the former can be more or less precisely determined, whereas the latter are intrinsically fuzzy, hard to
determine, and will differ from one preparation of A8-35 to another if the starting PAA batches do not
have exactly the same length distribution or if different amounts of shorter or longer polymers are lost
during the synthesis or purification.
Box 4.1 Introducing Biochemists to the Chemistry of Synthetic Polymers
Biologists are familiar with polymers: proteins, nucleic acids, and polysaccharides. However, the
mode of synthesis of biological polymers sets them apart from the synthetic polymers: biological
polymers tend to have well-defined sequences and lengths, which is not the case of synthetic
polymers, which are heterogeneous. Controlling, measuring, and expressing this heterogeneity calls
for specific synthetic, analytical, and description techniques. Some of the terminology used in this
chapter will be unfamiliar to most readers, such as weight- and number-average molar masses, as
well as the dispersity or molar mass dispersion (hM w i, hM n i, and Đ, respectively). Indeed, synthetic
polymers can only be described as populations of molecules that differ from each other by their
length and, for most heteropolymers, by the sequence of the various units that comprise them. This
is an ineluctable consequence of their mode of synthesis. Because of its complexity, this matter
cannot be treated in a few lines. Two expert colleagues, Fabrice Giusti and Bernard Pucci, have
kindly accepted to write up a non-exhaustive but helpful (we hope) overview of the most essential
notions. In order not to break the continuity of the text, this presentation has been organized in a
series of annexes collected at the end of the chapter (§ 4.6) and distributed as follows:
• Annex 4.1 exposes in their broad lines some of the reasons from which originates the
dispersity in size of synthetic polymers, explains the notions of average molar mass and
dispersity, and describes the method that is most commonly used to measure each of
these parameters and the way to express them.
• Annex 4.2 A good understanding of how to limit dispersity requires a knowledge of the
kinetic parameters that govern conventional radical polymerization (RP). This annex
treats in more depth the topic of free radical polymerization and related kinetic aspects,
providing a more detailed description of the origins of the dispersity, as well as setting
the stage for Annex 4.3.
• Annex 4.3 discusses the notion of degree of polymerization and its evolution in the
course of a synthesis.
• Annex 4.4 introduces and briefly discusses the two main processes that can be used to
limit the breadth of polymer size distribution, namely telomerization and controlled
radical polymerization (CRP).
• Annex 4.5 discusses the benefits that, besides achieving a lower molecular dispersity, can
be expected from the different CRP approaches.
• Annex 4.6 describes ways in which functional groups can be grafted onto polymers.
A8-35 is commercially available (Table 4.1). Users, however, may want to prepare it themselves,
e.g. to create new labeled forms or derivatives. The synthesis of A8-35 and its congeners (Fig. 4.2) is
simple on paper. In practice, carrying it out properly requires both care and experience. Apparently
trivial details may matter. Thus, a change in the source of poly(acrylic acid) (PAA) in the late 1990s
resulted in a long spell of failures to produce A8-35 preparations with the nominal structure and
behavior before the origin of the difficulties was identified and brought under control (for a discussion,
see Gohon et al. 2006). Protocol 4.1, given in § 4.5 of this chapter, is based on published protocols
(Tribet et al. 1996; Gohon et al. 2004, 2006; Giusti et al. 2014) and laboratory notes. It provides
detailed guidelines for synthesizing A8-35, along with some caveats.
4.2 Amphipol Chemical Structure and Synthesis
161
determine, and will differ from one preparation of A8-35 to another if the starting PAA batches do not
have exactly the same length distribution or if different amounts of shorter or longer polymers are lost
during the synthesis or purification.
Box 4.1 Introducing Biochemists to the Chemistry of Synthetic Polymers
Biologists are familiar with polymers: proteins, nucleic acids, and polysaccharides. However, the
mode of synthesis of biological polymers sets them apart from the synthetic polymers: biological
polymers tend to have well-defined sequences and lengths, which is not the case of synthetic
polymers, which are heterogeneous. Controlling, measuring, and expressing this heterogeneity calls
for specific synthetic, analytical, and description techniques. Some of the terminology used in this
chapter will be unfamiliar to most readers, such as weight- and number-average molar masses, as
well as the dispersity or molar mass dispersion (hM w i, hM n i, and Đ, respectively). Indeed, synthetic
polymers can only be described as populations of molecules that differ from each other by their
length and, for most heteropolymers, by the sequence of the various units that comprise them. This
is an ineluctable consequence of their mode of synthesis. Because of its complexity, this matter
cannot be treated in a few lines. Two expert colleagues, Fabrice Giusti and Bernard Pucci, have
kindly accepted to write up a non-exhaustive but helpful (we hope) overview of the most essential
notions. In order not to break the continuity of the text, this presentation has been organized in a
series of annexes collected at the end of the chapter (§ 4.6) and distributed as follows:
• Annex 4.1 exposes in their broad lines some of the reasons from which originates the
dispersity in size of synthetic polymers, explains the notions of average molar mass and
dispersity, and describes the method that is most commonly used to measure each of
these parameters and the way to express them.
• Annex 4.2 A good understanding of how to limit dispersity requires a knowledge of the
kinetic parameters that govern conventional radical polymerization (RP). This annex
treats in more depth the topic of free radical polymerization and related kinetic aspects,
providing a more detailed description of the origins of the dispersity, as well as setting
the stage for Annex 4.3.
• Annex 4.3 discusses the notion of degree of polymerization and its evolution in the
course of a synthesis.
• Annex 4.4 introduces and briefly discusses the two main processes that can be used to
limit the breadth of polymer size distribution, namely telomerization and controlled
radical polymerization (CRP).
• Annex 4.5 discusses the benefits that, besides achieving a lower molecular dispersity, can
be expected from the different CRP approaches.
• Annex 4.6 describes ways in which functional groups can be grafted onto polymers.
A8-35 is commercially available (Table 4.1). Users, however, may want to prepare it themselves,
e.g. to create new labeled forms or derivatives. The synthesis of A8-35 and its congeners (Fig. 4.2) is
simple on paper. In practice, carrying it out properly requires both care and experience. Apparently
trivial details may matter. Thus, a change in the source of poly(acrylic acid) (PAA) in the late 1990s
resulted in a long spell of failures to produce A8-35 preparations with the nominal structure and
behavior before the origin of the difficulties was identified and brought under control (for a discussion,
see Gohon et al. 2006). Protocol 4.1, given in § 4.5 of this chapter, is based on published protocols
(Tribet et al. 1996; Gohon et al. 2004, 2006; Giusti et al. 2014) and laboratory notes. It provides
detailed guidelines for synthesizing A8-35, along with some caveats.
4.2 Amphipol Chemical Structure and Synthesis
161