Soft Metal Interactions with Sulfur Containing Biological Molecules

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The sulfur chemistry of proteins and other biological molecules include the "soft" donor groups thiol, thioether, and disulfide. Specific examples of this group of biological molecules are antibiotics such as penicillin and cephalosporin, essential cofactors such as d-biotin, immunoglobins such as IgG and sulfur proteins such as metallothionein, papain, and liver alcohol dehydrogenase. Soft donor groups can complex selectivity with soft metal ions such as Ag(I), Cu(I), Au(I), Hg(II), and Pt(II). This selective Lewis acid-base interaction provides a basis for a new class of metal affinity separations named Immobilized Soft Metal (ISM) adsorption. ISM will complement Immobilized Metal Affinity (IMA) chromatography in that IMA uses borderline-hard acceptors such as Cu(II), Zn(II), and Ni(II) that interact with the exposed histidine residues of proteins. Pilot experiments have confirmed the utility of this technique in purifying d-biotin from a dilute mixture with its sulfur-deficient, biosynthetic precursor d- desthiobiotin. Also, metallothionein is shown to be removed from solution due to complexation with immobilized Ag(I) ions. It is proposed that ISM be explored as a new technique with broad applicability to biochemical separations. Experiments will provide data to establish a reactivity model explaining the interactions of biochemical functional groups with soft metal ions. ISM may also provide a unique tool for biosensor development through the use of the bioconjugate of proteins with d-biotin. Scanning Tunneling Microscopy (STM) has been used to obtain the first image of an immunoglobin molecule in aqueous solution. The interaction between Ag(I) and biotin conjugated antibodies in aqueous solution can be used to study immunoglobin structure and function through STM.