Mode of action of copper complexes of some 2,2'-bipyridyl analogs on Paracoccus denitrificans

Abstract

Copper complexes of 2,2'-bipyridyl and related compounds and CuSO4 inhibited the growth of paracoccus denitrificans. The copper(I) complex of 2,9-dimethyl-1,10-phenanthroline [Cu(DMP)2NO3] showed the highest activity, whereas the copper(II) complex of 1,10-phenanthroline and CuSO4 inhibited the growth to a lesser extent. The uncomplexed ligands (1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline) showed little activity, but in the presence of noninhibitory amounts of CuSO4 this activity increased markedly. Copper ions therefore proved to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium. No selective inhibition of deoxyribonucleic acid, ribonucleic acid, or protein synthesis was observed with Cu(DMP)2NO3. Respiratory electron transport of P. denitrificans appeared to be strongly inhibited by Cu(DMP)2NO3 and to a somewhat lesser extent by CuSO4. Both aerobic and anaerobic respirations were inhibited to the same extent, and from the cytochrome redox kinetics it is concluded that the site of this inhibition in the respiratory electron transport chain must be located before cytochrome b. Cu(DMP)2NO3 did not significantly influence the H+/O ratio with whole cells of P. denitrificans, suggesting that the efficiency of oxidative phosphorylation is not affected by CU(DMP)2NO3. Growing cultures of P. denitrificans showed a decrease in intracellular potassium ion content in the presence of increasing amounts of Cu(DMP)2NO3. It is concluded that interference with the cytoplasmic membrane, resulting in inhibition of respiratory electron transport, probably constitutes the main mode of action of copper complexes of 2,2'-bipyridyl analogs on P. denitrificans.