Acid-base properties of ellipticine bound to DNA, micelles and liposomes

We have determined the acid-base properties of the alkaloid ellipticine, bound to DNA and to micelles and liposomes, taken as models for membranes, in the prospect of characterizing the actual structure of the bound ligand, this being relevant to the mode of action of the drug. The acid-base properties of ellipticine bound to sonicated calf thymus DNA and SDS micelles are similar as regards their pK values and their dependence on NaCl concentrations. This observation is satisfactorily understood in terms of sodium ion condensation around the negative phosphate and sulphate groups. The slope of pK vs log(Na+) is -1, a value predicted by Friedman theory. The pK of ellipticine bound to cationic (CTAB, DDTAB) or to neutral (Triton X100) micelles and to neutral liposomes (PC) is significantly lower than water (7.4), and, in contrast to the situation in DNA and SDS micelles, does not vary with addition of NaCl. Interestingly, this result is good evidence for ellipticine having a specific pK when bound to a hydrophobic structure. This view is likely to hold for ellipticine bound to DNA.