Tuesday, April 04, 2017

Charge-transfer mechanism of drugs 2.

The electron-donating tendency of a molecule can be expressed in terms of the energy of its outermost HOMO electron, which is determined theoretically, or its ionization potential energy, which can be measured with a piece of lab equipment called a photoelectron spectrometer. There is good agreement between HOMO values and the ionization potential energy, adding to the predictive value of molecular orbital theory. From Kier, the figure below shows that Ehomo is related to ionization potential energy in electron volts.

The next figure shows a similar linear relationship, except that ionization potential energy is now plotted on the x-axis with Ehomo energies on the y-axis. The chemicals studied were phenethylamines and tryptamines.

The kHOMO and ionization potential energy have been studied with interest because the values can be used to predict whether a certain reagent is likely to participate in a chemical reaction, or form a charge-transfer complex. For example, in the next figure, the energy of formation of a donor-acceptor complex is linearly related to the HOMO energy of the electron donor molecule. An experiment was performed where the electron donors naphthalene (1), phenanthrene (2), pyrene (3), anthracene (4), and naphthacene (5), were mixed with electron acceptors trinitrobenzene (TNB), trinitrofluorenone (THF), and tetracyanoquinodimethane (TCNQ). Each electron donor molecule was mixed with an electron acceptor molecule, and the energy of formation was measured. The plot shows that the kHOMO of the electron donor is correlated to the energy of formation of different charge-transfer complexes.

These results show that a charge-transfer reaction relies, to a great extent, on the tendency of the electron donor molecule to part with one of its electrons.


Kier L. B. Molecular orbital theory in drug research. Academic Press, New York, 1971.

Ariens E. J. Drug design. Medicinal chemistry series, de Stevens G. (Ed.), Academic Press, New York, 1971.

Domelsmith L. N., L. L. Munchausen and K. N. Houk (1977). Photoelectron spectra of psychotropic drugs. 1. Phenethylamines, tryptamines, and LSD. Journal of the American Chemical Society 99, 4311-4321.