physics underlying the technique. Most importantly the subject has attracted successive generations of talented scientists who wanted to answer the really big
scientific problems of the age and were willing to push the subject to new limits
and develop techniques to study ever more complex systems. It was inconceivable
that when the structure of sodium chloride and zinc sulphide was initially solved in
1912 that within 50 years the same technique would be used to solve the structures of
myoglobin and haemoglobin and provide information concerning the structure of the
DNA which would revolutionise the field of genetics.
This extraordinary successful scientific endeavour has to a large extent made the
solving of small molecules structures routine, but the solution of many structures
within hours carries with it the responsibility to ensure that the structural information
is accurate and reproduceable and archived in a fashion which makes it accessible to
the whole scientific community. As the technology has developed, opportunities
have arisen to undertake crystallographic experiments that were not possible a few
years previously. These include the studies of structures as they are irradiated by
light, exposed to high pressures or other environmental conditions. The question of
crystallographic disorder has remained a continuing issue with structural determinations and cannot always be handled satisfactorily using automatic structure solution programmes. Distinguishing atoms which are adjacent in the periodic table and
very light atoms such as hydrogen have always been a problem for the technique
since X-ray scattering and diffraction depend on the number of electrons associated
with the atom. The use of quantum mechanical calculations to model the electron
densities in atoms and molecules has developed greatly in recent decades and
enabled scientists the opportunity to use this technique to investigate bonding issues
in molecules and solids [2, 3]. This introductory chapter introduces the historical
background to the discovery and exploitation of this technique. The subsequent
chapters written by world experts in small molecule crystallography discuss recent
developments and the prospects for the future. The extension of the technique to
molecules of biological systems has proved to be particularly successfully and has
resulted in many important and significant insights and will not be covered in this
volume, and the reader is directed to other excellent sources [4]. Examples of
excellent textbooks which present a more detailed account of the theoretical principles of X-ray diffraction and its practical aspects are given in references [5–14].
2 Early Experiments
In 1895 Wilhelm Conrad Röntgen [15] became the first person to detect and
appreciate the novel properties of X-rays, and he started the sequence of experiments
which led to the development of X-ray crystallography. Several centuries earlier the
discovery of the optical microscope enabled scientists to directly view objects which
were invisible to the naked eye and contributed greatly to the scientific revolution. In
1667 Robert Hooke improved the microscope first developed in 1590 by two Dutch
spectacle makers, Hans and Zacharias Janssen, and he explored and illustrated the
Early History of X-Ray Crystallography
3
scientific problems of the age and were willing to push the subject to new limits
and develop techniques to study ever more complex systems. It was inconceivable
that when the structure of sodium chloride and zinc sulphide was initially solved in
1912 that within 50 years the same technique would be used to solve the structures of
myoglobin and haemoglobin and provide information concerning the structure of the
DNA which would revolutionise the field of genetics.
This extraordinary successful scientific endeavour has to a large extent made the
solving of small molecules structures routine, but the solution of many structures
within hours carries with it the responsibility to ensure that the structural information
is accurate and reproduceable and archived in a fashion which makes it accessible to
the whole scientific community. As the technology has developed, opportunities
have arisen to undertake crystallographic experiments that were not possible a few
years previously. These include the studies of structures as they are irradiated by
light, exposed to high pressures or other environmental conditions. The question of
crystallographic disorder has remained a continuing issue with structural determinations and cannot always be handled satisfactorily using automatic structure solution programmes. Distinguishing atoms which are adjacent in the periodic table and
very light atoms such as hydrogen have always been a problem for the technique
since X-ray scattering and diffraction depend on the number of electrons associated
with the atom. The use of quantum mechanical calculations to model the electron
densities in atoms and molecules has developed greatly in recent decades and
enabled scientists the opportunity to use this technique to investigate bonding issues
in molecules and solids [2, 3]. This introductory chapter introduces the historical
background to the discovery and exploitation of this technique. The subsequent
chapters written by world experts in small molecule crystallography discuss recent
developments and the prospects for the future. The extension of the technique to
molecules of biological systems has proved to be particularly successfully and has
resulted in many important and significant insights and will not be covered in this
volume, and the reader is directed to other excellent sources [4]. Examples of
excellent textbooks which present a more detailed account of the theoretical principles of X-ray diffraction and its practical aspects are given in references [5–14].
2 Early Experiments
In 1895 Wilhelm Conrad Röntgen [15] became the first person to detect and
appreciate the novel properties of X-rays, and he started the sequence of experiments
which led to the development of X-ray crystallography. Several centuries earlier the
discovery of the optical microscope enabled scientists to directly view objects which
were invisible to the naked eye and contributed greatly to the scientific revolution. In
1667 Robert Hooke improved the microscope first developed in 1590 by two Dutch
spectacle makers, Hans and Zacharias Janssen, and he explored and illustrated the
Early History of X-Ray Crystallography
3