pH-dependent structural reorganization of phosphatidylcholine vesicle membranes by copolymers of 2-ethylacrylic acid and methacrylic acid

Copolymers of 2-ethylacrylic acid (EAA) and methacrylic acid (MAA) were prepared in bulk and in N,N-dimethylformamide (DMF). Best-fit terminal model reactivity ratios were determined by a non-linear least squares technique to be r$\sb{\rm MAA}$ = 1.14 and r$\sb{\rm EAA}$ = 0.23 in bulk, and r$\sb{\rm MAA}$ = 1.91 and r$\sb{\rm EAA}$ = 0.09 in 50% DMF solution, respectively. Examination of $\sp{13}$C NMR spectra provided convincing evidence for the formation of statistical copolymers. The pH-dependent structural reorganization of dipalmitoylphosphatidylcholine vesicle membranes could be effected in aqueous phosphate buffer solutions of EAA-MAA copolymers. The reorganization process is sensitive to the composition of the copolymer. Decreasing the 2-ethylacrylic acid content in copolymer shifted the \u27critical\u27 pH to lower values. Copolymers of 2-ethylacrylic acid content equal to or less than 40 mole % showed complicated aggregation in the interaction with dipalmitoyl phophatidylcholine vesicle membranes. Results from potentiometric titrations suggested that the shifts in the critical pH in the structural reorganization of DPPC vesicle membranes should be attributed to the different hydrophobic interactions of polymers. Photosensitive 3,3$\sp\prime$-dicarboxydiphenyliodonium bisulfate and hexafluorophosphate, which produced the strong acids (H$\sb2$SO$\sb4$, HPF$\sb6$) upon irradiation at 254 nm were prepared. Using these iodonium salts as proton sources, the structural reorganizations of phosphatidylcholine vesicle membranes by poly(2-ethylacrylic aicd) were demonstrated by optical density measurement and by monitoring the efflux of the calcein in entrapped vesicles. Copolymers of EAA and MAA were employed in specific enhancement of cytotoxicity of immunotoxins. It was found that the copolymer of 49 mole % 2-ethylacrylic acid content is not toxic to HeLa cells and potentiates the action of 5E7-gelonin immunotoxin. To improve the potentiating effect the copolymer was modified to have 0.9 and 1.6 mole % disulfide linkage in the side chain for attachment to the 5E7-gelonin molecule