Chemistry Reference
In-Depth Information
spanning the Rh-Rh bond via N7/N6 bridges.
33,37
Such observations again demon-
strate the potential for dirhodium complexes to form interstrand crosslinks. The
ability of dirhodium complexes to bind either adenine or guanine residues on
plasmid pUC19 DNA was recently demonstrated, further disproving previous con-
clusions concerning the inability of such species to bind double-stranded DNA.
38
10.3.3 Rhodium Complexes in Photodynamic Therapy
Owing to the d-electron availability and interchangeable redox properties of transi-
tion metals, such complexes have found application in the area of photodynamic
therapy (PDT).
39
The DNA toxicity of oxygen-derived intermediates from PDT are
well established, and light-induced formation of
1
O
2
, O
2−
and
•
OH in the vicinity of
DNA results in considerable degradation of DNA structure. The development of
novel photoreagents based on bimetallic rhodium complexes has received consider-
able attention, owing to the propensity of such species to induce metal-metal charge
transfer excited states to promote DNA cleavage. Dunbar and coworkers investi-
gated the complex Rh
2
( m - O
2
CCH
3
)
4
, for potential photocleavage of DNA (Figure
10.2 a).
40
The d
7
- d
7
Rh(II)-Rh(II) core was found to promote photoinduced cation
formation in the presence of an electron acceptor. Subsequent DNA 'nicking' then
occurred.
41
Following these observations, a series of potential photoactivated com-
plexes designed to interact with DNA both through coordination and intercalation
were developed (Figure 10.2b).
40,42,43
The complexes studied, with the exception of
[Rh
2
( m O
2
CCH
3
)
2
(CH
3
CN)
6
](BF
4
)
2
,
43
consisted of a chelating intercalating ligand on
one of the two rhodium centres, with labile
cis
ligands on the second to facilitate
covalent coordination to DNA nucleobases. Such species demonstrated DNA
nicking upon photolysis, and cytotoxicity towards human skin cell lines.
42
The dual
binding capability of the related complex
cis
- [Rh
2
(dap)( m - O
2
CCH
3
)
2
( h
1
-
O
2
CCH
3
)(CH
3
OH)](O
2
CCH
3
) (dap = 1,12 - diazaperylene) (Figure 10.2 c),
44
through
both coordination and intercalation interactions with DNA, was elegantly demon-
strated using 2D NMR studies.
45
Similar studies were recently performed on a com-
plex with two stable formamidinate and two labile trifl uoroacetate bridging groups.
37
cis -
Rh
2
(DTolF)
2
(O
2
CCF
3
)
2
(H
2
O)
2
(DTolF =
N,N
-
di
-
p - tolylformamidinate) (Figure
10.1e) has exhibited antitumour activity comparable to that of cisplatin against
Yoshida ascites and T8 sarcomas, with a signifi cant reduction in toxicity, showing
virtually no toxicity in mice.
22
Other heterobimetallic photodynamic species, bearing
a Rh-Ru core have been developed,
46
in which a low energy Ru-Rh metal-metal
charge transfer excited state results in direct DNA nicking in the absence of electron
acceptors.
The extensive and elegant work performed by Dunbar and others has shed
light on the potential mechanisms of activity of the structurally diverse dirhodium
complexes. Despite the obvious differences in structure and reactivity between
mononuclear cisplatin derivatives and the bimetallic rhodium complexes investi-
gated, such research has demonstrated that the mode of activity may indeed be
through formation of interstrand crosslinks between the rhodium metal centres and
adjacent guanine or adenine residues on DNA. Through increased understanding
′
