Sunday, December 06, 2015

Domelsmith 5, photoelectron spectra of DOB, DOM

Photoelectron spectroscopy is a technique that measures the ionization potential energy of a molecule. Domelsmith and colleagues used photoelectron spectroscopy to analyze the electron-donating ability of LSD and other amphetamines. In a previous section, we saw that the 2,5-dimethoxy substitution pattern significantly lowers the first ionization potential energy of amphetamine. This section will examine methyl or Bromo substitution of the parent molecule 2,5-dimethoxy-amphetamine, such as in the compounds DOM and DOB.

The photoelectron spectra of three dimethoxy-methyl-amphetamines are given in the figure below. DOM (2,5-dimethoxy-4-methyl-amphetamine) is the best electron donor in this series, with a first ionization potential energy of 7.62 eV, as compared to 7.68 eV in 2,4-dimethoxy-5-methyl-amphetamine and 7.83 eV in 4,5-dimethoxy-2-methyl-amphetamine. Shulgin and others have stated the importance of 4-substitution for psychotomimetic amphetamines, which is supported by the finding of an improvement in electron donating ability in DOM (first ionization potential energy 7.62 eV) versus 2,5-dimethoxy-amphetamine (7.70 eV) in these studies. The amount of energy needed to ionize an electron from a 2,5-dimethoxy-4-methyl configuration is 0.08 eV less than the amount of energy needed to ionize it from a 2,5-dimethoxy configuration.

Halogens can serve as electron-donating or electron-withdrawing substituents depending on the site of attachment. The photoelectron spectra of several brominated 2,5-dimethoxy-amphetamines are shown below.

In the case of 4-brom-2,5-dimethoxy-amphetamine (DOB), bromination at the 4-position caused little change in the electronic structure, and in fact, DOB was a poorer electron donor (first ionization potential energy 7.94 eV) as compared with the parent molecule 2,5-dimethoxy-amphetamine (7.70 eV). As compared to DOM, the photoelectron spectra of DOB had additional strong bands in the 10.2-10.4 eV region due to Bromine lone-pair ionizations. According to the ionization potential energies measured by Domelsmith, 3-brom-2,4-dimethoxy-amphetamine should be a better electron donor than 4-brom-2,5-dimethoxy-amphetamine (DOB), and no Bromine substitution should be even better.

Domelsmith commented on DOB as an outlier, when discussing the correlations between the ionization potential energy and hallucinogen potency in mescaline units. The authors wrote,
"The most significant deviation from either of these equations is observed for DOB, and this molecule was not included in the correlation." (Domelsmith,L.N. 1981)


Domelsmith L. N. and K. N. Houk (1978). Photoelectron spectra of psychotropic drugs. 3. Ionization potentials and partition coefficients as predictors of substituted amphetamine psychoactivities. International journal of quantum chemistry: quantum biology symposium 5, 257-268.

Domelsmith L. N., T. A. Eaton, K. N. Houk, G. M. Anderson 3rd, R. A. Glennon, A. T. Shulgin, N. Castagnoli Jr and P. A. Kollman (1981). Photoelectron spectra of psychotropic drugs. 6. Relationships between the physical properties and pharmacological actions of amphetamine analogues. Journal of Medicinal Chemistry 24, 1414-1421.