November 22, 1934
The Rockefeller Foundation
49 West Forty-ninth Street
New York City
Gentlemen:
For three years (1932-5) my researches have been supported by a grant of ten thousand
dollars per year made to the California Institute of Technology by the Rockefeller
Foundation. During this time my associates and I have been engaged in developing a
combined experimental and theoretical method of attack on difficult structural problems
such as arise in biochemistry. This preliminary work (mainly on relatively simple
molecules) has progressed very satisfactorily. We now feel, largely because of our
discovery of a new and powerful x-ray method, that we are ready to make an intensive
attack on the problem of the structure of haemoglobin and chlorophyll by application
of these newly-developed methods.
The haemoglobin project, as described in the following pages, will be difficult and
laborious. I feel confident, however, that definite and significant results can be
obtained regarding the structure of haemin and related compounds, the nature of the
bond to globin, and the process of addition of oxygen molecules, within three years.
I accordingly make application to you for a grant of ten thousand dollars per year
for three years, from July 1, 1935, to June 30, 1938, to be used in support of researches
on the structure of heamoglobin and other complex molecules of biological importance.
Although we have now developed our methods to
such an extent that they can be applied to complex biochemical problems with confidence,
I feel that it would be very short-sighted for us to abandon entirely the fundamental
investigations such as we have been carrying on, and I plan to continue these researches,
on a smaller scale, with the aid of a research fund provided by the California Institute.
The Trustees of the Institute have informed me, through Professor Millikan, that the
Institute will provide a research fund of five thousand dollars per year during the
three-year period 1935-1938, for support of researches relating to the haemoglobin
investigation.
I wish again to express my belief that the projected unified attack on the problem
of the structure of haemoglobin and related substances of biological importance, together
with the associated fundamental researches to be supported by the California Institute,
will lead to results of great interest.
Respectfully yours,
During the past year my research assistants and associates and I have devoted our
efforts mainly to three methods of attach on problems of structural chemistry; namely,
(1) the application of the quantum mechanics, (2) the study of the structure of gas
molecules by the diffraction of electron waves, and (3) the study of the structure
of crystals and other solid substances by the diffraction of x-rays.
(l) The Application of the Quantum Mechanics to Problems of Structural Chemistry. During the last year we have developed our quantum-mechanical methods (previously
applied to aromatic molecules and free radicals) to make them applicable to heterocyclic
molecules and other complex molecules containing nitrogen and oxygen atoms as well
as carbon and hydrogen. These methods have led to the formulation of a quantitative
theory of the very important phenomenon of directed substitution in the benzene ring.
A thorough treatment has also been given to the simpler heterocyclic molecules, including
pyrrole, an important constituent of the prophyrins and chlorins, which are characteristic
constituents of haemoglobin and chlorophyll. The theoretical treatment of the porphyrins
themselves has begun, and has already indicated that some of the assigned structural
formulas are incorrect.
Several other theoretical studies, dealing with hybridization of bond orbitals, normal
coordinates of vibrating molecules, van der Waals forces, etc., have been and are
being carried on.
(2) The Study of the Structure of Gas Molecules by the Diffraction of Electron Waves. We have developed and tested the electron-diffraction method of investigating the
structure of gas molecules until it rivals the spectrographic method in accuracy,*
and have applied it in determining the molecular configurations and interatomic distances
for about forty molecules. In particular, a study has been made of the
*The latter method is applicable only to very simple molecules, whereas the electron-diffraction
method can be used in studying even complex organic substances.
configuration of the pyrrole ring and of the effect of conjugation on interatomic
distances, this information being required for the formulation of the structure of
haemoglobin and chlorophyll. We are installing in our apparatus a device for vaporizing
substances of high molecular weight, and hop to investigate some of the porphyrins
themselves.
(3) The Study of the Structure of Crystals and Other Solid Substances by the Diffraction
of X-rays. Our knowledge of interatomic distances and bond angles has been increased by the
determination of the structures of several crystals during the last year. More important
than this, however, is the discovery of a new method of x-ray investigation. This
method depends on the use of the phenomenon of anomalous dispersion; in conjunction
with the Fourier series treatment developed by Warren and Patterson, it will permit
the straightforward investigation of the environment of iron atoms in haemin and should
permit a study to be made of the changes in this environment accompanying oxidation,
addition to globin, etc. It is this powerful method which will form our principal
type of experimental investigation of substances related to haemoglobin. The method
is laborious, requiring very accurate measurements and extensive calculations.
Our staff includes the following research men, in addition to several graduate students.
Research Fellows on Rockefeller Fund.
Dr. J. H. Sturdivant, x-ray work.
Dr. L.O.Brockway, electron diffraction.
Dr. G.W.Wheland, quantum mechanics of organic molecules(Harvard).
Dr. J.Sherman, computers and general assistants.
Dr. S.Weinbaum, computers and general assistants.
Additional Research Fellows.
Dr. L. E. Sutton, International Fellow in Organic Chemistry (Oxford). Electron Diffraction
Dr. L. Helmholz, National Research Fellow (Johns Hopkins). Crystal Structure.
Dr. L. K. Frevel, National Research Fellow (Johns Hopkins). Crystal Structure.
Dr. H. O. Jenkins, Commonwealth Fellow (Oxford). Electron diffraction.
Dr. L. La Coste, quantum mechanics (Texas).
[2 pages of Published Papers]
