High-throughput solubility measurements of polymer libraries in supercritical carbon dioxide{ Christopher L. Bray, Bien Tan, Colin D. Wood and Andrew I. Cooper* Received 4th October 2004, Accepted 27th October 2004 First published as an Advance Article on the web 24th November 2004 DOI: 10.1039/b415343j A new method has been developed which allows rapid parallel solubility measurements for libraries of materials in super- critical fluids (SCFs). The technique was used to evaluate the solubility of a mixed library of 100 synthetic polymers including polyesters, polycarbonates, and vinyl polymers. Supercritical carbon dioxide (scCO 2 ) is an inexpensive, non-toxic, and non-flammable solvent for materials synthesis and proces- sing, 1,2 and is a potential replacement solvent for applications such as dry-cleaning, lithography, and precision cleaning. 3 One technical barrier to the use of scCO 2 is the limited availability of inexpensive CO 2 -soluble surfactants, 4–6 ligands, 7–9 and phase transfer agents. 10 The majority of systems reported so far have been highly fluorine- substituted, 4–10 and the associated costs may prohibit industrial- scale use for many applications. In addition, fluorinated materials often have poor environmental degradability, and this could negate the environmental advantages associated with the use of scCO 2 . The discovery of inexpensive CO 2 -soluble polymers – as opposed to small molecules – is a particularly hard challenge: 11 CO 2 is a rather feeble solvent and, until recently, the only polymers found to have significant solubility in CO 2 under moderate conditions (,100 uC, ,400 bar) were amorphous fluoropoly- mers 12,13 and polysiloxanes. 14 Inexpensive poly(ether carbonate) (PEC) copolymers have been reported to be soluble in CO 2 under moderate conditions, 15,16 and could function as building blocks for cheap surfactants, but numerous practical difficulties remain. For example, polymer solubility does not in itself guarantee performance in the various applications of interest. Effective surfactants, in particular, tend to require asymmetric topologies such as diblock copolymers. 6 Other practical considerations are cost, biodegradability, thermal and chemical stability, and biocompatibility. It is difficult to predict CO 2 -soluble polymer structures, despite recent attempts to rationalize specific solvent–solute interactions by using ab initio calculations. 17 Only a few examples of CO 2 - soluble polymers currently exist and, as such, there are a limited number of ‘design motifs’ to draw upon. 18 Moreover, it is clear that polymer solubility in CO 2 is influenced by a large number of inter-related factors 11,18 such as specific solvent–solute intera- ctions, 15–19 backbone flexibility 15,16,18,20 topology, 18,20 and the nature of the end-groups. 20 Given the current limits of predictive understanding, the discovery of new CO 2 -soluble polymers might be accelerated using parallel or ‘high-throughput’ (HT) methodo- logy. The synthetic approaches for such a strategy are already well in place; for example, a growing number of methods exist whereby one may synthesize and characterize polymer libraries. 21 By contrast, there are no examples of techniques for the rapid, parallel determination of solubility for libraries of materials in scCO 2 or other supercritical fluids (SCFs). The conventional method for measuring polymer solubility in SCFs is cloud point measure- ment, 11,15,16,20 which involves the use of a variable-volume view cell. This technique is not suitable for rapid solubility measurement and would be impractical for large libraries of materials. Previously, we developed a simple method involving a 10-well reaction vessel whereby ten solubilities could be measured in parallel using compressed fluid solvents such as liquid R134a. 22 This method was used to discover a new, inexpensive, R134a- soluble stabilizer for dispersion polymerization, but suffers from a number of limitations; for example, the pressure limit is low (50 bar) and only compressed liquid solvents (as opposed to SCFs) can be used with this particular equipment. 22 In this communication, we report a new method for the rapid parallel solubility measurement of libraries of polymers or other materials in SCF solvents. The method is based on parallel gravimetric extraction. 23 In a typical experiment,{ polymer samples (ca. 100 mg) are accurately weighed into borosilicate glass sample tubes and loaded into a specially-designed sample holder which will accept up to 60 tubes on this scale. This holder is then placed into a custom-built (Thar Designs) SCF extractor consisting of a vertically-mounted 500 ml extraction vessel and computer-controlled syringe pump/back pressure regulator. CO 2 is then passed through the vessel at a controlled pressure, temperature, and flow rate for a predetermined period of time. Thus, all 60 samples are subjected, in parallel, to precisely the same extraction conditions. The CO 2 is then slowly vented, the sample holder removed from the vessel, and the samples reweighed individually to determine the sample mass loss (if any) under those extraction conditions. The procedure is then repeated (typically at progressively higher CO 2 pressures) in order to build a cumulative extraction profile for the library of samples. A low molecular weight material [e.g. azobis(isobutyronitrile), AIBN] of known CO 2 -solubility 12,13 was added as an internal standard for each run. Fig. 1 shows extraction results for a library of 100 materials (two separate runs) at five increasing CO 2 pressures. This method is very rapid in comparison with alternative techniques: once the equipment had been installed, tested, and validated, all of the data presented in this communication were collected over the course of five days. Four classes of materials were included in this study, as colour-coded in Fig. 1: (i) a library of aliphatic polyesters (PE, blue { Electronic supplementary information (ESI) available: preliminary reproducibility data and photograph of equipment layout for the high- throughput solubility measurements. See http://www.rsc.org/suppdata/jm/ b4/b415343j/ *aicooper@liv.ac.uk COMMUNICATION www.rsc.org/materials | Journal of Materials Chemistry 456 | J. Mater. Chem., 2005, 15, 456–459 This journal is ß The Royal Society of Chemistry 2005