Ruthenium-based bioconjugates: Synthesis and X-ray structure of the mixed ligand sandwich compound RuCpiPr(p-(CO2H)C6H4Tp) and labelling of amino acids and the neuropeptide enkephalin

Four mixed ligand sandwich ruthenium complexes with various cyclopentadienyl and tris(pyrazoyl)borate ligands have been synthesized and characterized. Cp i Pr Ru( p -BrC 6 H 4 )Tp has been converted to a complex with a benzoic acid-functionalized-Tp ligand, Cp i Pr Ru( p -(CO 2 H)C 6 H 4 )Tp, which has been structurally characterized by X-ray diffraction and further has been shown to undergo coupling to biomolecules both in solution and in solid phase peptide synthesis, providing amino acid and peptide bioconjugates. Four differently substituted mixed ligand sandwich complexes CpRu( p -BrC 6 H 4 )Tp ( 3 ), CpRu( p -BrC 6 H 4 )Tp Me ( 4 ), Cp ∗ Ru( p -BrC 6 H 4 )Tp ( 5 ), Cp i Pr Ru( p -BrC 6 H 4 )Tp ( 6 ), incorporating cyclopentadienyl (Cp) and functionalized tris(pyrazolyl)borate (Tp) ligands, have been synthesized and characterized. Air-stable 6 has been converted to benzoic acid-functionalized Cp i Pr Ru( p -(CO 2 H)C 6 H 4 )Tp ( 7 ), which has been structurally characterized in the solid state by X-ray diffraction. Compound 7 may be readily coupled to biomolecules as exemplified by the coupling to phenylalanine-methylester to give Cp i Pr Ru( p -(CO-Phe-OMe)C 6 H 4 Tp) ( 8 ). In a solid phase peptide synthesis (SPPS), 7 has been coupled to the pentapeptide Enkephalin, to provide Cp i Pr Ru( p -(CO-Tyr-Gly-Gly-Phe-Leu-OH)C 6 H 4 Tp) ( 9 ) as the first example of a mixed ligand sandwich ruthenium bioconjugate.