Antibiotic action of N-methylthioformohydroxamate metal complexes

Abstract

The antibiotic activity of metal complexes of N-methylthioformohydroxamic acid against gram-negative Escherichia coli NIHJ and gram-positive Staphylococcus aureus 209P was investigated. The kinetically labile, square-planar, divalent (Cu, Ni, and Pd) and octahedral, trivalent (Fe, Co, and Cr) complexes displayed activity, whereas the more inert platinum(II) or rhodium(III) complex displayed no activity, or activity only at elevated concentrations. The free ligand did not suppress the growth of the above organisms, and the sulfur atom of the ligand in its metal complexes appears crucial for activity. Uptake studies of radioactively labeled N-methylthioformohydroxamic acid, its nickel(II), platinum(II), iron(III), and rhodium(III) complexes were conducted in the Escherichia coli K-12 RW193 mutant, which is defective in the production of its native iron(III) transport agent, enterobactin. Uptake of (55)Fe or (63)Ni label from their metal complexes appeared to occur as free inorganic metal ions. The antibiotic activity of the iron(III) and nickel(II) complexes was not due merely to an enhanced accumulation of metal ions by the cell. Metal complexes of [(35)S]N-methylthioformohydroxamic acid enhanced the accumulation of (35)S label compared to that of the free ligand. The antibiotic activity and uptake data are discussed in terms of possible modes of action.