The team at the University of Vienna is developing a method to measure molecular loads

An international research team led by the University of Vienna has managed to develop a new method to directly. Moreover, measure partial loads in molecules. For example, The results. Meanwhile, now published in NatureProvide new information on molecular interactions and offer potential applications in the development of drugs and materials science.

Electrostatic forces – attractive. Meanwhile, repulsive interactions between atoms or molecules – are at the heart of all molecular interactions: they are fundamental on the way molecules assemble, line up and react. Moreover, In chemistry. Therefore, these forces are described in terms of partial loads: tiny imbalances in the way the electrons are distributed in a molecule.

These subtle changes in charge govern the way molecules interact with each other and their environment. However, They are essential to understanding chemical reactivity, team university vienna developing method biological function and material behavior. In medicine. for example, partial charges influence the way drugs are absorbed, distributed and metabolized – and can shape both their therapeutic effects and their potential side effects. However, despite their meaning, partial charges have remained purely theoretical: so far, there was no way to measure them directly.

Pierced in the extent of molecular loads – Team university vienna developing method

A research team led by Tim Grüne. head of the basic installation for the analysis of the crystalline structure, and Christian Schröder of the Department of Biological Computer Chemistry of the University of Vienna, has now developed a method that makes it possible to experimentally determine partial charges.

We used a technique called electron diffraction. This involves directing a fine bundle of electrons to a small crystal. Because the electrons are loaded. they are sensitive to the electrostatic potential in the crystal and therefore to the partial loads of team university vienna developing method the atoms. The tiny deviations resulting in the bundle were recorded using a new camera developed at the Paul Scherrer Institute. in Switzerland. “”

Tim Grüne, Chef, Core Facility for Crystal Structure Analysis, Department of Computational Biological Chemistry from the University of Vienne

The team has combined diffraction data with a new analysis method called Modeling Ionic Diffusion factors (ISFAC). In this approach, each atom of a molecule is modeled simultaneously as a neutral and loaded species. By comparing the model with the experimental data, the researchers were able to quantify the partial load of each atom.

“Until now, partial charges have been estimated using calculation methods,” explains Christian Schröder. “Some of these adjusted atomic charges to reproduce the molecular electrostatic potential, resulting in so -called electrostatic potential loads (ESP). Others share the electronic density itself among the atoms. Although widely used in molecular modeling, team university vienna developing method these methods can produce different values ​​depending on the algorithm. Our new experimental technique now provides a means of assessing and refusing these models of supply of experimental technique.

Large applicability between molecular types

To demonstrate the large applicability of their method. the researchers have examined a diversified set of crystalline compounds-including the ZSM-5 industrial catalyst, tyrosine and histidine of amino acids, tartaric acid of Austrian wine and largely used antibiotic ciprofloxacin. For ciprofloxacin. which appears on the list of essential drugs of the World Health Organization and is commonly administered in hydrochloride salt, the analysis has shown that the chloride ion (CL⁻), only carries 40% of a complete negative load. This shows how the environment of a molecule can influence the local distribution of loads.

Pharmaceutical. material design potential

The basic installation of the analysis of the crystal structure at the University of Vienna has played a key role team university vienna developing method in the progression of electrons crystallography in recent years. With this last breakthrough, the technique goes beyond determining atomic positions to experimentally reveal electronic properties. The capacity to measure partial charges opens up new possibilities for the design of pharmaceutical products with a higher specificity. fewer side effects, as well as functional materials with precisely adjusted properties.