The geometry of histamine

Histamine is a biologically active substance involved in the regulation of many functions of organisms. It is responsible for evolving of several pathological conditions, in particular allergic reactions.

Allergic action of histamine is expressed mainly in affecting several receptors located on the cell surface. Within this framework, histamine is often compared to the key, and receptors to locks the key opens and respectively launches a number of different physiological processes -- from headaches, skin rashes, and diarrhea, up to anaphylactic shock. Modern antiallergic medicines -- antihistaminic drugs -- are competing with histamine for receptors, preventing the "key" getting close to the "lock." Unfortunately, numerous experimental and theoretical studies still did not give a complete idea of the geometry of histamine, and this is the very begin of the beginning for assessing the properties and potential of this substance.

"It's very hard to get data on the geometric structure of histamine," says one of the authors of the article Doctor of Science Leonid Khaikin, a lead researcher at the Laboratory of Gas Electron Diffraction (Chemical Faculty of Lomonosov MSU). "It is due to the fact that in this case the geometry of the individual conformers constituting histamine is determined by so many factors influencing each other."

The experimental method used by researchers from Moscow State University was gas electron diffraction. Basically, it is a beam of fast electrons in high vacuum passing through the vapor of the investigated substance. Electrons are scattered after the collisions with the molecules and the resulting diffraction pattern is recorded.

"This pattern can be used to understand the geometry of the molecule, one can compare it to a fingerprint, which helps to determine its owner," Khaikin explains, "In other words, the diffraction pattern obtained is characteristic of histamine, and analyzing this picture, we can infer the geometric characteristics of the molecule encrypted in the pattern. The problem was also in the fact that such a "fingerprint" could be left by more than one "finger" (histamine conformer). Therefore, we had to carry out multiple quantum-chemical calculations and to use reported spectroscopic data for vibrational and rotational spectra, and so on."

This study can't be considered purely experimental. Most of the work had begun after the experiment, and it was a purely analytical work. According to Khaikin, analysis of the obtained diffraction pattern was the most difficult and the longest part of the work, which took several months of hard work. According to another co-author of the study, all of the experimental work has been carried out entirely in the MSU, the same applies to the theoretical part, except for a few significant calculations made by MSU graduate Denis Tikhonov in a cluster of University of Bielefeld (Germany).

As a result, MSU scientists were able to adjust all the available experimental and theoretical data on the structure of histamine. It was also possible to predict theoretically the mechanism of so-called tautomerization of histamine, a spontaneous transition of the molecule from one structural state to another. It has helped to reconcile the data observed in different experiments.

The results can now be used in different reference databases of structural and spectral data, for further development of theoretical concepts of structural chemistry, and evaluation of the reactivity of the compounds. As it often happens with the results of fundamental science, it will take a long time before we can talk about practical application of these results in medicine. Quite possibly that knowledge about the mechanism of histamine molecule transition from one structural state to another might help to find more effective drugs against allergies.