Research

Xiaodong Zou’s research has been development of electron crystallographic methods. Her group has developed several image and diffraction-based methods and software for accurate atomic structure determination of unknown crystals, and solved many complex structures, especially porous materials such as zeolites and metal-organic frameworks. She is also an expert in porous materials and has been working on design, synthesis and applications of novel porous materials. Recently her research interests have been extended in developing electron crystallographic methods for structure determination of protein crystals.

On-going projects

Xiaodong Zou’s research projects cover several research topics, including Electron crystallography and advanced TEM, X-ray and neutron crystallography, Materials for energy, Materials for health. They are summarized below.

Electron crystallography and analytical TEM

Revealing atomic structures, charge states and molecular interactions in macromolecules by microcrystal electron diffraction. Swedish Research Council (VR), 2020-2030.

Knowing the 3D atomic structures, charge states and protein-ligand interactions is crucial for understanding the functions of macromolecules and chemical processes in biological systems, as well as for modern drug design. This project aims at developing new methods based on electron diffraction (ED) to push the limits of current structure determination methods. We will develop

novel approaches for EM sample preparation
new strategies and techniques for data collection on both microcrystals and single macromolecules
and new approaches for phasing single particle ED data

By applying the new methods, we will obtain

accurate structure determination of macromolecules from nano/micron-sized crystals
3D structures of single macromolecules
structure and charge states of metals and amino acids in proteins and catalytic intermediates

To accomplish this we will create a strong environment with excellence in electron crystallography, protein crystallography, and biochemistry for the project. We will make ED as fast, feasible and accurate as X-ray crystallography. We will build an Electron Crystallography platform to spread the knowledge and techniques worldwide. We expect the project to open new opportunities and significantly strengthen the research in structural biology.

Electron crystallographic methods to probe 3D atomic structures and charge states in macromolecules. Knut and Alice Wallenberg Foundation (Wallenberg Scholars), 2020-2024. https://kaw.wallenberg.org/en/xiaodong-zou

Knowing the 3D atomic structures is crucial for understanding the functions of biological macromolecules. Many proteins are involved in redox processes and charge-transfer reactions, which are performed by accommodating different electronic and charged states. Obtaining both the geometric structure and charge states is thus central to understanding the chemical processes and mechanisms in biological systems. X-ray diffraction is presently the most important technique for determination of geometric structures of macromolecules but it requires large crystals and cannot determine the charge states. With the grant as a Wallenberg scholar, I want to develop new crystallographic methods based on electron diffraction, to determine both the geometric structure and the charge state of biological macromolecules. I will 1) develop new methods for accurate structure determination of macromolecules from crystals too small to be studied by X-ray diffraction; 2) determine 3D atomic structures and metal charge states in proteins and catalytic intermediates; 3) develop serial electron diffraction and high-throughput electron crystallography for studying protein-ligand interactions. My ambition is to make electron diffraction as fast, feasible and accurate as X-ray diffraction. To accomplish this I will create an environment with excellence in electron crystallography, method development, protein crystallography and biochemistry. Together we will utilize model systems to explore the power of electron diffraction. We expect electron diffraction to become a crucially important technique in life science both within and outside Sweden. We will make the methods available to the Swedish research community. Together with the Cryo-EM facilities at SciLifeLab, the new X-ray synchrotron source at MAX IV and the neutron source at ESS, we will promote Sweden’s leading position in structural biology.

Members: Hongyi (Justin) Xu, Jingjing Zhao, Max Clabber, Viktor Bengtsson, Molly Lightowler

Nanoporous materials: from synthesis and structure to catalysis; Subproject: Accurate atomic structures from nano- and micrometer-sized crystals by electron crystallography Swedish Research Council (VR), 2017-2022.

This is part of my VR project that aims at developing new strategies and methods for data collection using continuous rotation electron diffraction (cRED), and makeing the structure determination as fast, feasible and accurate as by X-ray crystallography. The new methods will be applied on various zeolites and metal-organic frameworks. We aim to locate hydrogen atoms and determine the oxidation states of atoms, which are not achievable by X-ray diffraction.

Structure characterization of nanoporous materials ExxonMobil Research & Engineering Co. 2017-2021.

X-ray and neutron crystallography

Nanoporous materials: from synthesis and structure to catalysis; Subproject: Fundamental understanding of reaction mechanisms in organic transformations using porous materials as catalyst supports. Swedish Research Council (VR), 2017-2022.

This is part of my VR project that aims at developing synchrotron-based in-situ/operando powder X-ray diffraction and X-ray absorption spectroscopy to identify active catalytic species during organic synthesis using a custom-built in-situ reactor. We will gain new insights on the reaction mechanisms and use them to improve the catalysts and optimize the catalytic reactions. We will introduce synchrotron-based in-situ/operando techniques to the organic chemistry community for developing new catalysts for organic synthesis.

Materials for energy

Nanoporous materials: from synthesis and structure to catalysis; Subproject: Rational design and synthesis of novel zeolites The Swedish Research Council (Vetenskapsrådet, VR), 2017-2022.

This is part of my VR project that aims at developing new approaches for rational design and synthesis of novel zeolites based on common structural features. This will revolutionize the zeolite synthesis from current trial-and-error to targeted synthesis.

Catalytic Composites for Sustainable Synthesis (CATSS); Subproject: Characterization, modeling and understanding of the catalytic materials Knut and Alice Wallenberg Foundation (KAW), 2017-2022.

The aim of this project is to develop novel multifunctional catalytic composites that use two of the most abundant and sustainable feedstocks, carbon dioxide and water, for organic synthesis. The composites first transform these resources into H2 or CO, which then react in situ with organic raw materials, transforming them into high-value organic compounds. To achieve this, we will combine two catalytic materials that work in concert, one electrocatalyst (e-Cat) and one product-forming catalyst (p-Cat) (Fig. 1). Their cooperation is made possible by immobilization of active metals in different supporting materials, allowing them to simultaneously work despite their different nature. With this strategy, handling of high-risk gaseous reagents is completely surpassed. With our combined expertise on synthesizing new materials, developing new techniques for their functionalization, advanced characterization methods, and new catalytic methodologies, we will contribute to positioning Sweden at the forefront of catalysis, and through innovation provide advances towards a sustainable society.

The project team consists of Prof. Belén Martín-Matute (main PI), Prof. Pher G. Andersson, and Prof. Jan-Erling Bäckvall from Department of Organic Chemistry, SU, Prof. Xiaodong Zou and Dr. Andrew Kentaro Inge from Department of Materials and Environmental Chemistry, SU, and Prof. Lichen Sun and Assoc. Prof. Mårten Ahlquist from KTH Royal Institute of Technology.

In the subproject, we will study the catalytic components and the reaction kinetics of the catalysts in action by applying diffraction, spectroscopy, electron microscopy techniques as well as computational methods, and by developing in situ synchrotron-based diffraction and X-ray absorption spectroscopy techniques. This will lead to an understanding of the structure and activity of the catalysts and of surface-modified materials, which is crucial for developing improved composites.

Materials for health

Access to potent medical drugs (APIs) through crystallization enabled by ionic liquids (ILs); Subproject: Crystallization from ILs – Techniques and Process Monitoring Tools. Knut and Alice Wallenberg Foundation (KAW) 2020-2024. About the project in Swedish

Access to potent medical drugs through polymorph-specific crystallization enabled by ionic liquids: Ensuring good health and well-being (SDG3) requires efficient drugs for the treatment of diseases. A critical step in drug development is its formulation, which involves bringing the active pharmaceutical ingredient (API) to the solid form. Most APIs are able to adopt different solid forms (polymorphs). Each of the forms has its own bioavailability, hence, effectiveness to act as a drug. For that reason, each new form has to receive regulatory approval, but also can be patented individually. Thus, it is desirable to develop techniques that allow crystallizing the desired form. In this, ionic liquids (ILs) as crystallization media open completely new opportunities. ILs are room temperature molten salts composed of large organic cations and anions which can be structurally varied and endowed with functional groups. Supramolecular interactions between an IL and the API change the free energy barriers of crystallization leading to the preferential crystallization of one polymorph. A thorough understanding about the IL-API interaction in the crystallization process is the key for the designed engineering of an IL for robust and reliable crystallization of the most efficient API form through structural variation of the IL ions. In this effort, our team brings together experts in crystal engineering, organic synthesis, structure analysis and computational modelling. The complementarities and synergies (including SciLifeLab, RISE, MAXIV, Swedish pharma) make it possible to attack a problem, which is too fundamental to be sponsored by industry and too complex to receive sufficiently large funding from basic funding agencies. However, if we can establish knowledge on how ILs can be used in the polymorph-specific crystallization of APIs, we could make a transformative contribution to drug development that will largely contribute societal welfare.

The project team consists of Prof. Anja-Verena Mudring (main PI), Prof. Dr. Matias Edén, Prof. Alexander Lyubartsev, and Prof. Xiaodong Zou from department of Materials and Environmental Chemistry, SU and Prof. Belén Martín-Matute from Department of Organic Chemistry, SU.

Last updated: December 16, 2019
Page editor: Bin Wang
Source: MMK

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