Relation Between Quinoid Structure and Bacteriostatic Activity of Tetramethyl-Diaminodiphenylmethane Derivatives

Abstract

Bacteriostatic assays conducted with certain triphenylmethane dyes and their leuco derivatives have been published in a foregoing paper (Fischer, Hoffmann, Prado, and Bon6, 1944). Among other results, it was found that the dye salt, the carbinol base, the bisulfite, and hydrosulfite derivatives of malachite green are bacteriostatically active against a strain of scarlet fever streptococcus (Dochez, N. Y. 5), all of them practically at the same level, whereas the leuco base, the leucocyanide, and the leucoamine have no action of comparable extent. It is somewhat difficult to draw definite conclusions from these facts about the relations between the chemical structure and the bacteriostatic activity of the substances in question. On first sight, no common features can be found among the members of the active group. The dye salt possesses a very particular structure, different from that of any colorless derivative. We cannot discuss here the real nature of the dye structure, which has been the subject of different theories. We adopt here simply the quinoid theory and shall use the expression "quinoid" and the corresponding chemical formulas to designate that particular structure on which the dye character depends, whatever the real nature of that structure may be. Besides the dye salt, three other substances, the carbinol base and the hydrosulfite and bisulfite derivatives, also showed bacteriostatic activity, as already mentioned. These substances are leuco derivatives and lack in consequence a quinoid structure. They are, however, able to obtain such a structure with relative facility. The easy transformation into the dye salt by the action of certain acids represents a most characteristic chemical property'of the carbinol bases. The same can be stated for the bisulfite and hydrosulfite derivatives which behave like "vat dyes," that is, transform into dye substance in the air if moistened, forming dye carbonate (Wieland, 1919). Thus, an actually present or easily achieved quinoid structure may be looked upon as a possible common feature of the bacteriostatically active derivatives. In contrast to these, the leuco base which is inactive must be oxidized before it can change into a quinoid substance. Other relatively inactive derivatives, that is the leucocyanide and the leucoamine, although not requiring an oxidative process for their quinoid transformation, are considerably stabler compounds than the members of the active group and resist to a greater extent the action of acids.

Comparative Bacteriostatic Assays with Rosaniline and Its Phenolic Analog (Rosolic Acid)

“…(1) The presence of three phenylic rings attached to the central methyl radical (i.e., the triphenylmethane structure) results in a considerably stronger action than does the presence of only two such rings (diphenylmethanes) (Kligler, 1918;Fischer et al, 1946).…”

“…The nonmethylated dye rosaniline, however, also is effective in the form of leucobase, although only in a lower degree (Fischer et al, 1944(Fischer et al, , 1946.…”