Aryl transition metal chemical warheads for protein bioconjugation

Abstract

Bioorthogonal organometallic chemistry using aryl transition metal reagents as coupling partners is a burgeoning field that holds great promise notably for the study of proteins.

Cyclometalated AuIII Complexes for Cysteine Arylation in Zinc Finger Protein Domains: towards Controlled Reductive Elimination

“…Recently, promising strategies have been developed to apply transition‐metal complexes to bioconjugation. The peculiar reactivity and selectivity of such complexes significantly broaden the scope of the chemical reaction tool boxes for biomolecule modification . Thus, the past decade has witnessed new ways of tagging proteins with fluorophores or other probes based on palladium‐mediated reactions that played a major role in modern organic synthesis, such as the Suzuki–Miyaura, Mizoroki–Heck, and Sonogashira cross‐coupling reactions …”

Click-Type Protein–DNA Conjugation for Mn2+ Imaging in Living Cells

“…Click chemistry is a class of reactions for joining small modular units together, with very high yields, minimal and inoffensive byproducts under simple reaction conditions . Due to its high efficiency and selectivity, and modular blocks, click chemistry has found broad applications in pharmaceutical science, materials chemistry, and biological chemistry since the concept was first introduced in 2001. − Moreover, its unique qualities, such as one-pot reaction in a benign solvent (such as water), as well as quick and irreversible yield of a single reaction product with high reaction specificity, make it particularly suitable to be used in complex biological environments. , Recently, various molecules in live cells were incorporated with click modular units for pulldown experiments, super-resolution imaging, and protein/nucleotide modification, , where the classic click reaction, the copper-catalyzed azide–alkyne cycloaddition (CuAAC), was widely applied. − While the click reactions with new modular blocks are still highly desired, especially for the site-specific conjugation between biomacromolecules.…”

Reductive Coupling of Bridging Diaryl Ligands in Half-Sandwich Cobalt(II) Dimers: Revisiting Triple-Decker Cobalt(I) Complexes

“…Aryl metal complexes of noble metals such as ruthenium, 2 iridium, 3 palladium, 4 and platinum 5 are known to moderate metal-catalyzed cross-coupling reactions, and they even facilitate the formation of C−S and C−C bonds onto protein substrates. 6 The studies of aryl metal complexes of cobalt, 7 iron, 8 and nickel 9 are important due to the significant interest in exploring inexpensive metal catalysts for homogeneous transformations. For example, aryl cobalt compounds have been found to be involved in cobalt(I)-mediated activation of aryl−halogen bonds 10 and decarbonylation of aromatic aldehydes.…”

“…The hydrogen atoms are omitted for clarity. Selected bond distances (Å): For 1a: Co1−Co2, 2.515(1); Co1−C1, 1.934(7); Co2−C1, 2.066(6); Co2−C2, 2.291(6). For 1b: Co1′−Co2′, 2.442(1); Co1′−C1′, 2.027(7); Co2′−C1′, 2.107(7).…”

“…For 1b: Co1′−Co2′, 2.442(1); Co1′−C1′, 2.027(7); Co2′−C1′, 2.107(7). For 2: Co1−Co2, 2.521(1); Co1−C1, 1.952(6); Co2−C1, 2.089(6); Co2−C2, 2.263(6).…”