Spectroscopic studies of lipids and biological membranes. Twenty-first Colworth medal lecture.

Abstract

My first interest in nuclear magnetic resonance (n.m.r.) spectroscopy began in 1964, when it seemed to me that spectroscopy, and in particular n.m.r., would be a most desirable way to analyse unknowns without smelling everything, or heating with sodium and checking for hydrogen evolution with a match (the classical A-level approach at the time). Unfortunately, I had to wait a couple of years for some hands-on experience with n.m.r. (a Varian A-60), but once an undergraduate, 1 was able to facilitate compound identifications in the organic laboratories (by after-hours use of the research instrument), although such a non-classical approach was not always appreciated. At the same time, Walter Moore’s prescient textbook question [ 11: ‘you have a biochemist friend who wants to study the transformation ATP-ADP in muscle using 31P n.m.r. ..: convinced me of the great potential of n.m.r. in biochemistry, and I started n.m.r. research in 1967. My first experiments were in conjunction with Jake MacMillan at Bristol, where I attempted to synthesize and characterize gibberellin glycosides, but 1 soon found that I was not particularly happy manipulating milligram quantities of natural products, and I began looking for a new research area. Around this time, I was then very fortunate to hear Dennis Chapman give an illuminating lecture on spectroscopic and other studies of lipids and membranes, and decided that this area had just the right blend of chemistry and biochemistry for me, so 1 started a Third Year BSc Honours Thesis with Geoffrey Eglinton in the summer of 1968. The project consisted of incorporating chlorophylls and quinones (plastoquinones and ubiquinones) into egg lecithin multibilayers, in an attempt to monitor electron transfer across the membrane upon illumination, in addition to using n.m.r. to study the interactions between the various membrane components. Fig. 1 shows some typical n.m.r. results thus obtained. Although crude, the indications were that n.m.r. could be used to investigate intermolecular interactions in model photosynthetic membranes, that some quinone peaks could be resolved, and that bacteriochlorophyll appeared to have a ‘condensing’ effect on the lipid molecules, in much the same way that cholesterol does (E. Oldfield, unpublished work, [2]). This seemed like a good area for future research, so I joined Dennis at the University of Sheffield in the Autumn of 1969 for postgraduate research. The 9 months required for an ultrasonicator to arrive provided sufficient time to reflect upon the advisability of using sonication to produce samples for high-resolution n.m.r. work, and I decided alternative approaches might be needed for characterizing lipids and biological membranes. Fortunately, we happened to have on hand a small quantity of perdeuterated dimyristo I lecithin, and Bill Derbyshire,