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 Kate Jolliffe has highlighted some of her favourite recent works. Take a look at what she thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Kate’s Selection: 

Rational Design of Small Molecule Fluorescent Probes for Biological Applications

Joomyung V. Jun, David M. Chenoweth and E. James Petersson

Kate’s comment: “New fluorophores are highly sought after for the development of tools for biological applications. This review provides a nice overview of the functional fluorescent probes and the factors effecting their photophysical properties. Importantly it provides general guidelines for the rational design of new fluorophores with tailored photophysical properties for applications in chemical biology.”

Find out more in our interview with the authors

One-pot synthesis of porphyrin-based [5]rotaxanes

Pablo Martinez-Bulit, Benjamin H. Wilson and Stephen J. Loeb

Kate’s comment: “The synthesis of mechanically interlocked molecules with high degrees of complexity frequently requires multiple synthetic steps, which limits the ability to explore their functionality. Here, Loeb and co-workers report a clever synthesis of porphyrin containing [5]rotaxanes , in a one-pot reaction, opening the door to the synthesis of a wide range of mechanically locked architectures that can be fine-tuned for specific applications.”

Find out more in our interview with the authors

Absolute handedness control of oligoamide double helices by chiral oxazolylaniline induction

Ling Yang, Chunmiao Ma, Brice Kauffmann, Dongyao Lia and Quan Gan

Kate’s comment: “The incorporation of a chiral group at the terminus of an aromatic oligoamide strand has been shown to provide complete chiral control in the self-assembly of synthetic antiparallel double helices from quinoline containing foldamers, opening opportunities for the future exploitation of these materials as chiral sensors or catalysts.”

Find out more in our interview with the authors

Facile synthesis of sulfotyrosine-containing α-conotoxins

Changpeng Li and Chunmao He

Kate’s comment: “Tyrosine sulfation is an important post-translational modification that is believed to modulate biological function but is underexplored because of difficulties with both the isolation and synthesis of sulphated peptides. Here, He and Li demonstrate the facile synthesis of sulfated conotoxins by combining the sulfate ester deprotection and folding steps into a one pot procedure. Importantly they show that, in the case of conotoxins, the sulfate ester is not as acid labile as expected.”

Find out more in our interview with the authors

Meet the Editor:

Katrina (Kate) Jolliffe received her BSc (Hons) in 1993 and PhD in 1997 from the University of New South Wales. She then held positions at Twente University, The Netherlands; the University of Nottingham, UK and the Australian National University before taking up an Australian Research Council QEII fellowship at The University of Sydney in 2002. In 2007 she became a Senior lecturer at the same institution and was promoted to Associate Professor in 2008 and to full Professor in 2009. She currently holds the position of Payne-Scott Professor at The University of Sydney. She is a Fellow of the Australian Academy of Science and has been awarded the Beckwith (2004), Biota (2006), Birch (2017) and H. G. Smith (2018) medals of the Royal Australian Chemical Institute. Her research interests are in the areas of supramolecular, peptide and organic chemistry, with a focus on the design and synthesis of functional molecules, such as molecular sensors capable of detecting anions in biological environments or cyclic peptides for application in biology and medicine.

Introducing the researchers:

Ling Yang was born in 1991 in Qian Jiang, Hu Bei, China. In 2012 she received her bachelor’s degree in Chemical Engineering and Technology from Hubei University. After that, she obtained her Ph.D. degree in January 2018 under the supervision of Prof. Hua Jiang at the Institute of Chemistry, Chinese Academy of Sciences, working toward the synthesis and the characterization of aryl-triazole foldamer receptors to anion recognition. In 2018/2019, she worked as a postdoctoral fellow at Huazhong University of Science and Technology under the guidance of Prof. Quan Gan.

Chunmiao Ma was born in Hubei, China. She received her bachelor’s degree in chemistry from China University of Geosciences, Wuhan in 2016. She is now working toward a Ph.D. under the supervision of Prof. Quan Gan at Huazhong University of Science & Technology, working on design, synthesis and characterization of artificial foldamers based on aromatic oligoamides.

Dr. Brice Kauffmann is Crystallographer and head of IECB’s Biophysical and Structural Chemistry core facility. After a PhD in protein crystallography (2003, University of Nancy I), Brice Kauffmann spent three years at the European Molecular Biology Laboratory (EMBL) in Hamburg (Germany) working on the development of a new synchrotron beamline (X12, DESY). He joined the European Institute of Chemistry and Biology in January 2006 as a CNRS Scientist.

Dongyao Li was born in Xiangyang, Hubei, China. In 2015 he received his BS degree in chemistry at Hubei Normal University. He obtained his MS degree from Huazhong University of Science and Technology in 2017 under the supervision of Prof. Gan. and is currently working toward a Ph.D. in the same group, focusing on design, synthesis and applications of artificial foldamers based on aromatic oligoamides.

Quan Gan was born in 1982 in Wuhan, China. He received bachelor’s degree and master’s degree in Organic Chemistry from Central China Normal University in 2005 and 2008. After that, he took part in a joint doctoral programme under the supervision of Prof. Hua Jiang at the Institute of Chemistry, Chinese Academy of Sciences and Dr. Ivan Huc at the European Institute of Chemistry and Biology, Bordeaux, working toward the synthesis and the characterization of aromatic foldamers to mimic the structures and functions of biomacromolecules, and received his Ph.D. degree in early 2013. In 2013/2014, he worked as a Marie Curie Postdoctoral Research Fellow at the University of Cambridge under the guidance of Prof. Jonathan Nitschke. He has been a Professor working on supramolecular chemistry at the Huazhong University of Science and Technology, China, since December 2014.

What inspired your research in this area?

The fantastic structures and functions of biomacromolecules always inspire our research.

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

The hybridization of single helices of aromatic foldamers with full handedness control can give rise to the complete chiral control of double helices.

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

To explore the functions such as chiral sensors or catalysts is the aim that we focus on with foldamers. Here, the complete chiral control of aromatic helices offering a stable chiral environment within the cavity would provide chances to develop these functions, and which is currently being made in our laborotary.

Read the full article: Absolute handedness control of oligoamide double helices by chiral oxazolylaniline induction

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

See all the full articles on our publishing platform

Introducing Dr Pablo Martinez Bulit, first author on “One-pot synthesis of porphyrin-based [5]rotaxanes”

Pablo was born in Mexico City, where he received his B.Sc. in Chemistry from Universidad Nacional Autónoma de México, (UNAM). He obtained his Ph.D. from the University of Windsor, Canada, in 2019, under the supervision of Prof. Stephen Loeb where his research was focused on crystalline materials incorporating rotaxanes and porphyrins. He is currently working as a Postdoctoral Research Associate at the University of Glasgow.

Dr. Pablo Martinez Bulit

What inspired your research in this area? 
The long-term focus of this research was to prepare metal-organic frameworks (MOFs) incorporating both a rotaxane linker and a porphyrin linker. We had some initial success and characterised the solvent dependent dynamics of a rotaxane wheel in the solid-state for a porphyrin-based MOF (https://pubs.acs.org/doi/abs/10.1021/acs.cgd.9b00669). However, it remained a challenge to synthesize complex linkers that combined multiple rotaxanes on a porphyrin backbone. This project was a nice challenge as it combined the different research areas of the Loeb Research Group: organic synthesis, supramolecular chemistry to make mechanically interlocked molecules, and crystallography.

What do you personally feel is the most interesting outcome of your study? 
The fact that you can make and isolate these molecules this easily still amazes me. As the paper shows, this method is tolerant to a variety of functional groups so the potential to tailor the porphyrin-rotaxane hybrids for different applications is readily achievable.

What directions are you planning to take with your research in future?
Upscale the syntheses to make gram quantities and explore their possible incorporation into MOFs. Ideally these types of dynamic rotaxane linkers can be used as mechanically interlocked  switches in the solid-state.

Read the full article: One-pot synthesis of porphyrin-based [5]rotaxanes

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

See all the full articles on our publishing platform

Left to right: E. James Petersson, Joomyung (Vicky) Jun, and David M. Chenoweth

Let’s meet the researchers!

Joomyung (Vicky) Jun was born in South Korea and received her B.Sc. degree in chemical biology at U. C. Berkeley in 2012, performing undergraduate research with Kenneth Raymond. She then worked with Ronald Zuckermann at the Molecular Foundry in Lawrence Berkeley National Laboratory until 2014. Her research (Ph.D. 2019) at University of Pennsylvania focused on the development of novel and underexplored fluorogenic small molecules. She was co-advised by Professors Chenoweth and Petersson. She is currently a postdoctoral scholar with Ronald T. Raines in the Department of Chemistry at Massachusetts Institute of Technology.

David M. Chenoweth was born in Indiana, USA and received his B.S. degree from Indiana University-Purdue University Indianapolis (IUPUI) in 1999. He worked at Dow AgroSciences and Eli Lilly before joining Peter Dervan’s group at the California Institute of Technology to pursue a Ph.D. After graduation in 2009, he was an NIH Postdoctoral Fellow with Timothy Swager at Massachusetts Institute of Technology. David was appointed Assistant Professor in the Department of Chemistry at the University of Pennsylvania in 2011 and was promoted to Associate Professor with tenure in 2017.  He is also a member of the Biochemistry and Molecular Biophysics Graduate Group in the Perelman School of Medicine and the Bioengineering Graduate Group in the School of Engineering and Applied Science.

E. James Petersson was born in Connecticut, USA and completed his undergraduate education at Dartmouth College and his graduate study under Dennis Dougherty at the California Institute of Technology. After receiving his Ph.D. in 2005, he was an NIH Postdoctoral Fellow at Yale University with Alanna Schepartz. He joined the Department of Chemistry at the University of Pennsylvania in 2008 and the Department of Biochemistry and Molecular Biophysics in the Perelman School of Medicine in 2018. His research has been recognized by several awards, including the Searle Scholar, an NSF CAREER award, and a Sloan Fellowship.

What inspires your interest in fluorescent probes?

It is said that “seeing is believing,” and fluorescent probes allow one to directly visualize molecules in complex biological processes, often with high specificity. Small molecule fluorophores enable highly sophisticated microscopy techniques for “seeing” into the body or into cells, techniques that are essential for basic biological research as well as for the diagnosis of diseases, which I find fascinating.

What primary research are you carrying out in the area?

Although numerous fluorescent probes are known, the vast majority of these probes consist of a diminutive set of classical “core” dyes such as coumarin, fluorescein, or BODIPY. Dr. Jun’s thesis research focused on developing underexplored or novel fluorescent cores based on modular scaffolds that exhibited advantages over classic and contemporary dyes.  Prof. Petersson and Prof. Chenoweth have collaborated for many years on various optically active probes, including genetic encoding of fluorescent unnatural amino acids from the Petersson laboratory and photo-convertible small molecules from the Chenoweth laboratory, as well as synergistic projects using tools from the Chenoweth laboratory in protein labeling.

How do you hope this review will help and inspire future research in the area?

One of the challenges in this field is the gap between new probe development and its practical application in a biological system, which are much more complicated than the in vitro system. Says Jun: “I hope this review can be helpful for both chemists and biologists to understand the underlying concept of fluorophore design and to reach a point where chemists can tailor the probe based on the specific biological system of interest.”

Read the full article: Rational Design of Small Molecule Fluorescent Probes for Biological Applications

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

See all the full articles on our publishing platform

Introducing the researchers:

Chunmao He received his Ph.D. in Bioinorganic Chemistry from the Max Planck Institute for Chemical Energy Conversion (formerly MPI Bioinorganic Chemistry), working on the understanding of the fundamentals in heme protein catalysis, under the direction of Prof. Wolfgang Lubitz. In 2013, he moved to the laboratory of Prof. Jeffrey Bode at ETH Zurich (also ITbM, Nagoya University) to learn peptide synthesis and modification/ligation techniques as a postdoc. Since Aug. 2016, he joined the faculty of the School of Chemistry and Chemical Engineering at the South China University of Technology, as a full Professor. For more information, please read his group page at: http://www2.scut.edu.cn/he/main.htm

Changpeng Li obtained his Master degree (2020) from the South China University of Technology in the group of Prof. Chunmao He. His research focused on the development of synthetic strategies for multiple Cys-containing toxins.

What inspired your research in this area?

Tyrosine sulfation, an important post-translational modification (PTM), has been shown to present in a number of a-conotoxins (a-CTX). The biological function of this PTM in a-CTX, however, has rarely been studied, mostly because of the lack of a reliable synthetic strategy.

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

The simple aqueous solution deprotection of the neopentyl protecting group of the sulphate ester, which is used in the standard Fmoc solid phase peptide synthesis, allowed for a one-pot synthetic strategy. Moreover, unlike what’s reported in the literature, the sulphate ester modification here is stable under typical RP-HPLC conditions, i.e. with 0.1% TFA, which greatly simplified our purification and improved the overall yield.

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

We are using the synthetic strategy developed here for the construction of many other related toxins, and more importantly, we are working on the elucidation of the biological impact of this important PTM on these toxins.

Read the full article: Facile synthesis of sulfotyrosine-containing α-conotoxins

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

See all the full articles on our publishing platform

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 Xiaohua Liu  has highlighted some of her favourite recent works. Take a look at what she thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Xiaohua’s Selection: 

Hydroquinone and benzoquinone-catalyzed aqueous Knoevenagel condensation

Ryoya Takakura, Kaho Koyama, Marina Kuwata, Tsuyoshi Yamada, Hironao Sajiki and Yoshinari Sawama

Xiaohua’s comments: “The combination of hydroquinone and benzoquinone makes the Knoevenagel condensation in water easier. The work of Sawama et al. provides a novel route to the synthesis of α,β-unsaturated nitrile derivatives and beyond.”

Find out more in our interview with the authors

Synthetic approaches and applications of sulfonimidates

Priscilla Mendonça Matos and Robert A. Stockman

Xiaohua’s comments: “The prominent applications of sulfonimidates result in an unfailing interest in these compounds. In this review, Stockman and co-workers summarised the synthesis of such cyclic and acyclic sulfur(VI) species from different sulfur reagents, discussing also the application of sulfonimidates towards other important organosulfur compounds. This work manifests the opportunities of sulfonimidate chemistry. “

Revisiting the role of acids and hydrogen bond acceptors in enamine formation

Zhichao Lu, Gerald B. Hammond and Bo Xu

Xiaohua’s comments: “Organo-enamine catalysis is powerful, and understanding the effect of acid additives and hydrogen-bonding acceptors in the enamine formation process is helpful. Systematic investigation from Hammond, Xu, and their co-workers makes these issues clear. Their study showed that acids could not change, or even destabilize enamine formation, but hydrogen bond acceptors, such as solvent and basic additives, will accelerate the equilibrium toward enamine formation.”

Find out more in our interview with the authors

Chemoselective Activation of Ethyl vs Phenyl Thioglycosides: One-pot Synthesis of Oligosaccharides

Cian Mc Carthy and Xiangming Zhu

Xiaohua’s comments: “Here, the selective activation of common ethyl thioglycoside donors over other popular phenyl thioglycoside donors, by the use of simple N-trifluoromethylthiosaccharine/TMSOTf system is disclosed. Chemoselectivity is high regardless of armed and disarmed patterns. Reactivity-based syntheses of disaccharides and even oligosaccharide assemblies are available in connection with sensible promoters. Thioglycoside chemistry keeps pushing forward oligosaccharide synthesis. This paper is part of our excellent “Glycosylation Collection” in OBC.”

Find out more in our interview with the authors

Meet the Editor: Xiaohua Liu is an Associate Editor for Organic & Biomolecular Chemistry since August 2020. Xiaohua Liu obtained her BSc degree from Hubei Normal University (2000), and obtained her MS (2003) and PhD (2006) from Sichuan University. She joined the faculty of Prof. Feng’s group in 2006, and was appointed as an associate professor. In 2010, she w  as promoted as a full professor. Her current research interests include asymmetric catalysis and chiral drug synthesis. To find out more about Xiaohua’s researches,  please visit her webpage.