Bactericidal Action of Selected Phenanthroline Chelates and Related Compounds

Abstract

Summary. Selected 1,10-phenanthroline hydrochlorides, quaternary salts and metal chelates are bactericidal to Staphylococcus aureus. Streptococcus pyogenes (Group A), Clostridium perfringens, Escherichia coli and Proteus vulgaris in serum broth in that general order of decreasing sensitivity; certain hydrochlorides and metal chelates are also bactericidal to Staphylococcus aureus in distilled water in the absence of added metal ion.Metal chelates with similar or identical bactericidal titres following 48 hours' incubation with Staphylococcus aureus. Streptococcus pyogenes (Group A) or Escherichia coli differ greatly in their rate of kill. Generally, the labile Gu(II), Gd(II), Zn(II) and Mn(II) phenanthroline chelates are rapidly lethal to these bacteria while the corresponding more inert Fe(II), Ni(II) and Ru(II) compounds are more slowly bactericidal; the Go(II) analogues are the most slowly lethal, probably owing to the formation of highly inert cobalt (III) species. These results suggest that the kinetic reactivity of the metal chelate is more important than its thermodynamic stability in governing rate of bactericidal action. Other important factors are the lipophilia of the active species, which may be the phenanthroline ligand or a metal-containing derivative, and the permeability of the organism to it.Gomparison of the bactericidal activity and rate of kill of Staphylococcus aureus and Escherichia coli by selected metal chelates and by a series of unrelated but clinically-useful antibacterials suggests that the former compounds warrant investigation for the sterilization of skin surfaces both prophylactieally and therapeutically. INTRODUCTION.The bacteriostatic activities of a series of metal chelates, quaternary salts and base hydrochlorides derived from 1,10-phenanthroline and 2,2'-bipyridine bases against a number of typical Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis have been reported by Dwyer, Reid, Shulman, Laycock and Dixson (1969). The present paper reports the bactericidal activities of selected phenanthroline metal chelates and related substances against a similar series of Gram-positive and Gram-negative bacteria and indicates that speed of chelate bactericidal action depends on the nature of both the metal ion and the ligand, that is, on the properties of the metal chelate as a whole. The bactericidal

Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes

“…Whereas metal-phen complexes can be bacteristatic (Dwyer et al, 1969) and bactericidal (Butler et al, 1969) towards many Grampositive bacteria they are relatively ineffective against Gram-negative organisms. In addition, dilute aqueous solutions of phen and its Cu(II) and Mn(II) complexes were highly toxic to clinical isolates of Candida species Geraghty et al, 1998).…”

“…1,10-Phenanthroline (phen) and substituted derivatives, both in the metal-free state and as ligands co-ordinated to transition metals, disturb the functioning of a wide variety of biological systems (Butler et al, 1969). Furthermore, when the metal-free N,N-chelating bases are found to be bioactive it is usually assumed that the sequestering of trace metals is involved, and that the resulting metal complexes are the active species (MacLeod, 1952;Dwyer et al, 1969) O (phen=1,10-phenanthroline; malH 2 =malonic acid) inhibit the growth of C. albicans by around 95% at a concentration of 5 mg/ml (Coyle et al, 2003).…”

Synthesis and X-ray crystal structure of [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells

“…1,10-Phenanthroline (phen) (Figure 1) and substituted derivatives, both in the metal-free state and as ligands co-ordinated to transition metals, disturb the functioning of a wide variety of biological systems (Butler et al 1969). Furthermore, when the metal-free N,N -chelating bases are found to be bioactive it is usually assumed that the sequestering of trace metals in situ is involved, and that the resulting metal complexes are the active species (MacLeod, 1952;Dwyer et al 1969).…”

Metallopeptidases produced by group B Streptococcus: Influence of proteolytic inhibitors on growth and on interaction with human cell lineages

“…DMSO, at the concentration used as a proteolytic inhibitor diluent, did not interfere with bacterial growth behavior (data not shown). PHEN and substituted derivatives, both in the metal-free state and as ligands co-ordinated to transition metals, disturb the functioning of a wide variety of biological systems (26). The in vitro antibacterial action of PHEN has been demonstrated on several species of bacteria, presenting bactericidal action towards many Gram-positive bacteria (27).…”