Synthetic strategies for efficient conjugation of organometallic complexes with pendant protein reactive markers

• Three methods for conjugation of organometallic complexes with bioreactive markers are described.
• Procedures are fast, efficient and do not alter metal coordination or bioreactive organic moiety.
• A small library of 10 bioorganometallic markers for proteases was synthesized.

Site-directed conjugation of metal centers to proteins is fundamental for biological and bioinorganic applications of transition metals. However, methods for the site-selective introduction of metal centers remain scarce. Herein, we present broadly applicable synthetic strategies for the conjugation of bioactive molecules with a range of organometallic complexes. Following three different synthetic strategies, we were able to synthesize a small library of metal conjugated protein markers featuring different types of protein reactive sites (epoxides, phenylphosphonates, fluorosulfonates and fluorophosphonate groups) as well as different late transition metals (iron, ruthenium, rhodium, palladium and platinum). The products were isolated in moderate to excellent yields and high purity. Furthermore, X-ray diffraction of the metalated protein markers corroborates structural integrity of the metal complex and the protein reactive site.

A focused library of organometallic Ru, Rh, Pd and Pt conjugates of protease reactive markers were synthesized and characterized.Figure optionsDownload as PowerPoint slide