Covalent and Selective Labeling of Proteins with Heavy Metals. Synthesis, X-ray Structure, and Reactivity Studies of N-Succinimidyl and N-Sulfosuccinimidyl Ester Organotungsten Complexes

Abstract

New functionally substituted η5-cyclopentadienyl and 2-oxaallyl (η1-enolate) tungsten complexes bearing an N-succinimidyl or an N-sulfosuccinimidyl ester have been prepared and fully characterized. The molecular structures of [η5-((succinimidooxy)carbonyl)cyclopentadienyl]methyltricarbonyltungsten(II) (2) and [η5-((succinimidooxy)carbonyl)cyclopentadienyl]iodotricarbonyltungsten(II) (5) were solved by X-ray crystallography. The reactivity of these activated esters toward a range of amines and amino acids has been studied. While the N-succinimidyl ester enolate was found to be unreactive, N-succinimidyl-substituted cyclopentadienyl complexes were quite reactive, leading to the expected stable organometallic amides. Bovine serum albumin (BSA), a 66 kDa molecular mass globular protein, could be labeled with fair yields, and conjugates were characterized by IR spectroscopy of the CO ligands. Organotungsten N-succinimidyl esters thus appear as promising reagents for the labeling of proteins with heavy metals.