http://www.nobel.se/chemistry/articles/malmstrom/index.html

The Nobel Prize in Chemistry:
The Development of Modern Chemistry
by Bo G. Malmstr?m
First published December 1999


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 (1879-1960) 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 (1862-1942) and his son, Sir 
Lawrence Bragg (1890-1971), 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 (1984-1966), 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 (1918- ) 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 (1980) 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 (1914- ) 
and Sir John Kendrew (1917-1997) 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  -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 (1916- ), James Watson (1928- ) and Maurice Wilkins 
(1916- ) "for their discoveries concerning the molecular structure of 
nucleic acids...". Two years later (1964) Dorothy Crowfoot Hodgkin 
(1910-1994) 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 (1919- ) 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 (1917- ) of Buffalo and Jerome Karle (1918- ) 
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 
(1926- ) 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 (1948- ), 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 (1943- ) and 
Robert Huber (1937- ), 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).