Propyl-Ended Hemifluorinated Surfactants: Synthesis and Self-Assembling Properties

Abstract

The advantages of using hemifluorinated surfactants as an efficient alternative to detergents for manipulating membrane proteins in aqueous solution have been demonstrated in recent reports. However, the large-scale synthesis of these surfactants is still considered as a major matter and has limited their use for biochemical purposes. We report herein the synthesis of a novel series of perfluorohexane-based surfactants endowed with a short propyl hydrocarbon tip and whose polar head size is modulated by the presence of two or three glucose moieties. The synthetic route is based on the radical addition of two alkenes onto the 1,6-diiodoperfluorohexane using AIBN as a radical initiator, affording the surfactants in satisfactory overall yields. The self-assembling properties of these hemifluorinated surfactants were studied by surface tension measurements, dynamic light scattering, as well as their behavior upon reversed-phase chromatography and were compared with those of their perfluorinated analogues. Our findings strongly suggest the predominant influence of the propyl tip on both adsorption and micellization phenomena as well as on the hydrophobic character of the surfactants, whereas as previously observed, the shorter ethyl tip does not greatly affect these properties when compared to the perfluorinated analogues. Moreover, all the surfactants reported here self-assemble into small and monodisperse aggregates, a feature of crucial importance for biochemistry applications.

Hemifluorinated Maltose‐Neopentyl Glycol (HF‐MNG) Amphiphiles for Membrane Protein Stabilisation

“…A recent report described an improved synthetic protocol for HFSs, but still the method involves multiple steps and low overall yields (< 10 %). [8] Maltose-neopentyl glycol (MNG) amphiphiles have recently been shown to be very promising for membrane protein solubilisation, stabilisation and crystallisation. [9] The use of MNGsolubilised proteins has provided high-resolution crystal structures of several GPCRs through lipidic cubic-phase (LCP)-based crystallisation.…”

Hybrid Double-Chain Maltose-Based Detergents: Synthesis and Colloidal and Biochemical Evaluation

“…Reduction of the C−I bond was also improved compared to our previous work where we employed stoichiometric quantities of Bu 3 SnH at 70 °C in a sealed tube under inert conditions. 17,19,21 Catalytic hydrogenation in the presence of Pd−C was chosen. This method was performed at room temperature in a hydrogenation reactor and led to the reduced compounds 8a−c in good yields.…”

“…The compounds were detected either by exposure to ultraviolet light (254 nm) or by spraying with sulfuric acid (5% ethanol) and/or ninhydrin (5% ethanol), followed by heating at ∼150 °C. 1 H, 13 C, and 19 F NMR experiments were performed at 400, 100, and 375 MHz, respectively. Chemical shifts are given in ppm relative to the solvent residual peak as a heteronuclear reference for 1 H and 13 C. The coupling constants J are given in hertz and the chemical shifts in parts-per-million (ppm).…”

The search for new amphiphiles: synthesis of a modular, high-throughput library

“…For the triple-chained tails, triol 15 was synthesised from tris(hydroxymethyl)methylamine (TRIS) and 4-pentynoic acid using ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), following a similar method to Pucci et al (Scheme 2) [33]. TRIS has been used previously for the synthesis of amphiphilic drug-delivery vehicles, with advantages including its inexpensive availability and non-toxic nature [34–35].…”