AMPHIPOLS: Design, synthesis and properties of amphipol A8-35

One of the first APols to be designed, called A8-35, has become by far the most extensively studied APol. A8-35 (refs. 6-8) is comprised of a relatively short polyacrylate chain (~70 acrylate residues), some of the carboxylates of which have been randomly grafted with octylamine (~17 of them) or isopropylamine (~28 units) (Fig. 2).

The ~25 acid groups that have remained free are charged in aqueous solutions (7), which makes the polymer highly water-soluble, while the octylamide moieties render it highly amphipathic. Isopropylamide residues lower the charge density. The average molecular mass of a molecule of A8-35 is 9-10 kDa.


Figure 2. Chemical structure of amphipol A8-35; x ≈ 0.35, y ≈ 0.25, and z ≈ 0.4. The average number of acrylate units is ~70 and the average molecular mass 9-10 kDa. From ref. 6.

In aqueous solutions, A8-35 forms well-defined, small, globular particles (8). Each A8-35 particle has a mass of ~40 kDa and, therefore, comprises an average of four A8-35 molecules (8).

Because the solubility of A8-35 depends on the presence of charges on its carboxylate groups, it is affected by every factor that will affect the latter, such as lowering the pH below neutrality or adding multivalent cations (8-11). This can create difficulties (due to aggregation) for some applications (see Table 1 in Applications), for which better-suited APols would be desirable (see Amphipols with different chemical structures). On the other hand, these limitations seldom turn out to be a serious hindrance.

Since it has proven quite difficult and lengthy to develop, validate and characterize alternative chemical structures presenting as satisfying properties as those of A8-35, most of the detailed studies of APols and MP/APol complexes to date have been carried out on the latter. This provides the putative user with a considerable body of information about what can and what can not be attempted using this particular APol.