Dication and trication which can increase the permeability of Escherichia coli outer membrane

Recent success in the preparation of the monomer, dimer and trimer in compound 48/80 prompted us to investigate the action of these compounds on Escherichia coli cells. It was found that compound 48/80 inhibited growth of E. coli cells, while the monomer, dimer and trimer in 48/80 did not. However, the following experiments showed that the dimer and trimer disrupted the permeability barrier of the outer membrane of E. coli. First, addition of the dimer or trimer in cell suspension stimulated the uptake of tetraphenylphosphonium cation. Second, the synergistic effect of the dimer on the action of gramicidin caused the efflux of K+. In experiments using isolated cytoplasmic membrane vesicles, addition of gramicidin alone caused the efflux of K+. Thus, it was speculated that, with whole cells, the dimer formed some defect structure in the outer membrane, through which gramicidin reached the cytoplasmic membrane and increased the K+ permeability. The temperature dependence of efflux K+ showed that the dimer in 48/80 rendered the outer membrane permeable to gramicidin at temperatures above the phase transition of the outer membrane.