New Bioconjugated Rhenium Carbonyls by Transmetalation Reaction with Zinc Derivatives

The transmetalation reaction between zinc dithiocarbamates
and rhenium carbonyls has been used as a new strategy to link biomolecules
to transition metals. The zinc­(II) dithiocarbamate of isonipecotic
acid (1) and the succinimidyl ester derivative (2) were prepared by straightforward procedures and were fully
characterized by spectroscopic and X-ray diffraction methods, showing
in both cases the presence of dinuclear complexes. Complex 2 reacted with all the primary and secondary amines studied (glycine
methyl ester, β-alanine methyl ester, 1-(2-methoxyphenyl)­piperazine,
and d-(+)-glucosamine) through the activated succinimidyl
ester group, linking the metallic fragment with the biomolecule by
the formation of a peptidic bond and leading to the respective bioconjugated
zinc complexes 3–6. In all cases,
these zinc complexes could be isolated from the reaction medium by
simple precipitation. These results evidence the potential of complex 2 to be used as a synthon to link the zinc dithiocarbamate
fragment to biomolecules that contain an amine group. Complexes 3–6 were characterized by the usual spectroscopic
methods, and all data agree with the proposed structures, which do
not contain significant interactions between the zinc fragment and
the functional groups of these biomolecules. The transmetalation reaction
between the zinc complexes 3–6 and
the rhenium carbonyl [ReBr3(CO)3]2– led to the expected rhenium dithiocarbamates 7–10 with no change in the organic dithiocarbamate fragments,
confirming the viability of this reaction as a tool for linking biomolecules
to transition elements. All complexes were characterized by spectroscopic
methods, and the crystal structure of 8 was studied by
X-ray diffraction analysis. All data demonstrated that the biomolecule
is positioned far away from the fac-{Re­(CO)3} fragment, and the octahedral coordination around the metal is completed
by the functionalized dithiocarbamate and a phosphine ligand. Finally,
analysis by ESI-MS spectrometry of the reaction between the zinc complex 4 and a water solution of [Re­(H2O)3(CO)3]+ at a very low concentration (10 ppm) showed
that the transmetalation reaction took place, even though the solubility
of the zinc complex in water medium was as low as 0.66 ppm. This preliminary
result supports the viability of this approach for the preparation
of rhenium and technetium target-specific radiopharmaceuticals, since
the preparations of these compounds are always performed in water
medium.