(1a) LOOKING BACK TO MY RESEARCH EFFORT (1962-1998)

(1b) Biography, J. Phys. Chem., 102, 5316-5317 (1998)

LOOKING BACK TO MY RESEARCH EFFORT (1962-1998)

Robert S. H. Liu

Department of Chemistry

University of Hawaii

I still vividly remember the morning when George Hammond showed up in my lab with a smile on his face and proceeded to explain to me his new concept of isomeric triplets of conjugated dienes based on the isoprene dimer data I gave him the week before. That was only near the end of my first year as a graduate student at Caltech. I could not follow all his reasoning. But his enthusiasm made me very happy and more importantly for the first time I had the feeling that I might be allowed to stay in Caltech.

Of course, that experience turned out to be more than keeping myself alive. Rather, by staying with George and the closely knit group under him, I finally learned part of the art of independent thinking and deductive reasoning. Subsequently, I also benefited from working under Howard Simmons at duPont and the sabbatical leaves in the laboratories of George Wald and George Porter.

In starting my own research career, whether because of the situations I was in (first in an industrial lab at duPont and then as a new faculty member in the relatively isolated State of Hawaii) or for some other reasons, I never considered myself very good at competing against others in popular research areas. Instead, I was quite lucky in picking projects in less popular fields, stumbling onto some photochemical results that violated rules of the accepted norm. Findings of this nature usually help to turn a few sympathetic ears, much needed when later I went out to look for money or other favors.

I guess I was the right person at the right time when the second triplet state project was launched at duPont. It started at a time (mid-sixties) when the 'non-vertical' excitation process was in vogue. And, the group of chemists at the old Radiation Laboratory (R. Kellogg, P. McCartin and R. Bennett) had just spectroscopically located the position of second triplet states of anthracenes. It was logical for me to carry out the series of triplet-triplet energy transfer experiments using T₂-donors. At that time such "violations" of Kasha's Rule were rare. We were fortunate not only to be the first to identify such a process but also were one step ahead of the spectroscopists in reporting the lifetime of an upper excited state (via chemical kinetics). The program continued through the early-seventies when more sensitive emission and double-laser equipment became available that allowed direct examination of such states as carried out elegantly by E. Lim, T. Scaiano and others.

Strangely, terpenes kept on popping up as startup systems for new projects of mine. I mentioned the role of isoprene dimers in the discovery of isomeric triplets. Myrcene helped me start a program to investigate modes of internal photocycloaddition. And, alloocimene opened the door to photoisomerization of polyenes.

The program for preparation of new stereoisomers of vitamin A started with the discovery of one-way triplet sensitized isomerization to produce the hindered 7-cis isomer of precursors of vitamin A. It was only after successful characterization of the hindered 7-cis geometry and well on our way to prepare new isomers of vitamin A, that we discovered an early paper by L. Pauling stating that such hindered 7-cis isomers were supposed to be too unstable for isolation. (The slightly less crowded 11-cis isomer was also considered unstable but was already characterized to be the chromophore in visual pigments.) But, of course Pauling's conclusions are still valid if they are limited to comparing relative thermodynamic stability of the isomers rather than predicting their kinetic stability at room temperature. The program later led to all previously unknown isomers of vitamin A and A₂. The collection of new stereoisomers allowed us to probe for the stereospecificity of the binding site of opsin on a broader basis. The finding cast doubt on the notion of a rigid, specific (lock & key interaction) binding site (also suggested by analog studies by P. Blatz, K. Nakanishi and others). The flexible binding site argued for possible inclusion of substituted vitamin A as the chromophore. Subsequently, many fluorinated and alkylated retinal analogs were prepared. Such substituents were useful reporters for information on specific protein-substrate interactions. More recently, we finally took up the courage to tackle pigments containing the larger and more sensitive fluorinated carotenoids.

A few years ago, Al Asato in my group prepared a series of compounds that we called "Mini-carotenes". Tomas Gillbro of Umea turned them into a wonderful set of compounds that systematically violated the Kasha's Rule, again -- by emitting from the second singlet state with varying intensity. (This work followed that of R. Christensen of other chain shortened carotenoids.) The best known compound that violates the Kasha's Rule is of course the azulene. Al Asato was able to attach to this chromophore polyenal side chains. Such highly colored retinal analogs eventually led to the first NIR absorbing analogs of bacteriorhodopsin and other polarized polyenes. (Nakanishi's group first reported an azulenic bR analog.)

In considering conditions for regioselective (especially cases of regiospecific) isomerization of polyenes including the visual chromophore, we came up with the "Hula-twist" model of isomerization -- simultaneous twisting of a pair of adjacent double and single bonds, a process that violates the NEER principle. We thought it could only be a high energy process taking place in a confined medium. For a while it did look like an unlikely high energy process because there were no new experimental evidence supporting this idea. It was a surprise to me that a decade later, high level calculations showed that the trajectory of deactivation of an excited singlet polyene traced a low energy pathway, via conical intersection, to such a two-bond twisted product (M. Olivucci et al.). And, photoisomerization of vitamin D compounds was shown to follow the "Hula-twist" process (W. Fuss) and isomerization data of exocyclic dienes suggested simultaneous two-bond twist (W. Leigh). When taken together with the early low temperature photochemical work on 1,3-butadiene and 1,3,5,7-octateraene (M. Squillacote & B. Kohler), there appear to be room again for this conceptually simple process (although admittedly I was guilty being excessively optimistic in presenting the model).

Originally appeared in Spectrum, 1998

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(1b) Biography

R. S. H. Liu Biography

by

Alfred E. Asato & Leticia U. Colmenares

We consider ourselves to be indeed fortunate to have had the opportunity to pursue our career objectives in chemistry under his tutelage. We hope that this biographical sketch does justice to his many accomplishments in the field of organic photochemistry.

Robert S. H. Liu was born in Shanghai, China in 1938. After graduation from a Baptist-affiliated high school, Dr. Liu was awarded a scholarship to attend Howard Payne College, a small Baptist college in Brownwood, Texas. Despite the difficulties of being a foreign student in a town with no Chinese restaurants, he excelled academically. Thereafter, in 1961 he was admitted to the graduate program in chemistry at the California Institute of Technology. Under the tutelage of his research advisor and mentor, George S. Hammond, he joined a select group of exceptionally talented graduate students who were to have a considerable influence on shaping the future of modern organic photochemistry. Among his compatriots were Nick Turro, Jack Saltiel, Bill Hardham, Bill Herkstroeter, Charles DeBoer and Don Valentine to name a few.

His thesis work focused on the photodimerization of conjugated dienes with the piece de resistance being the discovery of non-interconvertibility of isomeric triplets. Following his graduate school days at CalTech, Bob joined the research group of Howard Simmons at the Central Research Laboratories at E. I. duPont de Nemours Company where he continued his research in photochemistry for four more years. Of these formative years he proudly cites two major accomplishments--one being the discovery of the second excited triplet state and the second being his, meeting, courting, and ultimately marrying Regina Ro. Aspiring to a career in academia he joined the chemistry department at the University of Hawaii in 1968 with the rank of Associate Professor. It is said that not only did he bypass the lower rank of assistant Professor, but he also drove the most flashy white Oldsmobile Cutlass on the Islands and sported the flattest flattop crewcut on campus! In 1972 he was awarded the rank of Full Professor of Chemistry.

In 1974 Professor Liu took his sabbatical leave at Harvard University in the laboratory of George Wald, the father of vision chemistry. While there, with the help of Wm. deGrip of the University of Nijmegen of he succeeded in binding for the first time several of the 7-cis isomers of retinal to opsin. And thus was launched yet another phase of his career--the study of the binding site requirements of the visual protein, rhodopsin, and soon thereafter, the retinal-protein bacteriorhodopsin using as diagnostic probes a wide variety of retinal analogs including the extremely useful fluorinated derivatives. More recently his research interests have once again expanded to embrace the study of the carotenoprotein, crustacyanin (getting bigger and bigger!), using fluorinated astaxanthins.

In describing his research interests from the early studies of small conjugated molecules to much larger compounds such as retinoids, carotenoids and their protein complexes, and azulenic polyenes as potential NLO materials, Professor Liu humbly describes the transition as quite simply a natural evolution and not a result of clever design. With all due respect, we beg to differ! He took it upon himself to learn and ultimately master diverse areas of specialization including organic synthesis, selective photoisomerization, molecular modeling, protein extraction, binding and purification, and ¹⁹F NMR spectroscopy.

His major contributions include the syntheses of the remaining geometrical isomers of retinal, the "hula twist" mechanism of photoisomerization of the rhodopsin chromophore and the application of ¹⁹F NMR to the study of protein-substrate interactions. For these projects he had received continuous supports from the NIH, NSF, Army Research and others, totaling almost $5M. He had authored over 170 papers and has extensive collaboration with several research groups.

Apart from his research accomplishments Professor Liu is most justifiably proud of his teaching at the University of Hawaii. In recognition of his excellence in both teaching and research he has been awarded the UH Regents' Medal for Excellence in Research (1986), the UH Regents' Medal for Excellence in Teaching (1988) and the Resolution of Merit by Hawaii State Legislature (1988).

As a teacher, it is the students themselves who bestow him the highest honor. His organic chemistry classes are invariably over-subscribed, and for good reason. He has rightfully earned the reputation of being a witty and well-organized lecturer with a wry sense of humor and a penchant for surprising and delighting his students when he dons his Superchemist shirt or Mandarin outfit for his polymer "noodle" classroom demonstration. To them, he is "Yoda", the sage professor who compares the polarizability of atoms to the "compressibility" of "Konishiki", a familiar local sumo wrestler of gargantuan proportions, or uses 'Peanuts" comic strips to illustrate a point. To his students Professor Liu makes organic chemistry fun to learn as he makes it "shine like the sun."

For the many graduate students and postdocs who have had the good fortune to experience Dr. Liu's contagious exuberance for research and teaching, he remains a close friend, source of inspiration, and advisor to this day. George Hammond's legacy, passed on to Bob Liu, has now been extended to the next generation.

Originally appeared in J. Phys. Chem. 102, 5316-5317 (1998).

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