Osmium-labeled polynucleotides. Incorporation of additional heavy atoms (mercury) via ligand substitution reactions

The reaction of osmium tetroxide with biological materials, particularly nucleic acids, has considerable utility in electron microscopy and X-ray crystallography. This heavymetal label introduces an electrophilic center which may serve as a means of attachment of nucleophiles. Nucleophilic ligand substitution reactions have been exploited as a means of adding more heavy metals (mercury) onto the osmium label. Furthermore, the technique is quite general and could be used to modify the osmium label with, for example, fluorescent groups. The nucleophilic exchange reactions have also been studied using ¹H nmr spectroscopy with a representative heterocyclic osmate ester derivative, the bis(pyridine) osmate ester derivative of TMP. These studies have defined the nature of the ligands which lead to stable osmium labels.