Organic & Biomolecular Chemistry Blog

The Organic & Biomolecular Chemistry Editor’s collection is a showcase of some of the best articles published in the journal, hand selected by our Associate Editors and Editorial Board members.

For this month’s selection, Associate Editor Motomu Kanai has highlighted some of his favourite recent works.

Take a look at what he thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Motomu’s Selection:

The effect of deoxyfluorination and O-acylation on the cytotoxicity of N-acetyl-D-gluco- and D-galactosamine hemiacetals
Vojtěch Hamala, Lucie Červenková Šťastná, Martin Kurfiřt, Petra Cuřínová, Martin Balouch, Roman Hrstka, Petr Voňka and Jindřich Karban

Motomu’s comments:
Introducing fluorine atoms into biologically active molecules almost always induces interesting effects. Substitution of hydroxy groups in sugars with fluorine atoms is a typical example. Here Hamala et al. systematically synthesized deoxyfluorinated sugar analogues and studied their cytotoxicity to cancer cells. These molecules may be also interesting fluorine NMR probes, as well as tools for studying CH/π interactions between sugars and proteins.

Find out more in our interview with the authors

An air-stable, Zn²⁺-based catalyst for hydrosilylation of alkenes and alkynes
Kristina Groutchik, Kuldeep Jaiswal and Roman Dobrovetsky

Motomu’s comments:
Hydrosilylation of alkenes and alkynes is an important reaction in both chemical laboratories and industries, the latter of which produce silicon polymers such as rubbers and oils, which are essential for our daily life. Platinum catalysts are commonly used to promote this reaction. However, use of sustainable, earth abundant catalysts is more preferable. In this paper, Groutchik et al. report that an air-stable zinc complex generated from a hemilabile tetradentate ligand promotes efficient hydrosilylation of alkenes and alkynes. The rection proceeds thorough frustrated Lewis pair activation of hydrosilane. This achievement promises novel reactivity of metal complex catalysts based on smart ligand design.

Find out more in our interview with the authors

Deuteration of terminal alkynes realizes simultaneous live cell Raman imaging of similar alkyne-tagged biomolecules
Syusuke Egoshi, Kosuke Dodo, Kenji Ohgane and Mikiko Sodeoka

Motomu’s comments:
Alkynes are a unique tag for biorthogonal reactions as well as Raman imaging. For the latter, alkynes provide characteristic Raman signals in the region where other cellular molecules do not interfere. Thus, use of alkyne tags is beneficial to enhance the signal-to-noise ratio. In this paper, Egoshi et al. found that deuteration at the terminal carbon of alkyne tags markedly shifted the Raman signal by 135 cm-1. This finding enabled two-color in-cell Raman imaging, simultaneously using two similar tags containing either H or D at the alkyne terminus.

Find out more in our interview with the authors

Meet the Editor:
Motomu Kanai, OBC Associate Editor

Motomu Kanai obtained his PhD from Osaka University in 1995. Then, he moved to University of Wisconsin, USA, for postdoctoral studies with Professor Laura L. Kiessling. In 1997 he returned to Japan and joined Professor Masakatsu Shibasaki’s group at The University of Tokyo as an assistant professor. After being a lecturer (2000~2003) and an associate professor (2003~2010), he started his position as a professor at The University of Tokyo (since 2010) and a principal investigator of ERATO Kanai Life Science Project (2011~2017). He has received The Pharmaceutical Society of Japan Award for Young Scientists (2001), Thieme Journals Award (2003), Merck-Banyu Lectureship Award (MBLA: 2005), Asian Core Program Lectureship Award (2008 and 2010), and Thomson-Reuters The 4th Research Front Award (2016).

His research interests entail design and synthesis of functional (especially, biologically active) molecules.

Vojtěch Hamala	Roman Hrstka	Petr Voňka	Martin Balouch
Petra Cuřínová	Jindřich Karban	Lucie Červenková Šťastná	Martin Kurfiřt

Introducing the researchers:

Vojtěch Hamala obtained his MSc at the University of Chemistry and Technology in Prague in 2019. He is a PhD student at the Institute of Chemical Process Fundamentals in Prague under the supervision of Dr Jindřich Karban. His main interests focus on the synthesis of cytotoxic carbohydrate analogues and antitumor carbohydrate-organometallic complexes.

Roman Hrstka obtained his PhD degree in cellular and molecular biology at Masaryk University in Brno. Currently he works as a principal investigator at Masaryk Memorial Cancer Institute. His research is focused on cancer cell signalling and metastasis development. In parallel, he also serves in the Czech national node of the BBMRI-ERIC (European research infrastructure for biobanking).

Petr Voňka graduated in biochemistry and physical chemistry at Palacký University in Olomouc in 2017. He is currently studying for his PhD degree in experimental biology under the supervision of Assoc. prof. Roman Hrstka at Palacký University in Olomouc. His research is focused on the interactions of small molecules (steroids or organometallic compounds) with selected proteins.

 Martin Balouch obtained his MSc at the University of Chemistry and Technology in Prague where he continues to study for his PhD degree. He combines pharmaceutical research under prof. Stepanek (UCT Prague) with in silico permeation models under supervision of doc. Karel Berka (UP Olomouc). His research is focused on molecule/biomembrane interactions using both experimental and computational approaches.

Petra Cuřínová obtained her PhD in organic chemistry at the University of Chemistry and Technology in Prague. After the return from the Exeter University (UK) where she dealt with the synthesis and properties of anion-recognizing receptors, she continued her carrier at the Institute of Chemical Process Fundamentals in Prague. She won the O. Wichterle Award for young scientists in 2016. Her main areas of interest comprise preparation, characterisation and application of host-guest systems, chiral recognition and spectroscopic methods.

Jindřich Karban received his PhD in organic chemistry in 1998 under the supervision of Prof Miloslav Černý at Charles University in Prague. After a few years of practise in analytical chemistry and mass spectrometry, he continued his research in carbohydrate chemistry as a senior scientist at the Institute of Chemical Process Fundamentals in Prague. His research interests include the synthesis and properties of fluorinated sugar analogues and antitumor carbohydrate-organometallic conjugates.

Lucie Červenková Šťastná obtained her PhD in organic technology at the University of Chemistry and Technology in Prague where she studied fluorinated cyclopentadienyl complexes. Recently she started working as a researcher at the Institute of Chemical Process Fundamentals in Prague. Her research is focused on structure elucidation by NMR spectroscopy, catalysis and fluorinated sugar analogues.

Martin Kurfiřt obtained his MSc in the field of organic chemistry at the University of Chemistry and Technology in Prague in 2019. He is currently a PhD student at the Institute of Chemical Process Fundamentals in Prague under the supervision of Dr Jindřich Karban. His professional interests comprise the organic synthesis of carbohydrates and study of their interactions with proteins by NMR spectroscopy.

What inspired your research in this area?

Our research in this area was motivated by curiosity. Two separate facts had been known: (1) acylated 2-acetamido-pyranoses become moderately cytotoxic if we selectively deprotect the anomeric hydroxyl group and increase the acyl chain length at the remaining hydroxyls from acetyl to butyryl, (2) fluorination of some monosaccharides renders them cytotoxic. We wished to know what would happen to cytotoxicity if we combine these structural features in one molecule. Therefore, we synthesised fluorinated acylated glucosamine and galactosamine analogues possessing a free anomeric hydroxyl (hemiacetals) and two-to-four carbon acyl chains at the non-anomeric positions, and determined their cytotoxicity.

What do you personally feel is the most interesting/important outcome of your study?

We suggested a hypothesis that the observed cytotoxicity could be the result of the recently discovered nonspecific glycosylation of histidine residues termed S-glyco-modification (J. Am. Chem. Soc. 2020, 142, 9382–9388.) This reaction occurs when acylated amino sugar hemiacetals react with histidine residues by an elimination-addition mechanism in a protein microenvironment rich in lysine. Surprisingly, there was no correlation between the cytotoxicity of our compounds and their ability to react with the thiol group by the suggested mechanism in vitro. This indicates that our compounds probably exert their cytotoxic properties by other, so far unspecified or unknown mechanisms.

What directions are you planning to take with your research in future?

We want to prepare conjugates of some of the most cytotoxic fluorinated hemiacetals with cytotoxic or anti-invasive ruthenium complexes. We expect that conjugation of a ruthenium complex to a cytotoxic sugar may potentiate their antitumor properties. At the moment we work on a suitable synthetic method to link an antitumor ruthenium complex to fluorinated amino sugar hemiacetals.

Read the full article: The effect of deoxyfluorination and O-acylation on the cytotoxicity of N-acetyl-D-gluco- and D-galactosamine hemiacetals

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection

Syusuke Egoshi

Kosuke Dodo

Kenji Ohgane

Mikiko Sodeoka

Introducing the researchers:

Syusuke Egoshi received his PhD in 2015 under the supervision of Prof. Minoru Ueda at Tohoku University graduate school of science. He joined the group of Prof. Mikiko Sodeoka at RIKEN as postdoctoral fellows in 2016, and as special postdoctoral researcher in 2018, thereafter he was promoted to a research scientist. His research interests are the development of unique chemical imaging technologies including Raman tags/probes and their application for biological research of elucidating the mode of action of small bioactive molecules.

Kosuke Dodo graduated from the University of Tokyo in 1999 and received his PhD from Tohoku University in 2004. After the postdoctoral training at RIKEN, he was appointed as an assistant professor at the University of Tokyo in 2007. Then, he returned to RIKEN as a research scientist and a group leader in the ERATO Sodeoka Live Cell Chemistry Project from 2008 to 2013, thereafter he was promoted to a senior research scientist in 2014. His research interests span the development of unique chemical probes/technologies including Raman probes and their application for biological research related to cell death signaling.

Kenji Ohgane received his PhD (Pharmaceutical Science) in 2013 under the supervision of Prof. Yuichi Hashimoto at the University of Tokyo (the Laboratory of Bioorganic and Medicinal Chemistry at the Institute for Molecular and Cellular Biosciences). In 2013, he joined the group of Prof. Mikiko Sodeoka at RIKEN and performed chemical biology researches. After 4 years of postdoctoral research, he returned to the University of Tokyo as an Assistant Professor, and then moved to the Tokyo University of Science (Prof. Kouji Kuramochi) in 2020. In 2021, he started his laboratory at the Department of Chemistry, Ochanomizu University (Tokyo). His research group is currently focusing on small molecules that stabilize or destabilize their target proteins (screening, medicinal chemistry, and analysis of the mode of action), and also interested in understanding new bioactivities of sterols and lipids.

Mikiko Sodeoka received her BS, MS, and PhD degrees from Chiba University. After working at the Sagami Chemical Research Center, Hokkaido University, Harvard University, and the University of Tokyo, she became a Group Leader at the Sagami Chemical Research Center in 1996. She moved to the University of Tokyo as an Associate Professor and then to Tohoku University as a Full Professor in 2000. Since 2004, she has been a Chief Scientist at RIKEN. Her current researches cover development of new reactions based on transition metal chemistry and fluorine chemistry and development of new methodologies for chemical biology research.

What inspired your research in this area?

Raman imaging using alkyne tag is useful tool to observe small biomolecules in cells because alkyne exhibits a vibrational frequency in Raman-silent region that is free of interference from intracellular molecules. The development of various alkynes is important to observe a wide variety of biomolecules in cells. Therefore, we are working on the development of novel alkyne tags/ probes.

What do you personally feel is the most interesting/important outcome of your study?

The most interesting findings are the alkyne vibrational frequency shifts by 135 cm^-1 upon deuteration, and the D/H exchange of alkynes occurs depending on pH. The large difference in Raman shift of D/H alkynes successfully realized simultaneous two-color imaging of similar small molecules. The pH dependency of D/H exchange of alkynes indicates the potency of D-alkyne to monitor the intracellular dynamics.

What directions are you planning to take with your research in future? 

In the next step, we will develop various types of D-alkyne probes from H-alkyne probes and apply them for multi-color Raman imaging to observe small molecules in cells. In addition, we are planning to develop Raman probes using D/H exchange of D-alkynes, such as the pH sensor.

Read the full article: Deuteration of terminal alkynes realizes simultaneous live cell Raman imaging of similar alkyne-tagged biomolecules

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection

Roman Dobrovetsky

Kuldeep Jaiswal

Kristina Gruchik

Introducing the researchers:

Roman Dobrovetsky was born in Uzbekistan in 1979. At age of 12, his family moved to Israel. After finishing school in 1998, he joined the army. Soon after the army, he started his BSc in Technion. In 2005, he joined Prof. Apeloig’s group for his PhD studies in the field of silicon chemistry. After finishing his PhD, he moved to Toronto to work with Prof. Stephan, where he did his research in the field of frustrated Lewis pairs and Lewis acid catalysis. In 2015, he moved back to Israel to start his independent career at Tel Aviv University. His research interests are in the main group chemistry and transition-metal free catalysis.

Kuldeep Jaiswal was born in 1988 in Sonipat/India studied chemistry at the Hindu college Sonipat (2005-2008) and at the Kurukshetra University Kurukshetra (2008-2010) and completed his Ph.D. in Inorganic Chemistry under the supervision of Prof. Sanjay Singh (2012-2016) at the Department of Chemical Sciences, Indian Institute of Science Education and Research Mohali (India). His Ph.D is supported by a scholarship of the University Grants Commission (2012-2016). Kuldeep then joined the laboratory of Prof. Chunming Cui (State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, China) as a postdoctoral researcher (2016-18), and later joined Prof. Roman Dobrovetsky group (2018 onwards) at the School of Chemistry at Tel Aviv University.

Kristina Gruchik was born in Magadan, Russian Federation. Received her BSc and MSc from Tel-Aviv University. Currently, she is pursuing her PhD at the same institution under the supervision of Prof. Roman Dobrovetsky, exploring the chemistry of the main group elements.

What inspired your research in this area?

I’d say that what inspires me the most is a scientific curiosity. Questions like can we do chemistry that transition metals do with non-transition metal based complexes are very interesting to me.

What do you personally feel is the most interesting/important outcome of your study?

Actually, for me the most interesting and surprising in this chemistry was the fact that the Zn complex that we made was air- and moisture stable. This of course makes it more convenient for use in catalysis.

What directions are you planning to take with your research in future?

We’re now looking into other ligands at Zn-center and other main group elements and at other catalytic hydroelementation reactions that we can do with these new catalysts.

Read the full article: An air-stable, Zn²⁺-based catalyst for hydrosilylation of alkenes and alkynes

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection