Chemistry (Wiki) from alchemy and practice to Nobel.Pr.

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See Nobels to 2018Chemistry (by Wikipedia)  is a branch of  physical science that studies the composition, structure, properties and change of matter.[1][2]  the properties of different levels —  atoms,  chemical bonds and  compounds,  intermolecular forces and interactions between substances through chemical reactions to form different substances. Chemistry as the central science bridges other natural sciences, including physics, geology and biology.[3][4] (See differences and Comparison of chemistry and physics too[5] Etymology of this word  and  history of chemistryalchemy  millennia — the study of the composition of waters, movement, growth, embodying, disembodying, drawing the spirits from bodies and bonding the spirits within bodies (Zosimos, around 330).[7] An alchemist was called a ‘chemist‘ in popular speech, and later the suffix «-ry» was added to this to describe the art of the chemist as «chemistry».  The word alchemy in turn is derived from the Arabic word al-kīmīā (الکیمیاء) is borrowed from the Greek χημία or χημεία.[8][9] (which is in turn derived from the word Chemi or Kimi, which is the ancient name of Egypt in Egyptian.[8] Alternately, al-kīmīā may derive from χημεία, meaning «cast together».[10]

Definition

In retrospect, the definition of chemistry has changed over time, as new discoveries and theories add to the functionality of the science. The term «chymistry», in the view of noted scientist Robert Boyle in 1661, meant the subject of the material principles of mixed bodies.[11] In 1663 the chemist Christopher Glaser described «chymistry» as a scientific art, by which one learns to dissolve bodies, and draw from them the different substances on their composition, and how to unite them again, and exalt them to a higher perfection.[12]

The 1730 definition of the word «chemistry», as used by Georg Ernst Stahl, meant the art of resolving mixed, compound, or aggregate bodies into their principles; and of composing such bodies from those principles.[13] In 1837, Jean-Baptiste Dumas considered the word «chemistry» to refer to the science concerned with the laws and effects of molecular forces.[14] This definition further evolved until, in 1947, it came to mean the science of substances: their structure, their properties, and the reactions that change them into other substances — a characterization accepted by Linus Pauling.[15] More recently, in 1998, Professor Raymond Chang broadened the definition of «chemistry» to mean the study of matter and the changes it undergoes.[16]

History of chemistry

Democritus‘ atomist philosophy was later adopted by Epicurus(341–270 BCE).

Early civilizations, such as the Egyptians[17] Babylonians, Indians[18] amassed practical knowledge concerning the arts of metallurgy, pottery and dyes, but didn’t develop a systematic theory.

A basic chemical hypothesis first emerged in Classical Greece with the theory of four elements as propounded definitively byAristotle stating that that fire, air, earth and water were the fundamental elements from which everything is formed as a combination. Greek atomism dates back to 440 BC, arising in works by philosophers such as Democritus and Epicurus. In 50 BC, the Roman philosopher Lucretius expanded upon the theory in his book De rerum natura (On The Nature of Things).[19][20]Unlike modern concepts of science, Greek atomism was purely philosophical in nature, with little concern for empirical observations and no concern for chemical experiments.[21]

In the Hellenistic world the art of alchemy first proliferated, mingling magic and occultism into the study of natural substances with the ultimate goal of transmuting elements into gold and discovering the elixir of eternal life.[22] Alchemy was discovered and practised widely throughout the Arab world after the Muslim conquests,[23] and from there, diffused into medieval andRenaissance Europe through Latin translations.[24]

Chemistry as science

Under the influence of the new empirical methods propounded by Sir Francis Bacon and others, a group of chemists at Oxford,Robert Boyle, Robert Hooke and John Mayow began to reshape the old alchemical traditions into a scientific discipline. Boyle in particular is regarded as the founding father of chemistry due to his most important work, the classic chemistry text The Sceptical Chymist where the differentiation is made between the claims of alchemy and the empirical scientific discoveries of the new chemistry.[25] He formulated Boyle’s law, rejected the classical «four elements» and proposed a mechanistic alternative of atoms and chemical reactions that could be subject to rigorous experiment.[26]

Antoine-Laurent de Lavoisier is considered the «Father of Modern Chemistry».[27]

The theory of phlogiston (a substance at the root of all combustion) was propounded by the German Georg Ernst Stahl in the early 18th century and was only overturned by the end of the century by the French chemist Antoine Lavoisier, the chemical analogue of Newton in physics; who did more than any other to establish the new science on proper theoretical footing, by elucidating the principle of conservation of mass and developing a new system of chemical nomenclature used to this day.[28]

Prior to his work, though, many important discoveries had been made, specifically relating to the nature of ‘air’ which was discovered to be composed of many different gases. The Scottish chemist Joseph Black (the first experimental chemist) and the Dutchman J. B. van Helmont discovered carbon dioxide, or what Black called ‘fixed air’ in 1754; Henry Cavendish discoveredhydrogen and elucidated its properties and Joseph Priestley and, independently, Carl Wilhelm Scheele isolated pure oxygen.

In his periodic table, Dmitri Mendeleev predicted the existence of 7 new elements,[29] and placed all 60 elements known at the time in their correct places.[30]

English scientist John Dalton proposed the modern theory of atoms; that all substances are composed of indivisible ‘atoms’ of matter and that different atoms have varying atomic weights.

The development of the electrochemical theory of chemical combinations occurred in the early 19th century as the result of the work of two scientists in particular, J. J. Berzeliusand Humphry Davy, made possible by the prior invention of the voltaic pile byAlessandro Volta. Davy discovered nine new elements including the alkali metals by extracting them from their oxides with electric current.[31]

British William Prout first proposed ordering all the elements by their atomic weight as all atoms had a weight that was an exact multiple of the atomic weight of hydrogen. J. A. R. Newlands devised an early table of elements, which was then developed into the modern periodic table of elements[32] in the 1860s by Dmitri Mendeleev and independently by several other scientists including Julius Lothar Meyer.[33][34] The inert gases, later called the noble gaseswere discovered by William Ramsay in collaboration with Lord Rayleigh at the end of the century, thereby filling in the basic structure of the table.

Organic chemistry was developed by Justus von Liebig and others, following Friedrich Wöhler‘s synthesis of urea which proved that living organisms were, in theory, reducible to chemistry.[35]Other crucial 19th century advances were; an understanding of valence bonding (Edward Frankland in 1852) and the application of thermodynamics to chemistry (J. W. Gibbs and Svante Arrhenius in the 1870s).

Chemical structure

Top: Expected results:alpha particles passing through the plum pudding model of the atom undisturbed.
Bottom: Observed results: a small portion of the particles were deflected, indicating a small, concentrated charge.

At the turn of the twentieth century the theoretical underpinnings of chemistry were finally understood due to a series of remarkable discoveries that succeeded in probing and discovering the very nature of the internal structure of atoms. In 1897, J. J. Thomson ofCambridge University discovered the electron and soon after the French scientist Becquerel as well as the couple Pierre and Marie Curie investigated the phenomenon of radioactivity. In a series of pioneering scattering experiments Ernest Rutherford at theUniversity of Manchester discovered the internal structure of the atom and the existence of the proton, classified and explained the different types of radioactivity and successfully transmuted the first element by bombarding nitrogen with alpha particles.

His work on atomic structure was improved on by his students, the Danish physicist Niels Bohr and Henry Moseley. The electronic theory of chemical bonds and molecular orbitals was developed by the American scientists Linus Pauling and Gilbert N. Lewis.

The year 2011 was declared by the United Nations as the International Year of Chemistry[36] and 2019 — Periodic System of Mendellev — to 150 years — not of the International Union of Pure and Applied Chemistry, due to the United Nations Educational, Scientific, and Cultural Organization and chemical societies, academics, and institutions worldwide

Principles of modern chemistry

by Bo G. Malmström and Bertil Andersson*

1.1 Chemistry at the Borders to Physics and Biology

Chemistry is Science on the boundary of physics and biology,  living organisms as the most complex chemical systems. Each age it solves common challenges and new, modern chemistry  on the basis of electronic and quantum theory in connection with the new biochemistry. This defines the areas of modern chemistry, and Nobel as they evolve — from organic chemistry in 1870 (№1-2-5-10 -…) and physical chemistry (№1-3-9-18 -…) to  new elements, isotopes and their transformations, №4-6-8-11-21. Including Curie for the discovery of radium and polonium after the Nobel in physics for the discovery of radioactivity — their transformation as «modern alchemy» Rutherford NL №8, proved radiodecay uranium to helium+Po-Ra. Helium — «solar cell» became the first in the group of inert gases, for the discovery that pointed №4- Ramsay (together with a premium on low temperature physics co-author of this discovery Rayleigh). This group became the 0th to the PS Mendeleev, but the award at the suggestion of Bayer (1st of Jews) Muassanu for the discovery of fluorine and electric (both nominees had died during the year). Electron theory actually observed and prizes for physics, №1-6 (from X-rays to Thomson and Lorentz).

The history of chemistry and the Nobel Prizes will provide an analysis of  the Natural Sciences. Chemistry has a position in the center of the sciences, bordering onto physics, which provides its theoretical foundation, on one side, and onto biology on the other, living organisms being the most complex of all chemical systems.

In 1897 Sir Joseph John Thomson of Cambridge announced his discovery of the electron (Nobel Prize for Physics in 1906) — negatively charged ‘corpuscles’, with a mass 1000 times smaller than the hydrogen atom. Thomson’s discovery  showed that the atom is not an indivisible building block of chemical compounds.  Ernest Rutherford, who had worked in Thomson’s laboratory in the 1890s, received the Nobel Prize for Chemistry already in 1908 for his work on radioactivity (see Section 2). In 1911 he formulated an atomic model, according to which the positively charged atomic nucleus carries most of the mass of the atom but occupies a very small part of its volume, created by a cloud of electrons circling around the nucleus. Rutherford’s atomic model the stability of atoms was at variance with the laws of classical physics, since the electrons eventually fall into the nucleus. Niels Bohr from Copenhagen understood that  the spectra of atoms, the regularities of Balmer and Rydberg (1890) formulated in 1913 an alternative atomic model, in which only certain circular orbits of the electrons are allowed and light is emitted (or absorbed), when an electron makes a transition from one orbit to another. Bohr received the Nobel Prize for Physics in 1922 for his work on the structure of atoms.

Application of the electronic structure of atoms to chemistry was taken in 1907-16, when N.Morozov and Gilbert Newton Lewis suggested that strong (covalent) bonds between atoms involve a sharing of two electrons between these atoms (electron-pair bond). Lewis also contributed fundamental  textbook, Thermodynamics (1923), written together with Merle Randall, but never received a Nobel Prize.

The borderland between physics and chemistry in the 1890s (see Section 2) and the first Nobel laureat  Jacobus Henricus van’t Hoff, Svante Arrhenius and Wilhelm Ostwald, are generally regarded as the founders of a new branch of chemistry, physical chemistry. In more traditional chemical fields,  in organic chemistry and in the chemistry of natural products, that towards biology, already in 1907 with the prize to Eduard Buchner «for his biochemical researches and his discovery of cell-free fermentation» (1.2 The Mechanics of the Work in the Nobel Committee for Chemistry- According to the statutes … The number of nominations received has also increased dramatically from 20-40 during the first decade to 400-500 in the 1990s, 2,650 in 1998)/

In 1903 Arrhenius had been nominated both for the Prize for Chemistry and that for Physics, Peter Mitchell, who received the 1978 Nobel Prize for Chemistry, could with equal justice have been awarded the Prize for Physiology or Medicine.

Nobel’s will laid down that the prize should be awarded for work done during the preceding year,  excluded Stanislao Cannizzaro, since his work on drawing up a reliable table of atomic weights, helping to establish the periodic system, was done in the middle of the 19th century. Henry Eyring, whose brilliant theory for the rates of chemical reactions, published in 1935, was apparently not understood by members of the Nobel Committee until much later. As a compensation in 1977 the Berzelius Medal in gold.

 

2. The First Decade of Nobel Prizes for Chemistry

For the first prize in 1901 the Academy had to consider 20 nominations, but 11 of these named van’t Hoff. His thesis work in Utrecht in 1874 published his suggestion that the carbon atom has its four valences directed towards the corners of a regular tetrahedron, a concept which is the very foundation of modern organic chemistry. The Nobel Prize was, however, awarded for his later work on chemical kinetics and equilibria and on the osmotic pressure in solution, published in 1884 and 1886.

In his 1886 work van’t Hoff showed that most dissolved chemical compounds give an osmotic pressure equal to the gas pressure they would have exerted in the absence of the solvent. An apparent exception was aqueous solutions of electrolytes (acids, bases and their salts), but in the following year Arrhenius showed that this anomaly could be explained, if it is assumed that electrolytes in water dissociate into ions (in his doctoral thesis in Uppsala in 1884  supported by Ostwald in Riga, and then in Leipzig, and also with van’t Hoff in Berlin).  Arrhenius was awarded the Nobel Prize for Chemistry in 1903, he was since 1895 professor of physics in Stockholm. The award of the Nobel Prize for Chemistry in 1909 to Ostwald was chiefly in recognition of his work on catalysis and the rates of chemical reactions,  in his thesis in 1878, shown that the rate of acid-catalyzed reactions is proportional to the square of the strength of the acid, as measured by titration with base. His work offered support not only to Arrhenius’ theory of dissociation but also to van’t Hoff’s theory for osmotic pressure. Ostwald was founder and editor of  Zeitschrift für Physikalische Chemie, the publication of which is generally regarded as the birth of this new branch of chemistry.

Three of the Nobel Prizes for Chemistry during the first decade were awarded for pioneering work in organic chemistry. In 1902 Emil Fischer, then in Berlin,  for «his work on sugar and purine syntheses». devoted himself to the study of proteins, for the development of biochemistry.

«Syntheses in the Purine and Sugar Group» — Nobel Lecture— 12, 1902

18th century when men like Sigismund Marggraf in Berlin, Lavoisier
in Paris and this country’s great son, Carl Wilhelm Scheele studied it.  19th
century to separate it altogether from mineral chemistry …It replaced the animal and vegetable substances by many artificial products such as the hydrocarbons and
cyano compounds, wood tar and coal tar, wood alcohol, etc. and by pressing
into its service the synthetic methods of inorganic chemistry it appropriated
the fundamental problems of our science at the same time.
Wöhler’s famous synthesis of urea in 1828 was the starting-point for the
glorious evolution .. of chemical theories.
19th century under the guidance of Berzelius, Gay-Lussac and Davy.
A necessary consequence of this reorientation must be the reversion of
organic chemistry to the great problems of biology.
I shall attempt to explain to you with the aid of two examples, the purines
and the carbohydrates, what organic chemistry is capable of as the loyal ally
of physiology with refined methods of analysis and synthesis.
Currently the name «purines» is a generic term for a large class of nitrogenous organic compounds, some being certain animal excretions and others
the active constituents of important stimulating beverages.
The oldest member of the group is known by the rather unattractive name
of uric acid and was discovered in this country 126 years ago simultaneously
by Scheele and his famous friend Torbern Bergman as a constituent of urinary calculus and urine. To the physician it is familiar as the cause of painful
afflictions, e.g. gout. It appeals to zoologists as the main excrement of snakes
and as the reservematerial of insects. And finally the enlightened farmer knows
it to be a valuable constituent of guano.
Its chemical history is particularly rich because it was involved in the
famous studies by Liebig and Wöhler, by A. Strecker and by A. von Baeyer
without its chemical nature being ultimately determined.
Rather closely related to uric acid in composition and external characteristics are four other substances occurring in the bodies of animals, xanthine,
hypoxanthine, adenine and guanine, the first three of which were discovered
in the muscular substance and the last in guano. Thanks to the progress of
physiological chemistry we now know that these four substances are important constituents of the cell nucleus and therefore have great biological significance.
These animal products are joined by three substances from the vegetable
kingdom, caffeine, theobromine and theophylline. As the name immediately
suggests, the first is contained in coffee but occurs also and even in larger
amounts in tea and constitutes the pleasant stimulating principle of these two
staple stimulating beverages. Theobromine has the same effect in cocoa.
Both substances are also valuable medicines because they promote heart action and diuresis. They are hence factory-produced in appreciable quantities
by the extraction of tea and cocoa

In quantitative respect they
come far behind the second class of organic compounds which I intend discussing today, i.e. the carbohydrates. Not only are these the first organic
products formed in plants from the carbon dioxide in the air but in abundance, too, they surpass all substances that are current in the living world…from the elucidation of their elementary composition by Lavoisier before science prepared
them by artificial means. ..A distinction is made between two classes of carbohydrates in particular, the monosaccharides and the polysaccharides. Grape
sugar, found in grapes and in other sweet-tasting fruit, may serve as an instance of the former. Starch, the main constituent of all vegetable nutriment,
and cellulose, the main constituent of wood or of the other solid frameworks of plants, can be quoted as polysaccharides.
By a process termed hydrolysis all polysaccharides can be converted into
the simpler monosaccharides. Both starch and cellulose hydrolyse to form
grape sugar. With starch, for example, hydrolysis comes about under the
action of the gastric and intestinal juices when vegetable food is consumed.
A more potent chemical treatment is required to effect the same conversion
with cellulose. This substance is best hydrolysed by strong sulphuric acid and
yields the reputed wood sugar which, it is not infrequently claimed inpopular lectures, would one day solve the subsistence problem.
Conversely monosaccharides can be transformed into the more complex
poly-compounds by a process termed dehydratation.
Some 50 monosaccharides are at present known, ten of them occurring in
Nature. The others, as you will soon see, were prepared artificially and the
methods applied would be sufficient to produce hundreds more such substances. Since all these products are able to combine in bewildering variety
and varying quantitative ratios to form polysaccharides, it will readily be
appreciated what a plethora of forms there are.
Before the synthesis of this class of substances had been mastered, six
monosaccharides, commonly termed sugars, had been found in the animal
and vegetable kingdoms and their structure, too, had been elucidated with a
sufficient degree of accuracy by decomposition of the molecule. The first in
practical importance and in chronological sequence was grape sugar which
has already been referred to and which is known by the scientific name of
glucose. The insider will at once appreciate from the structural formula that
28 1902 E. FISCHER
in addition to a chain of six carbon atoms it contains five alcohol groups and
one aldehyde group, and that hence it is the aldehyde of a hexavalent alcohol. Surprisingly the same structural formula is also valid for various other
sugars, e.g. galactose. This phenomenon will be explained later. While
these two important sugars contain six carbon atoms, two others are found in
Nature which contain only five carbon atoms, i.e. arabinose and xylose.
Their structure is quite similar to that of grape sugar except that the carbon atom at the bottom with its attached hydrogen and oxygen atoms is
missing.
As is reasonable to expect in view of the importance of the problem there
has in the past been no lack of attempts to synthesize these compounds. But
success remained extremely scant, for only a single one of the many artificial
products reported in the older chemical literature and regarded as sugar-like
substances has stood the critical test of modern methods of examination.
And that is the sweet syrup which the Russian chemist Butlerov obtained 40
years ago from formaldehyde — nowadays more widely known as a disinfectant -by the action of lime water. Yet, as shown by more detailed study, this
product, too, is a complex mixture and contains only a tiny amount of a
substance, closely related to grape sugar, which will shortly be discussed. The
route chosen by Butlerov thus did not lead directly to its ultimate goal : success had to be sought under simpler conditions, and those I found in the relationships of grape sugar to glycerol. Outwardly the similarity is already apparent from the sweet taste which they have in common. Chemically the
relationship is not quite so great, as glycerol has only three carbon atoms,
i.e. half as many as sugar. Neither does it contain an aldehyde group, but it
is a polyvalent alcohol. Consequently, by reason of analogy, there were
grounds to expect that it would be converted, by gentle oxidation, into an
SYNTHESES IN THE PURINE AND SUGAR GROU P
29
aldehyde, which should correspond in some way to natural sugar. Experiment bore out this expectation. Under the action of dilute nitric acid, glycerol does indeed change into a product exhibiting the typical properties of
the sugars. To indicate this similarity as well as the origin of the substance, it
was called glycerose.
Here you will realize, ladies and gentlemen, the central position occupied
by glycerol in organic chemistry. Discovered by your countryman, Scheele,
140 years ago as a constituent of fat, glycerol, as you will soon see has become the gate through which synthesis gained access to the natural sugars.
And how wonderful are the changes of this sweet liquid! Under the action
of strong nitric acid it yields the terrible explosive nitroglycerin which,
through Dr. Nobel’s brilliant technical utilization of it, has become the powerful aid to human work. Conversely, under the action of dilute nitric acid it
changes into the new sugar-like substance just mentioned.
However, glycerose still differs strongly in its composition from the natural sugars, for it contains only half as much carbon and many conservative
chemists therefore had their misgivings at first about assigning it to the sugar
group. But this expulsion was short-lived, for glycerose soon provided a
new, and this time unassailable, proof for its close relationship with the old
sugars, i.e. under the action of dilute alkali it undergoes a change which we
term polymerization in conformity with Berzelius’ proposition. Two molecules combine to form a single system and the new product, which has been
given the name acrose, is a sugar with six carbon atoms and maximum similarity to the natural substances. It lacks only one property of the latter, i.e.
the capacity to rotate polarized light, but a small modification was sufficient
to add even this quality and convert the synthetic product freely into grape
sugar or the related natural substances.
The total synthesis of the latter has thus been achieved although at first
only in a roundabout way via glycerol. Nevertheless it was not long before
the process was shortened, for acrose was also found in the above-mentioned
sweet syrup formed from formaldehyde in accordance with Butlerov’s observation, and now, starting from the simplest materials of organic chemistry
or even from inorganic carbon dioxide, it is possible to form the most important natural sugars via readily comprehensible operations.
On the basis thus acquired, synthesis proceeds further still to synthetic
sugars with a higher carbon content in the following manner:
As demonstrated by Kiliani, natural sugars are capable, via their aldehyde
group, of fixing hydrocyanic acid which was discovered by Scheele, and —
301902 R
oh, wonder of wonders ! -from the sweet substance and the violent poison a
new, harmless substance is formed which has the property of the fruit acids,
e.g. tartaric acid. On further treatment with suitable reducing agents it loses
oxygen and changes into a new sugar containing one carbon atom more
than the starting material. The same procedure can then be repeated and
again leads to a new, still higher member of the group. In this way I have
already successfully synthesized sugars with up to nine carbon atoms, and
with time, trouble and money to spare it will be possible for someone to
climb a further few rungs up this ladder.
The upward expansion of the group inevitably awakened the desire to
find the simplest members too. According to the new hypothesis there
should exist below glycerose a further sugar with two carbon atoms, the
aldehyde of glycol. This product, too, could be prepared by simple, synthetic processes, and its properties leave no doubt that it is the simplest of the
monosaccharides. In particular it is polymerized by dilute alkali in the same
way as glycerose, when it yields the last missing sugar with four carbon
atoms.
The series is now complete from the simplest to the ninth member, and
chemical parlance must adapt itself to the expanded factual knowledge.
In conformity with a proven principle of our nomenclature the sugars are
now described according to their carbon content by the Greek numerals to
which is added the conventional sufffix «ose». Pentose, heptose, and nonose,
which are now part of the accepted word stock, were formed in this way and
the old sugars appear in modern nomenclature as hexoses.
Earlier only fleeting attention was paid to the observation that grape sugar
and galactose, which differ considerably from one another in their external
characteristics, have the same structure. The older theory had no explanation
for this type of isomerism. The chemists of the day contented themselves
with calling such substances physically isomeric, and this discrepancy was
not accounted for until the molecule was studied in spatial terms. As a result,
the further study of the sugars is linked very closely to the development of
so-called stereochemistry, a branch of chemistry originating particularly
from the study of those substances which, like the sugars, rotate the plane of
polarized light. Its first beginnings are to be found in L. Pasteur’s celebrated
studies of tartaric acids. Natural tartaric acid is contained in wine and rotates
polarized light to the right. Pasteur found its optical opposite, i.e. laevo-tartaric acid, and his speculative mind successfully attributed the cause of this
rotation to the asymmetrical structure of the molecule. He compared the two
SYNTHESES IN THE PURINE AND SUGAR GROU P
31
acids with the right and the left hands or, tantamount to the same analogy,
with an object and its mirror image.
It was only after organic chemistry had made the important advance constituted by the structural theory that this geometrical concept yielded results
for our science when in 1874, simultaneously and independently of each
other, Le Bel and Van’t Hoff attributed the asymmetry of the molecule to the
individual carbon atom.
Nowadays numerous observations from the most varied fields of organic
chemistry, but most especially the experimental knowledge of the sugar
group, testify to the correctness of their hypothesis.
In the sugar molecule several such asymmetrical carbon atoms, i.e. linked
with four different substances, are present in quite large numbers. The hexoses, to which grape sugar belongs, contain not less than four, and here the
conclusions of the theory relating to the number of isomers are particularly
interesting. Since each individual asymmetric carbon atom gives rise to a
dextro and a laevo form, calculation shows that not less than sixteen geometrically different substances with the structure of grape sugar must exist. This
hence afforded an excellent opportunity to compare broadly the results of
speculation with reality. The outcome has been a complete triumph for the
theory. Of the sixteen predicted forms no less than twelve are nowadays
known, constituting six optical pairs, and the four still missing members will
indubitably be obtained by means of the same experimental methods.
In the light of the theory it has also been possible to derive from the actual
observations the geometrical structure or, as it is commonly termed, the
configuration, of the molecule for the individual members of this group, and
a small modification of the customary structural formulae has been found a
convenient form of representing these results of stereochemical research.
Below are shown the modern formulae for the configurations of the
twelve known hexoses and of the four isomers still to be found. The four
asymmetrical carbon atoms have been left out and are only intimated in the
points of intersection between the vertical line and the four horizontal lines.
The position of the letters H and OH which signify hydrogen and hydroxyl,
then gives an idea of the geometrical arrangement at each asymmetrical
carbon atom. To the insider these formulae reveal with the conciseness and,
one may say, with the precision of a mathematical expression, the actually
examined relationships between the substances, and furthermore they allow
him to foresee a long series of modifications which in all probability are
confirmed by later observations.
Aldohexoses (Mannose COHCH2OHl-IdoseCOHCH2OHl-GalactoseCOHCH2OH(a) Mannitolseries

 

Of the
simple derivatives of grape sugar the physiologist is best acquainted with
glucuronic acid since the animal organism uses it to neutralize poisonous substances, such as phenol, chloral and turpentine. Its configuration, its relationship to grape sugar and its conjectural formation in the animal stomach
can readily be elucidated synthetically. Glucosamine, a peculiar nitrogenous
SYNTHESES IN THE PURINE AND SUGAR GROU P
33
substance first derived from lobster shells but which is now known to be
widespread throughout the animal kingdom, proved more difficult. Its
synthesis, which I successfully accomplished only in recent weeks, showed it
to be an intermediate between grape sugar and the cc-amino acids, so providing one of the longest sought-for bridges between the carbohydrates and
the proteins.
Of more general interest are also the results relating to the glucosides, substances which occur widely in the vegetable kingdom and which may be
regarded as compounds of the sugars with various other substances. Suitable
examples are amygdalin, a constituent of bitter almonds, or salicin, formerly
used medicinally as an antipyretic. Until 1879 its preparation was also one
of Nature’s privileges. In that year the American chemist, Michael, successfully synthesized a few of them but his process was restricted to a small
number and moreover was so laborious that it has since only rarely been
used.
These difficulties have now fortunately been overcome by a new process
of synthesis in which sugar is combined with alcohol or similar substances
by the simple action of dilute hydrochloric acid. Since then glucosides of
alcohol, of wood alcohol, of glycerol, and of lactic acid have become known
in abundance and their study led to the surprising realization that there is no
fundamental difference between the glucosides and the polysaccharides, the
latter being nothing other than the glucosides of the sugars themselves. This
fact is indicated not only by their behaviour on hydrolysis by acids or ferments, but even more strongly by the result of synthesis: by applying the
same methods which yield glucosides it has also been possible to prepare
dextrin-type substances, and recently in particular a series of synthetic disaccharides, one of which appears to be identical with natural melibiose. However scanty these achievements may appear compared with the profusion of
polysaccharides, they are nevertheless adequate to prove in principle the
possibility of synthesis. For all that there is still a long way to go before the
most important polysaccharides, starch and cellulose, can be synthetically
prepared; easier, more perfect methods will have to be sought to accomplish
those syntheses. But even now we can be perfectly confident that the
problem is not an impossibility.
The extreme limits of synthesis have been reached and it only remains for
me to illustrate with the aid of a few examples how the knowledge that has
been accumulated can be applied to solving biological problems.
Of the chemical aids in the living organism the ferments — mostly referred
34 1902 E.FISCHER
to nowadays as enzymes — are so pre-eminent that they may justifiably be
claimed to be involved in most of the chemical transformations in the living
cell. The examination of the synthetic glucosides has shown that the action
of the enzymes depends to a large extent on the geometrical structure of the
molecule to be attacked, that the two must match like lock and key. Consequently, with their aid, the organism is capable of performing highly specific
chemical transformations which can never be accomplished with the customary agents. To equal Nature here, the same means have to be applied,
and I therefore foresee the day when physiological chemistry will not only
make extensive use of the natural enzymes as agents, but when it will also
prepare synthetic ferments for its purposes.
The application of the new knowledge to the superb natural process
without which the living world could not exist, i.e. the assimilation of
carbon dioxide from the atmosphere by plants, seems even more interesting.
This leads as we know to the formation of sugar, Nature’s first organochemical product, from which all other constituents of the plant and animal
body are formed. As mentioned earlier this transformation can also be accomplished with purely chemical resources, although only in a very roundabout way. But there still remains one distinction between the natural and
the artificial synthesis. Above all, the latter invariably yields a mixture of
dextro- and laevo-rotatory sugars which must first be separated by special
operations. Nature, in contrast, produces exclusively the dextro sugar. Formerly this contrast seemed so wonderful that the direct preparation of optically active substances was regarded quite simply as the privilege of the
living organism. The experimental knowledge gained with the sugar group
has provided a simple explanation for that biological phenomenon, however, and in the light of the new conception it does not appear at all impossible to reproduce that asymmetrical synthesis artificially in the same way as
it occurs in the natural formation of sugars.
And so, progressively, the veil behind which Nature has so carefully concealed her secrets is being lifted where the carbohydrates are concerned.
Nevertheless, the chemical enigma of Life will not be solved until organic
chemistry has mastered another, even more difficult subject, the proteins, in
the same way as it has mastered the carbohydrates. It is hence understandable
that the organic and physiological chemists are increasingly turning their attention to it and I, too, have been concerned with it for a number of years.
It is true that on this hard ground the fruit ripens far more slowly and the
total amount of work that has to be done here is so enormous that in contrast

the elucidation of the carbohydrates seems child’s play. As against that, however, better methods and a far richer stock of resources are now available,
added to which the prize beckoning at the end attracts quite a number of
competitors. That is not without its implications for the success of research,
since mass production methods which dominate modern economic life have
also penetrated experimental science. The days have long since gone when
one man such as Berzelius could have a command of, and promote, all
branches of chemistry. The circle within which the individual research
worker, especially as an experimenter, can distinguish himself is continually
shrinking in size. Consequently the progress of science today is not so much
determined by brilliant achievements of individual workers, but rather by
the planned collaboration of many observers.

Fischer’s teacher, Adolf von Baeyer in Munich was awarded the prize in 1905 «in recognition of his services in the advancement of organic chemistry and the chemical industry…» (structure determination of organic dyes (indigo, eosin) and the study of aromatic compounds (terpenes). The third Laureate working in organic chemistry was  Otto Wallach in Göttingen, who, like von Baeyer, contributed to alicyclic chemistry, studying not only terpenes but also camphor and other components of ethereal oils. At the award ceremony in 1910 the importance of his discoveries for chemical industry was emphasized.

Nobel Prizes in Chemistry after 1905

Two of the early prizes were given for the discovery of new chemical elements.Sir William Ramsay from London received the 1904 Nobel Prize for Chemistry for his discovery of a number of noble gases, a new group of chemically unreactive elements. The first one isolated was argon («the inactive one»), which Ramsay discovered in 1894, in collaboration with Lord Rayleigh [John William Strutt Rayleigh] of the Royal Institution, who was awarded the Prize for Physics in the same year, his investigations of the density of air and other gases forming the basis for this discovery. The following year Ramsay found helium, observed earlier only in the solar spectrum (hence its name), in emanations from radium, thus anticipating later prizes for nuclear chemistry (see below). Later, in 1898 he also discovered, by fractional distillation of liquid air, neon («the new one»), krypton («the hidden one») and xenon («the strange one»).

The Rare Gases of the Atmosphere

… I trace the sequence of events which led to their investigation. My grandfather on my father’s side, William Ramsay, was a chemical manufacturer in Glasgow; he came of a long line of dyers, …to distil wood for the production of pyroligneous acid; and he purified it by «torrefying» the acetate of lime formed by its neutralization, and distilling with oil of vitriol. He also was the first to manufacture bichrome; and «Turnbull’s blue».My mother’s father was a medical man,  the author of a series of textbooks for medical students, Colloquia Chymica. Hence, I inherited the taste for chemistry from my ancestors on both sides of the family. While I was an assistant in Glasgow University, in 1879, it occurred to me that an easy method of determining the volumes of liquids at their boiling points and consequently their molecular volumes would be to use their own vapours, coming from the liquids boiling under atmospheric pressure, as a means of securing the desired temperature. ..a study of the critical phenomena of liquids; for by employing vapours as heating agents, …I was Professor of Chemistry from 1880 till 1887, …Kundt and Warburg, gave adiabatic curves for ethyl ether, both in the liquid and the gaseous state…But I must have read the well-known account of Cavendish’s classical experiment on the combination of the nitrogen and the oxygen of the air at that date; … passing electric sparks through a mixture of nitrogen with excess of oxygen, he had obtained a small residue, amounting to not more than 1/125th of the whole, I find that I had written the words «look into this «. …led me, in 1894, to suggest to Lord Rayleigh a reason for the high density which he had found for «atmospheric nitrogen».

With the discovery and properties of argon I do not propose to deal. Hence, I pass on to the discovery of terrestrial helium and of its congeners…argon is its forming no compounds; a circumstance which led to the choice of its name. …double line of sodium. ..first observed in the solar spectrum by P.J.C Janssen, during an eclipse of the sun, to observe which an expedition had been sent to India in 1868. It was suspected by Frankland and Lockyer that the line was due to hydrogen;…element unknown on the earth; and they gave it the name «helium», to suggest its solar origin. … density was found both by Langlet and myself to be nearly 2; it is therefore the lightest gas known, with the exception of hydrogen. These properties in common made it evident that helium and argon belong to the same natural family; and it was also obvious that there must exist at least three other elements of the same class; this is evident on inspection of the periodic table where the following elements are in apposition: In the belief that these elements would be discovered, I predicted, in the Presidential Address which I gave to the Chemical Section of the British Association when it met in Canada in 1897, the discovery of » a new element». I thought it well to be on the safe side; and the necessity of an element with the atomic weight 20 was evident, although it might have been maintained with almost equal probability that two other awaited discovery….various meteorites were heated, and their gases examined spectroscopically, after removing those gases which could be induced to enter into combination. … Dr. Hampson was working at his excellent machine for liquefying air, and he kept me informed of his progress… 1896 and 1897; the 15 litres of argon was prepared after Christmas, 1897. … the water from the Bath springs contains neon. …the use of liquid hydrogen has made it possible to cool a large quantity of helium to a very low temperature, and the condensed portion has been found to exhibit the spectrum of krypton. ..a bright yellow and a bright green line, of wavelengths 5571 and 5570.5, respectively. Although the density of the new gas, which we named «krypton» or «hidden» was found to be only 22.5, … the atomic weight 80,…we called «neon » or «new»; it showed a spectrum characterized by a brilliant flame-coloured light, consisting of many red, orange, and yellow lines. A preliminary determination of its density yielded the number 14.7, and after one fractionation, the density decreased to 13.7. …to argon the same relation as that of nickel to cobalt; and we christened it «metargon»…. 0.01183 (Schloesing) and 0.01186 (Kellas) part by volume in 1 part of «atmospheric» nitrogen.

The separation of the lighter and heavier gases fro

 

 

m argon gave occasion for a re-determination of the density of argon, using a pure sample. While the crude argon prepared by withdrawing the nitrogen from «atmospheric» nitrogen by the electric flame was found to have the density 19.94, and by the use of red-hot magnesium 19.941, the density of the purified sample gave the number 19.95. The refractivity, however, shows a greater difference; for the admixture of helium and neon in the crude sample lowers the refractivity from 0.9665 for the pure gas to 0.961 or 0.960.

In September, 1898, the discovery of another gas was announced; it was separated from krypton by fractionation, and possessed a still higher boiling point. We named it «xenon» or the «stranger». And during the next two years, Travers and I prepared a larger quantity of these gases, and purified them by fractionation; while Baly erected an apparatus for the accurate determination of the wavelengths of their spectral lines.

We procured from the «Brin» Oxygen Company one of Hampson’s airliquefiers, and from the Whitehead Torpedo Company, one of their compressors; the latter was driven electrically, by means of a S-horse-power motor. The motor has since been replaced by a more powerful one; but the compressor and liquefier have given no trouble, and still work as satisfactorily as when first purchased. In ten minutes after starting, without any preliminary cooling, liquid air begins to run; and the yield is over a litre an hour. By help of this machine, air was so fractionated as to furnish portions rich in the gases which we wished to investigate. The process was as follows. The air-liquefier furnished a supply of liquid air; the gas escaping from the liquefier consisted largely of nitrogen; this mixture was liquefied under pressure in a bulb cooled by the liquid air boiling under reduced pressure. When the bulb had been filled with liquid nitrogen, a current of air was blown through the liquid until some of the gas had evaporated. That gas was collected separately, and deprived of oxygen by passage over red-hot copper; it contained the major part of the neon and helium present in the air. The remainder of the nitrogen was added to the liquid air used for cooling the bulb in which the nitrogen was condensed. Having obtained a considerable quantity of this light nitrogen, it was purified from that gas in the usual manner, and the argon containing neon and helium was fractionated. By fractional distillation, it was possible to remove the greater portion of the helium and neon from this mixture of gases, leaving the argon behind.

The air used in these fractionations was allowed to evaporate in vacuum vessels, during the operations; but care was always taken to save the dregs, and collect them in a gas-holder. In this way, a large quantity of the heavier portions of the air was accumulated; we estimated the quantity of air thus concentrated as not less than 30 litres of liquid. After removal of oxygen and nitrogen, the argon was separated for the most part by fractional distillation, and the residue of crude krypton and xenon purified by repeated fractionation. While krypton has a considerable vapour pressure at the temperature of boiling air, the vapour pressure of xenon is hardly appreciable; hence their separation, although tedious, presented no particular difficulty.

It was otherwise with neon. It soon transpired that the neon was contaminated with helium, and many attempts were made to effect a separation, before they were crowned with success. Among these, was fractional solution in oxygen, followed by a systematic diffusion of the two gases; but it was not found possible to raise the density of the neon above the number 9-16, and its spectrum still showed helium lines. Neither neon nor helium can be liquefied by cooling with liquid air, and it soon became evident that without the aid of liquid hydrogen, no further progress could be made.

Dr. Travers therefore undertook, with the assistance of Mr. Holding, the laboratory mechanic, to construct an apparatus for liquefying hydrogen; and in doing this, he had to start from first principles, for no account had been published of the process. After two months’ work, a machine was produced, in which the hydrogen, after preliminary cooling with liquid air, entered a chamber in which air boiled at low pressure, at a temperature of -205°. This degree of cold was sufficient to carry it below the critical temperature for the development of the positive Joule-Thomson effect; so that, when it was allowed to expand, after traversing a regenerative coil it ran out in the liquid form.

With this powerful agent to help us, the separation was effected in less than an hour. The mixture of helium and neon, compressed into a bulb cooled with liquid hydrogen, deposited the neon in the liquid, or more probably in the solid state; the vapour pressure of liquid neon at that low temperature is not more than 17 millimetres of mercury; while helium is permanently gaseous. It was easy, therefore, to purify the neon from helium; though it would have been a difficult task to purify the helium from neon.

That these are all monatomic gases was proved by determining the ratio of their specific heats by Kundt’s method; and accurate determinations were made of their refractivities, their densities, their compressibilities at two temperatures, 11.2° and 237.3°; and the vapour pressures of argon, krypton, and xenon were determined, as well as their volumes at their boiling points, in the liquid state. The critical temperatures and pressures of the last three were also determined. It may be stated in general terms that these gases show a regular gradation of properties, from helium to xenon; and that they fill the gaps in the periodic table below and above argon, with the atomic weights: neon, 20; krypton, 82; and xenon, 128.

The amounts of neon and helium in air have since been measured; the former is contained in air in the proportion of I volume in 81,000; the latter, I volume in 245,000; the amounts of krypton and xenon are very much smaller — not more than 1 part of krypton by volume can be separated from 20,000,000, of air; and the amount of xenon in air by volume is not more than 1 part in 170,000,000.

In June, 1903, Mr. Baly published an account of his determination of the wavelengths of the lines in the spectra of neon, krypton, and xenon, photographed by help of a concave Rowland’s grating of ten feet radial curvature. In all, the positions of 2,400 lines were accurately measured.

The discovery that uranium emits «rays» capable of discharging an electroscope and impressing a photographic plate, made in 1896, was followed by the separation from pitchblende, the chief ore of uranium, of that remarkable element, radium, by Madame Curie, in 1898. In 1899, Giesel and Meyer and Schweidler in Germany and Austria, and Becquerel and P. Curie in France, found almost simultaneously that certain rays from radium, later called the b-rays, could be deviated by a magnetic field; and these rays have since been shown to be identical with the cathode rays, proceeding from the cathode of a highly exhausted tube. These rays possess great penetrating power, for they pass through considerable thicknesses of metal without absorption. It was not till 1900 that Madame Curie threw out the suggestion that the a-rays, which were stopped by small thicknesses of metal or glass, proceeding from polonium, might be of the nature of small particles, projected with great velocity, but which lost their energy in passing through matter. Strutt, in 1901, made the same suggestion for the a-rays from radium, which are not deviable except in a very powerful magnetic field. Rutherford, in 1902, determined the deviation of these rays in a known magnetic field, and also in an electrostatic field, and arrived at an estimate of the value of the ratio of mass to electric charge for each particle; and on the supposition that the charge is the same as that carried by an ion of say hydrogen, he arrived at an estimate of the mass of each particle. Calculation showed it to approximate to twice that of an atom of hydrogen.

After Schmidt and Madame Curie’s discovery in 1898 that compounds of thorium and the minerals containing it possessed properties similar to those of uranium, Owens found that the power of discharging an electroscope could be greatly modified by blowing a current of air over the specimen. And in I900, Rutherford proved that this was due to the fact that the thorium evolves a radioactive gas. This gas was investigated by Rutherford and Soddy, …it resisted the action of all oxidizing agents, and also of magnesium at a red heat. From these observations they concluded that the emanation «is an inert gas, analogous in nature to the members of the argon family». …

Mr. Soddy came to work in my laboratory in the spring of 1903; and we at once began to investigate the properties of the radium emanation; for its life is so much longer than that of the thorium emanation (in the proportion 463,000 to 87) that it is possible to deal with it by ordinary physical methods. … 80, which would imply a molecular weight of 160;…argon family; there is a vacant place for an element with atomic weight about 162. The rate of diffusion of the thorium emanation is even less satisfactorily determined; but it also appears to be high. It is still more unstable, and might perhaps have the atomic weight 215, for which there is a gap. And it is not inconceivable that the still more unstable emanation from the matter named actinium by Debierne and emanium by Giesel may be found to possess an even higher atomic weight than uranium; judging by the phenomenon of brilliant illumination when a preparation of emanium is held above a screen of zinc sulphide, the impression is formed that a very dense matter is falling down on the screen….entering the regions of speculation, where many roads lie open, but where a few lead to a definite goal. ..

From Nobel Lectures, Chemistry 1901-1921, 1966

 

 

The isolation of another element, fluorine, by Henri Moissan in Paris was honored with the 1906 Nobel Prize. In attempts to prepare artificial diamonds Moissan had also developed an electric furnace, and this was specifically mentioned in the prize citation, perhaps a reflection of the stipulation in Nobel’s will that the Prize for Chemistry can be given «for the most important discovery or improvement».

Ernest Rutherford [Lord Rutherford since 1931], professor of physics in Manchester, was awarded the Nobel Prize for Chemistry in 1908 for his investigations of the chemistry of radioactive substances. The discovery of radioactivity had already been recognized with the Nobel Prize for Physics in 1903, but what Rutherford established was the transformation of one element into another, earlier the alchemist’s dream. In his studies of uranium disintegration he found two types of radiation, named a— and b-rays, and by their deviation in electric and magnetic fields he could show that a-rays consist of positively charged particles. His demonstration that these particles are helium nuclei came in the same year as he received the Nobel Prize. Even if the importance of Rutherford’s work for chemistry is obvious, he naturally had also received many nominations for the Nobel Prize for Physics (see Section 1).

In 1897 Eduard Buchner, at the time professor in Tübingen, published results demonstrating that the fermentation of sugar to alcohol and carbon dioxide can take place in the absence of yeast cells. Earlier it had generally been considered that living cells possess a «vital force», which makes the life processes possible, even if a few prominent chemists, foremost Jöns Jacob Berzelius and Justus von Liebig, had advocated a chemical basis for life. The vitalistic outlook had been fiercely defended by Louis Pasteur, who maintained that alcoholic fermentation can only occur in the presence of living yeast cells. Buchner’s experiments showed unequivocally that fermentation is a catalytic process caused by the action of enzymes, as had been suggested by Berzelius for all life processes, and Buchner called his extract zymase («enzymes in yeast»). Because of Buchner’s experiment, 1897 is generally regarded as the birth date for biochemistry proper. Buchner was awarded the Nobel Prize for Chemistry in 1907, when he was professor at the agricultural college in Berlin. This confirmed the prediction of his former teacher, Adolf von Baeyer: «This will make him famous, in spite of the fact that he lacks talent as a chemist.»

3. The Nobel Prizes for Chemistry 1911-2000

A survey of the Nobel Prizes for Chemistry awarded during the 20th century, reveals that the development of this field includes breakthroughs in all of its branches, with a certain dominance for progress in physical chemistry and its subcategories (chemical thermodynamics and chemical change), in chemical structure, in several areas of organic chemistry as well as in biochemistry. Of course, the borders between different areas are diffuse, therefore many Laureates will be mentioned in more than one place.

3.1 General and Physical Chemistry

The Nobel Prize for Chemistry in 1914 was awarded to Theodore William Richards of Harvard University for «his accurate determinations of the atomic weight of a large number of chemical elements». Most atomic weights in Cannizzaros table (see Section 1.2) had already been determined in the 19th century, particularly by the Belgian chemist Jean Servais Stas, but Richards showed that many of them were in error, mainly because Stas had worked with very concentrated solutions, leading to co-precipitation. In 1913 Richards had discovered that the atomic weight of natural lead and of that formed in radioactive decay of uranium minerals differ. This pointed to the existence of isotopes, i.e. atoms of the same element with different atomic weights, which was accurately demonstrated by Francis William Aston at Cambridge University, with the aid of an instrument developed by him, the mass spectrograph. Aston also showed that the atomic weights of pure isotopes are, whithin the resolution of his experiment, integral numbers, with the exception of hydrogen, for which he obtained the atomic weight 1.008. For his achievements Aston received the Nobel Prize for Chemistry in 1922.

One branch of physical chemistry deals with chemical events at the interface of two phases, for example, solid and liquid, and phenomena at such interfaces have important applications all the way from technical to physiological processes. Detailed studies of adsorption on surfaces, were carried out byIrving Langmuir at the research laboratory of General Electric Company, and when he was awarded the Nobel Prize for Chemistry in 1932, he was the first industrial scientist to receive this distinction.

Two of the Prizes for Chemistry in more recent decades have been given for fundamental work in the application of spectroscopic methods to chemical problems. Spectroscopy had already been recognized with Prizes for Physics in 1952, 1955 and 1961, when Gerhard Herzberg, a physicist at the University of Saskatchewan, received the Nobel Prize for Chemistry in 1971 for his molecular spectroscopy studies «of the electronic structure and geometry of molecules, particularly free radicals». The most used spectroscopic method in chemistry is undoubtedly NMR (nuclear magnetic resonance), and Richard R. Ernst at ETH in Zürich was given the Nobel Prize for Chemistry in 1991 for «the development of the methodology of high resolution nuclear magnetic resonance (NMR) spectroscopy». Ernst’s methodology has now made it possible to determine the structure in solution (in contrast to crystals; cf. Section 3.5) of large molecules, such as proteins.

3.2 Chemical Thermodynamics

The first Nobel Prize for Chemistry, that to van’t Hoff, was in part for work in chemical thermodynamics, and many later contributions in this area have also been recognized with Nobel Prizes. Already in 1920 Walther Hermann Nernstof Berlin received this award for work in thermochemistry, despite a 16-year opposition to this recognition from Arrhenius [2]. Nernst had shown that it is possible to determine the equilibrium constant for a chemical reaction from thermal data, and in so doing he formulated what he himself called the third law of thermodynamics. This states that the entropy, a thermodynamic quantity, which is a measure of the disorder in the system, approaches zero as the temperature goes towards absolute zero. van’t Hoff had derived the mass action equation in 1886, with the aid of the second law which says, that the entropy increases in all spontaneous processes [this had already been done in 1876 by J. Willard Gibbs at Yale, who certainly had deserved a Nobel Prize, but his work had been published in an obscure place]. According to the second law, heat of reaction is not an accurate measure of chemical equilibrium, as had been assumed by earlier investigators. But Nernst showed in 1906 that it is possible with the aid of the third law, to derive the necessary parameters from the temperature dependence of thermochemical quantities.

To prove his heat theorem (the third law) Nernst carried out thermochemical measurements at very low temperatures, and such studies were extended in the 1920s by G.N. Lewis (see Section 1.1) in Berkeley. Lewis’s new formulation of the third law was confirmed by his student William Francis Giauque, who extended the temperature range experimentally accessible by introducing the method of adiabatic demagnetization in 1933. With this he managed to reach temperatures a few thousandths of a degree above absolute zero and could thereby provide extremely accurate entropy estimates. He also showed that it is possible to determine entropies from spectroscopic data. Giauque was awarded the Nobel Prize for Chemistry in 1949 for his contributions to chemical thermodynamics.

The next Nobel Prize given for work in thermodynamics went to Lars Onsagerof Yale University in 1968 for contributions to the thermodynamics of irreversible processes. Classical thermodynamics deals with systems at equilibrium, in which the chemical reactions are said to be reversible, but many chemical systems, for example, the most complex of all, living organisms, are far from equilibrium and their reactions are said to be irreversible. With the aid of statistical mechanics Onsager developed in 1931 his so-called reciprocal relations, describing the flow of matter and energy in such systems, but the importance of his work was not recognized until the end of the 1940s. A further step forward in the development of non-equilibrium thermodynamics was taken by Ilya Prigogine in Bruxelles, whose theory of dissipative structures was awarded the Nobel Prize for Chemistry in 1977.

3.3 Chemical Change

The chief method to get information about the mechanism of chemical reactions is chemical kinetics, i.e. measurements of the rate of the reaction as a function of reactant concentrations as well as its dependence on temperature, pressure and reaction medium. Important work in this area had been done already in the 1880s by two of the early Laureates, van’t Hoff and Arrhenius, who showed that it is not enough for molecules to collide for a reaction to take place. Only molecules with sufficient kinetic energy in the collision do, in fact, react, and Arrhenius derived an equation in 1889 allowing the calculation of this activation energy from the temperature dependence of the reaction rate. With the advent of quantum mechanics in the 1920s (see Section 3.4), Eyring developed his transition-state theory in 1935 and this showed that the activation entropy is also important. Strangely, Eyring never received a Nobel Prize (see Section 1.2).

In 1956 Sir Cyril Norman Hinshelwood of Oxford and Nikolay Nikolaevich Semenov from Moscow shared the Nobel Prize for Chemistry «for their researches into the mechanism of chemical reactions». Among Hinshelwood’s major contributions his detailed elucidation of the mechanism for the reaction between oxygen and hydrogen can be mentioned, whereas Semenov’s award was for his studies of so-called chain reactions.

A limit in investigating reaction rates is set by the speed with which the reaction can be initiated. If this is done by rapid mixing of the reactants, the time limit is about one thousandth of a second (millisecond). In the 1950s Manfred Eigenfrom Göttingen developed chemical relaxation methods that allow measurements in times as short as a thousandth or a millionth of a millisecond (microseconds or nanoseconds). The methods involve disturbing an equilibrium by rapid changes in temperature or pressure and then follow the passage to a new equilibrium. Another way to initiate some reactions rapidly is flash photolysis, i.e. by short light flashes, a method developed by Ronald G.W. Norrish at Cambridge and George Porter (Lord Porter since 1990) in London. Eigen received one-half and Norrish and Porter shared the other half of the Nobel Prize for Chemistry in 1967. The milli- to picosecond time scales gave important information on chemical reactions. However, it was not until it was possible to generate femtosecond laser pulses (10-15 s) that it became possible to reveal when chemical bonds are broken and formed. Ahmed Zewail (born 1946 in Egypt) at California Institute of Technology received the Nobel Prize for Chemistry in 1999 for his development of «femtochemistry» and in particular for being the first to experimentally demonstrate a transition state during a chemical reaction. His experiments relate back to 1889 when Arrhenius (Nobel Prize, 1903) made the important prediction that there must exist intermediates (transition states) in the transformation from reactants to products. Henry Taube of Stanford University was awarded the Nobel Prize for Chemistry in 1983 «for his work on the mechanism of electron transfer reactions, especially in metal complexes». Even if Taube’s work was on inorganic reactions, electron transfer is important in many catalytic processes used in industry and also in biological systems, for example, in respiration and photosynthesis. The latest prize for work in chemical kinetics was that to Dudley R. Herschbach at Harvard University, Yuan T. Lee of Berkeley and John C. Polanyi from Toronto in 1986. Herschbach and his student Lee introduced the use of fluxes of molecules with well-defined direction and energy, molecular beams. By crossing two such beams they could study details of the reaction between molecules at extremely short times. Another important method to investigate such reaction details is infrared chemiluminescence, introduced by Polanyi. The emission of infrared radiation from the reaction products gives information on the energy distribution in the molecules.

3.4 Theoretical Chemistry and Chemical Bonding

Quantum mechanics, developed in the 1920s, offered a tool towards a more basic understanding of chemical bonds. In 1927 Walter Heitler and Fritz London showed that it is possible to solve exactly the relevant equations for the hydrogen molecule ion, i.e. two hydrogen nuclei sharing a single electron, and thereby calculate the attractive force between the nuclei. For molecules containing more than three elementary particles, even the hydrogen molecule with Lewis’s two-electron bond (see Section 1.1), the equation can, however, not be solved exactly, so one has to resort to approximate methods. A pioneer in developing such methods was Linus Pauling at California Institute of Technology, who was awarded the Nobel Prize for Chemistry in 1954 «for his research into the nature of the chemical bond …» Pauling’s valence-bond (VB) method is rigorously described in his 1935 book Introduction to Quantum Mechanics (written together with E. Bright Wilson, Jr., at Harvard). A few years later (1939) he published an extensive non-mathematical treatment in The Nature of the Chemical Bond, a book which is one of the most read and influential in the entire history of chemistry. Pauling was not only a theoretician, but he also carried out extensive investigations of chemical structure by X-ray diffraction (see Section 3.5). On the basis of results with small peptides, which are building blocks of proteins, he suggested the a-helix as an important structural element. Pauling was awarded the Nobel Peace Prize for 1962, and he is the only person to date to have won two unshared Nobel Prizes.

alpha helix Pauling’s alpha-helix
alpha-carbon atoms are black, other carbon atoms grey, nitrogen atoms blue, oxygen atoms red and hydrogen atoms white; R designates amino-acid side chains. The dotted red lines are hydrogen bonds between amide and carbonyl groups in the peptide bonds.

 

Pauling’s VB method cannot give an adequate description of chemical bonding in many complicated molecules, and a more comprehensive treatment, the molecular-orbital (MO) method, was introduced already in 1927 by Robert S. Mulliken from Chicago and later developed further by him as well as by many other investigators. MO theory considers, in quantum-mechanical terms, the interaction between all atomic nuclei and electrons in a molecule. Mulliken also showed that a combination of MO calculations with experimental (spectroscopic) results provides a powerful tool for describing bonding in large molecules. Mulliken received the Nobel Prize for Chemistry in 1966.

Theoretical chemistry has also contributed significantly to our understanding of chemical reaction mechanisms. In 1981 the Nobel Prize for Chemistry was shared between Kenichi Fukui in Kyoto and Roald Hoffmann of Cornell University «for their theories, developed independently, concerning the course of chemical reactions». Fukui introduced in 1952 the frontier-orbital theory, according to which the occupied MO with the highest energy and the unoccupied one with the lowest energy have a dominant influence on the reactivity of a molecule. Hoffmann formulated in 1965, together with Robert B. Woodward (see Section 3.8), rules based on the conservation of orbital symmetry, for the reactivity and stereochemistry in chemical reactions.

Rudolph A. Marcus published during ten years, starting in 1956, a series of seminal papers on a comprehensive theory for the rates electron-transfer reactions, the experimental study of which had given Taube a Nobel Prize in 1983 (see Section 3.3). Marcus’s theory predicts how the rate varies with the driving force for the reaction, i.e. the difference in energy between reactants and products, and counter to intuition he found that it does not increase continuously, but goes through a maximum, into the Marcus inverted region, which has later been confirmed experimentally. Marcus was awarded the Nobel Prize for Chemistry in 1992.

The latest Nobel Prize for work in theoretical chemistry was given in 1998 toWalter Kohn of Santa Barbara and John A. Pople of Northwestern University (but a British citizen). The prize to Kohn, a theoretical physicist, was based on his development of density-functional theory, which facilitates detailed calculations both of the geometrical structures of complex molecules and of the energy map of chemical reactions. Pople, a mathematician (but now Professor of Chemistry), was awarded «for his development of computational methods in quantum chemistry». In particular, Pople has designed computer programs based on classical quantum theory as well as on density-functional theory.

3.5 Chemical Structure

The most commonly used method to determine the structure of molecules in three dimensions is X-ray crystallography. The diffraction of X-rays was discovered by Max von Laue in 1912, and this gave him the Nobel Prize for Physics in 1914. Its use for the determination of crystal structure was developed by Sir William Bragg and his son, Sir Lawrence Bragg, and they shared the Nobel Prize for Physics in 1915. The first Nobel Prize for Chemistry for the use of X-ray diffraction went to Petrus (Peter) Debye, then of Berlin, in 1936. Debye did not study crystals, however, but gases, which give less distinct diffraction patterns. He also employed electron diffraction and the measurement of dipole moments to get structural information. Dipole moments are found in molecules, in which the positive and negative charge is unevenly distributed (polar molecules).

Many Nobel Prizes have been awarded for the determination of the structure of biological macromolecules (proteins and nucleic acids). Proteins are long chains of amino-acids, as shown by Emil Fischer (see Section 2), and the first step in the determination of their structure is to determine the order (sequence) of these building blocks. An ingenious method for this tedious task was developed by Frederick Sanger of Cambridge, and he reported the amino-acid sequence for a protein, insulin, in 1955. For this achievement he was awarded the Nobel Prize for Chemistry in 1958. Sanger later received part of a second Nobel Prize for Chemistry for a method to determine the nucleotide sequence in nucleic acids (see Section 3.12), and he is the only scientist so far who has won two Nobel Prizes for Chemistry.

The first protein crystal structures were reported by Max Perutz and Sir John Kendrew in 1960, and these two investigators shared the Nobel Prize for Chemistry in 1962. Perutz had started studying the oxygen-carrying blood pigment, hemoglobin, with Sir Lawrence Bragg in Cambridge already in 1937, and ten years later he was joined by Kendrew, who looked at crystals of the related muscle pigment, myoglobin. These proteins are both rich in Pauling’s a-helix (see Section 3.4), and this made it possible to discern the main features of the structures at the relatively low resolution first used. The same year that Perutz and Kendrew won their prize, the Nobel Prize for Physiology or Medicine went to Francis Crick, James Watson and Maurice Wilkins «for their discoveries concerning the molecular structure of nucleic acids … .» Two years later (1964) Dorothy Crowfoot Hodgkin received the Nobel Prize for Chemistry for determining the crystal structures of penicillin and vitamin B12.

Two later Nobel Prizes for Chemistry in the crystallographic field were given for work on structures of relatively small molecules. William N. Lipscomb of Harvard received the prize in 1976 «for his studies on the structures of boranes illuminating problems of chemical bonding». In 1985 Herbert A. Hauptman of Buffalo and Jerome Karle of Washington, DC, shared the prize for «the development of direct methods for the determination of crystal structures». Their methods are called direct, because they yield the structure directly from the diffraction data collected, and they have been indispensable in the determination of the structures of a large number of natural products.

Crystallographic electron microscopy was developed by Sir Aaron Klug in Cambridge, who was awarded the Nobel Prize for Chemistry in 1982. With this technique Klug has investigated the structure of large nucleic acid-protein complexes, such as viruses and chromatin, the carrier of the genes in the cell nucleus. Many of the most important life processes are carried out by proteins associated with biological membranes. This is, for example, true of the two key processes in energy metabolism, respiration and photosynthesis. Attempts to prepare crystals of membrane proteins for structural studies were, however, for many years unsuccessful, but in 1982 Hartmut Michel, then at the Max-Planck-Institut in Martinsried, managed to crystallize a photosynthetic reaction center after a painstaking series of experiments. He then proceeded to determine the three-dimensional structure of this protein complex in collaboration with Johann Deisenhofer and Robert Huber, and this was published in 1985. Deisenhofer, Huber and Michel shared the Nobel Prize for Chemistry in 1988. Michel has later also crystallized and determined the structure of the terminal enzyme in respiration, and his two structures have allowed detailed studies of electron transfer (cf. Sections 3.3 and 3.4) and its coupling to proton pumping, key features of the chemiosmotic mechanism for which Peter Mitchell had already received the Nobel Prize for Chemistry in 1978 (see Section 3.12). Functional and structural studies on the enzyme ATP synthase, connected to this proton pumping mechanism, was awarded one-half of the Nobel Prize for Chemistry in 1997, shared between Paul D. Boyer and John Walker (see Section 3.12).

3.6 Inorganic and Nuclear Chemistry

Much of the progress in inorganic chemistry during the 20th century has been associated with investigations of coordination compounds, i.e., a central metal ion surrounded by a number of coordinating groups, called ligands. In 1893Alfred Werner in Zürich presented his coordination theory, and in 1905 he summarized his investigations in this new field in a book (Neuere Anschauungen auf dem Gebiete der anorganischen Chemie), which appeared in no less than five editions from 1905-1923. Compounds in which a metal ion binds several other molecules (ligands), for example, ammonia, had earlier been thought to have a linear structure, in accord with a theory advanced by the Swedish chemist Wilhelm Blomstrand in Lund. Werner showed that such a structure is inconsistent with some experimental facts, and he suggested instead that all the ligand molecules are bound directly to the metal ion. Werner was awarded the Nobel Prize for Chemistry in 1913. Taube’s investigations of electron transfer, awarded in 1983 (see Section 3.3), were mainly carried out with coordination compounds, and vitamin B12 as well as the proteins hemoglobin and myoglobin, investigated by the Laureates Hodgkin, Perutz and Kendrew (see Section 3.5), also belong to this category.

Another early prize for work in inorganic chemistry was that to Fritz Haberfrom Berlin in 1918 «for the synthesis of ammonia from its elements», i.e., from nitrogen and hydrogen. The importance of this synthesis is above all in its industrial application in the form of the Haber-Bosch method, which had been developed by Carl Bosch as an improvement (cf. Nobel’s will) of Haber’s original procedure. It allows the manufacture of ammonia on a large scale, and the ammonia can then be used for the production of many different nitrogen-containing chemicals. Bosch shared the Nobel Prize for Chemistry withFriedrich Bergius in 1931 (see Section 3.13).

Much inorganic chemistry in the early 1900s was a consequence of the discovery of radioactivity in 1896, for which Henri Becquerel from Paris was awarded the Nobel Prize for Physics in 1903, together with Pierre and Marie Curie. In 1911 Marie Curie received the Nobel Prize for Chemistry for her discovery of the elements radium and polonium and for the isolation of radium and studies of its compounds, and this made her the first investigator to be awarded two Nobel Prizes. The prize in 1921 went to Frederick Soddy of Oxford for his work on the chemistry of radioactive substances and on the origin of isotopes. In 1934 Frédéric Joliot and his wife Irène Joliot-Curie, the daughter of the Curies, discovered artificial radioactivity, i.e., new radioactive elements produced by the bombardment of non-radioactive elements with a-particles or neutrons. They were awarded the Nobel Prize for Chemistry in 1935 for «their synthesis of new radioactive elements».

Many elements are mixtures of non-radioactive isotopes (see Section 3.1), and in 1934 Harold Urey of Columbia University had been given the Nobel Prize for Chemistry for his isolation of heavy hydrogen (deuterium). Urey had also separated uranium isotopes, and his work was an important basis for the investigations by Otto Hahn from Berlin. In attempts to make transuranium elements, i.e., elements with a higher atomic number than 92 (uranium), by radiating uranium atoms with neutrons, Hahn discovered that one of the products was barium, a lighter element. Lise Meitner, at the time a refugee from Nazism in Sweden, who had earlier worked with Hahn and taken the initiative for the uranium bombardment experiments, provided the explanation, namely, that the uranium atom was cleaved and that barium was one of the products [3]. Hahn was awarded the Nobel Prize for Chemistry in 1944 «for his discovery of the fission of heavy nuclei», and it can be wondered why Meitner was not included. Hahn’s original intention with his experiments was later achieved by Edwin M. McMillan and Glenn T. Seaborg of Berkeley, who were given the Nobel Prize for Chemistry in 1951 for «discoveries in the chemistry of transuranium elements».

The use of stable as well as radioactive isotopes have important applications, not only in chemistry, but also in fields as far apart as biology, geology and archeology. In 1943 George de Hevesy from Stockholm received the Nobel Prize for Chemistry for his work on the use of isotopes as tracers, involving studies in inorganic chemistry and geochemistry as well as on the metabolism in living organisms. The prize in 1960 was given to Willard F. Libby of the University of California, Los Angeles (UCLA), for his method to determine the age of various objects (of geological or archeological origin) by measurements of the radioactive isotope carbon-14.

3.7 General Organic Chemistry

Contributions in organic chemistry have led to more Nobel Prizes for Chemistry than work in any other of the traditional branches of chemistry. Like the first prize in this area, that to Emil Fischer in 1902 (see Section 2), most of them have, however, been awarded for advances in the chemistry of natural products and will be treated separately (Section 3.9). Another large group, preparative organic chemistry, has also been given its own section (Section 3.8), and here only the prizes for more general contributions to organic chemistry will be discussed. In 1969 the Nobel Prize for Chemistry went to Sir Derek H. R. Barton from London, and Odd Hassel from Oslo for developing the concept of conformation, i.e. the spatial arrangement of atoms in molecules, which differ only by the orientation of chemical groups by rotation around a single bond. This stereochemical concept rests on the original suggestion by van’t Hoff of the tetrahedral arrangement of the four valences of the carbon atom (see Section 2), and most organic molecules exist in two or more stable conformations.

The Nobel Prize for Chemistry in 1975 to Sir John Warcup Cornforth of the University of Sussex and Vladimir Prelog of ETH in Zürich was also based on research in stereochemistry. Not only can a compound have more than one geometric form, but chemical reactions can also have specificity in their stereochemistry, thereby forming a product with a particular three-dimensional arrangement of the atoms. This is especially true of reactions in living organisms, and Cornforth has mainly studied enzyme-catalyzed reactions, so his work borders onto biochemistry (Section 3.12). One of Prelog’s main contributions concerns chiral molecules, i.e. molecules that have two forms differing from one another as the right hand does from the left. Stereochemically specific reactions have great practical importance, as many drugs, for example, are active only in one particular geometric form.

Organometallic compounds constitute a group of organic molecules containing one or more carbon-metal bond, and they are thus the organic counterpart to Werner’s inorganic coordination compounds (see Section 3.6). In 1952 Ernst Otto Fischer and Sir Geoffrey Wilkinson independently described a completely new group of organometallic molecules, called sandwich compounds (see figure below). In such compounds a metal ion is bound not to a single carbon atom but is «sandwiched» between two aromatic organic molecules. Fischer and Wilkinson shared the Nobel Prize for Chemistry in 1973.

Sandwich compounds
Sandwich compounds

 

Work on the interaction of metal ions with organic molecules was also recognized by the prize in 1987, which was shared by Donald J. Cram of UCLA,Jean-Marie Lehn from Strasbourg (and Paris) and Charles J. Pedersen of the Du Pont Company. These three investigators have synthesized molecules with a ring structure, in which the hole in their middle specifically recognizes and binds different metal ions. They can, for example, distinguish between closely related ions, such as those of sodium and potassium, and thus they mimic enzymes in their specificity. The first such compound was synthesized by Pedersen in 1967, and later Lehn and Cram developed increasingly sophisticated organic compounds with cavities and cages in which not only metal ions but other molecules are bound. This research has applications in the whole spectrum of the chemical field, from inorganic chemistry to biochemistry.

George A. Olah from the University of Southern California was awarded the Nobel Prize for Chemistry in 1994 «for his contributions to carbocation chemistry». Already in the 1920s and 1930s chemists had suggested that positively charged ions of hydrocarbons are formed as short-lived intermediates in organic chemical reactions. Such carbocations were, however, thought to be so reactive and unstable that it would be impossible to prepare them in quantity. Olah’s investigations, starting in the 1960s, contradicted this supposition, since he showed that stable carbocations can be prepared by the use of a new type of extremely acidic compounds («superacids»), and carbocation chemistry now has a prominent position in all modern textbooks of organic chemistry.

The preparation of a new form of carbon compounds was also recognized by the Nobel Prize for Chemistry in 1996 to Robert F. Curl, Jr., of Rice University,Sir Harold W. Kroto of the University of Sussex and Richard E. Smalley of Rice University. These investigators had in 1985 discovered compounds, called fullerenes, in which 60 or 70 carbon atoms are bound together in clusters in the form of a ball (see figure below). The designation fullerenes is taken from the name of an American architect, R. Buckminster Fuller, who had designed a dome having the form of a football for the 1967 Montreal World Exhibition.

fullerenes
Fullerenes

3.8 Preparative Organic Chemistry

One of the chief goals of the organic chemist is to be able to synthesize increasingly complex compounds of carbon in combination with various other elements, such as hydrogen, oxygen, nitrogen, sulfur and phosphorus. The first Nobel Prize for Chemistry recognizing pioneering work in preparative organic chemistry was that to Victor Grignard from Nancy and Paul Sabatier from Toulouse in 1912. Grignard had discovered that organic halides can form compounds with magnesium. These compounds, now generally called Grignard reagents, are very reactive, and they are consequently widely used for synthetic purposes. Sabatier was given the prize for developing a method to hydrogenate organic compounds in the presence of metallic catalysts. With his method oils can be converted to saturated fats, and it is, for example, used for margarine production and other industrial processes.

The prize in 1950 was presented to Otto Diels from Kiel and Kurt Alder from Cologne «for their discovery and development of the diene synthesis», also called the Diels-Alder reaction. In this reaction, which was developed already in 1928, organic compounds containing two double bonds («dienes») can effect the syntheses of many cyclic organic substances. During the decades following the original work several industrial applications of the Diels-Alder reaction have been found, for example, in the production of plastics, which may explain the lateness of the prize.

The German organic chemist Hans Fischer from Munich had already done significant work on the structure of hemin, the organic pigment in hemoglobin, when he synthesized it from simpler organic molecules in 1928. He also contributed much to the elucidation of the structure of chlorophyll, and for these important achievements he was awarded the Nobel Prize for Chemistry in 1930 (cf. Section 3.5). He finished his determination of the structure of chlorophyll in 1935, and by the time of his death he had almost completed its synthesis as well.

Robert Burns Woodward from Harvard is rightly considered the founder of the most advanced, modern art of organic synthesis. He designed methods for the total synthesis of a large number of complicated natural products, for example, cholesterol, chlorophyll and vitamin B12. He received the Nobel Prize for Chemistry in 1965, and he would probably have received a second chemistry prize in 1981 for his part in the formulation of the Woodward-Hoffmann rules (see Section 3.4), had it not been for his early death. Work in synthetic organic chemistry was also recognized in 1979 with the prize toHerbert C. Brown of Purdue University and Georg Wittig from Heidelberg, who had developed the use of boron- and phosphorus-containing compounds, respectively, into important reagents in organic synthesis. Another master in chemical synthesis is Elias James Corey from Harvard, who received the prize in 1990. He had made a brilliant analysis of the theory of organic synthesis, which permitted him to synthesize biologically active compounds of a complexity earlier considered impossible.

The Nobel Prize for Chemistry in 1984 was given to Robert Bruce Merrifield of Rockefeller University «for his development of methodology for chemical synthesis on a solid matrix». Specifically, Merrifield applied this ingenious idea to the synthesis of large peptides and small proteins, for example, ribonuclease (cf. Section 3.12), but the principle has later also been applied to nucleic acid chemistry. In earlier methods each intermediate in the synthesis had to be isolated, which resulted in a drastic drop in yield in syntheses involving a large number of consecutive steps. In Merrifield’s method these isolation steps are replaced by a simple washing procedure, which removes by-products as well as remaining starting materials, and in this way substantial losses are avoided.

The Nobel Prize in Chemistry 2001

William S. Knowles and Ryoji Noyori

«for their work on chirally catalysed hydrogenation reactions»

K. Barry Sharpless  «for his work on chirally catalysed oxidation reactions»

3.9 Chemistry of Natural Product

The synthesis of complex organic molecules must be based on detailed knowledge of their structure. Early work on plant pigments was carried out byRichard Willstätter, a student of Adolf von Baeyer from Munich (see Section 2). Willstätter showed a structural relatedness between chlorophyll and hemin, and he demonstrated that chlorophyll contains magnesium as an integral component. He also carried out pioneering investigations on other plant pigments, such as the carotenoids, and he was awarded the Nobel Prize for Chemistry in 1915 for these achievements. Willstätter’s work laid the ground for the synthetic accomplishments of Hans Fischer (see Section 3.8). In addition, Willstätter contributed to the understanding of enzyme reactions.

The prizes for 1927 and 1928 were both presented to Heinrich Otto Wielandfrom Munich and Adolf Windaus from Göttingen, respectively, at the Nobel ceremony in 1928. These two chemists had done closely related work on the structure of steroids. The award to Wieland was primarily for his investigations of bile acids, whereas Windaus was recognized mainly for his work on cholesterol and his demonstration of the steroid nature of vitamin D. Wieland had already in 1912, before his prize-winning work, formulated a theory for biological oxidation, according to which removal of hydrogen (dehydrogenation) rather than reaction with oxygen is the dominating process.

Investigations on vitamins were recognized in 1937 and 1938 with the prizes toSir Norman Haworth from Birmingham and Paul Karrer from Zürich and toRichard Kuhn from Heidelberg. Haworth did outstanding work in carbohydrate chemistry, establishing the ring structure of glucose. He was the first chemist to synthesize vitamin C, and this is the basis for the present large-scale production of this nutrient. Haworth shared the prize with Karrer, who determined the structure of carotene and of vitamin A. Kuhn also worked on carotenoids, and he published the structure of vitamin B2 at the same time as Karrer. He also isolated vitamin B6. In 1939 the Nobel Prize for Chemistry was shared between Adolf Butenandt from Berlin and Leopold Ruzicka (1887-1976) of ETH, Zurich. Butenandt was recognized «for his work on sex hormones», having isolated estrone, progesterone and androsterone. Ruzicka synthesized androsterone and also testosterone.

The awards for outstanding work in natural-product chemistry continued after World War II. In 1947 Sir Robert Robinson from Oxford received the prize for his studies on plant substances, particularly alkaloids, such as morphine. Robinson also synthesized steroid hormones, and he elucidated the structure of penicillin. Many hormones are of a polypeptide nature, and in 1955 Vincent du Vigneaud of Cornell University was given the prize for his synthesis of two such hormones, vasopressin and oxytocin. Finally, in this area, Alexander R. Todd (Lord Todd since 1962) was recognized in 1957 «for his work on nucleotides and nucleotide co-enzymes». Todd had synthesized ATP (adenosine triphosphate) and ADP (adenosine diphosphate), the main energy carriers in living cells, and he determined the structure of vitamin B12 (cf. Section 3.5) and of FAD (flavin-adenine dinucleotide).

3.10 Analytical Chemistry and Separation Science

Inorganic chemists, organic chemists and biochemists develop analytical methods as part of their regular research. It is consequently natural that not many Nobel Prizes have been awarded for contributions specifically in analytical chemistry. One such prize was, however, that to Fritz Pregl from Graz in 1923 for his development of organic microanalysis. The medical biochemist from Uppsala, Olof Hammarsten, who gave the presentation speech as Chairman of the Nobel Committee for Chemistry, stressed that Pregl’s work constituted an improvement rather than a discovery, in accord with Nobel’s will. Pregl modified existing methods for quantitative elemental analysis of organic substances to handle very small quantities, which saved time, labor and expense. Another prize in analytical chemistry was given toJaroslav Heyrovsky from Prague in 1959 for his development of polarographic methods of analysis. In these a dropping mercury electrode is employed to determine current-voltage curves for electrolytes. A given ion reacts at a specific voltage, and the current is a measure of the concentration of this ion.

The analysis of macromolecular constituents in living organisms requires specialized methods of separation. One such method is ultracentrifugation, developed by The Svedberg from Uppsala a few years before he was awarded the Nobel Prize for Chemistry in 1926 «for his work on disperse systems» (see Section 3.11). Svedberg’s student, Arne Tiselius, studied the migration of protein molecules in an electric field, and with this method, named electrophoresis, he demonstrated the complex nature of blood proteins. Tiselius also refined adsorption analysis, a method first used by the Russian botanist, Michail Tswett, for the separation of plant pigments and named chromatography by him. In 1948 Tiselius was given the prize for these achievements. A few years later (1952) Archer J.P. Martin from London andRichard L.M. Synge from Bucksburn (Scotland) shared the prize «for their invention of partition chromatography», and this method was a major tool in many biochemical investigations later awarded with Nobel Prizes (see Section 3.12).

3.11 Polymers and Colloids

Polymeric substances in solution, including life constituents, such as proteins and polysaccharides, are in a colloidal state, i.e., they exist as suspensions of particles one-millionth to one-thousandth of a centimeter in size. In the case of the biological polymers the individual molecules are so large that they form a colloidal suspension, but many other substances can be obtained in a colloidal state. A much-studied example is aggregates of gold atoms, and the Nobel Prize for Chemistry for 1925 was given to Richard Zsigmondy from Göttingen for demonstrating the heterogeneous nature of such gold sols. He did this with the aid of an instrument, the ultramicroscope, which he had developed in collaboration with scientists at the Zeiss factory in Jena. With this instrument the particles and their motion can be observed by the light they scatter at a right angle to the direction of the illuminating light beam. Early work in colloid chemistry had also been carried out by Wolfgang Ostwald, son of the 1909 Laureate Wilhelm Ostwald, but this was not of a caliber earning him a Nobel Prize.

The Svedberg who received the Nobel Prize for Chemistry in 1926, also investigated gold sols. He used Zsigmond’s ultramicroscope to study the Brownian movement of colloidal particles, so named after the Scottish botanist Robert Brown, and confirmed a theory developed by Albert Einstein in 1905 and, independently, by M. Smoluchowski. His greatest achievement was, however, the construction of the ultracentrifuge, with which he studied not only the particle size distribution in gold sols but also determined the molecular weight of proteins, for example, hemoglobin. In the same year as Svedberg got the prize the Nobel Prize for Physics was awarded to Jean Baptiste Perrin of Sorbonne for developing equilibrium sedimentation in colloidal solutions, a method which Svedberg later perfected in his ultracentrifuge. Svedberg’s investigations with the ultracentrifuge and Tiselius’s electrophoresis studies (see Section 3.10) were instrumental in establishing that protein molecules have a unique size and structure, and this was a prerequisite for Sanger’s determination of their amino-acid sequence and the crystallographic work of Kendrew and Perutz (see Section 3.5).

In the 1920s Hermann Staudinger from Freiburg developed the concept of macromolecules. He synthesized many polymers, and he showed that they are long chain molecules. The large plastic industry is largely based on Staudinger’s work. In 1953 he received the Nobel Prize for Chemistry «for his discoveries in the field of macromolecular chemistry». The prize in 1963 was shared by Karl Ziegler of the Max-Planck-Institute in Mülheim and Giulio Natta from Milan for their discoveries in polymer chemistry and technology. Ziegler demonstrated that certain organometallic compounds (see Section 3.7) can be used to effect polymerization reactions, and Natta showed that Ziegler catalysts can produce polymers with a highly regular three-dimensional structure. Another Nobel Prize for contributions in polymer chemistry was given to Paul J. Flory of Stanford in 1974. Flory carried out fundamental theoretical as well as experimental investigations of the physical chemistry of macromolecules, but his work also led to such important polymers as nylon and synthetic rubber. In 1977 a paper entitled «Synthesis of electrically conducting organic polymers: Halogen derivates of polyacetylene» was published in the Journal of the American Chemical Society, Chemical Communications. The authors of this paper, Alan J. Heeger of the University of California at Santa Barbara, Alan G. MacDiarmid of the University of Pennsylvania and Hideki Shirakawa of the University of Tsukuba, Japan were awarded the Nobel Prize for Chemistry in 2000 for this discovery. The conducting polymers have already given rise to a number of applications such as photodiodes and light-emitting diodes and have future potential to generate microelectronics based upon plastic materials.

3.12 Biochemistry

The second Nobel Prize for discoveries in biochemistry came in 1929, when Sir Arthur Harden from London and Hans von Euler-Chelpin from Stockholm shared the prize for investigations of sugar fermentation, which formed a direct continuation of Buchner’s work awarded in 1907. With his young co-worker, William John Young, Harden had shown in 1906 that fermentation requires a dialysable substance, called co-zymase, which is not destroyed by heat. Harden and Young also demonstrated that the process stops before all sugar (glucose) has been used up, but it starts again on addition of inorganic phosphate, and they suggested that hexose phosphates are formed in the early steps of fermentation. von Euler had done important work on the structure of co-zymase, shown to be nicotinamide adenine dinucleotide (NAD, earlier called DPN). As the number of Laureates can be three, it may seem appropriate for Young to have been included in the award, but Euler’s discovery was published together with Karl Myrbäck, and the number of Laureates is limited to three.

The next biochemical Nobel Prize was given in 1946 for work in the protein field. James B. Sumner of Cornell University received half the prize «for his discovery that enzymes can be crystallized» and John H. Northrop together with Wendell M. Stanley, both of the Rockefeller Institute, shared the other half «for their preparation of enzymes and virus proteins in a pure form». Sumner had in 1926 crystalized an enzyme, urease, from jack beans and suggested that the crystals were the pure protein. His claim was, however, greeted with great scepticism, and the crystals were suggested to be inorganic salts with the enzyme adsorbed or occluded. Just a few years after Sumner’s discovery Northrop, however, managed to crystalize three digestive enzymes, pepsin, trypsin and chymotrypsin, and by painstaking experiments shown them to be pure proteins. Stanley started his attempt to purify virus proteins in the 1930s, but not until 1945 did he get virus crystals, and this then made it possible to show that viruses are complexes of protein and nucleic acid. The pioneering studies of these three investigators form the basis for the enormous number of new crystal structures of biological macromolecules, which have been published in the second half of the 20th century (cf. Section 3.5).

Several Nobel Prizes for Chemistry have been awarded for work in photosynthesis and respiration, the two main processes in the energy metabolism of living organisms (cf. Section 3.5). In 1961 Melvin Calvin of Berkeley received the prize for elucidating the carbon dioxide assimilation in plants. With the aid of carbon-14 (cf. Section 3.6) Calvin had shown that carbon dioxide is fixed in a cyclic process involving several enzymes. Peter Mitchell of the Glynn Research Laboratories in England was awarded in 1978 for his formulation of the chemiosmotic theory. According to this theory, electron transfer (cf. Sections 3.3 and 3.4) in the membrane-bound enzyme complexes in both respiration and photosynthesis, is coupled to proton translocation across the membranes, and the electrochemical gradient thus created is used to drive the synthesis of ATP (adenosine triphosphate), the energy storage molecule in all living cells. Paul D. Boyer of UCLA and John C. Walker of the MRC Laboratory in Cambridge shared one-half of the 1997 prize for their elucidation of the mechanism of ATP synthesis; the other half of the prize went to Jens C. Skou in Aarhus for the first discovery of an ion-transporting enzyme. Walker had determined the crystal structure of ATP synthase, and this structure confirmed a mechanism earlier proposed by Boyer, mainly on the basis of isotopic studies.

Luis F. Leloir from Buenos Aires was awarded in 1970 «for the discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates». In particular, Leloir had elucidated the biosynthesis of glycogen, the chief sugar reserve in animals and many microorganisms. Two years later the prize went with one half to Christian B. Anfinsen of NIH and the other half shared byStanford Moore and William H. Stein, both from Rockefeller University, for fundamental work in protein chemistry. Anfinsen had shown, with the enzyme ribonuclease, that the information for a protein assuming a specific three-dimensional structure is inherent in its amino-acid sequence, and this discovery was the starting point for studies of the mechanism of protein folding, one of the major areas of present-day biochemical research. Moore and Stein had determined the amino-acid sequence of ribonuclease, but they received the prize for discovering anomalous properties of functional groups in the enzyme’s active site, which is a result of the protein fold.

Naturally a number of Nobel Prizes for Chemistry have been given for work in the nucleic acid field. In 1980 Paul Berg of Stanford received one half of the prize for studies of recombinant DNA, i.e. a molecule containing parts of DNA from different species, and the other half was shared by Walter Gilbert from Harvard and Frederick Sanger (see Section 3.5) for developing methods for the determination of the base sequences of nucleic acids. Berg’s work provides the basis of genetic engineering, which has led to the large biotechnology industry. Base sequence determinations are essential steps in recombinant-DNA technology, which is the rationale for Gilbert and Sanger sharing the prize with Berg. Sidney Altman of Yale and Thomas R. Cech of the University of Colorado shared the prize in 1989 «for their discovery of the catalytic properties of RNA». The central dogma of molecular biology is: DNA –> RNA –> enzyme. The discovery that not only enzymes but also RNA possesses catalytic properties have led to new ideas about the origin of life. The 1993 prize was shared byKary B. Mullis from La Jolla and Michael Smith from Vancouver, who both have given important contributions to DNA technology. Mullis developed the PCR («polymerase chain reaction») technique, which makes it possible to replicate millions of times a specific DNA segment in a complicated genetic material. Smith’s work forms the basis for site-directed mutagenesis, a technique by which it is possible to change a specific amino-acid in a protein and thereby illuminate its functional role.

3.13 Applied Chemistry

A few Nobel Prizes for Chemistry have recognized contributions outside the conventional basic chemical fields. The prize in 1931 went to Carl Bosch andFriedrich Bergius , both from Heidelberg, «for the invention and development of chemical high pressure methods». Bosch had modified Haber’s method for ammonia synthesis (see Section 3.6) to make it suitable for large-scale industrial use. Bergius used high-pressure methods to prepare oil by the hydrogenation of coal, and Bosch, like Bergius working at the large concern I. G. Farben, later improved the procedure by finding a good catalyst for the Bergius process.

Work in agricultural and nutritional chemistry led to the award of Artturi Ilmari Virtanen from Helsinki in 1945. The citation particularly stressed his development of the AIV method, so named after the inventor’s initials. Virtanen had first carried out biochemical studies of nitrogen fixation by plants with the aim of producing protein-rich crops. He then found that the fodder could be preserved with the aid of a mixture of sulfuric and nitric acid (AIV acid).

Finally, basic work in atmospheric and environmental chemistry was recognized in 1995 with the prize to Paul Crutzen, from the Netherlands, working at Stockholm University and later at the Max-Planck-Institute in Mainz,Mario Molina of MIT and F. Sherwood Rowland of UC, Irvine. These three investigators have studied in detail the chemical processes leading to the formation and decomposition of ozone in the atmosphere. In particular, they have shown that the atmospheric ozone layer is very sensitive to emission chemicals produced by human activity, and these discoveries have led to international legislation.

4. Concluding Remarks

The first hundred years of Nobel Prizes for Chemistry give a beautiful picture of the development of modern chemistry. The prizes cover the whole spectrum of the basic chemical sciences, from theoretical chemistry to biochemistry, and also a number of contributions to applied chemistry. From a quantitative point of view, organic chemistry dominates with no less than 25 awards. This is not surprising, since the special valence properties of carbon result in an almost infinite variation in the structure of organic compounds. Also, a large number of the prizes in organic chemistry were given for investigations of the chemistry of natural products of increasing complexity and thus are on the border to biochemistry.

As many as 11 prizes have been awarded for biochemical discoveries. Even if the first biochemical prize was already given in 1907 (Buchner), only three awards in this area came in the first half of the century, illustrating the explosive growth of biochemistry in recent decades (8 prizes in 1970-1997). At the other end of the chemical spectrum, physical chemistry, including chemical thermodynamics and kinetics, dominates with 14 prizes, but there has also been 6 prizes in theoretical chemistry. Chemical structure is another large area with 8 prizes, including awards for methodological developments as well as for the determination of the structure of large biological molecules or molecular complexes. Industrial chemistry was first recognized in 1931 (Bergius, Bosch), but many more recent prizes for basic contributions lie close to industrial applications, for example, those in polymer chemistry.

Science is a truly international undertaking, but the western dominance of the Nobel scene is striking. No less than 49 scientists in the United States have received the Nobel Prize for Chemistry, but the majority have been given the prize after World War II. The first US prize was awarded in 1915 (for 1914, Richards), and only two more Americans got the prize before 1946 (Langmuir in 1932, Urey in 1934). German chemists form the second most awarded group with 26 Laureates, but 14 of these received the prize before 1945. Of the 25 British investigators recognized, on the other hand, no less than 19 got the prize in the second half of the century. France has 7 Laureates in chemistry, Sweden and Switzerland 5 each, and the Netherlands and Canada 3. One prize winner each is found in the following countries: Argentina, Austria, Belgium, Czechoslovakia, Denmark, Finland, Italy, Norway and Russia.

Extrapolating the trend of the 20th century Nobel Prizes for Chemistry, it is expected that in the 21st century theoretical and computational chemistry will flourish with the aid of the expansion of computer technology. The study of biological systems may become more dominant and move from individual macromolecules to large interactive systems, for example, in chemical signaling and in neural function, including the brain. And it is to be hoped that the next century will witness a wider national distribution of Laureates.

 


 

5. References

Westgren, A., Nobel – The Man and His Prizes, ed. Odelberg, W. (Elsevier, New York, 1972), pp. 279-385.

Kormos Barkan, D., Walther Nernst and the Transition in Modern Physical Science, (Cambridge University Press, 1999).

Rife, P., Lise Meitner and the Dawn of the Nuclear Age, (Birkhäuser, 1999).

 


 

* This article was published as a chapter of the book: «The Nobel Prize: The First 100 Years», Agneta Wallin Levinovitz and Nils Ringertz, eds., Imperial College Press and World Scientific Publishing Co. Pte. Ltd., 2001.

Bo G. Malmström (b. 1927, d. 2000) was Professor of Biochemistry at Göteborg University in 1963-1993, a member of the Nobel Committee for Chemistry in 1972-1988 and its chairman in 1977-1988.

Bertil Andersson (b. 1948) is professor in Biochemistry and President of Linköping University, Sweden (1999-2003). He was head of the Dept. of Biochemistry (1987-1995), Dean of the Faculty of Chemical Sciences and prodean of the Science Faculty, (1996-1999) at the University of Stockholm. Member (and chairman) of the Nobel Committee for Chemistry 1989- (1997);  275 papers in photosynthesis research, biological membranes, protein and membrane purification, and light stress.

The Nobel Prize in Chemistry 2015

Tomas Lindahl, Paul Modrich and Aziz Sancar

«for mechanistic studies of DNA repair»

The Nobel Prize in Chemistry 2014

Eric Betzig, Stefan W. Hell and William E. Moerner

«for the development of super-resolved fluorescence microscopy»

The Nobel Prize in Chemistry 2013

Martin Karplus, Michael Levitt and Arieh Warshel

«for the development of multiscale models for complex chemical systems»

The Nobel Prize in Chemistry 2012

Robert J. Lefkowitz and Brian K. Kobilka

«for studies of G-protein-coupled receptors»

The Nobel Prize in Chemistry 2011

Dan Shechtman

«for the discovery of quasicrystals»

The Nobel Prize in Chemistry 2010

Richard F. Heck, Ei-ichi Negishi and Akira Suzuki

«for palladium-catalyzed cross couplings in organic synthesis»

The Nobel Prize in Chemistry 2009

Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath

«for studies of the structure and function of the ribosome»

The Nobel Prize in Chemistry 2008

Osamu Shimomura, Martin Chalfie and Roger Y. Tsien

«for the discovery and development of the green fluorescent protein, GFP»

The Nobel Prize in Chemistry 2007

Gerhard Ertl

«for his studies of chemical processes on solid surfaces»

The Nobel Prize in Chemistry 2006

Roger D. Kornberg

«for his studies of the molecular basis of eukaryotic transcription»

The Nobel Prize in Chemistry 2005

Yves Chauvin, Robert H. Grubbs and Richard R. Schrock

«for the development of the metathesis method in organic synthesis»

The Nobel Prize in Chemistry 2004

Aaron Ciechanover, Avram Hershko and Irwin Rose

«for the discovery of ubiquitin-mediated protein degradation»

The Nobel Prize in Chemistry 2003

«for discoveries concerning channels in cell membranes»

Peter Agre

«for the discovery of water channels»

Roderick MacKinnon

«for structural and mechanistic studies of ion channels»

The Nobel Prize in Chemistry 2002

«for the development of methods for identification and structure analyses of biological macromolecules»

John B. Fenn and Koichi Tanaka

«for their development of soft desorption ionisation methods for mass spectrometric analyses of biological macromolecules»

Kurt Wüthrich

«for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution»

The Nobel Prize in Chemistry 2001

William S. Knowles and Ryoji Noyori

«for their work on chirally catalysed hydrogenation reactions»

K. Barry Sharpless

«for his work on chirally catalysed oxidation reactions»

The Nobel Prize in Chemistry 2000

Alan J. Heeger, Alan G. MacDiarmid and Hideki Shirakawa

«for the discovery and development of conductive polymers»

The Nobel Prize in Chemistry 1999

Ahmed H. Zewail

«for his studies of the transition states of chemical reactions using femtosecond spectroscopy»

The Nobel Prize in Chemistry 1998

Walter Kohn«for his development of the density-functional theory»
John A. Pople«for his development of computational methods in quantum chemistry»