while the electrostatic interactions may occur at any phosphate
site along the phosphate backbone.
13,14
These interactions can cause changes in the
DNA structure, affecting cellular processes and potentially leading to cell death.
4,8,10
10.3 Rhodium - DNA Interactions
10.3.1 Rhodium( I ) Complexes
Encouraged by the promising chemotherapeutic properties of cisplatin, a number
of groups in the 1970s began to investigate the potential antineoplastic activity of
other platinum group transition metal complexes, including rhodium. Preliminary
work investigated the effects of
cis
-, square planar organometallic Rh(I) complexes
of type [Rh(COD)L
2
]
+
(L = 2,2
- bipyridine; 1,10 - phenanthroline; piperidine) on
growth of a number of tumours.
15
In all cases, however, the Rh(I) complexes were
less active than cisplatin. Similar observations were made on a series of related
′
