Synthesis and characterization of the azido-functionalized ruthenocene analogue [TpmRu(p-N_3C_6H_4)Tp]Cl and its attachment to biomolecules by copper-catalyzed azide-alkyne cycloaddition

摘要

The mixed-ligand tris(pyrazolyl)borate sandwich compound [TpmRuTp′]Cl (2) was prepared by microwave-assisted synthesis from Tp′Ru(COD)Cl (1) [Tp = tris(pyrazolyl)borate; Tp′ = p-bromophenyltris(pyrazolyl)borate; Tpm = tris(pyrazolyl)methane; COD = 1,4-cyclooctadiene]. Subsequently, 2 was converted to the azide-functionalized [TpmRu(p-N_3C_6H _4Tp)] (3), which can be readily coupled to biomolecules by Cu-catalyzed azide-alkyne cycloaddition (Cu-AAC) in solution, as exemplified by the covalent attachment to pentyne-functionalized HC(CH_2) _2-CO-Val-OtBu (4), and an alkyne derivative of the neuropeptide enkephaline HC(CH_2)_2-CO-ENK-OH (ENK = enkephaline, Tyr-Gly-Gly-Phe-Leu). The resulting triazole compounds [TpmRu({p-C _2N_3H-(CH_2)_2-CO-Val-OtBu}Tp)]Cl (5) and [TpmRu({p-C_2N_3H-(CH_2)_2-CO-ENK- OH}Tp)]Cl (6), represent the first [3+2] cycloaddition products of azide-functionalized Tp compounds. They were characterized by NMR spectroscopy and mass spectrometry. Furthermore, 1, 2, and 3 as well as the reaction intermediate [(κ~2-N,N′-Tpm)RuCl(Tp′)] (2a) were characterized in the solid state by single-crystal X-ray diffraction.