Published on: 2026-04-08
Source: Novosibirsk State University –
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When studying the effect of high pressure on one of the polymorphic modifications of the antidiabetic drug chlorpropamide using synchrotron radiation, scientists from the Department of Solid State Physics of the Faculty of Natural Sciences of Novosibirsk State University discovered the formation of a new high-pressure phase. Taking advantage of the brightness of synchrotron radiation beams, they were able to detect the existence of an intermediate incommensurately modulated phase and establish its structure.Post-laboratory experiments have added valuable information about the possibility of obtaining the final high-pressure phase, bypassing intermediate stages and at significantly lower pressures than in synchrotron experiments. These results indicated to researchers the difference between the results of synchrotron experiments at different installations and how it can affect the interpretation of the results. The new data will help better understand the mechanisms of structural transformations in organic crystals under various external influences, as well as look at X-ray experiments from a different angle.The results of the study are presented in the article “A new modulated δ-phase of N-propylamide at high pressure: when the experimental setup matters,” published inin the specialized journal of the International Union of Crystallographers IUCrJ, relating to Q1 (IF: 3.6).
—Chlorpropamide is a rather unique compound. On the one hand, it is an antidiabetic drug used for the treatment of type 2 diabetes, so, like all pharmaceutical substances, it receives increased attention and strict control. For this purpose, detailed and comprehensive studies are conducted using a wide variety of methods and under various conditions. What makes it even more interesting is that chlorpropamide is among the record holders for the number of registered polymorphs — compounds with the same chemical composition but different spatial structures.To date, more than a dozen of its forms have been described, 7 of which are stable under normal conditions, making it an excellent model system for studying the response of crystal structures to external influences: pressure or temperature. Compounds with such a number of polymorphic modifications are known to be few, so d-lorpyramid can be considered a unique object. Such a wealth of forms in one compound requires comprehensive research. The subject of our work was d-lorpyramid, a form that has the highest calculated density but has not been studied under high-pressure conditions.— said the senior lecturer of the Department of Solid State Physics of the Faculty of Natural Sciences of NSUNikita Bogdanov.
Single crystals of δ-lorpropamide were obtained at the Department of Solid State Chemistry and studied by single-crystal X-ray diffraction methods using synchrotron radiation source and under laboratory conditions. The experiments were conducted in a high-pressure cell with diamond anvils, which allows studying the compound’s structure in situ by single-crystal X-ray diffraction methods. The study was carried out at the European Synchrotron Radiation Facility (ESRF, Grenoble, France), which at that time was a source of third-generation synchrotron radiation.Unexpected results were obtained during the experiments.
During the study of samples under high pressure, a phase transition was discovered — a structural transformation of matter, where an increase in pressure causes a change in the crystal lattice. From the initial phase, a high-pressure phase formed, characterized by tripling one of the unit cell parameters. Notably, the structural transformation occurred through the formation of an intermediate phase — a misfit-modulated structure.
—The formation of an incommensurately modulated structure is a very rare phenomenon in the world of molecular organic crystals. To date, only two examples possessing this property have been described in the literature, and both were found by scientists of the Department of Solid State Physics at FEN NGU. We faced the task of deciphering this structure, which represents an intermediate state between the low-pressure phase and the high-pressure phase, and determining exactly how the phase transition occurred. For this purpose, two synchrotron experiments were conducted at different stations.However, synchrotron measurements are quite limited in time, which led to the idea of repeating the study of the structure of δ-lorpropiamide using a state-of-the-art laboratory diffractometer at the Rigaku RESE demonstration center (Frankfurt, Germany), where there are no such limitations, in an attempt to collect the most detailed structural data possible. However, this time we did not observe the disproportionately modulated structure. And, what is even more interesting, the formation of the high-pressure phase was observed at a significantly lower pressure value than in the experiment at the synchrotron radiation source., — saidNikita Bogdanov. Â
Using bright beams of synchrotron radiation combined with modern detectors that provide fast data collection, scientists have been able to detect that the phase transformation at high pressure occurs through the formation of an intermediate incommensurately modulated phase and to identify its crystal structures. Even the most advanced laboratory diffractometers were unable to provide this information.However, it was precisely thanks to laboratory studies that scientists learned about the possibility of forming a high-pressure phase without passing through intermediate stages and at significantly lower pressures than in synchrotron experiments. This indicated to scientists the difference between the results of experiments using different sources of X-ray radiation. Thanks to the combination of these two approaches, it was possible to decipher the structure of δ-lorpropamide in all phases and to fully describe the mechanism of phase transition with atomic-scale accuracy in space.Researchers are confident that the new data can shed more light on the mechanisms of structural transformations in other organic crystals, helping to better understand the nature of the response of crystal structures to external influences.
—There are subtle structural changes that can be recorded exclusively at synchrotron sources. The commissioning of the Siberian Circular Photon Source (SKIF) will allow scientists to conduct appropriate studies, which will significantly expand and possibly considerably advance the understanding of mechanisms of fundamental physico-chemical processes.It is precisely synchrotron sources that allow one to see structural aspects and trace the transformation of substances from one state to another, which is not accessible to other methods, but at the same time, laboratory studies should not be neglected, since it is they that help to reveal, for example, more extended effects over time, the study of which on a synchrotron source is not always advisable due to the limited time available for research,— explainedNikita Bogdanov.
Thus, the obtained results not only made it possible to identify and establish an unusual mechanism of phase transition, which can be applied to the study of other systems. They contributed to a more detailed understanding of the nature of structural transformations and became evidence of the novelty of combining laboratory and synchrotron research methods.
The discovery that a phase transition can occur through the formation of an intermediate incommensurately modulated phase, for the detection of which the use of synchrotron radiation is indispensable, can provide scientists with additional information for future studies of phase transformations.The very fact that other phases of substances, detectable only by synchrotron radiation, can exist may also have practical significance, including for the pharmaceutical industry, since intermediate phases are often significantly more reactive and therefore more active, which can serve as an additional incentive for studying their structure and properties.
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