Chemistry Reference
In-Depth Information
10
Rhodium - and Tin - DNA
Interactions and Applications
Kenneth D. Camm and Patrick C. McGowan
10.1 Introduction
The ubiquity of transition metals employed in biological processes is a direct con-
sequence of the versatile chemistry such metals exhibit. In particular, the multiple
oxidation states and diverse structural motifs accessible to transition metals have
resulted in their incorporation into complex 'bioinorganic' species in nature. These
same properties have facilitated the development of artifi cial transition metal com-
plexes, designed to modify or regulate many biological processes.
1
The Lewis acidity
of transition metals, and consequently their affi nity for Lewis bases such as N, O or
S donor ligands, renders transition metal complexes suitable for interaction with a
multitude of biologically relevant species, including nucleic acids (DNA and RNA).
Cellular function and replication relies on the chemistry and interactions of nucleic
acids, and consequently these species have frequently been targeted in therapeutic
protocols for diseases as varied as cancer and arthritis.
2
The fi rst, and to-date most successful, inorganic complex employed in the treat-
ment of cancer, [Pt(NH
3
)
2
Cl
2
] (cisplatin, Figure 10.1 a)
3,4
and its derivatives, is highly
effective against testicular and ovarian cancer, and in other malignancies including
cervical, bladder, head and neck tumours. The cytotoxic activity of cisplatin is a
direct consequence of covalent interactions between the Pt centre and N7s of adja-
cent guanine residues on DNA, to form a covalent 1,2-intrastrand d(GpG)crosslink.
4
