Understanding Drugs at the Supramolecular Level using Structural Chemistry – an Interview with Professor Izabela Madura, Warsaw University of Technology
December 6, 2022
In this blog we talked to Professor Izabela Madura, Faculty of Chemistry at the Warsaw University of Technology in Poland, about her team's use of the Cambridge Structural Database (CSD) and software to understand the structure, behaviour and properties of chemicals, in this case pharmaceuticals.
Professor Madura’s research focuses on structural chemistry, particularly associated with bioactive molecules.
“The aim of my research is not only to determine the crystal structure of new molecules but to understand how the changes introduced to molecules or crystals influence the physicochemical properties of bioactive compounds.”
What Role Does Crystallography Play in Your Research?
“Crystallography was my love from the beginning of my undergraduate studies, mainly because it combined chemistry, physics, and mathematics. At that time, I met my mentor, now Professor Janusz Zachara, who introduced me to the study of X-ray diffraction and showed me the beauty of the structure correlation methods.”
“I always carefully analyse each structure and compare it to similar ones to get a broader view and try to understand why molecules interact the way they interact. I often wonder if it is possible to change the interaction hierarchy and find a different polymorph, co-crystal, or solvate. Now, together with my colleagues from the Faculty of Pharmacy of the Medical University of Warsaw, we are trying to “correct” important drugs at the supramolecular level. Crystallography is where I come in.”
How Is the CSD and CSD Software Used in Your Work?
“The CSD and CCDC software are the foundations of my work. I use ConQuest to quickly search structures, both organic and organometallic, to see if similar compounds are present in the database. If they are, I focus on fragment similarity and try to discover how the differences influence various structural aspects and further compound properties.”
“3D search allows a quick check to identify if there are any outliers and then analyse the structural aspects of similar compounds. Mercury is invaluable for visualizing, comparing, and analysing structures.”
What Is Your Latest Drug Development Project Using the CSD?
New CCDC software releases inspire Professor Madura to take on more and more crystallographic challenges.
“We recently analysed the structures of two new modifications of the antifungal drug Tavaborole.  We identified unusual hydrogen bonds in both structures, which made us start testing new modules in CSD-Materials.”
Tavaborole. CSD refcode IKACUT.
“Polymorph assessment seemed particularly interesting, but we also performed other tests for the full picture. It was insightful to learn about each structure and its modified forms, to further understand the structure-properties relationship. We were able to propose a new polymorphic form of one of these newly designed drugs, and in time we hope to identify its crystal structure.”
“The Aromatic Analyzer module, based on a neural network, allows quantitative analyses of the interactions between phenyl rings. When analysing structures containing only weak hydrogen bond donors and aromatic fragments, I have often hesitated about which interactions should be considered the most important. Now, thanks to this module, I have an additional valuable tool for analysing the hierarchy of crystal interactions.”
What New CSD Software Features Have You Used?
“The latest CCDC software modules are very inspiring, and I see many uses for them in my research. Working with colleagues from the Faculty of Pharmacy, we often design and synthesize co-crystals, look for new polymorphs and solvates, and analyse drug–protein interactions. Co-Crystal Design, Polymorph Assessment, Solvate / Hydrate Analysers, and Full Interaction Maps modules facilitate and accelerate our research.”
“We intend to use CSD-Discovery for docking research. I am also fascinated by programs using AI methods. Currently I am an end-user, but maybe I will start a collaboration in this area in the future. I am also inspired by the CSD-Particle modules, which are useful for studying crystal growth and properties. The detailed tutorials and educational materials available on the CCDC website are a great support in my research and teaching.”
Did the Use of the CSD and the CCDC Software Give Results That You Found Surprising?
“The CCDC software helped me clear up many “question marks” every time I studied a larger group of related compounds. Even if the analysis of the structures indicated something “odd” at the beginning, it was possible to solve and justify it. I consider CSD and CCDC software great tools for understanding properties at the atomic level using a new AI perspective.”
1. Anna M. Dąbrowska, Agnieszka Adamczyk-Woźniak and Izabela D. Madura, Effect of substituents in novel bioactive tavaborole derivatives on the intermolecular interaction hierarchy, CrystEngComm, 2022,24, 3586-3596. https://doi.org/10.1039/D2CE00279E.