3.5.2
Novel Structures of Fluorinated Surfactants
The development of a wide range of novel (H)FSs specifically designed for MP biochemistry
applications was undertaken, in the early 1990s, thanks to a long-term collaboration between our
laboratory and that of Bernard Pucci, after which several other groups developed their own molecules.
The first molecules to be tested had as polar head formed by a short hydrophilic oligomer derived
from tris-(hydroxymethyl)aminomethane (THAM) and a perfluorinated hydrophobic moiety (“FTAC” in Fig. 3.25A; Chabaud et al. 1998; Barthélémy et al. 1999; Breyton et al. 2004). In a second
stage, the tail was hemifluorinated (“HF-TAC” in Fig. 3.25A; Barthélémy et al. 1999; Chaudier et al.
2001, Breyton et al. 2004). These molecules yielded very promising results, judging from their ability
to keep soluble and stabilize several test MPs, including BR and the cytochrome b 6 f complex
(Chabaud et al. 1998; Breyton et al. 2004), and most of the early applications of (H)FSs were
developed thanks to them.
The oligomeric polar head of (H)F-TAC – where “(H)F-” refers indifferently to the fluorinated or
the hemifluorinated form – however, was a concern from the start because it is chemically polydispersed. From the biochemist’s point of view, this means that (H)F-TAC batches consist of a mixture
of molecules with slightly different properties and that this mixture will never be exactly the same
from one batch to the next. Replacing the poly-THAM oligomer with a monodisperse head group
turned out to be a highly frustrating endeavor. Indeed, grafting (hemi)fluorinated chains onto monodisperse polar heads that, when associated to alkyl chains, yield efficient detergents – such as an
aminoxyde (Chaudier et al. 2002), a monodisperse polyethylene glycol group (see Breyton et al. 2009),
or saccharidic groups derived from galactose (Chabaud 1997; Chabaud et al. 1998), lactose (Lebaupain
et al. 2006), or maltose (Polidori et al. 2006) – resulted in surfactants featuring unsatisfactory
properties. A recurrent problem was that most of the molecules thus obtained tended to form huge
polydisperse micelles by themselves and highly polydisperse MP/(H)FS complexes (for a discussion,
see Breyton et al. 2009). This behavior suggested that the bulky hydrophobic moiety of (H)FSs
requires a bulkier hydrophilic head than classical detergents do in order to create the overall molecular
asymmetry that leads to the formation of small globular micelles (cf. Israelachvili et al. 1977, Tanford
1980, Israelachvili 2011; see Chap. 1, Table 1.1). A systematic investigation was therefore undertaken,
in which polar heads carrying one, two, or three glucose moieties were grafted onto perfluorinated,
hemifluorinated, or hydrogenated hydrophobic chains (Abla et al. 2008). This study led to the
identification of two chemically defined (H)FSs, F 6 -DiGlu and H 2 F 6 -DiGlu (Fig. 3.25B), which
form with MPs small, well-defined complexes in which MPs are stabilized as compared to detergent
solutions (Breyton et al. 2009).
Among the many new types of (H)FSs that have been described over the past decade, one may
cite the following ones:
• Partially fluorinated surfactants, dubbed FASBs (fluorinated amidosulfobetaines), in which
the tip of the hydrophobic chain is perfluorinated but a more or less extended hydrocarbon
region is inserted between it and an amidosulfobetaine polar head (Starita-Geribaldi et al.
2007; Thebault et al. 2007).
• Hemifluorinated maltose-neopentyl glycol derivatives (HF-MNG), which carry fluorinated
groups at the end of their two hydrocarbon arms (Fig. 3.25D; Cho et al. 2013).
• A hemifluorinated surfactant (H 3 F 6 H 3 DigluM) featuring a branched diglucosylated polar
head group and an apolar tail consisting of a perfluorohexane core terminated by a
hydrogenated propyl tip (Fig. 3.25C; Abla et al. 2015).
• A partially fluorinated version of octylmaltoside called F 6 OM (Fig. 3.25F) and a variant
thereof carrying a phosphocholine polar head (F 6 OPC; Frotscher et al. 2015).
130
3 Alternatives to Detergents for Handling Membrane Proteins in Aqueous Solutions
Novel Structures of Fluorinated Surfactants
The development of a wide range of novel (H)FSs specifically designed for MP biochemistry
applications was undertaken, in the early 1990s, thanks to a long-term collaboration between our
laboratory and that of Bernard Pucci, after which several other groups developed their own molecules.
The first molecules to be tested had as polar head formed by a short hydrophilic oligomer derived
from tris-(hydroxymethyl)aminomethane (THAM) and a perfluorinated hydrophobic moiety (“FTAC” in Fig. 3.25A; Chabaud et al. 1998; Barthélémy et al. 1999; Breyton et al. 2004). In a second
stage, the tail was hemifluorinated (“HF-TAC” in Fig. 3.25A; Barthélémy et al. 1999; Chaudier et al.
2001, Breyton et al. 2004). These molecules yielded very promising results, judging from their ability
to keep soluble and stabilize several test MPs, including BR and the cytochrome b 6 f complex
(Chabaud et al. 1998; Breyton et al. 2004), and most of the early applications of (H)FSs were
developed thanks to them.
The oligomeric polar head of (H)F-TAC – where “(H)F-” refers indifferently to the fluorinated or
the hemifluorinated form – however, was a concern from the start because it is chemically polydispersed. From the biochemist’s point of view, this means that (H)F-TAC batches consist of a mixture
of molecules with slightly different properties and that this mixture will never be exactly the same
from one batch to the next. Replacing the poly-THAM oligomer with a monodisperse head group
turned out to be a highly frustrating endeavor. Indeed, grafting (hemi)fluorinated chains onto monodisperse polar heads that, when associated to alkyl chains, yield efficient detergents – such as an
aminoxyde (Chaudier et al. 2002), a monodisperse polyethylene glycol group (see Breyton et al. 2009),
or saccharidic groups derived from galactose (Chabaud 1997; Chabaud et al. 1998), lactose (Lebaupain
et al. 2006), or maltose (Polidori et al. 2006) – resulted in surfactants featuring unsatisfactory
properties. A recurrent problem was that most of the molecules thus obtained tended to form huge
polydisperse micelles by themselves and highly polydisperse MP/(H)FS complexes (for a discussion,
see Breyton et al. 2009). This behavior suggested that the bulky hydrophobic moiety of (H)FSs
requires a bulkier hydrophilic head than classical detergents do in order to create the overall molecular
asymmetry that leads to the formation of small globular micelles (cf. Israelachvili et al. 1977, Tanford
1980, Israelachvili 2011; see Chap. 1, Table 1.1). A systematic investigation was therefore undertaken,
in which polar heads carrying one, two, or three glucose moieties were grafted onto perfluorinated,
hemifluorinated, or hydrogenated hydrophobic chains (Abla et al. 2008). This study led to the
identification of two chemically defined (H)FSs, F 6 -DiGlu and H 2 F 6 -DiGlu (Fig. 3.25B), which
form with MPs small, well-defined complexes in which MPs are stabilized as compared to detergent
solutions (Breyton et al. 2009).
Among the many new types of (H)FSs that have been described over the past decade, one may
cite the following ones:
• Partially fluorinated surfactants, dubbed FASBs (fluorinated amidosulfobetaines), in which
the tip of the hydrophobic chain is perfluorinated but a more or less extended hydrocarbon
region is inserted between it and an amidosulfobetaine polar head (Starita-Geribaldi et al.
2007; Thebault et al. 2007).
• Hemifluorinated maltose-neopentyl glycol derivatives (HF-MNG), which carry fluorinated
groups at the end of their two hydrocarbon arms (Fig. 3.25D; Cho et al. 2013).
• A hemifluorinated surfactant (H 3 F 6 H 3 DigluM) featuring a branched diglucosylated polar
head group and an apolar tail consisting of a perfluorohexane core terminated by a
hydrogenated propyl tip (Fig. 3.25C; Abla et al. 2015).
• A partially fluorinated version of octylmaltoside called F 6 OM (Fig. 3.25F) and a variant
thereof carrying a phosphocholine polar head (F 6 OPC; Frotscher et al. 2015).
130
3 Alternatives to Detergents for Handling Membrane Proteins in Aqueous Solutions