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LCGC North America has awarded its 2012 Lifetime Achievement in Chromatography Award to Lloyd Snyder, a man who has made countless contributions to the field of chromatography.
LCGC North America
has awarded its 2012 Lifetime Achievement in Chromatography Award to Lloyd Snyder, a man who has made countless contributions to the field of chromatography. He is known not only for his many important contributions to an understanding of high performance liquid chromatography (HPLC), but also for his teaching, mentoring, and acclaimed articles and books.
recently talked to Snyder about his career.
Readers can also learn more about him in an article about the 2012 LCGC awards that appears in the March issue of LCGC North America, and through Snyder’s contribution to our “History of Chromatography” series in the April issue of LCGC North America.
LCGC: What events shaped your career in chromatography?
Snyder: Too many to count, but they were generally characterized by unanticipated events, disappointments based on counterproductive desires, and fortuitous encounters. An example of the first was a request in 1955 to help set up a gas chromatography (GC) system. This happened soon after I came out of grad school while working at the Shell Oil refinery in Houston; before then, I had only the dimmest idea of what chromatography was. The second event is illustrated by three invitations during the 1970s and 1980s to interview for tenured positions at different universities. In each case I was eager, but in each case rejected. On reflection, I realize that I am fundamentally mismatched to the university system, and if any of these offers had materialized, it would have proved a disappointment to both parties (fortunately, the universities seem to have anticipated this).
Finally, fortuitous encounters were many, but some stand out above the others. I first met Jack Kirkland in 1968, and that meeting led to a long and productive interaction that involved almost three decades of an ACS short course on high performance liquid chromatography (HPLC), coauthorship of two books in five separate editions (1974–2010), and collaborations on several projects. My next “find” was John Dolan, who joined my HPLC group at the Technicon Corporation in 1977. I can’t say enough about John, as he is my perfect complement — covering all my weaknesses, while bringing his own well-known strengths to the relationship. After the work at Technicon, John and I joined in 1984 to create LC Resources Inc. and have been working together ever since. Still another fortuitous encounter was with Pete Carr in the mid-1980s, leading to over a dozen joint publications, and countless emails that also shared our very similar interests outside chromatography.
LCGC: Who were the scientific mentors you remember?
Snyder: Mainly one, my research advisor Don Noyce at the University of California at Berkeley. Before then, I was pretty much on my own, and in my various jobs afterward I found myself generally in charge of projects or, at Shell Oil, sharing joint responsibility. Noyce was a guy who preferred to leave his students to their own devices, after describing the problem and pointing them to the relevant literature. As I have always been a “self starter,” this was a great situation. If we broaden the idea of mentoring, however, there were a number of people with whom I worked who influenced my thinking and served as role models. Jack, John, and Pete fall into this category.
LCGC: What work do you find most satisfying, what work least satisfying?
Snyder: Well, let’s start with what I do poorly — and who enjoys what they know they do poorly? Work in the laboratory has never been a strength of mine. There was some question of whether I would be allowed to continue my graduate research after I broke two sets of very expensive quartz UV cells in 1952. Similarly, concern with equipment “innards” has never been at the top of my priorities. Nevertheless, I did spend most of my time in the laboratory until 1971, fortunately with tasks that did not tax my manipulative or equipment skills. What is most satisfying to me is working with the product of the lab, and to a lesser extent designing experiments for the lab. Seeing results that support or fit my prior expectations is satisfying, but the real “high” comes when quantitative correlations based on a reasonable model emerge — especially when the basis of the model was unanticipated.
LCGC: Which of your accomplishments do you feel had the most significant impact on the practice of HPLC?
Snyder: My first book — Principles of Adsorption Chromatography (Dekker, 1968) — received a lot of attention at the time, and one person claimed it as the inspiration to start an HPLC company (taken with a grain of salt!). I believe its main contribution was to show how the principles of physical–organic chemistry and modeling could contribute to chromatographic theory. The book also described the phenomenon of adsorbate localization, which was later shown to largely explain solvent selectivity for adsorption chromatography.
In 1966, I began crude experiments on what would later be called HPLC and was able to use the technique for practical work for the next five years. This may have helped in a small way to push the technique forward, but its main effect was to propel me into the field of HPLC.
But the linear-solvent-strength (LSS) model of gradient elution is likely the contribution with the greatest impact on everyday operation in the HPLC laboratory. This transformed gradient elution from a confusing technique in the laboratory to one that could be looked at in the same way as isocratic elution, which was well understood after 1970. The LSS model was first put forth in 1964, successively refined in 1969 with Dennis Saunders, and fully formulated in 1980 with John Dolan and Russell Gant. Further work over the next 25 years would culminate in a book with John Dolan: High-Performance Gradient Elution (Wiley, 2007).
LCGC: Many people would also cite your development of the solvent-selectivity triangle in 1973 as one of your greatest accomplishments. How did that development come about?
Snyder: It started at a meeting in 1973, when Lutz Rorhschneider presented a massive collection of data for 80 different solvents. These results allowed me to create the solvent-selectivity triangle as a means for predicting how to choose a “strong” solvent for a change in selectivity. This work received hundreds of citations in the literature, and later contributed to an early form of automatic method development for reversed-phase chromatography by Joe Glajch and Jack Kirkland. Together with adsorbate localization (noted above), the triangle also provided the first reliable guide to solvent selection in adsorption chromatography.
LCGC: Another important development of yours was the hydrophobic-subtraction model of column selectivity. How does that model work?
Snyder: This was another technical highlight, developed with John Dolan, Pete Carr, Dan Marchand and others from 1998 until the present time. It was analogous to my first book on adsorption chromatography, in that it presented a quantitative model that was consistent with physical-organic chemistry. Previous explanations of column selectivity were limited by assumptions, lacked experimental verification, or were incomplete. Many labs are now using our approach (via the website of the United States Pharmocopeia) to select columns of the right selectivity.
LCGC: Can you tell us about your work in improving HPLC method development?
Snyder: Predictable HPLC method development was an ongoing goal from the 1970s onward. The development with John Dolan of computer simulation software (DryLab) in the mid-1980s allowed trial-and-error method development to be reduced to as few as two experimental separations, followed by reliable prediction of conditions for maximum resolution. This software was expanded over the next 25 years, most recently by Imre Molnár in Germany. With a larger number of initial experiments, the effects on separation of a larger number of separation conditions can be reliably predicted and optimized. Combined with an overall strategy of method development, this work would have a major impact on everyday practice.
LCGC: You are also known for your work teaching short courses. How did you get started teaching? And what did you like most and least about teaching?
Snyder: The need for an HPLC short course was obvious to Jack and me by late 1969. Teaching was something I was awkward at initially, but content proved more important than presentation, and the popularity of the first HPLC short course was an adrenalin boost. Teaching mainly appealed to me in that my ideas about HPLC — and especially method development — might change laboratory practice for the better. That’s been a primary driving force over the years. What did I like least? Eventually the sheer volume of teaching, and the related travel, wore me down and led me to prefer other activities.
Apart from the ACS short course and related books mentioned above, an even larger number of students were reached through similar courses offered by John Dolan, Tom Jupille, and me at LC Resources from 1984 on. The content of the courses and related books was to a considerable extent built around the experience and research of Jack, John, and myself. I think we may have reached more than 20,000 students in this way.
LCGC: Were there any developments that initially seemed exciting but did not end up being as useful?
Snyder: Some innovative HPLC concepts seemed promising at the time, but had little (if any) application outside our laboratory. These included segmented-flow open-tubular gel filtration (1979) for the on-line deproteinization of serum samples, and boxcar chromatography (1981) for increasing sample throughput by as much as 10-fold, each developed with John Dolan at Technicon. Later developments marginalized both of these inventions.
LCGC: What advice would you offer to the next generation of HPLC researchers?
Snyder: First, I would remind them that chromatography and HPLC are applied sciences. Before tackling a problem, consider whether the study is likely to prove applicable in the laboratory, or might generate information of a more fundamental nature. Chromatographic knowledge that cannot be applied directly or used elsewhere is of little value. And tackle significant, but doable problems!
Second, given a topic for study (such as reversed-phase retention), be careful of pushing theory beyond experiment, unless the underlying principles (such as physical-organic chemistry) are quantitative and applicable to the phenomenon studied. Especially worrisome are forced correlations that involve fitting-parameters whose relevance to the problem studied is uncertain. In this vein, I find that the application of chemometrics in chromatography can be problematic, sometimes leading to questionable conclusions. In any case, be cautious about forming conclusions, and carefully consider alternative explanations of results. Numerous examples of data correlations based on straight-line fits have failed to survive further examination.
LCGC: If you had not become a chromatographer, or even a chemist, what other career path might you have followed?
Snyder: In high school, my English teacher thought I should aspire to a writing career. She was not far off the mark in that I really enjoy writing. In fact, if you Google my name, most of the results refer to books I have coauthored.
LCGC: What do you like to do when you are not in the lab or the classroom?
Snyder: As noted above, I have not been in the lab much for the past 40 years, instead spending most of my time lecturing or in my office at my computer. A lot of time is now spent on books outside the field of chemistry. Since 2000 I have checked out over 100 books each year from the local library, mainly biographies or histories. An example of a book that especially engaged me is State vs Defense by Stephen Glain (Crown, 2011). It’s the most detailed and comprehensive account I have seen of how the military-industrial complex (Eisenhower’s description) has led our government to place increasing emphasis on defense, at the expense of diplomacy – with far reaching consequences for our government, our economy, and our relations with other countries.
LCGC: Is there a little-known fact about Lloyd Snyder that you can share with the chromatography community?
Snyder: What comes to mind is something that I suspect is not “little known.” I am a pretty narrow fellow, in that whatever interests me at the moment tends to exclude everything else. So I am much more motivated by doing than by second-hand learning. You can appreciate that this tendency would have been a big impediment to a university career.