Dissolving biomolecules and modifying biomedical implants with supercritical carbon dioxide*

We describe two methodologies for dissolving ionic/polar species in scCO 2 . Both lead to a broadening of the range of applications for scCO 2 . Fluorinated surfactants may be used to prepare water in carbon dioxide microemulsions to allow solubilization of ionic and biological species. We outline also the preparation of scCO 2 soluble metal precursors that can be impregnated efficiently into polymeric substrates. Further processing by heat or UV light leads to metallic particles distributed throughout a polymer substrate. The clean synthesis of such composites can be applied to the development of improved medical implants. SOLVING THE INSOLUBLE In the last decade, supercritical fluids have attracted great interest as environmentally acceptable replacements for a wide range of processes that currently rely on conventional organic solvents. There have been several recent review articles and books describing the potential and current uses of supercritical fluids, ranging from commercial scale extraction to catalytic and asymmetric synthesis of pharmaceutical intermediates [1–4]. Supercritical fluids are versatile solvents that possess a unique combination of gasand liquid-like properties. Like gases they have high diffusivity and low viscosity, but like liquids they have appreciable densities and can dissolve other species. Moreover, the density and, hence, solvating power of supercritical fluids is tuneable, allowing a degree of control which is not present in conventional solvents. However, supercritical fluids are not “super-solvents”. For example, the most commonly used fluid, supercritical carbon dioxide (scCO 2 ), has solvating properties characteristic of both fluorocarbon and hydrocarbon. Thus, polar compounds and charged species are largely insoluble in scCO 2 . In this paper we describe methods for the solubilization of polar and charged species in scCO 2 , with particular reference to biological molecules and metals or their salts. Water in scCO2 microemulsions One potential method for solubilizing hydrophilic species in scCO 2 was to develop surfactants to support water in scCO 2 microemulsions (Fig. 1). The key problem was to identify a surfactant capable of supporting water in scCO 2 microemulsions. . Examples of such microemulsions in supercritical propane had been reported using the surfactant aerosol OT [5]. This work led to a significant body of research into microemulsions in supercritical alkane systems [6]. However, the challenge was to develop such systems in scCO 2 , a more environmentally attractive supercritical solvent. Much work has focused on the design of surfactants capable of supporting water in CO 2 , taking into account factors such as favorable CO 2 -tail interactions, properties affecting the curvature of the micellar interface and surfactant volatility [7]. The first successful example of water in scCO 2 microemulsions was reported in 1996 and focused 1348 P. B. WEBB et al. © 2000 IUPAC, Pure and Applied Chemistry 72, 1347–1355 on a commercially available carboxylic acid-terminated perfluoropolyether (PFPE) [8]. The surfactant itself was prepared by the formation of the ammonium carboxylate salt of the PFPE (Fig. 1). The microemulsions formed from this surfactant are optically transparent, thermodynamically stable, and were fully characterized by cloud point studies, on-line FTIR, and UV-visible spectroscopy. Figure 2 shows an FTIR spectrum of an scCO 2 solution in which an inactive surfactant is used. Only bands assigned to free (unassociated) water, surfactant, and CO 2 are readily observed. However, in the presence of the active PFPE ammonium carboxylate surfactant, significant differences are observed in the FTIR spectrum (Fig. 3). Most importantly, IR bands appear which indicate the presence of bulk, H-bonded water thus proving the presence of microemulsions. Unfortunately, commercial samples of this original PFPE material (molar mass 800) have recently proved difficult to obtain commercially. Thus, we have begun to investigate alternatives. A range of carboxylic acid-terminated PFPE materials are commercially available from DuPont under the collective brand name KrytoxTM. They have differing average molar masses of 2500 M W (Krytox FSL), 5000 M W (FSM), and 7500 M W (FSH). The carboxylic acid-terminated molecule must first be converted to the ammonium carboxylate salt to prepare an active surfactant. The conversion process is the same method as that used in our earlier work [8], and FTIR spectroscopy is used to monitor the process for each precursor conversion (Fig. 4). We have utilized in situ FTIR spectroscopy to determine whether a given surfactant forms water in scCO 2 microemulsions. Preliminary results show that the higher molar mass surfactants (FSM and FSH) do not allow the formation of microemulsions in scCO 2 . By contrast, the ammonium carboxylate F3C-[(O-CF2-CF(CF3))n-(O-CF2)m]O-CF2-COO NH4 + C Water Fig. 1 Schematic diagram of water in scCO 2 microemulsion.