Microwave-assisted synthesis of the Tp sandwich compound TpRu(p-Br-C6H4Tp) and application of its benzoic acid derivative TpRu(p-(CO2H)-C6H4Tp) in the covalent labelling of biomolecules

Abstract

An improved synthesis for the mixed-ligand tris(pyrazolyl)borate sandwich compound TpRu(p-BrC₆H₄Tp) 1 by microwave-assisted synthesis starting from RuTp(COD)Cl (COD: 1,4-cyclooctadiene, Tp: hydrido-tris(pyrazolyl)borate) was developed. Air-stable 1 was characterized by an X-ray single crystal structure and has been converted to the acid-functionalized TpRu(p-(CO₂H)-C₆H₄Tp) 2, which may be readily coupled to biomolecules as exemplified by the covalent attachment to valine-tert-butylester to give TpRu(p-(CO-Val-OtBu)-C₆H₄Tp) 3. In solid phase peptide synthesis (SPPS), 2 has been coupled to the pentapeptide Enkephalin, providing TpRu(p-(CO-Tyr-Gly-Gly-Phe-Leu-OH)-C₆H₄Tp) 4 as the first example of a ruthenium Tp sandwich bioconjugate.