THE BIOLOGICAL ACTIONS OF 1,10‐PHENANTHROLINE AND 2,2′‐BIPYRIDINE HYDROCHLORIDES, QUATERNARY SALTS AND METAL CHELATES AND RELATED COMPOUNDS

Abstract

Summary The bacteriostatic activities of stable, inert, coordinately‐saturated Ru(II) chelates of substituted 1.10‐phenanthroline and 2,2′‐bipyridine bases are reported together with those of the corresponding chelates of Ni(II), Fe(II), Co(II), Cu(II), Zn(II), Cd(II) and Mn(II). the hydrochlorides and quaternary salts of the bases and miscellaneous compounds; the principal test organisms, in order of decreasing general seasitivity. were M. tuberculosis, Staph. aureus, Strep. pneumoniae, Cl. perfringens, E. coll and Pr. culgaris. The active component of the Ru(II) chelates is the cation as a whole which can only exert antibacterial action by weak Coulombic and short‐range forces and possibly by interference in biological redox reactions. However, metal chelates which are labile or have low stability may act by other mechanisms. Metal chelates generally were more active than corresponding base hydrochlorides and quaternary salts and phenanthroline derivates more active than the corresponding bipyridines. While the Ru(II) chelatc of 5‐NO 2 ‐ 1,10‐phenanthroline was much less active than the outstandingly antitubercular chelates of the other seven transition metals, few other differences in bacteriostatic activity were detected by the present method between chelates differing only in the metal ion. Since progressive methylation of each type of compound generally increased antibacterial activity, penetration to or accumulation at vital sites are most likely important factors in determining activity. While useful clinically as topical antimicrobials, selected compounds when administered parenterally were found to be chemotherapeutically ineffective against experimental infection due to Staph. aureus, Strep. pneumoniae or M. tuberculosis. Significant microbial resistance to selected metal chelates does not appear to develop.