|Title||Capturing the fleeting existence of a reaction intermediate|
Capturing the fleeting existence of a reaction intermediate
For the first time in the world, the IBS Center for Catalytic Hydrocarbon Functionalizations has successfully captured the existence of intermediates that are generated during a chemical reaction. The Center elucidated the structure and reactivity of 'transition-metal-nitrene' intermediates, which are formed transiently during nitrogenation reactions of hydrocarbons. The research results were published in the journal 'Science' in August.
Nitrogen compounds are essential molecules for physiological activity, as they are included in about 90% of pharmaceuticals. They also play a vital role in various fields, including pharmaceuticals, materials, and materials. Chemists are focusing on the development of catalysts that can efficiently convert naturally abundant hydrocarbons, such as petroleum and natural gas, into nitrogen compounds.
Back in 2018, IBS Center for Catalytic Hydrocarbon Functionalizations developed a catalytic reaction that synthesizes lactams (raw material for pharmaceuticals) from hydrocarbons using dioxazolone (a reagent used for amide synthesis) and a transition-metal (iridium) catalyst. At that time, the group proposed that the key intermediate that triggers the amination reaction is the transition-metal-nitrene. Subsequently, more than 120 research teams worldwide continued the study of amination reactions using dioxazolone reagents. However, although the structure was determined through computational chemistry, the direct observation of the transition-metal-nitrene intermediate had not been achieved.
Most catalytic reactions occur in solution. Molecules in a solution constantly interact with other molecules, making it very difficult to characterize rapidly reacting and disappearing intermediates such as transition-metal-nitrenes. To overcome this limitation, the research team proposed the use of photocrystallography, which is an analytical method that uses single-crystal X-ray diffraction analysis to observe structural changes at the molecular level when samples are exposed to light. As a result, they captured the entire process of breaking chemical bonds, formation of intermediates, and reaction among intermediates and other substances to form new chemical bonds.
First author JEONG Hoi-min explained, "Determining the sequences of catalytic intermediates that are formed during a chemical reaction further helps us improve the mechanism of the reaction and provides important clues for developing more efficient next-generation catalysts."
Q&A session below:
Q. Please introduce yourself.
I'm Dr. JEONG Hoi-min, a postdoctoral researcher in the Center for Catalytic Hydrocarbon Functionalizations within the Institute for Basic Science (IBS). I received my doctoral degree in chemistry from KAIST under the guidance of Professor CHANG Suk-bok in February of this year (2023). Associate Director BAEK Moo-hyun from the same department was also my co-advisor.
Q. Tell us about the Center for Catalytic Hydrocarbon Functionalizations.
The IBS Center for Catalytic Hydrocarbon Functionalizations conducts research to convert common molecules found in our surroundings into more valuable materials. In particular, we focus on developing catalytic reactions that convert hydrocarbon resources like petroleum into raw materials for pharmaceuticals and next-generation materials. The Center has been operating for over ten years since its inception in December 2012 under the leadership of Director CHANG Suk-bok, and it is currently operated under the leadership of Associate Directors BaAEK Moo-hyun and HONG Seung-woo. Director Chang's group is mainly engaged in the development and mechanistic study of catalytic reactions that involve the activation of hydrocarbons. Meanwhile, Associate Director Baek's group explores new catalysis and reaction control principles based on simulations (computational modeling) of chemical reactions. Associate Director Hong's group is working on reaction systems applicable to medicinal chemistry in addition to the development of catalytic reactions.
Director Chang's group is primarily focusing on reactions that introduce nitrogen functional groups into hydrocarbon using transition-metal catalysts and a nitrogen precursor called dioxazolone.
Q. We would like to know about your main research area.
I have been involved in the development of a catalytic reaction that introduces an amide functional group into hydrocarbons and conducted research on the mechanism of catalytic reactions. Director CHANG Sukbok's group is primarily responsible for the development of chemical reactions and experimental studies on their mechanisms. In contrast, Associate Director BAEK Moo-hyun's group seeks ways to improve reactions through simulations based on computational chemistry. Both groups synergize in understanding reaction mechanisms, especially in the context of reaction mechanisms. This understanding has been the basis for our research, where we focus on developing catalytic reactions that exhibit new reactivity and selectivity.
Q. Tell us about what motivated you to start this research.
I entered graduate school in 2018, back when the group published a paper about synthesizing y-lactams using an iridium catalyst and diaxolozone in Science. At the time, there was interest in the iridium-acylnitrene compound, which is a key intermediate that triggers the catalytic reaction. However, it was very challenging to observe it directly due to the intermediate's high reactivity. In the early days after entering graduate school, I observed the reactivity of dioxazolone with various transition metal catalysts such as ruthenium and rhodium and developed a more selective and highly reactive amination reaction involving hydrocarbons. However, I believed that a more efficient catalytic reaction could be developed if we could directly observe and better understand the properties of the transition metal-nitrene intermediates in these reactions.
Q. How long have you been interested in this field?
The detection of this intermediate has been a challenge for the Center for a while. There were efforts to detect the transition-metal-nitrene spectroscopically in solution as well as attempts to understand its properties based on computational chemistry. Meanwhile, I learned of a report that unstable reaction intermediates could be observed through photocrystallography. Since this is an approach that has never been tried at the research center until now, we thought that intermediate detection might be possible by using this method.
Q. What were the results??
In particular, in 2023, we successfully elucidated the core intermediate of the catalytic amination reaction, which introduces a nitrogen functional group into hydrocarbons. This achievement was published in the journal 'Science'. As I mentioned earlier, we had anticipated that the transition metal-nitrene would be the key intermediate in the hydrocarbon amination reaction, but this study marks the first actual observation of this intermediate.
Most catalytic reactions occur in a liquid state, making it very challenging to elucidate rapidly reacting and disappearing intermediates like the transition metal-nitrene. To overcome these limitations, we had the idea of using single-crystal X-ray diffraction analysis at the atomic level to observe structural changes that occur when solid-state samples are exposed to light.
For this experiment, we devised a new rhodium (Rh) based catalyst that responds to light. We expected that this catalyst, in combination with diaxolozone, would form the transition metal-nitrene through a reaction when exposed to light. By using the X-ray crystallography method at the Pohang Accelerator Laboratory, we were able to analyze the structure and properties of the previously unobserved 'rhodium-acyl nitrene' intermediate for the first time in the world. Furthermore, we used the same method to analyze the process in which the rhodium-acyl nitrene intermediate reacts with other molecules. These results can be likened to a camera capturing the entire process, from the breaking of chemical bonds to the formation of new chemical bonds within solid samples.
Q. Could you explain what photocrystallography is.
Photocrystallography, as the term suggests, combines "light" (photo) and "crystallography." In the case of X-ray crystallography, X-rays are directed at a crystal sample, and the resulting diffraction pattern is analyzed to determine the 3D structure of molecules. In addition to this, crystals can undergo chemical changes in response to external stimuli (in this case, light other than X-rays). The field of photocrystallography is concerned with experimentally observing or tracking these changes caused by external light at the atomic level.
Typically, conducting X-ray diffraction experiments using laboratory-level equipment can take several hours to even a day or more, making it challenging to perform analysis using photocrystallography. This is where the utilization of a synchrotron accelerator can be beneficial. Accelerators can significantly reduce data collection time (down to seconds ~ minutes) and provide intense X-ray beams. The research I introduced earlier was conducted at the Pohang Accelerator Laboratory, and many photocrystallography analyses are also performed at various synchrotron facilities worldwide.
To understand this better, we need an introduction to crystallography and the related X-ray diffraction analysis. Crystallography is a field that deals with the repetitive features and symmetry inherent in lattice structures, which can be arbitrarily defined. Diffraction is the physical phenomenon that allows the experimental observation of information related to these repetitions and symmetries. When it comes to crystal samples where molecules are arranged repeatedly on the order of angstroms (1 angstrom = 0.1 nanometers), using X-ray diffraction analysis is a valid approach. It utilizes X-rays of the same order of magnitude in wavelength, which lets us gain detailed information at the atomic level. This includes parameters like atomic distances, angles, positions, and the surrounding coordinate environments of metal atoms, which are impossible to observe with the naked eye. If you think of getting an X-ray in a hospital to examine your bones, it's a similar concept. Just the subject and purpose change to studying the sample and determining its structure.
Q. Were there any challenges you faced in your research, and how did you overcome them?
There were indeed challenges, especially concerning the limited beamtime shared by multiple researchers at facilities like accelerators. It was crucial to maximize the efficiency of the work within this restricted beamtime. Additionally, preparing suitable samples for photocrystallography experiments within the allotted beamtime was quite challenging. Thankfully, Dr. KIM Dongwook from our research group had prior experience with experiments using the synchrotron accelerator, so setting up the photocrystallography experiment was relatively straightforward.
The most significant challenge was realistically finding samples suitable for photocrystallography. We made every effort to prepare potential samples each time the beamtime became available, hoping that they would be suitable for the experiment. After several failed attempts and adjustments, we finally obtained the structure of the rhodium-acylnitrene in November 2022.
During the research process, many colleagues and professors offered valuable advice and practical assistance, such as sharing beamtime, which greatly contributed to achieving positive results. For that, I'm grateful.
Q. How can the research findings be used to develop the next generation of catalysts? We're curious about how capturing the key intermediate of the amination reaction might change everyday life.
This research holds two significant implications. First, a solid-state environment allows us to observe key intermediates that were previously challenging to study. This provides valuable insights into the structures of key intermediates in catalytic reactions, which can be instrumental in explaining the mechanisms of future reactions. Therefore, the understanding gained from the rhodium-nitrene intermediate in this experiment is expected to be a substantial aid in developing new reactions that were previously unobserved.
Second, the importance lies in the ability to capture the entire process from reactants to products step by step. In the long term, this could lead to the development of a technology that allows for the step-by-step imaging of rapidly occurring reaction processes in catalytic chemistry. Such a development could potentially revolutionize the landscape of catalyst reaction development by enabling a detailed understanding of fast reaction processes.
Q. What are your future research plans?
I would like to continue tackling challenging research in the field of catalysis. Recently, there has been a growing need to address energy issues, and some proposals include the conversion of greenhouse gases like carbon dioxide and methane into high-value materials. Additionally, research into recycling non-biodegradable materials like plastics back into raw materials can significantly contribute to solving environmental problems. Through catalysis, I aim to address these issues and become a scientist who can contribute to environmental solutions.
Q. What kind of support do you think you'll need for your future research?
I believe that the most crucial support for future research is the collaboration with excellent fellow researchers. The achievement of this study was by no means something I could have accomplished alone. In particular, the assistance of Research Fellow KIM Dongwook, who was responsible for crystal structure analysis, was the most significant support. In the future, I hope to meet exceptional colleagues to explore new fields of research.
Q. Finally, is there anything else you'd like to say.
The direction and methodology of this research were actually established around 2019, but it took quite a long time, about four years, for the results of this research to be made public. In a way, you could consider it a long-term study, and it was made possible due to the support from the director, associate director, and the IBS. Also, I feel grateful that we could conduct such research using resources in our country.