Larry Miller, Amgen, Cambridge, Massachusetts and Larry Taylor, Department of Chemistry, Virginia Tech, Blacksburg, Virginia
The 7th International Symposium on Packed Column SFC (SFC 2013) — dedicated to bringing scientists together to discuss the latest advances in supercritical fluid chromatography (SFC) — was held in Boston, Massachusetts, on July 10–12, 2013. The conference is organized annually by the Green Chemistry Group and alternates between the United States and Europe. The conference attracted more than 170 scientists from 10 countries, and 11 exhibitors displayed equipment and stationary phases for SFC use. The conference included 19 oral presentations, 36 poster presentations, and two vendor workshops. A short course dedicated to SFC theory and achiral, chiral, and preparative SFC was held before the conference. The program and many of the oral and poster presentations from SFC 2013 and previous SFC conferences can be found at http://www.greenchemistrygroup.org/index.html
Plenary LecturesEach day of the conference began with a plenary lecture from a recognized expert in the field of supercritical fluids. Jerry King from Genesis (Arkansas) began the first day of the conference with a presentation titled "The Symbiosis Between SFE and SFC." King gave a history of supercritical fluid extraction (SFE) and discussed advances made over the past 30 years. One of the main highlights of his presentation was a discussion of SFE operated at higher pressures (1000 bar). Higher pressures have not been utilized for SFE processing until recently because of the high equipment costs. However, these have now been evaluated and implemented for a number of processes. Higher-pressure operation provides extract concentrates with enriched levels of active ingredients not viable at lower extraction pressures. Depending on the application, >1000-bar SFE processing and equipment costs can be competitive. A 1000-bar SFE plant is currently under construction in Hawaii, with an on-line date of January 2014.
The second day kicked off with a plenary lecture by the recipient of the first annual Averica Award: Bill Farrell of Pfizer, La Jolla (San Diego, California). Farrell reported on the use of SFC to solve analytical challenges of reaction optimization screens. These analyses can be difficult for two reasons: There is a wide array of organic solvents and catalysts; and the presence of both soluble and insoluble materials and the high complexity of the samples. Although high performance liquid chromatography–mass spectrometry (HPLC–MS) can work for these analyses, Farrell has found SFC provides higher resolution. The advantages of SFC relative to HPLC were highlighted by an assay developed to monitor reaction optimization for boronate chemistry. These products are notoriously unstable in water and exhibit rapid hydrolysis. The boronic acid degradant forms in situ on the column when performing HPLC with an aqueous mobile phase, whereas the product, starting material, and reaction by-products are well separated using SFC. In addition, no water is present in the mobile phase and in situ degradation is not observed, which produces accurate data. In the year since the switch from HPLC–MS to SFC in Farrell's laboratory, the number of reaction optimization samples being analyzed by SFC has increased nearly fivefold.
The main application of SFC remains purification, but the use of analytical SFC is increasing. This has been facilitated by the introduction of advanced SFC equipment allowing the use of smaller-particle-size stationary phases as well as offering limits of detection and sensitivity approaching those seen in HPLC. The opportunities possible with this new generation of equipment were evident in the presentation by Robert Campbell of the Dow Chemical Company (Michigan). Campbell reported on the use of high-efficiency SFC to solve separation difficulties associated with highly complex mixtures. Many of his examples involved polymer mixtures where higher efficiency SFC separations led to increased analytical information as well as drastically shorter separation time. The use of 1.7-µm columns for Triton-X100 analysis showed more than a 15-fold reduction in analysis time relative to a 5-µm column. Numerous examples demonstrated how the low pressure drop of SFC allows columns to be coupled that generate more than 100,000 plates for a 1.7-µm, 30-cm column. Campbell closed his talk with some requests for the next generation of analytical SFC equipment including lower extracolumn system volumes and higher pressure ratings.
Ruben De Pauw from Vrije Universiteit (Brussels, Belgium) presented a comparison of constant pressure and constant flow rate for gradient elution separations in SFC. Using simulated and experimental data, De Pauw demonstrated that working under constant pressure mode and optimal flow rates results in a 40% decrease in analysis time and higher peak capacity relative to the constant flow rate mode.
Ray McClain from Merck (Philadelphia, Pennsylvania) presented the results of an academic collaboration between Merck and Pusan National University (Busan, South Korea) concerning the design and synthesis of novel achiral stationary phases for SFC. The design of the stationary phases takes advantage of advances from over the past two decades: Exploration of amide and urea linkage lengths; and the introduction of a chiral center to move the basic aromatic ring out of plane with the linker, allowing simultaneous multipoint interactions. They synthesized 10 stationary phases and analyzed them using 28 test molecules. The analysis determined that simultaneous multipoint interactions do not have a significant impact on retention compared to their planar counterparts; positional substitution of pyridines has a dramatic impact on retention; and amide and urea linkages improve chromatographic performance relative to phases without hydrogen bonding capability.