Leopold RužičkaForMemRS (pronounced[rǔʒitʃka];[3] bornLavoslav Stjepan Ružička; 13 September 1887 – 26 September 1976)[5] was a Croatian-Swiss scientist and joint winner of the 1939Nobel Prize in Chemistry "for his work onpolymethylenes and higherterpenes"[6][7] "including the firstchemical synthesis ofmale sex hormones."[8] He worked most of his life in Switzerland, and received eight doctorateshonoris causa in science, medicine, and law; seven prizes and medals; and twenty-four honorary memberships in chemical, biochemical, and other scientific societies.
Ružička was born inVukovar (until 1918 in theAustria-Hungary, today inCroatia). His family of craftsmen and farmers was mostly ofCroat origin,[9] with aCzech great-grandparent,Ružička, and a great-grandmother and a great-grandfather fromAustria.[6] He lost his father, Stjepan, at the age of four, and his mother, Amalija Sever, took him and his younger brother Stjepan, to live inOsijek.[5]
Ružička attended the classics program at thegymnasium (secondary school) in Osijek. He changed his originalidea of becoming a priest and switched to studying technical disciplines.[10]Chemistry was his choice, probably because he hoped to get a position at the newly openedsugar refinery built in Osijek.[5]
Owing to the excessive hardship of everyday and political life, he left and chose the High Technical School inKarlsruhe in Germany. He was a good student in areas he liked and that he thought would be necessary and beneficial in the future, which wasorganic chemistry. That is why hisphysical chemistry professor,Fritz Haber (Nobel laureate in 1918), opposed hissumma cum laudedegree. However, in the course of his studies, Ružička set up excellent cooperation withHermann Staudinger (aNobel laureate in 1953). Studying within Staudinger's department, he obtained his doctoral degree in 1910, then moved toZürich as Staudinger's assistant.
Ružička's first works originated in the field of chemistry of natural compounds.[11] He remained in this field of research all his life. He investigated the ingredients of theDalmatian insect powderPyrethrum (from the herbTanacetum cinerariifolium), a highly esteemedinsecticide found inpyrethrins, which were the focus of his work with Staudinger. Ružička later said of this time: "Toward the end of five and a half years of mainly synthetic work on the pyrethrins I had come to the firm conclusion that we were barking up the wrong tree." In this way, he came into contact with the chemistry ofTerpineol, afragrant oil of vegetable origin, interesting to the perfumeindustry. He and Staudinger split company when he started cooperation with the Chuit & Naef Company (later known asFirmenich) inGeneva.[10][5]
In 1916–1917, he received the support of the oldest perfume manufacturer in the worldHaarman & Reimer, ofHolzminden, Germany. He became a Swiss citizen in 1917,[5] and published hisHabilitation in 1918.[10] Fornasir and he isolatedlinalool in 1919.[10]
With expertise in the terpene field, he became senior lecturer in 1918, and in 1923, honorary professor at theETH (Eidgenössische Technische Hochschule) as well as theUniversity of Zurich. Here, with a group of his doctoral students, he proved the structure of the compoundsmuscone andcivetone,macrocyclic ketone scents derived from themusk deer (Moschus moschiferus) and thecivet cat (Viverra civetta).[12] These were the firstnatural products shown to have rings with more than six atoms, and at the time that Ružička inferred that civetone as having a 17-member ring.[13] Synthetic techniques at the time were only known for rings of up to eight members.[14] Muscone had been isolated in 1904[15] but was not identified as 3-methylcyclopentadecanone[16] until Ružička suspected amacrocycle, having characterised civetone. He also developed a method for synthesising macrocycles, now known as theRužička large ring synthesis,[17] which he demonstrated by preparing civetone in 1927.[14][18]
Leopold Ružička Memorial Museum in his house inVukovar,Croatia
In 1921, the Geneva perfume manufacturersChuit & Naef asked him to collaborate.[5] Working here, Ružička achieved financial independence, but not as big as he had planned, so he left Zürich to start working for theBasel-basedCIBA.[citation needed] In 1927, he took over the organic chemistry chair atUtrecht University in the Netherlands. In the Netherlands, he remained for three years and then returned toSwitzerland, which was superior in its chemical industry. A synergistic upheaval in both the administration and chemistry departments coincided to make his good fortune.[5]
Ružička was the first to synthesizemusk at an industrial scale. Firmenech named this productExaltone. Other Swiss manufacturers andDuPont were in competition with them.[19]
In 1934, Ružička synthesized the male hormoneandrosterone and also proved "its constitutional and configurational relation to thesterols." This was followed in 1935 by the partial synthesis of the much more active male hormonetestosterone. Both discoveries led to the pre-eminence of the Swiss industry in the steroid hormone field.[5] At ETH Zurich he became a professor of organic chemistry and started the most brilliant period of his professional career. He widened the area of his research, adding to it the chemistry of higher terpenes andsteroids. After the successful synthesis in 1935 of sexhormones (androsterone andtestosterone),[20] his laboratory became the world centre of organic chemistry.[21] He was awarded in 1936 an honorary degree fromHarvard University.[20]
In 1939 he won theNobel Prize in Chemistry withAdolf Butenandt.[6] Over the period 1934–1939 he published 70 papers in the field of medicinally important steroid sex hormones, and filed several dozen patents besides.[5]
In 1940, following the award, he was invited by theCroatian Chemical Association, where he delivered a lecture to an over-packed hall of dignitaries. The topic of the lecture wasFrom the Dalmatian Insect Powder to Sex Hormones. In 1940 he became a foreign member of theRoyal Netherlands Academy of Arts and Sciences,[4] in 1942 he was elected a foreign member of theRoyal Society,[5] and in 1944 he became an international member of the USNational Academy of Sciences.[22] DuringWorld War II, some of his excellent collaborators were lost, but Ružička restructured his laboratory with new, younger and promising people; among them was young scientist and future Nobel laureateVladimir Prelog. With new people and ideas new research areas were opened.
Following 1950, Ružička returned to chemistry, which had entered a new era of research. Now he turned to the field ofbiochemistry, the problems ofevolution and the genesis of life, particularly to thebiogenesis of terpenes. In 1953, he published his hypothesis, theBiogenetic Isoprene Rule (that the carbon skeleton of terpenes is composed variously of regularly or irregularly linkedisoprene units), which was the peak of his scientific career.[24] In 1952,Oskar Jeger and he supervised a team which isolatedlanosterol and established the link between terpenes and steroids.[25] Ružička retired in 1957, turning over the running of the laboratory to Prelog.[26]
Ružička married twice: to Anna Hausmann in 1912, and in 1951 to Gertrud Acklin.[6] From 1929, he lived at Freudenbergstrasse 101 until the last years of his life.[5] He died inMammern,Switzerland, a village onLake Constance at the age of 89.[20]
^His great-grandparents included a Czech, from whom the name Ružička stems, an Upper Austrian and his wife from Wurtemberg, the other five being Croats
^abcdeAlbert Eschenmoser: "Leopold Ruzicka – From the Isoprene Rule to the Question of Life's Origin" CHIMIA 44 (1990)
^Ruzicka, L.; Lardon, F. (1946). "Zur Kenntnis der Triterpene. (105. Mitteilung) Über das Ambreïn, einen Bestandteil des grauen Ambra".Helvetica Chimica Acta.29 (4):912–921.Bibcode:1946HChAc..29..912R.doi:10.1002/hlca.19460290414.
^Voser, W., M. U. Mijovik, H. Heusser, O. Jeger u. L. Ruzicka: Über die Konstitution des Lanostadienols (Lanosterins) und seine Zugehörigkeit zu den Steroiden. Helv. chim. Acta 35, 2414 (1952).
^Shampo, M. A.; Kyle, R. A.; Steensma, D. P. (2007). "Leopold Ruzicka—1939 Nobel Prize in chemistry".Mayo Clinic Proceedings.82 (1): 1p preceding table of contents.PMID17285778.
