An international research team led by the University of Vienna has developed a groundbreaking method to directly measure partial charges in molecules. This innovative technique, recently published in the prestigious journal Nature, promises to revolutionize our understanding of molecular interactions and has potential applications in drug development and materials science.
Electrostatic forces, which are the attractive or repulsive interactions between atoms or molecules, are fundamental to how molecules assemble, align, and respond to one another. In chemistry, these forces are expressed in terms of partial charges, which are tiny imbalances in electron distribution within a molecule. These subtle shifts in charge dictate how molecules interact with each other and their surroundings, playing a crucial role in chemical reactivity, biological functions, and material behavior.
Breakthrough in Measuring Molecular Charges
Leading the charge in this scientific breakthrough are Tim Grüne, Head of the Core Facility for Crystal Structure Analysis, and Christian Schröder from the Department of Computational Biological Chemistry at the University of Vienna. The team has developed a method that allows for the experimental determination of partial charges. “We used a technique called electron diffraction,” explains Grüne. “It involves directing a fine beam of electrons at a tiny crystal. Because electrons are charged, they are sensitive to the electrostatic potential within the crystal and thus to the partial charges of atoms. The resulting tiny deflections in the beam were recorded using a new camera developed at the Paul Scherrer Institute in Switzerland.”
The researchers combined the diffraction data with a novel analysis method known as ionic scattering factor modelling (iSFAC). This approach models each atom of a molecule simultaneously as a neutral and a charged species. By comparing the model with the experimental data, the researchers successfully quantified the partial charge of each atom.
“Until now, partial charges were estimated using computational methods,” says Christian Schröder. “Our new experimental technique now provides a means to assess and refine these theoretical models by offering a direct link.”
Broad Applicability Across Molecular Types
To demonstrate the wide-ranging applicability of their method, the researchers examined a diverse set of crystalline compounds. These included the industrial catalyst ZSM-5, the amino acids tyrosine and histidine, tartaric acid from Austrian wine, and the widely used antibiotic Ciprofloxacin. Ciprofloxacin, which is on the World Health Organization’s list of essential medicines and is commonly administered as a hydrochloride salt, showed that the chloride ion (Cl⁻) carries only about 40 percent of a full negative charge. This finding underscores how significantly a molecule’s environment can influence local charge distribution.
Potential for Pharmaceuticals and Materials Design
The Core Facility for Crystal Structure Analysis at the University of Vienna has been at the forefront of advancing electron crystallography in recent years. With this latest breakthrough, the technique has moved beyond merely determining atomic positions to experimentally revealing electronic properties. The ability to measure partial charges opens new possibilities for designing pharmaceuticals with greater specificity and fewer side effects, as well as functional materials with precisely tuned properties.
This development represents a significant leap forward in molecular science, with the potential to impact a wide range of fields. As researchers continue to explore the implications of this technique, it may soon become a standard tool in laboratories worldwide, driving innovation in both pharmaceuticals and materials science.
As the scientific community absorbs these findings, the next steps will likely involve refining the technique and exploring its applications in more complex molecular systems. The implications for future research and industry are vast, promising a new era of precision in molecular design and interaction understanding.
