The receptor as part of a nucleic acid

The chief physical properties studied were (a) electron distribution, particularly as manifest in ionization the degree of which could facilitate or forbid the combination of a drug with its receptor, and (b) stericproperties, which governed access to the correct receptor and a good fit upon arrival there. Both of these factors came to the fore in studies of the aminoacridines described briefly here, and more fully in Section 10.3.1. 

This work was undertaken by my colleagues and me for the Australian Army, 

it was shown that the bacteriostatic action of these topical antibacterials was proportional to the fraction ionized as cation (Albert, Rubbo and Goldacre, 1941). At first, it seemed puzzling that, of the five possible aminoacridines, two were highly anti-bacterial, whereas three had little activity. At that time, almost nothing was known about the ionization of heterocyclic bases, so we began to determine the values of a great many examples, and later we 

Cationic resonances which make 3-and 9-aminoacridines strong bases 

Acridine 2.16) is a weak base. With its pA a of5.3, it is only 1% ionized at pH 7.3. It turned out that the 3-amino- and 9-amino-acridines had a resonance in their cation that was lacking in the neutral species [e.g. 2.17) — 2.IS) and 2.19) — 2.20), respectively and this made them very strong bases. The other three aminoacridines could not, for reasons of valence, acquire this resonance stabilization and, hence, were very little stronger than acridine itself (see Table 2.2). We called this the 4-aminopyridinium type of base-strengthening resonance, because we had demonstrated it first in 4-aminopyridine. 

---