Chemistry Reference
In-Depth Information
has an IC
50
value of 2.4μm for binding to cloned human dopamine transporter cells [89]. Analogous Tc and Re complexes
containing a ketanserin analogue (
25
) to image serotonin 5-HT
2
receptors have also been reported [90]. other derivatives
aimed at receptor sites within the brain have been described [91, 92], but a recent paper has shown that there may be a
problem with the monothiolate ligand undergoing exchange with glutathione, which raises questions as to the validity of the
'3 + 1' approach [93]. Although not immediately with a radiopharmaceutical application, the reactivity of the monodentate
site has been exploited in the complex
26,
which is a potent inhibitor of the endopeptidase cathepsin B binding to a cysteine
at the active site [94]. This has been utilised in the construction of a combinatorial system for the synthesis of analogues of
cyclophilin hCyp-18 protein, which inhibits a prolyl isomerise enzyme. one part of the binding motif is attached to the nS
3
ligand and the other to the thiolate. Combinations these are then assembled at the Reo core, and the most active species
selected out, an example being
27
. Affinity constants of the order of 10-20 μm were achieved by this strategy [95, 96].
6.2.2
di- and tri-oxo complexes
It was shown early on that neutral n
4
ligands such as cyclam gave cationic m(V) dioxo-complexes with Tc and Re (
29
).
Unfortunately the yield of the
99
Tc complex was only 7% and such complexes have been little pursued subsequently [97, 98].
However diphosphines react with pertechnetate to give
trans
dioxo-complexes and the
99m
Tc complex
28
is used extensively
clinically for myocardial imaging under the name myoview [99]. An interesting more recent development has been the
synthesis of Re dioxo complexes (
30
) with 4-carbene ligands by reaction of an Re(V) precursor with the carbanion of the
imidazolyl group [100]. A review on Tc and Re carbene complexes has also been published [101]. It remains to be seen if
this type of ligand can be adapted for radiopharmaceutical applications (Figure 6.9).
The tris(pyrazolyl)borate trioxo complex [Tco
3
(HBpz
3
)] (pz = pyrazolyl) was reported in 1991, and the chemistry of the Re
analogue was also established [102]. In general, the trioxo core is better developed for Re with examples with nitrogen
heterocyclic ligands [103, 104] and the complex [Reo
3
(oxine)], which is luminescent [105]. The last complex is included
in a review of the excited state properties such as emission of high oxidation state Re complexes, which may be of interest in
the context of developing dual mode imaging agents [106]. In this high oxidation state the oxo-ligands are reactive, and it was
shown in 1988 that in an analogous manner to oso
4
two oxo groups undergo a [3 + 2] addition reaction with olefins to give a
diol [107]. This was later extended to the addition of diphenylketene to give a substituted diol (
31
) (Figure 6.10) [108]. The
area of trioxo Tc and Re chemistry is now being revisited with the recognition that the [l
3
mo
3
] type of complex has structural
similarities with the tricarbonyl system discussed below, but it is smaller and more hydrophilic and the radiopharmaceutical
+
+
R
2
P
R
2
P
+
N
O
O
HN
NH
O
L
L
L=
Re
Tc
Tc
N
L
L
O
O
NH
R
2
R
2
HN
O
R=CH
2
CH
2
OEt
28
29
30
fIgure 6.9
Examples of metal dioxo complexes.
H
N
N
HN
NH
Tc
NH
HN
O
Tc
O
O
O
O
O
O
O
OAc
O
O
N
O
L
Re
AcO
Ph
O
2
N
OAc
L
O
N
Ph
L
OAc
L
3
= HBPz
3
, Clbipy etc
31
32
33
fIgure 6.10
Examples of trioxo complexes.
