Bioconjugates of Enantiomerically Pure Organopalladium Compounds by Metal-Assisted Positional Selective Transesterifications at Palladium Enolates

The synthesis of enantiomerically pure palladatricyclo[4.1.0.02,4]heptanes and their modification by an unprecedented and very efficient positional selective transesterification is described. The mild reaction conditions are most probably based on an acceleration of the transesterification due to assistance by the metal. This novel approach allows straightforward access to a large number of structurally diverse organometallic complexes. The functional groups on the newly installed ester moieties were modified by using standard peptide synthesis protocols, Sonogashira reactions, and nucleophilic substitution reactions. The cellular uptake of these organometallic species was traced by confocal microscopy and their biological activity was evaluated by using different cell lines. Inhibition of cell growth and induction of apoptotic cell death by these novel palladium heterocycles are equivalent to Cisplatin. Getting connected: Selective modification of the ester groups proximal to the metal center allows the synthesis of conjugates of chiral palladacycles with biomolecules and fluorescence dyes (see figure).