Seeing the structure of our molecule for the first time was the biggest “wow” moment, says Vladimír Šindelář
prof. Ing. Vladimír Šindelář, Ph.D.
Head of Supramolecular Chemistry group
Department of Chemistry and RECETOX
Vladimír Šindelář studied at the University of Chemical Technology in Prague, where he obtained his PhD at the Department of Polymers. He completed postdoctoral internships at Heriot-Watt University, Great Britain, and the University of Miami, USA. Since 2005 he has been working at our faculty, where he is engaged in the preparation of cyclic and non-cyclic compounds that serve as hosts in supramolecular chemistry and the description of host-guest interactions using advanced analytical and physical methods.
Vladimír Šindelář with a model of the bambusuril compound he and his team created. Photo: Helena Brunnerová
Your project “Chiral Bambusurils (2018−2020)” won the GAČR Chairman’s Award this year. Congratulations. What did the GAČR appreciate about your project?
In my opinion, our project was recognised because it deals with an interesting topic with real application possibilities and because of the number of quality publications associated with the project, i.e. 11 articles, some in prestigious journals, and a chapter in a book.
How many years have you been dealing with the topic of bambusurils?
Our first article was published in early 2010, i.e. 11 years ago. If we add the years of research and development that preceded it, it would be about 15 years.
What was behind the creation of this interesting compound?
At some stage in our research, we found that we had a new, as yet unknown, compound that did not occur in nature. We were the first to prepare this molecule and to recognise and describe its properties. For that reason, we had the right to name it.
So why the name “bambusuril”?
It consists of two parts. First, “bamboo” describes the shape of this macrocycle. As you can see in the picture below, it is specifically curved like one section of a bamboo stem, while “uril” refers to urea, which makes up the building blocks of bamburil termed glycolurils. The second reason for the chosen name was the relationship between the new macrocycle and the previously described compound cucurbituril (from “Cucurbitaceae” = Czech “gourds”). Both macrocycles have the same building block in glycoluril, and we also wanted to be inspired by nature when creating the name.
What were the significant moments during the development of bambusuril?
Before we published its discovery, we had to patent the compound, which we did back in 2009. Then, there were other challenges. For example, the first bambusuril was insoluble in water. Water solubility, however, would be an important property for possible applications of bambusuril, such as anion monitoring or medical use. In 2015, we finally managed to produce a water-soluble bambusuril. The next step in the toward future use of bambusuril was to make so-called chiral bambusuril, which is why we wrote the project.
What else is interesting about bambusuril, in terms of its future applications?
Bambusuril has several unique properties. In the picture below, you can see how an orange ball, representing an anion, is bound within the black structure of the bambusuril model. Simply put, when you dissolve bambusuril in powder-form in water and add table salt (sodium chloride), the chloride anion “sneaks” into the bambusuril cavity like the orange ball in the model. The anion is not tightly bound in the molecule as it hold inside by a non-covalent interaction, hence the anion itself is capable of both binding with bambusuril and then escaping from it. This has a number of potential applications. For example, bambusuril is capable of removing various anions from solution, and can thus be used for wastewater treatment or water desalination.
Another area of bambusuril application may be the transport of anions within the human body. In this case, the body is made up of cells and anions, among other things, can flow through the cell wall via channels in the form of proteins and other natural substances. Sometimes, however, transport is prevented, which manifests itself in the form of disease. In cystic fibrosis, for example, the problem is that the transporters are dysfunctional and chloride anions cannot pass through the cell wall properly. The solution may be to develop an artificial transporter, e.g. bambusuril, which would anchor to the cell wall and allow anion exchange to start working again. This is a highly specific example; however, our research is still at the basic level where we are primarily developing new substances and describing their properties. Nevertheless, we are gradually getting to the stage where we look at specific applications for bambusurils.
Other possible applications may be in the monitoring of anions. For example, we may want to know whether there is a toxic anion in the environment (e.g. in food) or, in the case of an organism, whether it shows increased anion concentrations, possibly indicating disease. As the ability to rapidly monitor such anions on-site is highly desirable, research into the use of bambusuril is also moving in this direction.
Are these goals also related to your work at RECETOX?
Certainly. At RECETOX, we are part of the Chemical Instruments for Diagnostics and Therapy research group and we contribute to the research goals of the centre through the further development of bambusurils, which can be used to monitor toxic anions and diagnose diseases.
What does the term “chiral” mean? And how would this form of bambusuril be useful for future application?
There are many, so-called, chiral substances in nature. These are pairs of almost identical substances, called enantiomers, that are mirror images of each other but cannot be identified when overlapping. It’s very similar to your right and left hand when you have their palms toward you.
This is how many substances occur in nature. Usually, however, only one of the two enantiomers will be biologically active; with ibuprofen, for example, one enantiomer is a drug and the other is not. In such cases, it may be beneficial to separate both enantiomers or to detect the presence and relative proportions of the two forms. Unfortunately, this is quite difficult using conventional methods. To address this, we decided to create a chiral bambusuril, which would be shaped something like a “snail shell” into which only the enantiomer oriented in the direction and shape of the “shell” could fit. In this way, the chiral bambusuril would act as a means of identifying only the desired enantiomer.
What goals did you set in the award-winning Chiral Bambusurils project?
One of the main goals of the project was to find out whether a chiral bambusuril could be prepared, and, as far as possible, examine its properties. Next would be to assess whether, when put into a mixture of two enantiomers, it would preferentially bind one of them in its cavity. We were able to show that the synthesis does indeed work and that bambusuril is able to selectively bind just one of two enantiomers. We also tested different ways to use bambusurils in conjunction with spectral methods to both identify the enantiomer and assess the ratio of enantiomers in the study solution. Unfortunately, however, we were not able to achieve this within the project.
Where could chiral bambusurils be applied?
The ability of chiral bambusurils to bind to a particular enantiomer is certainly interesting. As I have already mentioned, only one of two enantiomers is usually used in the pharmaceutical industry. In practice, enantiomers are separated using chiral chromatography. The principle here is that one has a tube (column) filled with a substance capable of interacting differently with each of a pair of enantiomers - and bambusuril could be such a substance. As a solution of both enantiomers passes through the column, bambusuril would only bind to one, the flow of which would be slowed down. Thus, first one enantiomer would come out of the column and then the other.
What has been the response of the scientific community to the creation and development of bambusuril?
The fact that we were the first to prepare such a compound, with such interesting application potential, has been really beneficial for our research group. The compound is now recognised worldwide, especially within the supramolecular chemistry community. We are now trying to make this substance more and more visible by advertising its interesting properties and possible applications. It’s just nice to have your own compound.
What was it like when you first realised that you had managed to prepare an interesting compound?
Behind that is a whole history. I came to Masaryk University at the end of 2005, after my postdoctoral work abroad. I then founded a group which had its first Bachelor student, Jan Švec, in 2006. He was tasked with creating the fabric that would eventually lead to the building block for bambusuril. Not that we had bambusuril in our heads, but something like it. Unfortunately, Jan failed to prepare the material during his Bachelor’s studies and devoted himself to another project. However, he returned to the project when he began his Doctoral studies, and went on to prepare not only the building block but subsequently the whole compound. It was summer and my wife and I were going on vacation. I told him to try a reaction that would lead to the desired barrel-shaped molecule; and when I returned, he told me that he had prepared “it”. Then we analysed “it” to see what it really was. We were sure it was some form of barrel-shaped molecule but we didn't know what it looked like. Only after analysis on an X-ray diffractometer did we finally see a picture of the molecule and know what it was.
How did you feel at the moment you first said to yourself “that’s it; we wanted to create it and we did it?
I probably experienced the biggest “wow moment” the moment I saw the crystal structure of bambusuril for the first time. Only then did I really realise that something extraordinary had been prepared. We had been waiting for this moment for quite a long time - a few months - because you need to have a crystal in the X-ray diffractometer, but the substance did not want to crystallise. When it worked out and we saw the structure of the molecule, it was really exciting.
When talking of the creation of bambusuril, you speak of “chance”. What do you mean?
In the scientific world especially, the term “serendipity”, which means a happy coincidence or an unexpected discovery, is often used. A large number of such discoveries have been described in the past and bambusuril is now one of them. In our case, we aimed to prepare a barrel-shaped molecule but had no idea what the final shape would be. Importantly, even though it was not the target compound, we were able to recognise that it was something interesting; ultimately, much more interesting than what we had originally thought.
What results do you value most from the project?
Of all the publications written during the project, I most value the article in ‘Chemistry A European Journal’ (2018). It was in this article that we were able to demonstrate that synthesis of chiral bambusuril was possible. I also really value our publication in the journal ‘Chem’ (2019), which was written in collaboration with Dr. Hennie Valkenier from the Universite libre de Bruxelles. In it, we dealt with bambusurils as transporters of anions through cell walls. Lastly, I should also mention our publication on molecular machines, published in ‘Angewandte Chemie’ (2019).
Involving students in research is a priority for the faculty. Do students perceive how important such projects are for future scientists?
Much depends on the workplace and also whether it is a student working on a Bachelor’s, Master’s or Doctoral thesis. In a Bachelor’s study, the student looks around and the fact that there is a ‘project’ behind his research activities is not so visible to him. They are aware that they are part of a project, but do not come into contact with the administrator or other members of the project. However, by the time they come to do a Master’s thesis, it can be quite different. Masaryk University, for example, provides projects specifically for Master’s students, and this was the case with one of my graduates. Doctoral students, on the other hand, can already fully appreciate the benefits of project money. On the one hand, they may be part of a research team, where the Doctoral student may be employed part-time from project money, on the other, they will also have the opportunity of applying for grants themselves, such as the South Moravian Region’s ‘PhD Talent’ grants.
How do you relax after work?
I like my job very much, but sometimes it’s good to get away from it completely. This is a bit complicated when there are so many electronic devices that allow continuous connection with work. So, the best thing is to go somewhere camping with your family and if I only check my emails once a day, or even once every few days, I consider that a success. I also like playing beach volleyball or squash or going cycling.
Thank you for the interview.
Translation: Kevin Roche