Figure 13.—Survey of alcoholic fermentation, 1951. The “well-known scheme of alcoholic fermentation” according to Albert Jan Kluyver (1888-1956), presented before the Society of Chemical Industry in the Royal Institution, March 7, 1951. In Chemistry & Industry, 1952, page 136 ff., Kluyver restates that “... the fermentation of one molecule of glucose is indissolubly connected with the formation of two molecules of adenosine triphosphate (ATP) out of two molecules of adenosine diphosphate (ADP).”
Shortly after this experience had been gained, it became valuable for understanding the chemical nature of a new substance extracted from a natural organ. This substance was named lecithin by its discoverer, Nicolas Théodore Gobley[27] (1811-1876), because he obtained it from egg yolk (in Greek, lékidos). He used ether and alcohol for this extraction. Had he used water and mineral acid instead, he would not have found lecithin, but only its components. As Gobley and, slightly later, Oscar Liebreich (1839-1908), subjected lecithin to treatment with boiling water and acid, they separated it into three parts. One of them was the glycerophosphoric acid of Pelouze, the second was the well-known stearic acid of Chevreul, but the third was somewhat mysterious. This third substance was the same as one previously noticed when nerves had been subjected to an extraction by boiling water and acid and, therefore, called nerve-substance or neurine. Adolf Friedrich Strecker (1822-1871) established the identity of this neurine with a product he had extracted from bile and which went under the name of choline. Adolphe Wurtz (1817-1884) succeeded in synthesizing this substance from ethylene oxide, CH2.O.CH2 and trimethylamine N(CH3)3.[28] Thus, all three parts were identified, and Strecker put them together to construct a chemical formula for lecithin, glycerophosphoric acid combined with a fatty acid and with choline (a hydrate of neurine).
| { | OH | } | ||
| N | (CH3)3 | Choline | ||
| C2H4O | ||||
| C18H33O2 | } | HO | } | ||
| PO | |||||
| C16H31O2 | C3H5O | ||||
| Fatty Acids | Glycerophosphate | ||||
| '—————v————' | |||||
| Lecithin | |||||
| according to Strecker | |||||
This formula was not quite correct. Richard Willstätter showed that an internal neutralization takes place between the amino group and the free acidic residue. This is expressed in his lecithin formula of 1918.
Lecithin (1918)
When the aim was to distill elementary phosphorus out of an organic material, it did not matter whether this was fresh or putrified. For obtaining lecithin out of egg yolk and similar materials, it was essential to use it in fresh condition. Otherwise, enzymes would have decomposed it. Through more recent work, four enzymes have been separated, which act specifically in decomposing lecithin. Enzyme A removes one fatty acid and leaves a complex residue, called lysolecithin, intact. Enzyme B attacks this residue and splits off the remaining fatty acid group from it, enzyme C liberates only the choline from lecithin, and enzyme D opens lecithin at the ester bond between glycerol and phosphoric acid. This is shown in the following diagram.
| Enzymatic Splitting of Lecithins | ||
|---|---|---|
| Enzyme | Substrate | Products |
| A | Lecithin | Lysolecithin and fatty acids. |
| B | Lysolecithin | Glycero-phospho-choline and fatty acids. |
| C | Lecithin | Phosphatidic acid and choline. |
| D | Lecithin | Phosphoryl choline and diglyceride. |
Several fatty acids can be present in lecithin from various sources: palmitic and oleic acid, besides the stearic acid which at first had been thought the only one involved. In another group of extracts from brain or nerve tissue, amino-ethanol H2NCH2CH2OH is found instead of the choline of lecithin. The variations include the alcohol, to which the fatty acids and choline phosphate are attached, for example, glycerol can be replaced by the so-called meat-sugar, inositol, which has six hydroxyl groups in its hexagon-shaped molecule C6H6(OH)6.
Figure 14.—Eduard Buchner (1860-1917) received the Nobel Prize in Chemistry for his discovery of cell-free fermentation, the first step in finding the role of phosphate in fermentations (1907).
The generally similar behavior of these phosphate-and fat-containing substances was emphasized by Ludwig Thudichum (1829-1901). He coined the name phosphatides for this group of substances from seeds and nerves.[29] His work on the phosphates in brain substance aroused particular interest. When William Crookes drew his highly imaginative picture of an “evolution” of the chemical elements, he put into it “phosphorus for the brain, salt for the sea, clay for the solid earth....”[30] But phosphatides occur in many places of organisms, in bacteria, in leaves and roots of plants, in fat and tissues of animals. And where phosphatides are found, there are also enzymes that specifically act on them. They are called phosphatases to imply that they split the phosphatides. In addition, enzymes are present, which transfer phosphate groups from one compound to another. They are more abundant in seeds of high fat content than in the more starch-containing seeds, but even potatoes and orange juice have phosphatases.[31]
Thus, from phosphatides, phosphoric acid is generated, and they could also be called phosphagens. Since 1926, however, the name phosphagens has been reserved for a group of organic substances that release their phosphoric acid very readily. The link between phosphorus and carbon is provided by oxygen in the phosphatides, by nitrogen in the phosphagens. In vertebrates, the basis for the phosphoric acid is creatine, whereas invertebrates have arginine instead.
Nuclein and Nucleic Acids
All parts of an organism are essential for life. Only with this in mind does it make sense to say that the most important part of the cell is its nucleus. From the nuclei of cells in pus and in salmon sperm, Johann Friedrich Miescher (1811-1887) obtained a peculiar kind of substance, which he named nuclein (1868). Its phosphate content was easily discovered, but to find the exact proportions and the nature of the other components required special methods of separation from phosphatides and other proteins. It was difficult to develop such methods at a time when little was known about the properties, and particularly the stability, of a nuclein. For preparing nuclein from yeast cells, Felix Hoppe-Seyler (1825-1895) described the following details: Yeast is dispersed in water to extract soluble materials, like salts or sugars. After a few hours, the insoluble material is separated, washed once more with water, and then extracted with a very dilute solution of sodium hydroxide. The slightly alkaline solution, freed from insoluble residues, is slowly added to a weak hydrochloric acid. A precipitate forms which is separated by filtration, washed with dilute acid, then with cold alcohol, and finally extracted by boiling alcohol. The dried residue is the nuclein.[32] It contains six percent phosphorus. A little more washing with water, a slightly longer treatment with acid or alcohol gives products of lower phosphorus content. Many experimental variations were necessary to establish the procedure that leads to purification without alteration of the natural substance.
This was also true for the methods of chemical degradation, carried out in order to find the components of nucleins in their highest state of natural complexity. It was learned for example, that the special kind of carbohydrate present in nucleins was very susceptible to change under the conditions of hydrolysis by acids. Phoebus Aaron Theodor Levine (1869-1940), therefore, used the digestion by a living organism. With E. S. London, he introduced a solution of nucleic acid into, e.g., the gastrointestinal segment of a dog through a gastric fistula and withdrew the product of digestion through an intestinal fistula. Fortunately, the products obtained in such degradations were not new in themselves. The carbohydrate in this nucleic acid proved to be identical with D-ribose, which Emil Fischer had artificially made from arabinose and named ribose to indicate this relationship (1891). The nitrogenous products of the degradation were identical with substances previously prepared in the long study of uric acid. In the course of this study, Emil Fischer established uric acid and a number of its derivatives as having the elementary skeleton of what he called “pure uric acid,” abbreviated to purine. Out of Adolf Baeyer’s work on barbituric acid came the knowledge of pyrimidine and its derivatives.
Figure 15.—Albrecht Kossel (1853-1927) received the Nobel Prize in Medicine and Physiology in 1910 for his work on nucleic substances, which contain a high proportion of phosphorus. The chemical bonds of this phosphorus in the molecules of nucleic substances were determined in later work. (Photo courtesy National Library of Medicine, Washington, D.C.)
From these findings, together with what Oswald Schmiedeberg (1838-1921) had established concerning the presence of four phosphate groups in the molecule (1899), Robert Feulgen (1884-1955) constructed the following scheme of a nucleic acid. Feulgen’s formula of 1918 is:
Phosphoric acid—Carbohydrate—Guanine
Phosphoric acid—Carbohydrate—Cytosine
Phosphoric acid—Carbohydrate—Thymine
Phosphoric acid—Carbohydrate—Adenine
Of the four basic components on the right, thymine occurs in the nucleic acid from the thymus gland. Yeast contains uracil instead. The difference between these two bases is one methyl group: thymine is a 5-methyluracil. In all of these basic substances, the structure of urea
C=O
\
NH2
is involved, and they form pairs of oxidized and reduced states:
| Purine | Pyrimidine | |
| (reduced) Adenine | + | (oxidized) Thymine |
| (oxidized) Guanine | + | (reduced) Cytosine |
Pyrimidine
Purine
Adenine
Guanine
Uracil
Cytosine
The carbohydrate is ribose or deoxyribose.
Arabinose
l-Ribose
Fischer and Piloty, 1891
Deoxyribose
The exact position of phosphoric acid was established after long work and verified by synthesis.[33]
A compound of adenine, ribose, and phosphoric acid was found in yeast, blood, and in skeletal muscle of mammals. From 100 grams of such muscle, 0.35-0.40 grams of this compound were isolated. If the muscle is at rest, the compound contains three molecules of phosphoric acid, linked through oxygen atoms. It was named adenosine triphosphate or adenyltriphosphoric acid,[34] usually abbreviated by the symbol ATP. It releases one phosphoric acid group very easily and goes over in the diphosphate, ADP, but it can also lose 2 P-groups as pyrophosphoric acid and leave the monophosphate, AMP.
This change of ATP was considered to be the main source of energy in muscle contraction by Otto Meyerhof.[35] The corresponding derivatives of guanine, cytosine, and uracil were also found, and they are active in the temporary transfer of phosphoric acid groups in biological processes.
Thus, the study of organic phosphates progressed from the comparatively simple esters connected with fatty substances of organisms to the proteins and the nuclear substances of the cell. The proportional amount of phosphorus in the former was larger than in the latter; the actual importance and function in the life of organisms, however, is not measured by the quantity but determined by the special nature of the compounds.
Figure 16.—Otto Meyerhof (1884-1951) received one-half of the Nobel Prize in Medicine and Physiology in 1922 for his discovery of the metabolism of lactic acid in muscle, which involves the action of phosphates, especially adenosine duophosphates. (Photo courtesy National Library of Medicine, Washington, D.C.)
Figure 17.—Arthur Harden (1865-1940), left, and Hans A. S. von Euler-Chelpin (b. 1875), right, shared the Nobel Prize in Chemistry in 1929. Harden received it for his research in fermentation, which showed the influence of phosphate, particularly the formation of a hexose diphosphate. Euler-Chelpin received his award for his research in fermentation. He found coenzyme A which is a nucleotide containing phosphoric acid.
Figure 18.—George de Hevesy (b. 1885) received the Nobel Prize in Chemistry in 1943 for his research with isotopic tracer elements, particularly radiophosphorus of weight 32 (ordinary phosphorus is 31).
Figure 19.—Carl F. Cori (b. 1896) and his wife, Gerty T. Cori (1896-1957) received part of the Nobel Prize in Medicine and Physiology in 1947 for their study on glycogen conversion. In the course of this study, they identified glucose 1-phosphate, now usually referred to as “Cori ester,” and its function in the glycogen cycle. (Photo courtesy National Library of Medicine, Washington, D.C.)
The study of this function is the newest phase in the history of phosphorus and represents the culmination of the previous efforts. This newest phase developed out of an accidental discovery concerning one of the oldest organic-chemical industries, the production of alcohol by the fermentative action of yeast on sugar. A transition of carbohydrates through phosphate compounds to the end products of the fermentation process was found, and it gradually proved to be a kind of model for a host of biological processes.
Specific phosphates were thus found to be indispensable for life. In reverse, the wrong kind of phosphates can destroy life. As a result, an important part of the new phase in phosphorus history consisted in the study—and use—of antibiotic phosphorus compounds.
Phosphates in Biological Processes
The first indication that phosphorus is important for life came from the experience that plants take it up from the substances in the soil. They incorporate it in their body substance. What makes phosphorus so important that they cannot grow without it? The next insight was that animals acquire it from their plant food. It is then found in bones, in fat and nerve tissue, in all cells and particularly in the cell nuclei. What are its functions there?
The answers to such questions were developed from the study of a long-known process, the conversion of carbohydrates into carbon dioxide and alcohol by yeast. It started with Eduard Buchner’s discovery of 1890, that fermentation is produced by a preparation from yeast in which all living cells have been removed. When yeast is dead-ground and pressed out, the juice still has the ability to produce fermentation.
It is strange, but in many ways characteristic for the process of science, that the “riddle” of phosphorus in life was solved by first eliminating life. In such “lifeless” fermentations, Arthur Harden found that the conversion of sugar begins with the formation of a hexose phosphate (1904). The “ferment” of yeast, called zymase, proved to be a composite of several enzymes. Hans von Euler-Chelpin isolated one part of zymase, which remains active even after heating its solution to the boiling point. From 1 kilogram of yeast, he obtained 20 milligrams of this heat-stable enzyme, which he called cozymase and identified as a nucleotide composed of a purine, a sugar, and phosphoric acid.[36] In the years between the two World Wars, zymase was further resolved into more enzymes, one of them the coenzyme I, which was shown to be ADP connected with another molecule of ribose attached to the amide of nicotinic acid, or diphosphopyridine nucleotide:
Figure 20.—Fritz A. Lipmann (b. 1899) shared with Hans Adolf Krebs the Nobel Prize in Medicine and Physiology in 1953 for his work on coenzyme A. He discovered acetyl phosphate as the substance in bacteria, which transfers phosphate to adenylic acid.
Figure 21.—Alexander R. Todd (b. 1907) received the Nobel Prize in Chemistry in 1957 for his research on nucleotides. He determined the position of the phosphate groups in the molecule and confirmed it by synthesis of dinucleotide phosphates.
Its function is connected with the transfer of hydrogen between intermediates formed through phosphate-transferring enzymes. Fermentation proceeds by a cascade of processes, in which phosphate groups swing back and forth, and equilibria between ATP with ADP play a major role.
Many of the enzymes are closely related to vitamins. Thus, cocarboxylase A, which takes part in the separation of carbon dioxide from an intermediate fermentation product, is the phosphate of vitamin B1. Others of the B vitamins contain phosphate groups, for example those of the B2 and B6 group, and in B12, one lonely phosphate forms a bridge in the large molecule that contains one atom of cobalt: C63H90N14O14PCo. The formation of vitamin A from carotine occurs under the influence of ATP.
The first stages in fermentation are like those in respiration, which ends with carbon dioxide and water. These two are the materials for the reverse process in photosynthesis. When light is absorbed by the chlorophyll of green plants, one of the initial reactions is a transfer of hydrogen from water to a triphosphopyridine nucleotide, which later acts to reduce the carbon dioxide. Under the influence of ATP, phosphoglyceric acid is synthesized and further built up by way of carbohydrate phosphates to hexose sugars and finally to starch. In many starchy fruits, a small proportion of phosphate remains attached to the end product.
The synthesis of proteins is under the control of deoxyribonucleic acid or ribonucleic acid, abbreviated by the symbols DNA and RNA. The genes in the nucleus are parts of a giant DNA molecule. RNA is a universal constituent of all living cells. Where protein synthesis is intense, the content in RNA is high. Thus, the spinning glands of silkworms are extraordinarily rich in RNA.[37]
In his research on the radioactive isotope P32, George de Hevesy gained some insight into the surprising mobility of phosphates in organisms: “A phosphate radical taken up with the food may first participate in the phosphorylation of glucose in the intestinal mucose, soon afterwards pass into the circulation as free phosphate, enter a red corpuscle, become incorporated with an adenosine triphosphoric-acid molecule, participate in a glycolytic process going on in the corpuscle, return to circulation, penetrate into the liver cells, participate in the formation of a phosphatide molecule, after a short interval enter the circulation in this form, penetrate into the spleen, and leave this organ after some time as a constituent of a lymphocyte. We may meet the phosphate radical again as a constituent of the plasma, from which it may find its way into the skeleton.”[38] Much has been added in the last 30 years to complete this picture in many details and to extend it to other biochemical processes, including even the changes of the pigments in the retina in the visual process, or in the conversion of chemical energy to light by bacteria and insects.
Medicines and Poisons
In the delicate balance of these processes, disturbances may occur which can be remedied by specific phosphate-containing medicines. Thus, adenosine phosphate has been recommended in cases of angina pectoris and marketed under trade names like sarkolyt, or in compounds named angiolysine. A considerable number of physiologically active organic phosphates can be found in the patent literature.[39] Yeast itself is considered to be a valuable food additive.
On the other hand, there are phosphate compounds that act as poisons. One group of such compounds was discovered in 1929 by W. Lange, who wrote: “Of interest is the strong action of mono-fluorophosphate esters on the human body—the effect is produced by very small quantities.”[40] Diisopropyl fluorophosphate has since become a potential agent for chemical warfare. It inactivates an enzyme which controls the transmission of nerve impulses to muscle, acetylcholine esterase.
Organic esters of phosphoric acids are used as insecticides. The hexa-ethylester of tetraphosphoric acid, prepared by Gerhard Schrader by heating triethylphosphate with phosphorus oxychloride,[41] actually contains tetraethylpyrophosphate (TEPP) among others. Bayer’s Dipterex, the dimethyl ester of 2,2,2-trichloro-1-hydroxyethyl-phosphonate, has been modified to dimethyl-2,2-dichlorovinyl-phosphate and is especially active against the oriental fruit fly.[42]
Bayer's L 13/59
(Dipterex)
Schradan
Octamethylpyrophosphoramide
Figure 22.—Arthur Kornberg (b. 1918) and Severo Ochoa (b. 1905) shared the Nobel Prize in Medicine and Physiology in 1959. Kornberg received it for research on the biological synthesis of deoxyribonucleic acid. In particular, he found that four triphosphate components and a small amount of the end product as a “template” had to be present for the enzymatic synthesis. Ochoa received his share of the prize for research in ribonucleic acid and deoxyribonucleic acid. In particular, Ochoa synthesized polyribonucleotides and used the radioactive isotope, P32. The synthetic polyribonucleotides were found to resemble the natural substances in all essentials.
Figure 23.—Melvin Calvin (b. 1911) received the Nobel Prize in Chemistry in 1961 for his research in photosynthesis, in which he specified the function of phosphoglyceric acid as an intermediate in the synthesis of carbohydrates from carbon dioxide and water by green plants.
The story of phosphorus, which began 300 years ago, has acquired new importance in this century. Many scientists have contributed to it: 13 of them have received Nobel Prizes for work directly bearing on the chemical and biological importance of phosphorus compounds. In chronological order, they are: Eduard Buchner, Albrecht Kossel, Otto Meyerhof, Arthur Harden, Hans von Euler-Chelpin, George de Hevesy, Carl F. Cori, Gerty T. Cori, Fritz Lipmann, Lord Alexander Todd, Arthur Kornberg, Severo Ochoa, and Melvin Calvin. The developers of industrial production and commercial utilization of phosphate compounds have had other rewards.
Some impression of the continuing growth in this field[43] can be gained from the following data.
Phosphate Rock
annually “sold or used by producer” in the United States in million long
tons (2,240 lbs.)
| 1880 | 0.2 |
| 1890 | 0.5 |
| 1900 | 1.5 |
| 1910 | 2.655 |
| 1920 | 4.104 |
| 1930 | 3.926 |
| 1940 | 4.003 |
| 1945 | 5.807 |
| 1950 | 11.114 |
| 1955 | 12.265 |
| 1955 | (world: about 56) |
| 1960 | 17.202 |
| 1962 | 19.060 |
Sources: U.S. Bureau of the Census. Historical Statistics of the United States 1789-1945 (1949); Statistical Abstract of the United States.
Elemental Phosphorus
annually produced in the United States in short tons (2,000 lbs.)
| 1939 | 43,000 |
| 1944 | 85,679 |
| 1950 | 153,233 |
| 1956 | 312,200 |
| 1958 | 335,750 |
| 1959 | 366,350 |
| 1960 | 409,096 |
| 1961 | 430,617 |
| 1962 | 451,970 |
Source: U.S. Department of Commerce.
FOOTNOTES:
[1] Wilhelm Homberg, Mémoires Académie, 1666-1699 (Paris, 1730), vol. 10, under date of April 30, 1692, pp. 57-61.
[2] Fortunio Licetus, Lithiophosphorus sive de lapide Bononiensi (Venice, 1640).
[3] Cited in Peter Joseph Macquer Chymisches Wörterbuch, 2nd ed. (Leipzig: Weidmann, 1789), vol. 4, p. 508, footnote “c” as “Kletwich (de phosph. liqu. et solid. 1689, Thes. II).”
[4] Ferdinand Hoefer, Histoire de la Chimie (Paris, 1843), vol. 1, p. 339.
[5] G. W. von Leibniz, Mémoires Académie (Paris, 1682); Akademie der Wissenschaften, Miscellanea Berolinensia (Berlin, 1710), vol. 1, p. 91.
[6] Jean Hellot, Mémoires Académie 1737 (Paris, 1766), under date of November 13, 1737, pp. 342-378.
[7] Macquer, op. cit. (footnote 3), p. 551.
[8] A. S. Marggraf, Akademie der Wissenschaften, Miscellanea Berolinensia (Berlin, 1743), vol. 7, 342 ff.; see also Wilhelm Ostwald Klassiker der Exakten Naturwissenschaften (Leipzig: Engelmann, 1913), no. 187.
[9] G. Hanckewitz, [Hankwitz], Philosophical Transactions of the Royal Society of London, 1724-1734, abridged (London, 1809), vol. 7, pp. 596-602.
[10] Antoine Laurent Lavoisier, “Sur la Combustion du Phosphore de Kunckel, Et sur la nature de l’acide qui resulte de cette Combustion,” Mémoires Académie 1777, (Paris, 1780), pp. 65-78.
[11] Guyton de Morveau and others, Méthode de Nomenclature Chimique, Proposée par MM. de Morveau, Lavoisier, Bertholet, & de Fourcroy (Paris, 1787), plate 9.
[12] Macquer, op. cit. (footnote 3), p. 513.
[13] Marie Boas, Robert Boyle and Seventeenth Century Chemistry (New York: Cambridge University Press, 1958), p. 226; see also Wyndham Miles, “The History of Dr. Brand’s Phosphorus Elementarus,” Armed Forces Chemical Journal (November-December 1958), p. 25.
[14] Archibald Clow and Nan L. Clow, The Chemical Revolution (London: Batchworth Press, 1952), p. 451.
[15] Émile Kopp, Comptes-rendus hebdomadaires des Séances de l’Académie des Sciences, Paris (1844), vol. 18, p. 871; Wilhelm Hittorf, Annalen der Chemie und Pharmazie, suppl. to vol. 4, p. 37; Anton Schrötter, Annales de Chimie et de Physique, series 3, vol. 24 (1848), p. 406; see also Schrötter’s report on “Phosphor und Zündwaaren” in A. W. von Hofmann, Bericht über die Entwicklung der Chemischen Industrie (Braunschweig: Vieweg, 1875), pp. 219-246.
[16] R. Glauber, Furni Novi Philosphici (Amsterdam, 1649), vol. 2, pp. 12 ff.
[17] Hermann Schelenz, Geschichte der Pharmazie (Berlin: Springer, 1904), p. 598.
[18] J. Personne, Comptes-rendus ..., Paris (1869), vol. 68, pp. 543-546.
[19] A. Wurtz, Dictionnaire de Chimie (Paris, 1876), vol. 2, part 2, p. 951.
[20] Karl W. Scheele, Nachgelassene Briefe und Aufzeichnungen, edit. A. E. Nordenskiöld (Stockholm: Norstedt, 1892), pp. 38, 144.
[21] J. J. Berzelius, Lehrbuch, transl. F. Wöhler (Dresden, 1827), vol. 3, part 1, p. 96.
[22] Thomas Graham, Philosophical Transactions of the Royal Society of London (1833), pp. 253-284.
[23] Justus Liebig’s Annalen der Pharmacie (1838), vol. 26, p. 113 ff.
[24] A. Wurtz, Annales de Chimie et de Physique, series 3, vol. 16 (1846), p. 190.
[25] Carroll D. Wright, The Phosphate Industry in the United States, sixth special report of the Commissioner of Labor (Washington, 1893).
[26] J. Stoklasa, Biochemischer Kreislauf des Phosphat-Ions im Boden, Centralblatt für Bakteriologie ... (Jena: Fischer, March 22, 1911), vol. 29, nos. 15-19.
[27] N. T. Gobley, Comptes-rendus ..., Paris (1845), vol. 21, p. 718.
[28] A. Wurtz, Comptes-rendus ..., Paris (1868), vol. 66, p. 772.
[29] L. Thudichum, Die chemische Constitution des Gehirns des Menschen und der Tiere (1901); see also H. Wittcoff, The Phosphatides (New York: Reinhold, 1951).
[30] William Crookes, British Association for the Advancement of Science, Reports (1887), sec. B, p. 573.
[31] J. E. Courtois and A. Lino, Progress in the Chemistry of Organic Natural Products, edit. L. Zechmeister (Vienna: Springer Verlag, 1961), vol. 19, p. 316-373.
[32] A. Wurt, Dictionnaire de Chimie, supp. part 2, [n.d.] p. 1087; A. Kossel, Zeitschrift für physiologische Chemie, series 3 (1879), p. 284.
[33] Alexander Todd, Les Prix Nobel en 1957 (Stockholm).
[34] Hans von Euler-Chelpin, Les Prix Nobel en 1929 (Stockholm).
[35] O. Meyerhof and E. Lundsgaard, Naturwissenschaften (Berlin, 1930), vol. 18, pp. 330, 787.
[36] K. Lohmann, Naturwissenschaften (Berlin, 1929), vol. 17, p. 624; C. H. Fiske and Y. Subbarow, Science (Washington, 1929), vol. 70, p. 381 f.
[37] J. Brachet, Scientia, Revista di Scienza (1960), vol. 95, p. 119.
[38] George de Hevesy, Les Prix Nobel en 1940 (Stockholm). See also Eduard Farber, Nobel Prize Winners in Chemistry, 2nd ed. (New York: Schuman, 1963), p. 179.
[39] See, e.g., Chemical Week, vol. 77 (September 3, 1955), p. 79 f.; J. Bolle, Chimie et Industrie (1960), vol. 83, p. 252.
[40] W. Lange, Berichte der Deutschen Chemischen Gesellschaft (Berlin, 1929), vol. 62, p. 793; vol. 65 (1932), p. 1598.
[41] Gerhard Schrader, U.S. patent 2,336,302 of 1943 (priority in Germany, 1938); S. A. Hall and M. Jacobson, Industrial and Engineering Chemistry (1943), vol. 40, p. 694.
[42] A. M. Mattsen and others, Journal of Agriculture and Food Chemistry (1955), vol. 3, p. 319.
[43] John B. Van Wazer, Phosphorus and its Compounds, 2 vols. (vol. 1, Chemistry; vol. 2 Technology, Biological Functions and Applications), New York: Interscience, 1958, 1961.
U.S. GOVERNMENT PRINTING OFFICE: 1965
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INDEX
Aristotle, 179
Baeyer, Adolf, 193
Bechil, Achild, 179
Berthelot, Marcellin, 189
Berzelius, Jöns Jakob, 182
Black and Bell, plant at Stratford, 182
Boussingault, Jean Baptiste, 185
Calvin, Melvin, 200
Casciarolo, Vicenzo, 179
Chevreul, Michel, 189
Cori, Carl F., 200
Cori, Gerti T., 200
Crookes, William, 192
Davy, Sir Humphry, 185
De la Vega, Garcilaso, 185
De Saussure, Théodore, 185
Euler-Chelpin, Hans von, 197, 200
Fernelius, Jean, 179
Feulgen, Robert, 193
Fischer, Emil, 193
Gahn, Johann Gottlieb, 182
Gay-Lussac, Joseph Louis, 182
Gobley, Nicolas Théodore, 191
Hankwitz, Gottfried, 180
Hartmann, Immanuel Peter, 181
Hellot, Jean, 180
Henry II, King of France, 179
Hittorf, Wilhelm, 181
Hoefer, Ferdinand, 179
Holmberg, Wilhelm, 178
Hoppe-Seyler, Felix, 193
Humboldt, Alexander von, 185
Huygens, Christiaan, 179
Incas, 185
Kletwich, Johann Christopher, 179
Koppe, Émile, 181
Kornberg, Arthur, 200
Kossel, Albrecht, 200
Kraft, Johann Daniel, 179
Kramer, Dr. ——, 181
Kunckel, Johann, 179
Lange, W., 199
Lavoisier, Antoine Laurent, 181, 185
Laws, John Bennet, 186
Leibnitz, Gottfried Wilhelm von, 179
Lennox, Charles, third Duke of Richmond, 185
Leonhardi, Johann Gottfried, 179
Levine, Phoebus Aaron Theodor, 193
Liebreich, Oscar, 191
Lipmann, Fritz, 200
London, E. S., 193
Macquer, Peter Joseph, 180
Marggraf, Andreas Sigismund, 180
Miescher, Johann Friedrich, 192
Muspratt, James, 186
Nietzsche, Friedrich, 186, 187, 189
Ochoa, Severo, 200
Pelouze, Théophile Juste, 189
Rouelle, Guillaume François, 181
Scheele, Karl W., 182
Schmiedeberg, Oswald, 193
Schrader, Gerhard, 199
Schrötter, Anton, 181
Stoklasa, Julius, 186
Strecker, Adolf Friedrich, 191
Thudichum, Ludwig, 192
Todd, Lord Alexander, 200
Willm, Edmond, 182
Willstätter, Richard, 191