Mechanism of acridine uptake by submitochondrial particles.

Acridines were compared regarding their ability to be taken up by submitochondrial particles under energized conditions. pH dependence of uptake was explored, and it was found that acridines fell into three classes independently of their pK_a value: acridines which are not taken up, acridines taken up at all pH values, and acridines taken up only at alkaline pH. Partition measurements between H₂O and chloroform phase showed a similar pattern, and affinity for the organic phase seemed to parallel uptake. Acridines which are taken up by submitochondrial particles at acidic pH under energized conditions despite a high pK_a value could also be extracted into chloroform at acidic pH, thus implying that the dye's uncharged form has a high affinity for the organic phase. By supplementing the aqueous medium with lipophilic anions, the dye may also be extracted in its charged form. The data support a mechanism for acridine uptake in which diffusion of the uncharged form across the membranes is an obligatory step. Some previously reported inhibitory anion effects on uptake may be explained by ion pair formation, which allows release of the accumulated charged form.