Substances that are more biologically active when ionized

3 Substances that are more biologically active when ionized 

It is now known that many kinds of organic cations are antibacterial, but this knowledge came only in the second quarter of this century. It had been found 

The first rigorous proof of a positive correlation between ionization and biological action was made 17 years later (Albert, Rubbo and Goldacre, 1941). This work showed that a quantitative relationship existed between antibacterial action and the percentage ionized as cations in the aminoacridine series. This correlation was then confirmed and extended (Albert etaL, 1945). 

Acridine 2.16) is a planar, feebly basic molecule. However, two of the five possible monoaminoacridines are rather strong bases, namely the 3- and 9-amino isomers this strength comes from the resonance immanent in their cations as explained in Section 2.2 (p. 33). For reasons of valency there can be no extra resonance in 2- or 4-aminoacridine, and there is little in the 1-isomer because an orthoc u nono d disposition of bonds (which it would require) is energetically unfavoured (Albert and Goldacre, 1946 Albert, Goldacre and Phillips, 1948). 

Acridine Minimal bacteriostatic concentration for Strept. pyogenes (48 hours incubation in 10% serum broth at 37°C pH 7.3) Per cent ionized as cation (pH 7.3,37°C) 

Preliminary experiments in 1939 had convinced my colleagues and myself that acridines became more antibacterial in proportion as they became more ionized, i.e. as cations (Albert, et al. 1941). These results were extended to loi acridines and 22 species of bacteria (Albert, Rubbo and Goldacre, 1945 Albert and Goldacre, 1948). Some typical results are given in Table 10.6, which is an expansion of Table 2.2, in terms of derivatives tested. For comparison of 100 derivatives, see Albert (1966, p. 437). 

Of the five possible mono-aminoacridines, two are well ionized at pH 7, 

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