Chemistry Reference
In-Depth Information
Figure 10.1
Dinuclear Rh complexes
supporting the proposed rearrangement mechanism.
31
The introduction of labile
equatorial ligands may also facilitate ligand rearrangement to the equatorial posi-
tion, and may therefore provide an explanation of the increased activity observed
through introduction of electron-withdrawing groups, such as in Rh
2
( m - O
2
CF
3
)
4
, that
exhibited activity comparable to that of cisplatin.
32
In an extension to this work,
dirhodium interactions with single-stranded oligonucleotides containing GG sites
were investigated. This work further corroborated the correlation between lability
of the ligands present and nucleic acid binding affi nity, wherein the affi nity of the
dirhodium complexes were compared to cisplatin derivatives:
cis -
[Pt(NH
3
)
2
(H
2
O)
2
]
2+
≈
R h
2
( m - O
2
CCF
3
)
4
>
cis
- [Pt(NH
3
)
2
Cl
2
]
>
>
cis
- [Rh
2
( m - O
2
CCH
3
)
2
(NCCH
3
)
6
](BF
4
)
2
Rh
2
( m O
2
CCH
3
)
4
.
17,33,34
More recent work has refuted the conclusions of earlier studies that suggested
dirhodium complexes did not interact with double-stranded DNA. Indeed, interac-
tion of a number of species demonstrated the presence of covalently linked DNA
adducts. Signifi cantly, these studies demonstrated the formation of stable DNA
interstrand crosslinks
35
Although specifi c binding has yet to be ascertained, the pres-
ence of a mixture of mono- and bifunctional adducts, including the more stable
equatorial adducts was observed. Once again, the binding modes determined in
model studies corroborated with data from the studies performed on double-
stranded DNA, wherein an increased lability of the leaving groups corresponds to
an increase in occurrence of interstrand crosslinks.
36
As observed for binding of
guanine residues to dirhodium complexes, bidentate equatorial binding of adenine
residues on dinucleotide d(ApA) was observed, with the d(ApA) fragment
>
