Sunday, December 06, 2015

LSD charge-transfer complexes 1. LSD-tetracyanoethylene

The electron donor molecule LSD forms a charge-transfer complex with the electron acceptor tetracyanoethylene (TCNE). The charge-transfer complex has a characteristic absorption band, allowing the detection of the presence of LSD. When LSD or other hallucinogen drugs are applied to a silica gel plate and then sprayed with either TCNE or other electron acceptor drugs, a color band is detected.

In 1968, Millie and colleagues studied the electronic properties of methoxylated indoles and tryptamines by their ability to form charge-transfer complexes with TCNE or 1,3,5-trinitrobenzene (TNB), another electron acceptor. Many indoles and phenothiazines form a charge-transfer complex with TCNE or TNB; the wavelength of the absorption maximum of the complex is often between 300-720 nm. As shown in the figure below, the authors found a correlation between the absorption maximum of the acceptor-TCNE or acceptor-TNB complexes and kHOMO values of the donator indoles and tryptamines. The x-axis is the kHOMO while the y-axis is 1000/lambda, where lambda is the maximum absorption wavelength of the charge-transfer reaction product.

1-methyl-LSD was among the indoles and phenothiazines that were tested. The charge-transfer complex of TCNE and 1-methyl-LSD (letter p, Figure 1 above) had an absorption maximum at 520 nm. As determined by Huckel calculations, 1-methyl-LSD had kHOMO=0.487. This kHOMO value is larger than Ehomo=0.218 obtained for LSD by Karreman in 1959, though on the whole these values suggest good electron donating ability. According to the figure above, the electron-donating ability of 1-methyl-LSD (p) lies between 4-methoxy-indole (i) and 6-methoxy-indole (k).

TCNE-bezene complexes are used to study the electron-donating properties of different benzene derivatives

There is no mystery about the physical and chemical forces that bind a hallucinogen drug to biological receptors. The forces may be compared with the physical and chemical forces that bind TCNE to benzene or indoles. For example, the ionization potential of an electron donor molecule can predict the rate of formation of its drug-TCNE complex, as shown by Domelsmith et al. in 1977. Several different benzene derivatives were mixed with the electron acceptor TCNE, and the rate of formation of benzene-TCNE complexes was measured. When the apparent enthalpy of formation of the benzene-TCNE complexes was plotted versus the average of the first and second ionization potential energies of the benzene molecules, an excellent linear correlation was obtained (Figure 12 below).

Quantum mechanics is the method used to calculate the kHOMO energy. The dose of structurally diverse hallucinogens to produce consciousness alteration is correlated with the drug's kHOMO value, so it is very likely that quantum electronic properties of matter play a role in the mechanism of consciousness alteration.


Fulton A. and L. E. Lyons (1967). Electron-accepting strength of NAD+. Australian Journal of Chemistry 20, 2267-2268.

Millie P., J. P. Malrieu, J. Benaim, J. Y. Lallemand and M. Julia (1968). Researches in the indole series. XX. Quantum mechanical calculations and charge-transfer complexes of substituted indoles. Journal of Medicinal Chemistry 11, 207-211. 10.1021/jm00308a003

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.

No comments: