Chemistry Reference
In-Depth Information
results were previously reported by Platz et al.
86
in the photochemistry of
3-nitrophenyl azide.
Keana et al.
84
also investigated the photochemistry of iodosubstituted perfluoro-
phenyl azides since this halogen atom could be replaced by the radioactive analog for
PAL experiments. In comparison with perfluorophenyl azide, relatively low yields of
C
H insertion products were formed on photolysis of iodo derivatives.
The halogen atom enhances ISC due to heavy atom effect.
84
Furthermore, when iodine
atom and azide group are located in the same aromatic ring, some photodeiodination
takes place and a complex mixture of products is actually obtained.
63,87
Another interesting substituent effect was realized by Pandurangi et al.
65
H and N
In
cyclohexane, photolysis of
N
-alkyl perfluorophenyl azide gave low yields of C
H
insertion products. In dicyclohexylamine, N
H insertion was quite significant, and
this azide was shown to be quite useful for protein photoaffinity labeling.
88
The relative photochemical reactivity of several perfluorophenyl azides has been
investigated with hydrocarbons and amines. However, the affinity of these reactive
azides with biomolecules has not been investigated. Furthermore, the insertion
efficiencies of perfluorophenyl nitrenes with functional groups present in biomole-
cules need to be studied for a better application of aryl azides in PAL.
65
Metal chelates play an important role in nuclear medicine.
89
Attachment of a
radiolabeled molecular probe to antibodies or antibody fragments is a versatile
technique to target the molecular probes to specific biological sites either for imaging
or therapy of cancer. The most promising metal chelates as probes of biological
systems are transition metals such as technetium, palladium, rhodium, and renium,
since they have useful diagnostic and therapeutic radioisotopes (
99m
Tc,
109
Pd,
105
Rh,
and
188
Re).
A conventional bifunctional chelating agent
90
contains a metal chelating group and
a chemically reactive group like succinimide or COOH. This latter group is activated to
form a covalent bond with an amino acid residue of a macromolecule in chemically
affinity labeling. Most of the chemical methods developed thus far for peptides and
proteins have focused on attaching bifunctional chelates at theN-terminal amino group
(in amino acids) and C-terminal carboxyl group (in aspartic and glutamic acids).
However, these functional groupsmay be essential for bioactivity and any alterations of
these residues may result in loss of affinity of the antibody or its fragments for the target
tissue. Direct attachment in the hydrocarbon side chains of amino acids (valine,
leucine) would preserve the functional groups needed for binding antigens.
8
In PAL, a photochemical analog
65
is used that contains a photoactive moiety (like
an aryl azide) and a chelating agent (to chelate a transition metal) separated spatially
and electronically. In this case, the covalent bond results from photochemical
activation. In principle, the PAL method does not require specific functional groups
in the biomolecule since labeling could be achieved by a highly reactive singlet
nitrene intermediate generated on photolysis.
12
Photochemical bifunctional chelating agents (BFCAs) must have several impor-
tant characteristics. (i)
In vivo
stability of the coordination bonds between the metal
and the chelating part of the molecule. (ii) Retention of photochemical insertion
properties after chemical reactions like derivatization and metal chelation.
65
