In 1926, Pauling was awarded a
Guggenheim Fellowship to travel to Europe, to study under German physicist
Arnold Sommerfeld in Munich, Danish physicist
Niels Bohr in Copenhagen and Austrian physicist
Erwin Schrödinger in
Zürich. All three were experts in the new field of
quantum mechanics and other branches of physics. Pauling devoted the two years of his European trip to this work and decided to make it the focus of his future research. He became one of the first scientists in the field of quantum chemistry and a pioneer in the application of quantum theory to the structure of molecules. In 1927, Pauling took a new position as an assistant professor at
Caltech in
theoretical chemistry. He launched his faculty career with a very productive five years, continuing with his
X-ray crystal studies and also performing quantum mechanical calculations on atoms and molecules. He published approximately fifty papers in those five years, and created the five rules now known as
Pauling's rules. By 1929, he was promoted to associate professor, and by 1930, to full professor. The following year, Pauling published what he regarded as his most important paper, in which he first laid out the concept of
hybridization of atomic orbitals and analyzed the
tetravalency of the
carbon atom. At Caltech, Pauling struck up a close friendship with
theoretical physicist Robert Oppenheimer at the
University of California, Berkeley, who spent part of his research and teaching schedule as a visitor at Caltech each year. Pauling was also affiliated with Berkeley, serving as a visiting lecturer in physics and chemistry from 1929 to 1934. Oppenheimer even gave Pauling a stunning personal collection of minerals. The two men planned to mount a joint attack on the nature of the chemical bond: apparently Oppenheimer would supply the mathematics and Pauling would interpret the results. Their relationship soured when Oppenheimer tried to pursue Pauling's wife, Ava Helen. When Pauling was at work, Oppenheimer came to their home and blurted out an invitation to Ava Helen to join him on a tryst in Mexico. She flatly refused, and reported the incident to Pauling. He immediately cut off his relationship with Oppenheimer. Pauling introduced the concept of
electronegativity in 1932. Using the various properties of molecules, such as the energy required to break bonds and the
dipole moments of molecules, he established a scale and an associated numerical value for most of the elementsthe
Pauling Electronegativity Scalewhich is useful in predicting the nature of bonds between atoms in molecules. In 1936, Pauling was promoted to chairman of the division of chemistry and chemical engineering at Caltech, and to the position of director of the Gates and Crellin Laboratories of Chemistry. He would hold both positions until 1958.
Nature of the chemical bond In the late 1920s, Pauling began publishing papers on the nature of the
chemical bond. Between 1937 and 1938, he took a position as George Fischer Baker Non-Resident Lecturer in Chemistry at
Cornell University. While at Cornell, he delivered a series of nineteen lectures and completed the bulk of his famous textbook
The Nature of the Chemical Bond. In the 30 years after its first edition was published in 1939, the book was cited more than 16,000 times. Even today, many modern scientific papers and articles in important journals cite this work, more than seventy years after the first publication. Part of Pauling's work on the nature of the chemical bond led to his introduction of the concept of
orbital hybridization. While it is normal to think of the electrons in an atom as being described by
orbitals of types such as
s and
p, it turns out that in describing the bonding in molecules, it is better to construct functions that partake of some of the properties of each. Thus the one 2s and three 2p orbitals in a carbon atom can be (mathematically) 'mixed' or combined to make four equivalent orbitals (called sp3 hybrid orbitals), which would be the appropriate orbitals to describe carbon compounds such as
methane, or the 2s orbital may be combined with two of the 2p orbitals to make three equivalent orbitals (called sp hybrid orbitals), with the remaining 2p orbital unhybridized, which would be the appropriate orbitals to describe certain
unsaturated carbon compounds such as
ethylene. Other hybridization schemes are also found in other types of molecules. Another area which he explored was the relationship between
ionic bonding, where electrons are transferred between atoms, and
covalent bonding, where electrons are shared between atoms on an equal basis. Pauling showed that these were merely extremes, and that for most actual cases of bonding, the
quantum-mechanical wave function for a polar molecule AB is a
combination of wave functions for covalent and ionic molecules. Here Pauling's
electronegativity concept is particularly useful; the electronegativity difference between a pair of atoms will be the surest predictor of the degree of ionicity of the bond. The third of the topics that Pauling attacked under the overall heading of "the nature of the chemical bond" was the accounting of the structure of
aromatic hydrocarbons, particularly the prototype,
benzene. The best description of benzene had been made by the German chemist
Friedrich Kekulé. He had treated it as a rapid interconversion between two structures, each with alternating single and
double bonds, but with the double bonds of one structure in the locations where the single bonds were in the other. Pauling showed that a proper description based on quantum mechanics was an intermediate structure which was a blend of each. The structure was a superposition of structures rather than a rapid interconversion between them. The name "
resonance" was later applied to this phenomenon. In a sense, this phenomenon resembles those of hybridization and also polar bonding, both described above, because all three phenomena involve combining more than one electronic structure to achieve an intermediate result.
Ionic crystal structures In 1929, Pauling published
five rules which help to
predict and explain
crystal structures of
ionic compounds.
Biological molecules In the mid-1930s, Pauling, strongly influenced by the biologically oriented funding priorities of the Rockefeller Foundation's
Warren Weaver, decided to strike out into new areas of interest. Although Pauling's early interest had focused almost exclusively on inorganic molecular structures, he had occasionally thought about molecules of biological importance, in part because of Caltech's growing strength in biology. Pauling interacted with such great biologists as
Thomas Hunt Morgan,
Theodosius Dobzhanski,
Calvin Bridges and
Alfred Sturtevant. His early work in this area included studies of the structure of
hemoglobin with his student
Charles D. Coryell. He demonstrated that the hemoglobin molecule changes structure when it gains or loses an
oxygen molecule. It took eleven years for Pauling to explain the problem: his
mathematical analysis was correct, but Astbury's pictures were taken in such a way that the protein molecules were tilted from their expected positions. Pauling had formulated a model for the structure of hemoglobin in which atoms were arranged in a
helical pattern, and applied this idea to proteins in general. In 1951, based on the structures of
amino acids and
peptides and the planar nature of the
peptide bond, Pauling,
Robert Corey and
Herman Branson correctly proposed the
alpha helix and
beta sheet as the primary
structural motifs in protein
secondary structure. This work exemplified Pauling's ability to think unconventionally; central to the structure was the unorthodox assumption that one turn of the helix may well contain a non-
integer number of amino acid residues; for the alpha helix it is 3.7 amino acid residues per turn. Pauling then proposed that
deoxyribonucleic acid (DNA) was a
triple helix; his model contained several basic mistakes, including a proposal of neutral phosphate groups, an idea that conflicted with the acidity of DNA.
Sir Lawrence Bragg had been disappointed that Pauling had won the race to find the alpha
helix structure of proteins. Bragg's team had made a fundamental error in making their models of protein by not recognizing the planar nature of the peptide bond. When it was learned at the
Cavendish Laboratory that Pauling was working on molecular models of the structure of DNA,
James Watson and
Francis Crick were allowed to make a molecular model of DNA. They later benefited from unpublished data from
Maurice Wilkins and
Rosalind Franklin at
King's College which showed evidence for a helix and planar base stacking along the helix axis. Early in 1953 Watson and Crick proposed a correct structure for the DNA double helix. Pauling later cited several reasons to explain how he had been misled about the structure of DNA, among them misleading density data and the lack of high quality X-ray diffraction photographs. Pauling described this situation as "the biggest disappointment in his life". During the time Pauling was researching the problem, Rosalind Franklin in England was creating the world's best images. They were key to Watson's and Crick's success. Pauling did not see them before devising his mistaken DNA structure, although his assistant Robert Corey did see at least some of them, while taking Pauling's place at a summer 1952 protein conference in England. Pauling had been prevented from attending because his passport was withheld by the State Department on suspicion that he had Communist sympathies. This led to the legend that Pauling missed the structure of DNA because of the politics of the day (this was at the start of the
McCarthy period in the United States). Politics did not play a critical role. Not only did Corey see the images at the time, but Pauling himself regained his passport within a few weeks and toured English laboratories well before writing his DNA paper. He had ample opportunity to visit Franklin's lab and see her work, but chose not to. He was also among the first scientists to postulate that the binding of
antibodies to antigens would be due to a complementarity between their structures. Along the same lines, with the physicist turned biologist
Max Delbrück, he wrote an early paper arguing that
DNA replication was likely to be due to
complementarity, rather than similarity, as suggested by a few researchers. This was made clear in the model of the structure of DNA that Watson and Crick discovered.
Molecular genetics In November 1949, Pauling,
Harvey Itano,
S. J. Singer and Ibert Wells published "
Sickle Cell Anemia, a Molecular Disease" in the journal
Science. It was the first proof of a human disease being caused by an abnormal protein, and
sickle cell anemia became the first disease understood at the molecular level. (It was not, however, the first demonstration that variant forms of hemoglobin could be distinguished by electrophoresis, which had been shown several years earlier by
Maud Menten and collaborators). Using
electrophoresis, they demonstrated that individuals with
sickle cell disease have a modified form of hemoglobin in their
red blood cells, and that individuals with
sickle cell trait have both the normal and abnormal forms of hemoglobin. This was the first demonstration causally linking an abnormal protein to a disease, and also the first demonstration that
Mendelian inheritance determines the specific physical properties of proteins, not simply their presence or absence – the dawn of
molecular genetics. His success with sickle cell anemia led Pauling to speculate that a number of other diseases, including mental illnesses such as
schizophrenia, might result from flawed genetics. As chairman of the Division of Chemistry and Chemical Engineering and director of the Gates and Crellin Chemical Laboratories, he encouraged the hiring of researchers with a chemical-biomedical approach to mental illness, a direction not always popular with established
Caltech chemists. In 1951, Pauling gave a lecture entitled "Molecular Medicine". In the late 1950s, he studied the role of enzymes in brain function, believing that mental illness may be partly caused by enzyme dysfunction. In the 1960s, as part of his interest in the effects of nuclear weapons, he investigated the role of mutations in evolution, proposing with his student Emile Zuckerkandl, the molecular evolutionary clock, the idea that mutations in proteins and DNA accumulate at a constant rate over time .
Structure of the atomic nucleus On September 16, 1952, Pauling opened a new research notebook with the words "I have decided to attack the problem of the structure of nuclei." On October 15, 1965, Pauling published his Close-Packed Spheron Model of the atomic nucleus in two well respected journals,
Science and the
Proceedings of the National Academy of Sciences. For nearly three decades, until his death in 1994, Pauling published numerous papers on his spheron cluster model. The basic idea behind Pauling's spheron model is that a nucleus can be viewed as a set of "clusters of nucleons". The basic nucleon clusters include the
deuteron [np],
helion [pnp], and
triton [npn].
Even–even nuclei are described as being composed of clusters of
alpha particles, as has often been done for light nuclei. Pauling attempted to derive the shell structure of nuclei from pure geometrical considerations related to
Platonic solids rather than starting from an independent particle model as in the usual
shell model. In an interview given in 1990 Pauling commented on his model: ==Activism==