Richard Willstätter

A Nobel Prize winning chemist, Richard Willstätter (1872-1942) studied the chemical composition of chlorophyll and other plant pigments.

Agifted experimentalist, Richard Willstätter's pioneering work on natural products, especially chlorophyll and anthocyanins (plant pigments), was honored with the 1915 Nobel Prize in chemistry. In 1924 Willstätter, who was Jewish, resigned from his position at the University of Munich in protest against the anti-Semitism of some of the faculty. This act of conscience seriously hampered his research activity. In 1939 the anti-Semitic policies of the Third Reich forced him to emigrate to Switzerland, where he spent the remaining few years of his life.

Richard Martin Willstätter was born in Karlsruhe, Germany on August 13, 1872, the second of two sons of Max and Sophie Ulmann Willstätter. Willstätter's father was a textile merchant and his mother's family was in the textile business. Willstätter's education began in the classical Gymnasium in Karlsruhe. When he was eleven years old, his father moved to New York in search of better economic opportunities and to escape the circumscribed life in Karlsruhe; although this separation was meant to be short, it lasted seventeen years. Willstätter's mother took him and his brother to live near her family home in Nürnberg, a change to which Willstätter had difficulty adjusting, in part because of the more overt anti-Semitism he experienced there.

One effect of the move to a new school was that, although receiving good grades in his other subjects, he did poorly in Latin, the most important subject in the gymnasia of the time. A family council decided he should switch to the Realgymnasium and be educated for business instead of a profession. Ironically, it was at this time, stimulated by some home experiments and good teachers, that he decided to become a chemist. In his autobiography, Willstätter observed that excellence in academic subjects caused one to be disliked, while athletic excellence resulted in popularity. He was also attracted to medicine and might have become a physician instead of a chemist, but because of the longer schooling required his mother would not permit him to change. An interest in biological processes remained with him, though, and is evident in the kinds of chemical problems he attacked. Much later, while teaching at Zurich, he still thought of studying physiology and internal medicine, but the death of his wife ended the idea.

In 1890 the eighteen-year-old Willstätter entered the University of Munich and also attended lectures at the Technische Hochschule. In 1893 he began his doctoral studies and was assigned to do his research under Alfred Einhorn on some aspects of the chemistry of cocaine. It was at this time that Adolf von Baeyer, the leading organic chemist in Germany, began to take Willstätter under his wing. Although Willstätter never worked directly for Baeyer, he thought of himself as Baeyer's disciple. Willstätter completed his doctoral work in a year and stayed on doing independent research, becoming a privatdocent, or unsalaried lecturer, in 1896.

In his work with Einhorn, Willstätter had come to suspect that the structure assigned to cocaine by Einhorn and others was incorrect. When he started his independent research, Einhorn forbade him to work on the cocaine problem. Willstätter, with Baeyer's approval, decided to work instead on the closely related chemical tropine, whose structure was suspected to be similar to that of cocaine; once the structure of tropine was known, the structure of cocaine could be easily derived. Willstätter showed that, indeed, the cocaine structure was not what it had been thought to be; for the remainder of his stay at Munich, Einhorn refused to speak to him. In 1902 Willstätter was appointed professor extraordinarius (roughly equivalent to associate professor), although Baeyer thought he should have accepted an industrial position. Baeyer, himself partly Jewish, also recommended that Willstätter be baptized, an act that would have removed the legal barriers he faced as a Jew. This Willstätter refused to consider. During Easter vacation in 1903 Willstätter met the Leser family from Heidelberg, and that summer he and Sophie Leser were married. Their son Ludwig was born in 1904 and their daughter, Margarete, in 1906.

In 1905 Willstätter accepted a call to the Eidgenössische Technische Hochscuhle in Zurich as professor of chemistry, beginning the most productive phase of his career. While at Munich he had begun an investigation into the chemical nature of chlorophyll, the green pigment in plants that converts light into energy through photosynthesis; at Zurich, he and his students made great strides in understanding this important material. They developed methods for isolating chlorophyll from plant materials without changing it or introducing impurities. Willstätter was then able to prove that the chlorophyll from different plants (he examined over two hundred different kinds) was substantially the same—a mixture of two slightly different compounds, blue-green chlorophyll a and yellow-green chlorophyll b, in a 3 to 1 ratio.

He also showed that magnesium, which had been found in chlorophyll by earlier workers, was not an accidental impurity but an essential component of these chlorophyll molecules, bonded in a way very similar to that in which iron is bonded in hemoglobin, the oxygen-carrying constituent of blood. The later work of others, especially Hans Fischer, in elucidating the detailed structures of the chlorophylls and hemoglobin would not have been possible without the pioneering work of Willstätter and his students. In 1913, Willstätter, in collaboration with his former student and good friend, Arthur Stoll, reviewed the work on chlorophyll in a book, Untersuchungen über Chlorophyll. In all, between 1913 and 1919, Willstätter published twenty-five papers in a series on chlorophyll. A preliminary step in the isolation of chlorophyll from plant materials yielded a yellow solution that on further study proved to contain carotenoid pigments. These had been described before, but Willstätter's work marked the beginning of our understanding of these materials that produce the color of tomatoes, carrots, and egg yolk.

In 1908, Willstätter suffered a devastating blow in the death of his wife after an operation for appendicitis had been delayed for thirty-six hours after the appendix had ruptured. He consoled himself with the care of his two children and with his work; in his autobiography he wrote that he took no vacations for the next ten years. During his stay at Zurich, Willstätter also did work on quinones and the mechanism of the oxidation of aniline to aniline black—a process of importance to the dye industry. He also completed a project begun eight years earlier, by synthesizing the chemical cyclooctatetraene and showing that it did not behave as an aromatic compound despite its structural similarities to benzene.

The Kaiser Wilhelm Institutes were founded in 1910 to afford outstanding scientists the chance to do research on problems of their own choosing, free of any teaching obligations. In 1911 Willstätter accepted the position of director of the Kaiser Wilhelm Institute of Chemistry and in 1912 moved into the new building at Berlin-Dahlem. The institute was situated next to the Institute for Physical Chemistry and Electrochemistry, headed by Fritz Haber, and a deep and lasting friendship developed between the two directors.

At Zurich, Willstätter had initiated a study of the pigments of various red and blue flowers, a class of compounds now known as anthocyanins. He began with dried cornflowers, or bachelor's button, because it was winter and they were commercially available. This choice, as it turned out, was not a good one; cornflowers only contained a percent or less of the pigment. In Berlin, Willstätter planted fields of double cornflowers, asters, chrysanthemums, pansies, and dahlias around the Institute and his residence. In these fresh flowers he found a much higher pigment content, up to 33 percent in blue-black pansies. Before World War I brought an end to this line of research, Willstätter published eighteen papers in an anthocyanin series between 1913 and 1916. He showed that the various shades of red and blue in these flowers as well as in cherries, cranberries, roses, plums, elderberries, and poppies all arose mainly from three closely related compounds, cyanidin, pelargonidin, and delphinidin chlorides, and were very dependent on the acidity or alkalinity of the flower. During the first year of the war, most of Willstätter's coworkers went into military service, and the flowers were taken to military hospitals instead of to the laboratory. Willstätter was bitterly disappointed by this interruption and could not bring himself to return to the problem after the war.

In 1915 Haber, who was in charge of Germany's chemical warfare work, asked Willstätter's assistance in developing the chemical absorption unit for a gas mask that would protect against chlorine and phosgene (a severe respiratory irritant). In five weeks, Willstätter came up with a canister containing activated charcoal and hexamethylenetetramine (also called urotropin). The use of charcoal was not new, but the use of hexamethylenetetramine was. When asked after the war how he had come to try so unusual a compound, he said that the idea had just popped into his head. For this work he received an Iron Cross, Second Class. He was also involved in an industrial research project with Friedrich Bergius on the hydrolysis of cellulose with hydrochloric acid to give dextrose, which could then be fermented to produce alcohol. The process, which was only perfected later, is now known as the Bergius-Willstätter process.

In the spring of 1915 Willstätter's ten-year-old son, Ludwig, died suddenly, apparently from diabetes. Willstätter wrote that his memory of the months following was blurred. Ironically, in November, while engaged in the work on gas masks, Willstätter learned that he had been awarded the 1915 Nobel Prize in chemistry in recognition of his work on chlorophylls and anthocyanins. Because of wartime conditions he did not travel to Stockholm to receive the prize until 1920, when a ceremony was held for a group of those who had been honored during the war. Willstätter made the trip in the company of fellow German awardees Max Planck, Fritz Haber, Max von Laue, and Johannes Stark.

An offer of a full professorship to succeed Baeyer at Munich also came in 1915. This offer, recommended by Baeyer, was precipitated by an offer to succeed Otto Wallach, a pioneer in natural product chemistry, at Göttingen. Willstätter maintained that left to his own inclinations, he would have preferred Göttingen, because a medium-sized university would provide more contact with colleagues and greater interaction with different disciplines than was possible at large institutions. However, he accepted the appointment as professor and director of the state chemical laboratory in Munich and moved there in the spring of 1916.

He made two major demands before accepting the offer: that the old institute building be remodeled and a large addition to the chemical institute be built housing laboratories and a large lecture hall, and that a full professorship in physical chemistry be established. The first of these was contrary to the advice that the physical chemist Walther Nernst gave him before he left Berlin, "Don't ever build!" In fact, the construction, delayed by the war and post-armistice turmoil in Munich, was not completed until the spring of 1920.

At Munich, as before, Willstätter experienced the anti-Semitism that had troubled him during his earlier residence, and that finally brought about his resignation in 1924. The final straw was the refusal of the faculty to appoint the noted geochemist Victor Goldschmidt of Oslo, Norway, to succeed the mineralogist Paul von Groth, who had himself named Goldschmidt as the only one who could take his place. The sole reason for the refusal was that Goldschmidt was Jewish. When Willstätter's resignation became known, students and faculty joined in expressions of respect and confidence, urging him to reconsider. Nonetheless, he remained only for the time needed to see his students finish their research and to install Heinrich Wieland in his place. He received offers of positions at universities and in industry in Germany and abroad, but he declined all of them, finally leaving the university in September 1925 never to return.

Some of Willstätter's assistants continued work at the University, and in 1928 Wieland made room in what had been Willstätter's private laboratory for Willstätter's private assistant, Margarete Rohdewald, one of his former students. From 1929 until 1938 she collaborated with him in a series of eighteen papers on various aspects of enzyme research. It was an odd collaboration, conducted almost entirely over the telephone; Willstätter never saw her at work in the laboratory.

During the few years at Munich before his resignation, Willstätter began to concentrate his research on the study of enzymes. He had first encountered these biological catalysts in his early work on chlorophyll. Now he worked to develop methods for their separation and purification. His method for separation was to adsorb the materials on alumina or silica gel and then to wash them off using solutions of varying acidity, among other solvents. In this connection, Willstätter carried out a systematic study (comprised of nine papers) of hydrates and hydrogels during which he, with his assistants Heinrich Kraut and K. Lobinger, was able to show that aluminum hydroxide, silicic acid, ferric hydroxide, and stannic hydroxide do actually exist in solution and are not colloidal sols (dispersions of small solid particles in solution) of the corresponding oxides. Willstätter reported that this foray of an organic chemist into inorganic chemistry was not well received by inorganic chemists.

The enzyme studies were not as successful, in part because Willstätter thought that enzymes were relatively small molecules absorbed on a protein or some other giant (polymer) molecule. The modern view, of course, is that enzymes are themselves proteins. Though Willstätter's chemical intuition failed him, there were positive results— for example, the enzymatic reduction of chloral and bromal resulted in the formation of trichloroethanol, a sedative (Voluntal), and tribromoethanol, an anesthetic (Avertin).

In 1938 the situation for Jews in Germany was becoming impossible. On a visit to Switzerland, Stoll tried to persuade Willstätter to stay, but he insisted on returning to Munich. There, after some trouble with the Gestapo, he was ordered to leave the country. After much red tape, which entailed the confiscation of much of his property, papers, and art collection, and an abortive attempt to leave unofficially, he entered Switzerland in March 1939 to stay for a while with Stoll and then to settle in the Villa Eremitaggio in Muralto. There he wrote his autobiography to pass the time. On August 3, 1942, Willstätter died of cardiac failure in his sleep. Among the honors received by Willstätter in addition to the Nobel prize were honorary membership in the American Chemical Society (1927), honorary fellowship in the Chemical Society (1927), the Willard Gibbs Medal for distinguished achievement in science from the Chicago Section of the American Chemical Society (1933), and election as foreign member of the Royal Society (1933). Willstätter's obituary by Sir Robert Robinson in Obituary Notices of Fellows of the Royal Society, has an eleven page bibliography, probably incomplete, listing over three hundred papers between 1893 and 1940.

Further Reading

Dictionary of Scientific Biography, Volume 14, Scribner, 1976, pp. 411-412.

Obituary Notices of Fellows of the Royal Society, Volume 8, Morrison & Gibb, 1954, pp. 609-634.

Partington, J. R., A History of Chemistry, Macmillan, 1964, pp. 860-866.

Huisgen, Rolf, "Richard Willstätter," in Journal of Chemical Education, Volume 38, number 1, 1961, pp. 10-15.

Robinson, Robert, "Willstätter Memorial Lecture," in Journal of the Chemical Society, 1953, pp. 1012-1026. □

WILLSTäTTER, RICHARD

(b. Karlsruhe, Germany, 13 August 1872; d. Locarno, Switzerland, 3 August 1942)

organic chemistry.

Willstätter was the son of Max and Sophie Ulmann Willstätter. Raised in a well-to-do German Jewish mercantile family, Willstätter attended school in Karlsruhe and then at the Realgymnasium in Nuremberg. Upon graduation in 1890, he entered the University of Munich. It was there that he came under the influence of Adolf von Baeyer, who took great interest in Willstätter’s carrer, and recommended him to his colleague A. Einhorn, with whom Willstätter did his research for the Ph.D. (1894). Two years later Willstätter became Privatdozent, and in 1902 he was appointed extraordinary professor in Baeyer’s institute. The following year he married Sophie Leser; they had two children before her untimely death in 1908. In 1905 he became professor of chemistry at the Eidgenössische Technische Hochschule in Zurich, but left in 1912 to become director of the new Kaiser-Wilhelm Institute of Chemistry in Berlin-Dahlem.

In 1916 Willstätter succeeded Baeyer as professor of chemistry at the University of Munich, but resigned in 1924 in protest of the vote of the faculty to deny V. M. Goldschmidt appointment as the successor of Groth. After 1925 most of Willstätter’s research was conducted by Margarete Rohdewald in a laboratory provided by Wieland, Willstätter’s successor at Munich. With the rise of Hitler, and the threat of arrest during the anti-Semitic campaign of 1938, Willstätter had to leave Germany; after considerable difficulty, he succeeded in emigrating to Switzerland in March 1939.

Willstätter’s doctoral work with Einhorn dealt with the structure of cocaine, for which the latter had proposed a formula in 1893. After the completion of his Ph.D., Willstätter continued to work on the tropine alkaloids related to cocaine; and through a series of brilliant chemical degradative and synthetic researches during 1894–1898, he demonstrated that earlier formulas were incorrect and that these alkaloids belonged to a family of bicyclic compounds having a seven-member ring. During succeeding years he returned occasionally to the tropine alkaloids; thus, in 1918, he described an elegant synthesis of ecgonine. His studies in this field also led him to prepare cyclooctatetraene in 1913.

Another area of organic chemistry that Willstätter illuminated early in his career was the chemistry of quinones and quinone imines. In 1905 he prepared the hitherto unknown o -benzoquinone, and the succeeding seven years saw a series of important studies on the Wurster dyes, formed by the oxidation of p -phenylenediamines, and on “aniline black,” a product of the oxidation of ani-line.

The high point of Willstätter’s chemical work was attained during 1905–1914, in his studies on chlorophyll and the anthocyanins. Although there had been much earlier work on chlorophyll–and its chemical relation to the porphyrin of hemoglobin was appreciated–it was Willstätter who laid the groundwork for the later complete elucidation of the structure of chlorophyll by Hans Fischer. Willstätter separated chlorophyll from green plants into two components (chlorophyll a and b), and showed them to be magnesium complexes of a porphyrin derivative (pheophytin) in which one of the two carboxyl groups is esterified by a longchain alcohol (phytol). Through a series of chemical degradations with acid and alkali, Willstätter and his associates produced a series of well-characterized chemical intermediates on the way to the simpler porphyrins. During the course of his work on chlorophyll, he found that in the presence of ethanol, an enzyme present in plant tissue (chlorophyllase) catalyzes the transesterification of phytol by ethanol. This observation awakened his interest in enzymes. the principal subject of his last researches. The work on the chemistry of chlorophyll was followed, during 1915–1916, by studies on its role in photosynthesis, and on the assimilation by green plants of carbon dioxide: but these researches did not lead to clearcut conclusions.

Willstätter’s studies on the anthocyanin pigments of flowers, in particular on cyanin and pelargonin, led to his establishment of their structures as oxonium salts derived from hydroxychromanes, whose hydroxyl groups are linked to sugar units. These brilliant studies were terminated by the advent of World War I but served as the basis for the further development of the subject by R. Robinson. In 1915 Willstätter was awarded the Nobel Prize for chemistry in recognition of his “pioneer researches on plant pigments, especially chlorophyll.”

With the resumption of his work after the war, Willstätter turned his attention to the nature of enzymes. From 1918 to 1925 he and his associates attempted to develop methods for the purification of a variety of enzymes: peroxidase, lipase, trypsin, and amylase. An important consequence of these efforts was the introduction, into enzyme chemistry, of reproducible adsorption methods (for example, the use of aluminum hydroxide) and of improved assay procedures for the determination of enzymic activity. Willstätter advocated the idea that enzymes are substances of low molecular weight that are merely adsorbed on colloidal carriers; he also questioned J. B. Sumner’s claim (1926) to have isolated the enzyme urease in the form of a crystalline protein the integrity of which was essential for catalytic activity. Although some of Willstätter’s students (notably E. Waldschmidt-Leitz) continued to defend his view into the 1930’s, the isolation of pepsin and other enzymes as crystalline proteins led to its rejection. In his final years of research, with M. Rohdewald, Willstätter studied the biochemical transformation of glycogen and the role of polysaccharides in alcoholic fermentation: this work did not have a significant impact.

BIBLIOGRAPHY

I. Original Works. Willstätter’s works include Untersuchungen über Chlorophyll (Berlin, 1913), written with Arthur Stoll, trans. by F. M. Schertz and A. R. Merz, as Investigations on Chlorophyll (Lancaster, Pa., 1928). Willstätter and Stoll also collected their papers on photosynthesis, in Untersuchungen über die Assimilation der Kohlensäure (Berlin, 1918). The papers on enzymes are collected in Untersuchungen über Enzyme, 2 vols. (Berlin, 1928); see also Problems and Methods in Enzyme Research (Ithaca, N.Y., 1927). Willstätter wrote an autobiography, Aus meinem Leben, A. Stoll, ed. (Weinheim, 1948), trans, by L. S. Hornig as From My Life (New York, 1965).

II. Secondary Literature. Appreciations of Willstätter’s work are R. Huisgen, in Journal of Chemical Education,38 (1961), 10–15; R. Robinson, in Journal of the Chemical Society (1953), 999–1026; and in Obituary Notices of Fellows of the Royal Society,8 (1953), 609–634; and J. Renz, Helvetica Chimica Acta,56 (1973), 1–14.

Joseph S. Fruton

Richard Willstätter

1872-1942

German organic chemist who did foundational research on chlorophyll and its role in photosynthesis, for which he received the 1915 Nobel Prize for Chemistry. Willstätter also analyzed the chemical structure of cocaine and other alkaloids, and discovered new quinones and quinone imines. After World War I, he concentrated on enzyme research. He later resigned his post as professor of chemistry at Munich in protest over the treatment of a fellow Jewish scholar, and fled to Switzerland in 1939 to escape the Nazis.