MILESTONES IN CHEMISTRY

Marco Fontani The shy angel who missed the Nobel Prize

MARCO FONTANI1*, MARY V. ORNA2 *Corresponding author 1. University of , Department of Chemistry “Hugo Schiff”, via della Lastruccia 13, Sesto F.no Firenze, 50019, 2. College of New Rochelle, New Rochelle, NY, USA

The famous organic chemist Adolf von Baeyer (1835-1917) saw ABSTRACT in the young man a sure promise for Italian science and in 1897 Angelo (Angel, in English) Angeli (1864-1931) was one he convinced Angeli to compete for the general chemistry chair of the greatest organic chemists that Italy ever had. It at the peripheral University of Palermo. In those years Angeli’s is widely held – in retrospect – that the Austrian-born- behaviour retrogressed and he became more introverted. He Italian chemist should have been selected for the Nobel found it difficult to speak in public and from that time on, he Prize in Chemistry. He was nominated several times, but never participated in conferences or international meetings. Also was never awarded the prize. he loathed speaking on or hearing a voice on the telephone. In 1905, after the death of Augusto Piccini (1854-1905), Angelo Angeli was called to Florence to take up the vacant chemistry chair at the Istituto di Studi Superiori Pratici e di EARLY LIFE Perfezionamento (3). The physicist Antonio Roiti (1843-1921), Dean of the Faculty of he had on its faculty two supreme Sciences, communicated the news to Hugo Schiff (1834-1915) 58 chemists: the German Hugo Schiff (1834-1915), and Angelo with the following telegram: “Angeli accepts. He will write very Angeli, who was born in Tarcento (the former Austro-Hungarian soon; reply encouraging him because he is extremely shy”. T th th Empire) on August 20 1864. Neither Schiff nor Angeli was able Although Angeli was the symbolic figure of the 19 century to cultivate a scientific “nursery” and neither of them created scientist, who devoted his existence to science, as noted, he a “school” in the modern sense of the term. Thus, it is difficult to was extremely shy and suspicious of any human relationship. At imagine that a series of experiments performed almost a century the end of World War I he was awarded a gold medal for his ago, which today might appear as astonishingly simple as carefully efforts in developing new anti-gas masks for the Regio Esercito opening an egg, would shake the very foundations of the discipline (Royal Army). He declined this prestigious acknowledgment, and open the door to the era of modern organic-chemistry. and instead formulated an unusual request to the Ministry of Angeli developed a great passion for chemistry early in life. University and Public Education. The reply of the Ministry was While still a child, he started to perform experiments with his sent to the Istituto di Studi Pratici e Perfezionamento: “Due to maternal uncle, Giovanni Carnelutti (1850-1901), an industrial his excessive shyness, it is recommended that Professor Angeli chemist. Angeli attended the Technical Institute of Udine and be released from all his academic duties, such as teaching or later moved to the Technische Hochschule (Polytechnic) of public speeches”. Vienna, but he soon went to the University of Padua where he met (1826-1910) and Giacomo Ciamician (1857-1922). The latter recognized that Angeli had a keen and acute intelligence. In 1889, when Professor Ciamician moved to Bologna, although he was still a student, he asked Angeli to follow him as his private assistant. The young Angeli graduated in 1891 and two years later his colleagues suggested that he qualify as a university faculty member. Even though in 1895, he finished first in the academic competition for the analytical chemistry chair, bureaucratic impediments obliged him to withdraw from the position. In 1896 Angelo Angeli and independently Enrico Rimini (1874-1917) discovered the reaction between an aldehyde and a sulfonamide to form a hydroxamic acid, and they published it in the same year (1). The reaction was mainly used as a chemical test in the dairy Figure 1. May 1928: Angelo Angeli, third from the right, with his co-workers and industry for the detection of aldehydes for food storage. assistants, standing in the courtyard of the Istituto di Chimica in Florence. The Angeli-Rimini reaction has recently been applied in solid-phase synthesis (2).

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CLOSE TO THE NOBEL PRIZE For many reasons - some of them still undisclosed-, the 1924 Nobel Prize for Chemistry was not awarded. It is thought that the Nobel Despite the desire of Angeli to live in the background of academic Committee seriously considered Angeli for the award that year, life, his scientific credit spread throughout many European but it seems rather unlikely. countries. In 1924 Richard Willstätter (1872-1942), reported (4): “The Luigi Rolla (1882-1960) nominated his illustrious colleague at the work of Professor Angeli exceeds that of all other Italian chemists, University of Florence in that very year, partially with the secret and for its originality and its value it is worthy of the highest hope of publicizing the University of Florence and emphasizing his consideration”. Angelo Angeli was repeatedly a candidate for discovery of element 61, which he called florentium after the city the Nobel Prize (Table 1) from 1911 to his death. He played a key of Florence. Nomination to the Nobel Prize in Chemistry was by role in the work of organic synthesis. While one frontier of chemistry invitation only. bordered on physics, another was developing on the interface The Nobel Committee for Chemistry sent confidential forms to with the life sciences: organic and biological chemistry. Between persons who were competent and qualified to nominate (Qualified the two decades 1911-1931, the Royal Swedish Academy of Nominators or Q.N.s). While Rolla’s nomination was quickly Science awarded the Nobel prizes for Chemistry equally distributed rejected, Guido Pellizzari (1858-1938), professor at the Faculty of between physical and inorganic chemistry on the one hand, and Pharmacy in Florence and official Italian Q. N., nominated his biological and organic chemistry on the other (5). friend Angeli several times. In 1915, following the death of Hugo Schiff, he taught general chemistry and after (1916) he held the organic chemistry chair which was purposely created for him. He remained at the University of Florence until his death refusing in 1922 to replace his teacher, Giacomo Ciamician (6), at the University of Bologna (7). He always refused any kind of personal honours and eschewed public ceremonies, with the unique exception of the Cross of War, awarded “for services rendered to the Motherland” (per i servizi resi alla Madrepatria). Angeli’s scientific works were characterized by a high level of innovation and originality. In about forty years of research, he published more than 220 articles and monographs. Noteworthy are his five most famous monographs which enjoyed a wide circulation. Their titles and dates follow: 1906 On some oxygenated compounds of nitrogen; 1911 Action of nitrous and nitric acids on indole and pyrrole; 1916 On the constitution of azo-compounds; 1924 On behavioural analogies between some benzene Table 1. Angeli Nomination to the Nobel Prize. derivatives and corresponding derivatives of the aliphatic 59 series;

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1930 Research and considerations on the structures of diazo- the Florentine University had ever enrolled, from this unfortunate compounds. episode (15). He died alone in his bedroom in an unpretentious and This led him to formulate the theory of Vernachlassingung modest hotel (16) where he had lived since his arrival in Florence des Benzolkerns (negligibility of benzoic nucleus). in 1905. Angelo Angeli was entombed close to his beloved brother Angeli was also a gifted experimenter and devoted his abilities Virgilio (1872-1918) in the Porte Sante (Holy Gates) Cemetery on to the analytical chemistry of natural substances. He studied the San Miniato al Monte Hill in Florence. Virgilio and Angelo Angeli the relationship between “molecular constitution and smell”, never married nor had children. The Angeli ascendance (Table 2) and formulated the hypothesis that olfactory activity could be was carried on by the youngest brother Vincenzo Angeli (1879- associated with an oxidation process. He was a forerunner and 1942). His daughter, Verdelaura (b. 1915) still lives near the former put in evidence the linkage between chemistry and olfactory Angeli villa. She is probably the last living person to preserve fresh physiology (8). memories (17) of the illustrious chemist, who used to spend summer Mostly due to his elusiveness and shyness, Angeli was not able holidays at the family’s villa in Tarcento near Udine. to create a school of organic chemistry. However, Livio Cambi When Angeli died in 1931, the Italian scientific community lost one (1885-1968) and Raoul Anna Poggi (1899-1961) proudly claimed of the truly great chemists of all time. Although he was recognized Angeli as their mentor. During his life he was mostly esteemed as during his lifetime (18) for his remarkable achievements, his life a synthetic organic chemist (9). Presently the figure of Angelo stands now and for the future as an example to aspiring young Angeli is linked to the recent determination that Angeli’s salt (10) scientists. In conclusion, it is worth telling a curious episode related

(Na2N2O3) may have a clinical application as a nitrogen oxide to the 1931 Nobel Prize Award: the Swedish poet Erik Axel Karlfeldt donor for treatment of cardiovascular diseases (11). Na2N2O3 is (19) – whose dates of birth and death were the same of Angelo regarded as a classical nitroxyl (NO-) donor, but under certain Angeli – was awarded the Nobel Prize posthumously. From 1974, conditions evolution of NO is also observed (12). What it is now the Statutes of the Nobel Foundation stipulate that a Nobel Prize called Angeli’s salt was discovered more than a century ago. cannot be awarded posthumously. Angelo Angeli found that “salts of nitroxylaminic acid are readily resolved into the corresponding nitrites and the unsaturated residue nitroxyl” (13), and he suggested their use as possible in vitro REFERENCES AND NOTES and in vivo sources of HNO, but the physiological properties of this molecule didn’t draw too much attention until the very end of the 1. A. Angeli, Gazz. Chim. Ital., 26, p. 17, (1896); E. Rimini, Gazz. Chim. Ital., XX century. 31, p. 84 (1901). 2. A. Porcheddu, G. Giacomelli, J. Org. Chem., 71(18), p. 7057 (2006). 3. In 1924 its name became the “Royal University of Florence”. THE LACERATED CONSCIENCES OF FLORENTINE 4. Nobel prize winner in chemistry 1915. CHEMISTS AND DEATH 5. E. Crawford, J.L. Heilbron et al., The Nobel Population (1901–1937): A census of the Nominators and Nominees for the Prizes in Physics and Chemistry, Berkeley: Office for History of Science and Technology, p. In November 1929 in the Institute of Chemistry directed by Luigi 337 (1987). 60 Rolla, something happened that upset the entire university: Moisè 6. A. Pieroni, Commemorazione tenuta a Bologna alla sezione Emiliana della Bigiavi (1898-1929), assistant to Angelo Angeli (1864-1931) took his Associazione Italiana di Chimica, June 28th 1931, Bologna, p. 19 (1931). own life. Although discipline and harmony seemed to reign in the 7. The University of Bologna was also simply called “Alma Mater”. This Institute, in fact this was not so. The incident was unexplainable; university was not only the most ancient one in the world, but also, at the section of Organic Chemistry was directed by Angeli, who least in the 1920s, the most famous and prestigious one in Italy. was universally recognized as an upright man and an admirable 8. A.R. Poggi, L’Industria Chimica, p. 6 (1931). scientist. 9. E. Ferroni, Storia dell’Ateneo Fiorentino, Ed. F. & F. Parretti Grafiche, Firenze, 2, p. 625 (1989). 10. A. Angeli, F. Angelico, Gazz. Chim. It., 30(i), p. 593 (1900); A. Angeli, Atti Regia Accademia dei Lincei Roma, 5, 10(II), p. 158, (1901); A. Angeli. F. Angelico, Atti Regia Accademia dei Lincei, 5, 10(v), p. 249 (1901). 11. K.M. Miranda, A.S. Dutton et al., J. Am. Chem. Soc., 127(2), p. 722 (2005); N. Paolocci., D.A. Wink, American Journal of Physiology, 296(5, Pt. 2), H1217 (2009). 12. S.I. Liochev, I. Fridovich, Free Radic Biol Med., 34(11), p. 1399 (2003). 13. A. Angeli, F. Angelico, J. Chem. Soc. Abstr., 80(I), 322 (1901). 14. In 1930 Rolla fired his co-worker and the presumptive co-discoverer of the elusive element of atomic number 61 (florentium), because he believed it was not possible to isolate it as a naturally occurring element. Fernandes counterattacked and had a summons issued Table 2. The Angeli Ascendance. against his former boss. Angeli immediately took up the defense of the young assistant, but nothing could help Fernandes, as his reputation was being destroyed. Soon after Angeli’s death Fernandes fled to But if the flames were burning in Organic Chemistry, the coals had France where he remained until 1943. already been smouldering in the Institute of Chemistry for a long 15. M. Fontani, M. Costa, DE REDITV EORVM: sulle tracce degli elementi time. A running dispute ravaged by a vicious diatribe between scomparsi, Ed. Società Chimica Italiana, Centro Stampa de Vittoria Lorenzo Fernandes (1902-1977) and Luigi Rolla about retraction Srl., p. 326 (2009). of the discovery of florentium (14) broke out into the open at 16. L. Cambi, Giornale di Chimica Industriale ed Applicata, 6, p. 61 the beginning of 1930; it was the second sign that tormented (1931); L. Cambi, Gazz. Chim. Ital., 63, p. 527 (1933). the consciences and pitted colleagues one against the other. 17. For further information contact Emilia Dellacà Di Giusto, Angeli’s grandnephew, at [email protected]. Called to arbitrate between the opposing parties were the Dean 18. He was an honorary member of scholarly societies in numerous of Pharmacy, Guido Pellizzari (1858-1938), Giusto Coronedi (1863- countries and a few days before his sudden death he was elected an 1941), and the mild and impartial professor Angeli, but the already honorary member of the Gesellschaft Deutscher Chemiker. He was tested fibre of the tough Friulian could not hold up and on Sunday also the only Italian who ever received the “Ludwig Mond Award”. May 31, 1931, a fatal attack of pulmonary edema removed 19. In 1905 Karlfeldt became a member of the Nobel Institute of the probably the most genial but impressively reclusive personality Academy and in 1907 of the Nobel Committee.

chimica oggi/Chemistry Today - vol. 30 n. 4 July/August 2012