Hans Fischer
Hans Fischer
The German organic chemist Hans Fischer (1881-1945) was awarded the Nobel Prize in Chemistry in 1930 for his researches into the constitution of hemin and chlorophyll and especially for his synthesis of hemin.
Hans Fischer, the son of Dr. Eugen Fischer, a manufacturer of chemicals, was born at Höchst am Main, on July 27, 1881. He entered the University of Lausanne in 1899, read chemistry and medicine, and subsequently transferred to the University of Marburg, where he graduated in chemistry in 1904. Two years later he qualified in medicine at Munich. In 1908 he graduated as a doctor of medicine at Munich. He was assistant to the chemist Emil Fischer at Berlin (1908-1910) and did some early work on bile pigments at Munich (1910-1912).
After a year as a teacher of internal medicine and three as lecturer in physiology at Munich, Fischer held the chair of medical chemistry at Innsbruck (1916-1918) and then at Vienna (1918-1921). From 1921 until his death he was professor of organic chemistry at the Technische Hochschule in Munich.
From 1911 Fischer studied the pyrrole group of the heterocyclic compounds. In 1915 he showed that the urine and feces of a case of congenital porphyria, a disease then recently discovered, contained uroporphyrin and coproporphyrin.
Structure of Hemoglobin
Fischer then began to study hemoglobin, a very important member of the pyrrole group. Its molecule consists of the pigment heme combined with the protein globlin. Heme contains iron, and its chloride, which is easier to work with, is hemin. Hemoglobin possesses the unique property of forming a loose reversible combination with oxygen, so that oxygen taken up by it in the lungs can be given off in the tissues. In this loose combination the active part is heme, and heme combined with any other protein except globin does not possess the property of giving up combined oxygen. It was already known, partly through the work of Fischer himself, that hemin has the formula C34H32O4N4FeCl, and his problem now was to determine the steric arrangement of the 76 atoms in this molecule of hemin.
When Fischer started his work it was known that, when the iron atom is removed from hemin, porphyrins are formed. These substances occur widely in nature, and, though their exact chemical composition was unknown, it >was realized that they all contained the pyrrole ring, consisting of four carbon atoms with a nitrogen atom closing the ring. His first problem was therefore to clarify the structure of the porphyrins. At a later stage of this investigation he synthesized the substance "porphin," which is not known to occur naturally. Porphin consists of four pyrrole rings, arranged as at the four points of the compass. These four rings are linked together by four methene bridges (=CH—) so that the whole forms a closed square. Fischer then showed that all porphyrins contain this porphin nucleus, in which, in each of the four pyrrole rings, the two carbon atoms most distant from the nitrogen atom are each linked with an atom of hydrogen. He also showed that, in all naturally occurring porphyrins, these hydrogen atoms are replaced by substitution groups (methyl, ethyl, vinyl, and so on). The possible permutations are therefore considerable.
In 1926 Fischer discovered porphyrin syntheses, and he synthesized over 130 isomers. It was recognized that the iron atom in hemin was situated at the center of the porphin nucleus. He studied the substance ooporphyrin, a constituent of the spots on the eggs of certain birds. He found it identical with the protoporphyrin previously described by Kämmerer, and by introducing iron complexly into it Fischer produced hemin. By a short-term putrefaction of hemoglobin he produced protoporphyrin; and by putrefaction carried on for several months he produced deuterohemin, from which he obtained deuteroporphyrin by splitting off the iron.
By the mild reduction of hemin the substance called mesoporphyrin had previously been obtained. Fischer found that, by decarboxylating mesoporphyrin, etioporphyrin was formed, and he determined that etioporphyrin contained four methyl and four ethyl groups. He then found that, by introducing four methyl and four ethyl groups into the porphin nucleus, etioporphyrin was obtained. But, depending on the position assumed by these residues as side chains in the porphin nucleus, this introduction could be effected in four different ways. He synthesized these four etioporphyrins and related them to the ooporphyrins. He then turned to a study of the mesoporphyrins and found that there were 15 possible isomers. He synthesized 12 of the 15. He found also that mesoporphyrin IX was identical with the mesoporphyrin obtained from hemin. Further, mesoporphyrin IX was derived from etioporphyrin III, and the arrangement of the side chains in hemin was thus determined.
Fischer next determined the formula for deuteroporphyrin and synthesized that substance. By the introduction of iron, deuterohemin was obtained, and by a complex process two acetyl residues were introduced into the latter, producing diacetyl-deuterohemin. Partial reduction of diacetyl-deuterohemin yielded hematoporphyrin, and from it protoporphyrin was produced by the removal of two molecules of water. On the introduction of iron into protoporphyrin, a synthetic hemin was produced that was indistinguishable from natural hemin obtained from hemoglobin. Fischer completed this synthesis in 1929.
Structure of Chlorophyll
Meanwhile Fischer had also been working on chlorophyll. During his career he wrote nearly 130 papers on that subject. Richard Willstätter had shown about 1912 that plants contain two chlorophylls: chlorophyll a and chlorophyll b. From chlorophyll he obtained three different porphyrins, and from these etioporphyrin, which he considered identical with the etioporphyrin obtained from hemoglobin. Fischer started his researches here, and from the three porphyrins he obtained two distinct etioporphyrins. He synthesized very many isomers, and he converted pyroporphyrin into his mesoporphyrin IX. He then worked on the substance phylloerythrin, found in the gastrointestinal tract of ruminants. He showed that it is a porphyrin and that it exhibited an atypical linkage of two of the pyrrole nuclei. It was known that chlorophyll contains magnesium, and Fischer determined that the magnesium atom was situated at the center of the porphin nucleus.
Even with the lead that phylloerythrin gave Fischer, it required many years to enable him to put forward his formula for the structure of chlorophyll a, a formula which seems to be correct. This formula is notable not only for the atypical linkage of two of the pyrrole nuclei, but also for the presence of two surplus hydrogen atoms in 7-and 8-positions, and of a very complex phytyl group in the 7-position. He found that the formula for chlorophyll b is the same as that for chlorophyll a, except that in the former a formyl group replaces the methyl group in pyrrole ring II of the latter.
Bile Pigments
All Fischer's important work on this subject was done during the last few years of his life. Although the pigments biliverdin and bilirubin had been known for nearly a century, when Fischer began his investigations practically nothing was known of their chemical composition. He showed that, whereas the molecule of the porphyrins consists of four pyrrole rings linked by four carbon linkages to form a closed ring (the porphin nucleus), the molecule of a bile pigment is the same except that it lacks one of the carbon linkages. The pigment molecule can therefore be regarded either as an open ring or as a linear chain of four pyrrole nuclei linked by three carbon linkages. Fischer worked out the structural formulas for both biliverdin and bilirubin. In 1942 he synthesized biliverdin, and in 1944 he effected the even more difficult synthesis of bilirubin.
Later Life
Fischer was not only a superb research chemist but also a very fine administrator of a research institute, and he was extremely popular with his staff and students. He was a keen mountaineer, skier, and motorist, despite the fact that as a young man he had suffered from serious surgical tuberculosis. In addition to innumerable scientific papers Fischer was the author, with two colleagues, of a standard work on pyrrole chemistry, Die Chemie des Pyrrols (3 vols., 1934-1940).
The title of Privy Councilor (Geheimrat) was conferred on Fischer in 1925. He received the Liebig Memorial Medal in 1929 and the Davy Medal in 1937. In 1936 Harvard University conferred on him an honorary doctorate. He died in Munich on March 31, 1945.
Further Reading
There is a biography of Fischer in Nobel Lectures, Chemistry, 1922-1941 (1966), which also contains his Nobel Lecture. For the chemical background to Fischer's work see P. Karrer, Organic Chemistry (trans. by A. J. Mee, 4th ed. 1950). See also C. W. Carter, R. V. Coxon, D. S. Parsons, and R. H. S. Thompson, Biochemistry in Relation to Medicine (3d ed. 1959), and A. White, P. Handler, and E. L. Smith, Principles of Biochemistry (3d ed. 1964, and later editions). □
Fischer, Hans
FISCHER, HANS
(b Höchst am Main, Germany, 27 July 1881; d. Munich, Germany, 31t March 1945)
chemistry.
Fischer’s father, Eugen, was a dye chemist in the large dye works of Mister. Lucius, and Bruning in Höchst; and while the boy was still young, the father became director of the laboratory of the Kalle Dye Works in Biebrich, near Wiesbaden. Young Fischer thus was early acquainted with the chemistry of pigments. He began the study of medicine and chemistry at Marburg, where, under the influence of Theodor Zincke, he decided to specialize in chemistry. After graduating in 1904 he continued his medical studies at Munich and spent a year in Berlin as assistant to Emil Fischer (no relation), working on peptides and sugars.
In 1910 Fischer went to a medical clinic in Munich, where he began to study the constitution of the bile pigment bilirubin; and his Habilitationsschrift (1912) was based on these studies. He accepted the chair of medical chemistry at the University of Innsbruck, as successor to Adolf Windaus, in 1916: and two years later he assumed a similar position in Vienna. During World War I and the reconstruction period that followed, he was unable to carry on any continuous research. In 1921. however. Fischer became head of the Institute of Organic Chemistry at the Technische Hochschule of Munich, succeeding Heinrich Wieland. He remained there for the rest of his life, and it was there that he conducted his most important studies.
In 1935 Fischer married Wiltrud Haufe, who was thirty years younger than he. It was a happy marriage. Although he suffered from tuberculosis at the age of twenty and had had a kidney removed in 1917, he was active in mountaineering and skiing and enjoyed long automobile trips. During World War II, Fischer became severely depressed, especially when his institute was almost totally destroyed by bombing. Convinced that his lifework had been shattered, he committed suicide in March 1945.
When Fischer began his research in Munich, he continued his earlier work on bile pigments and related substances. The general outlines of porphyrin chemistry were known, and in 1912 W. Küster had proposed a formula for the porphyrin ring that was essentially correct. It was Fischer’s task to establish the accuracy of the earlier work and to carry it to its logical conclusion. He recognized that the significant feature of bilirubin was its content of four pyrrole rings and that the pigment itself was a degradation product of he in, the active portion of the hemoglobin molecule. In addition, he soon learned that in the pathological condition known as porphyria, several other porphyrin ring compounds were excreted, including coproporphyria and uroporphyrin . Other porphyrins were found in a wide variety of natural sources. Chlorophyll, the green pigment of leaves, was also a porphyrin, differing from hem in in its content of magnesium instead of iron. Fischer found that the various porphyrins were distinguished from one another chiefly by the presence of differing substi-tuents on the pyrrole rings.
He therefore began a systematic study of a number of synthetic pyrrole derivatives and became an authority on pyrrole chemistry, writing the definitive monograph on this subject (1934-1940). While working on the syntheses of various porphyries, Fischer developed microana-lytical techniques so successfully that more than 60,000 microanalyses were carried out in his laboratory. He found reactions by which two pyrrole rings could be combined into dipyrrylmethenes. which in turn could be combined to form porphyrin rings. In 1926 he carried out the first synthesis of a porphyrin, and in 1929 he was able to prepare hem in. For the latter achievement he received the 1930 Nobel Prize in chemistry. It was only later that Fischer finally determined the structure of bilirubin, the compound with which he had begun his research. Since hem in was closely related to chlorophyll, he next studied the plant pigment. He identified the pyrrole rings of chlorophyll but died before completing its synthesis, which was accomplished in 1960 at Munich and, independently, at Harvard.
The author of over 300 papers, Fischer also received the Davy Medal of the Royal Society and an honorary doctorate from Harvard.
BIBLIOGRAPHY
I. Original Works. Fischer’s chief book is Die Chemise des Pyrrols 3 vols. (Leipzig. 1934- 1940), written with Hans Orth. An extensive review of his own work is “Hemin und Porphyrine” in Verhandhlungen der Deutsche Gcsellschaft für inner Medizin45 (1933). 7-27.
II. Secondary Literature. Fischer’s scientific work is reviewed by F. Baumgärtel. “Zur Erforschung der Blut- und Gallenfarbstoffe. Hans Fischer zum Gedächtnis.” inMedizinische Klinik.42 (1947), 3 1 - 34. Biographical details are given by Karl Keile, “Das Lebenswerk Hans Fischers,” in Naturwissenschaften,33 (1946), 289-291; H. Wieland, “Hans Fischer und Otto Hönigschmid zum Gedächtnis,” in Angewandte Chemise,62 (1950). 1-4-the portion relating to Fischer has been translated by Ralph Oesper in E. Farber, ed.. Great Chemists (New York, 1961), 1527-1533: and Alfred Treibs. “Hans Fischer, 1881-1945.” in Chemise in unsererZeit.1 (1967), 58-61.
Henry M. Leicester
Hans Fischer
Hans Fischer
1881-1945
German chemist whose investigation of the properties of blood and bile led to the synthesis of bilirubin, a compound produced by the breakdown of hemoglobin from red blood cells. Fischer worked at the Second Medical Clinic in Munich, and the First Berlin Chemical Institute, before becoming a lecturer on internal medicine and later physiology in Munich. His studies of blood pigments, bile, and leaves, specifically haem and haemoglobin, earned him the 1930 Nobel Prize for Chemistry.