Inspired by nature: dynamic stimuli responsive catalysis based on molecular motors

Catalysis is a fundamental concept in chemistry, allowing chemists to effectively carry out difficult transformations to access valuable materials with precision and control. For the most part, research has focused on the development of new catalysts for optimized performance to achieve high conversion and selectivity. However, special attention is now being paid to engineering catalysts whose activity can be tuned through external stimuli. This concept is ubiquitous in nature and its implementation into artificial systems offers unique opportunities and promising future applications.

A recent OBC publication by Prof. Ben Feringa of the University of Groningen Nijenborgh discusses his group’s success in developing two novel bisthiourea catalysts which display dynamic control over activity and stereoselectivity in the Henry reaction using light and heat as external stimuli.

This catalyst design is based on a molecular motor previously reported by Feringa and inspired by nature where control over function, activity and selectivity can be attained through conformational changes within the catalyst’s active site induced by external stimuli.

In the current publication, upon irradiation of the catalyst in its stable trans state, (R,R)-(P,P)-trans (see Scheme), an unstable cis state is obtained, (R,R)-(M,M)-cis, in which the catalytic groups A and B are brought into proximity to carry out the desired enantioselective transformation. The catalyst can then be converted through heating to a stable cis state, the (R,R)-(M,M)-cis isomer, via a thermal helix inversion. In this conformation, the two active groups A and B remain within reaction proximity, however, as the helicity of the motor core is inverted, a pseudoenantiomeric catalytic environment is produced which results in the formation of the opposite enantiomer.

This is the first example of a tunable bisthiourea catalyst and represents an important advancement in the field of dynamic stimuli responsive catalysis. This new area of research offers great potential for advanced materials and solving long-standing challenges that have thus far been impossible to overcome using conventional methodologies.

To find out more see:
Dynamic control over catalytic function using responsive bisthiourea catalysts
M. Vlatković,  
DOI:10.1039/C7OB01851G


Victoria Corless is currently completing her Ph.D. in organic chemistry with Prof. Andrei Yudin at The University of Toronto. Her research is centred on the synthesis of kinetically amphoteric molecules which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.

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Organic & Biomolecular Chemistry partners with Publons

Organic & Biomolecular Chemistry has partnered with Publons (a third-party reviewer recognition service) so you can keep a record of every review you complete.

We really value your reviewing and editorial contributions and want to ensure you get more recognition for them.

How it works
When you submit a review to a participating journal you will be asked if you want to opt in to Publons, you can then instantly start building your verified peer review and editorial record to showcase the full extent of your contributions and influence in your field. Publons tracks your reviews without compromising reviewer anonymity, by default, only the year of the review and the journal title will be shown on reviewer profiles for our journals.

Read more about the partnership on our news pages

For more information about Publons, visit publons.com/benefits/researchers

 

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Poster Prize Winners at the Tri-Institutional Chemical Biology Symposium

From the whole Organic & Biomolecular Chemistry team, we’d like to say congratulations to all the poster prize winners at the Tri-Institutional Chemical Biology Symposium 2017!

We were pleased to present prizes to the following winners:


Rudolph Pisa
(Graduate student with Professor Tarun Kapoor, The Rockefeller University) – Chemical Science poster prize
A rational strategy to design probes for the chemical genetic analysis of AAA+ proteins

Darren Johnson (Graduate student with Professor Daniel Bachovchin, Memorial Sloan Kettering Cancer Centre) – Chemical Society Reviews poster prize
DPP8 and DPP9 are therapeutic targets for acute myeloid leukemia

Michaelyn Lux (Graduate student with Professor Derek Tan, Memorial Sloan Kettering Cancer Centre) – Organic & Biomolecular Chemistry poster prize
Diastereoselective palladium-catalyzed cascade to form pyranobenzofurans and furobenzofurans

Dr Nathan Westcott (Postdoc with Professor Howard Hang, The Rockefeller University) – Organic & Biomolecular Chemistry poster prize
Chemical proteomics reveals ADP-ribosylation of small GTPases during oxidative stress

 

You can read some related papers publishing in Organic & Biomolecular Chemistry below:

A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site
James C. Burnett, Chaemin Lim, Brian D. Peyser, Lalith P. Samankumara, Marina Kovaliov, Raffaele Colombo, Stacie L. Bulfer, Matthew G. LaPorte, Ann R. Hermone, Connor F. McGrath, Michelle R. Arkin, Rick Gussio, Donna M. Huryn and Peter Wipf
From themed collection 2017 Hot Articles in Organic and Biomolecular Chemistry

Structure-based design of 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines as inhibitors of myeloid cell leukemia-1 (Mcl-1)
L. Chen, P. T. Wilder, B. Drennen, J. Tran, B. M. Roth, K. Chesko, P. Shapiro and S. Fletcher
From themed collection New Talent

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Self-assembly of bioactive peptides, peptide conjugates, and peptide mimetic materials

Molecular self-assembly has become one of the most prominent fields of nanotechnology in recent years. Inspired by nature, many scientists around the world are attempting to utilize it as a tool to design novel nanostructures with desired biomedical properties.

To achieve this goal, it is necessary to understand how self-assembly works and how molecular forces and other conditions drive this self-assembly and define the structure of a specific supramolecular complex.

In a recent Organic & Biomolecular Chemistry publication, Professor Charlotte J. C. Edwards-Gayle and Professor Ian W. Hamley from the University of Reading, UK, have reviewed some of the most prominent self-assembled peptide amphiphiles and their potential applications. These include tissue scaffolds, antimicrobial peptides and drug transporters.

One of the distinct features of self-assembling amphiphiles, which makes them attractive candidates for many applications, is their diversity to form various structures such as micelles, vesicles, nanotubes, fibrils and sheets (Fig.1). The self-assembly of PAs can also be tuned by several factors including amino acid sequence, peptide length, temperature, pH, and concentration.

 

These features make them perfect, novel tools to create biomaterials which can be responsive to different environmental cues. However, the review points out that the key question of whether there is a relationship between bioactivity and self-assembly of peptide amphiphiles has still remained unanswered, despite the advancement in the field.

Extending the success in designing various structures, together with distinct applications, have made peptide amphiphile self-assembly a vibrant field in which researchers will continue to develop functional constructs with novel applications.

To find out more please see:

Self-assembly of bioactive peptides, peptide conjugates, and peptide mimetic materials
Charlotte J. C. Edwards-Gayle and Ian W. Hamley
DOI: 10.1039/C7OB01092C


Zahra Bahrami Dizicheh is a PhD candidate in molecular biology with Dr. Giovanna Ghirlanda at Arizona State University. She does research on photo-electrochemical hydrogen production with designing and developing interconnection between conductive materials and redox proteins to develop dye-sensitized photo-electrochemical cells.

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Diversity-oriented synthesis of biaryl-containing macrocycles

Developing efficient protocols for the synthesis of macrocycle-containing molecules has been a longstanding challenge in chemistry. In a recent OBC publication, collaborative efforts between Prof. Tomás Torroba of the University of Burgos and Prof. Luis Miranda of Universidad Nacional Autónoma de México have resulted in a diversity oriented synthetic strategy for the synthesis of biaryl-containing macrocycles.

Macrocyclic structures have utility in many different areas of chemistry and have significant applications in medicine due to their broad range of biological activities. Compared to small molecules, macrocycles offer unique functional advantages in terms of selectivity and potency as their cyclic framework enables a high degree of structural preorganization such that key functional groups can interact across extended binding pockets without a major loss of entropy. Moreover, macrocycles display favourable drug-like properties such as improved solubility, lipophilicity, membrane penetration and stability.

Of interest are peptide macrocycles containing an endo aryl-aryl bond which constitute an important class of biologically active macrocyclic natural products. In terms of established synthetic approaches, two strategies have been commonly implemented 1) construction of the biaryl unit followed by a cyclization and 2) ring closure through the formation of the aryl-aryl bond.

These routes are limited however by the synthesis of the peptide backbone which typically requires challenging multi-step sequences.

To circumvent this issue, Torobba and Miranda proposed a sequence combining a Ugi four component reaction (Ugi-4CR) with a Suzuki-Miyaura cross-coupling for rapid access to the desired macrocycles in a diversity oriented approach. This synthetic strategy is composed of four steps: 1) Ugi-4CR using two bifunctional building blocks, the mono-Boc protected diamine and iodine containing carboxylic acid; 2) Boc cleavage; 3) a second Ugi-4CR involving a MIDA protected boron-containing carboxylic acid and finally 4) Suzuki-Miyaura cross-coupling-based macrocyclization.

After optimisation, the synthesis of a small collection of biaryl-containing macrocycles was carried out with good overall yields (35-65% isolated yield) and their cytotoxicity evaluated against eight human cancer cell lines.

The ease with which this synthetic sequence can be reproduced in combination with their preliminary biological results will no doubt open doors for the future evaluation of larger collections of this class of biaryl-containing macrocycles and in determining their full potential in drug discovery.

To find out more see:

Diversity-oriented synthesis and cytotoxic activity evaluation of biaryl-containing macrocycles
Karell Pérez-Labrada, Marco A. Cruz-Mendoza, Alejandra Chávez-Riveros, Eduardo Hernández-Vázquez, Tomás Torroba and Luis D. Miranda
DOI: 10.1039/C6OB02726A


Victoria Corless is currently completing her Ph.D. in organic chemistry with Prof. Andrei Yudin at The University of Toronto. Her research is centred on the synthesis of kinetically amphoteric molecules which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.

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Synthesis of challenging oligosaccharides by harnessing glycosyltransferase activity directly from human breast milk

Synthetic oligosaccharides and glycoconjugates are being increasingly used to solve important problems within biological research for vaccine development and drug discovery purposes. However, due to their complicated isolation and characterization from biological fluids, as well as a lack of general and efficient protocols for their preparation, progress within the field has been limited.

A recent OBC publication from Prof. Carmen Galan of the University of Bristol seeks to overcome this longstanding challenge using imidazolium-labeled (ITag) glycosides. Ionic liquid-based labels are emerging as a new class of covalent chemical labels that provide a unique handle for facile identification and purification of substrates from complex reaction mixtures using mass spectroscopy.

It was hypothesised that the ITag-glycan probes could be used to harness the natural biosynthetic machinery present in human breastmilk (i.e. glycosyltransferases) to access biologically important oligosaccharides. This study circumvents lengthy and costly chemical syntheses as well as the need to isolate a specific enzyme which can be challenging to express and applicable only to small-scale production.

In a matter of days, the group was able to access a series of highly desirable oligosaccharides, including LacNAc-ITag, ITag-Lewisx and ITAg-Lewisa through incubation of a labelled glycoside in readily sourced human breast milk. The capability of ITag to aid in the synthesis of oligosaccharides from a complex, multi-enzyme environment is pivotal. This technology could revolutionize the way in which synthetic, enzymatic transformations are carried out and has the potential to expand outside of carbohydrate chemistry.

To find out more see:

Imidazolium-labeled glycosides as probes to harness glycosyltransferase activity in human breast milk
I. Sittel and M. C. Galan
DOI: 10.1039/C7OB00550D


Victoria Corless is currently completing her Ph.D. in organic chemistry with Prof. Andrei Yudin at The University of Toronto. Her research is centred on the synthesis of kinetically amphoteric molecules which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.

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Introducing Professor Motomu Kanai, OBC Associate Editor

Professor Motomu Kanai has joined Organic & Biomolecular Chemistry as an Associate Editor. We are delighted to welcome him to the team and look forward to working with him over the coming years.

 

Motomu Kanai was born in 1967 in Tokyo, Japan, and received his bachelor degree from The University of Tokyo (UTokyo) in 1989 under the direction of late Professor Kenji Koga. In the middle of his PhD course in UTokyo (in 1992), he obtained an assistant professor position in Professor Kiyoshi Tomioka’s group of Osaka University. He obtained his PhD from Osaka University in 1995 before moving to the 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 in UTokyo as an assistant professor, being a lecturer (2000~2003) and an associate professor (2003~2010). He is currently a professor at UTokyo and is a principle investigator of the 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 focus on the design and synthesis of functional (especially, biologically active) molecules.

 

Professor Kanai’s recent articles in OBC include:

5-Position-selective C–H trifluoromethylation of 8-aminoquinoline derivatives
Org. Biomol. Chem., 2016, 14, 8092-8100, Paper

Directing activator-assisted regio- and oxidation state-selective aerobic oxidation of secondary C(sp3)–H bonds in aliphatic alcohols
Org. Biomol. Chem., 2016, 14, 4378-4381, Communication

This article is part of the themed collection: 2016 Hot Articles in Organic and Biomolecular Chemistry

 

Find out more about Professor Kanai and his research on his lab’s webpage.

Submit your work for Professor Kanai to handle today.

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Insights into temperature controlled enantioselectivity in asymmetric catalysis

The rare phenomenon of enantioselectivity reversal, using a simple change in reaction temperature control, is presented in the latest HOT article published in OBC.

The ability to mimic nature’s stereochemical control in the production of complex molecules has been a longstanding challenge in chemistry. There are numerous strategies chemists have implemented to generate stereochemically complex structures, however, with the advent of asymmetric catalysis, highly stereoselective reactions can be achieved using chiral reagents and catalysts.

In a recent OBC publication by Prof. Kenso Soai of Tokyo University and researchers from Merck, one of the very few examples in which the enantioselective outcome of a reaction is controlled through temperature was presented. Gaining enantioselective control by changing simple reaction parameters has been an attractive and long sought after advancement within the field of asymmetric catalysis. While there are examples of enantioselective control using solvent, metals and additives, very few examples exist that use temperature alone.

The study outlines the effect of temperature on the asymmetric autocatalysis of pyrimidal alkanol in the addition reaction of diisopropyl zinc to the pyrimidine-5-carbaldehyde. After reaction initiation using a chiral initiator, the product alkanol behaves as an asymmetric catalyst for its own formation and infers its chirality to the product in an autocatalytic cycle. When the reaction was performed at 0 ºC in the presence of (S)-1-phenyl-ethyl alcohol, as expected, (S)-pyrimidal alkanol was afforded in high enantiomeric excess. Interestingly, when the reaction was cooled to -44 ºC, the opposite enantioselectivity was observed though with a slightly lower enantiomeric excess of the desired alkanol.

The exact mechanism through which this reversal happens is still unclear however, it’s speculated that the relationship between temperature and the relative enthalpic vs. entropic contributions to free energy may play a part or the temperature dependent aggregation of zinc alkoxide may also be involved.

It’s important to remember that the temperature effect on reactions involving organozinc reagents is not always straight forward and may not always lead to the best outcome.

Regardless, this study provides interesting insight into temperature controlled enantioselectivity that may lead to a more detailed understanding of such processes and how they can be synthetically exploited.

To find out more see:

Unusual reversal of enantioselectivity in the asymmetric autocatalysis of pyrimidyl alkanol triggered by chiral aromatic alkanols and amines
Arimasa Matusmoto, Satoshi Fujiwara, Yui Hiyoshi,aKerstin Zawatzky, Alexey A. Makarov, Christopher J. Welch and Kenso Soai
DOI: 10.1039/C6OB02415G


Victoria Corless is currently completing her Ph.D. in organic chemistry with Prof. Andrei Yudin at The University of Toronto. Her research is centred on the synthesis of kinetically amphoteric molecules, which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.

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Enhancing nonlinear optical imaging through porphyrin-based dyes

Over the past several decades, advances in cell imaging have dramatically transformed biology and medicine. Fluorescence spectroscopy and microscopy are currently the most popular imaging techniques however, there are intrinsic limitations; many substrates are non-fluorescent or weakly fluorescent, fluorescent labels are often perturbative for small molecules and peptides and, perhaps most importantly, labelling or staining with fluorophores are not recommended for in vivo medicinal applications in humans. Hence, the search for highly sensitive optical imaging methods is increasingly desirable in biomedical and material sciences.

Nonlinear optical imaging is an emerging technology that encompasses a range of optical phenomena. In a recent study by Prof. Koen Clays of the University of Leuven and Prof. Harry Anderson of Oxford University, a new group of chromophores based on pyropheophorbide-a methyl ester (PPa-OMe) was developed for the linear and nonlinear optical imaging of membrane potentials as well as biological imaging of structures through two-photon excited fluorescence (TPEF) and second harmonic generation (SGH) microscopy.

In TPEF, a fluorophore is excited by the simultaneous absorption of two photons in the infrared spectral range. In conventional one-photon fluorescence, the same transition to higher energy levels requires photons in the ultraviolet or visible range. The longer incident wavelength in TPEF leads to improved depth penetration in tissues, with reduced potential for photolytic damage. SHG, on the other hand, is a nonlinear process where two photons interact with a nonlinear material and are effectively combined to generate new photons with twice the energy. This process does not involve absorption of photons but relies on virtual energy states and can only occur in materials that exhibit a non-centrosymmetric structure.

Unlike incoherent processes such as fluorescence, coherent nonlinear optical spectroscopies generate different optical signals depending on the underlying processes. They have broad utility as biomedical tools, offering contrasting mechanisms to fluorescence emissions and provide a useful alternative to label-based imaging.

In this OBC publication, the electronic structure of PPa-OMe (1a) was altered to tune it’s linear and nonlinear optical properties. Porphyrins and related porphyrinoid chromophores inherently possess excellent linear and nonlinear optical properties due to their large, conjugated π-system. By incorporating both electron-donating and –accepting groups, a push-pull type system was generated in which greater SHG intensity was observed due to the increased polarization of its π-system. A hydrophilic group, bis-triethyleneglycol (TEG) amide, was attached to make PPa-OMe amphiphilic and was then suspended in lipid-based water in oil monolayer droplets—a simple model system used to probe potentials across cellular membranes. TPEF and SHG images of the bis-TEG amide attached dyes revealed that the TPEF and SHG involve transition dipole moments in different orientations. While TPEF is detectable in all directions around the sample, SHG is detected in the forward direction of the incident light meaning there is an overall cancelling of the SHG signal from anti-parallel dyes. In order to improve these systems, control over orientation within cell membranes is crucial however, chromophores based on these PPa-OMe derivatives are promising prototypes for future cell imaging studies.

To find out more see:

Push-pull pyropheophorbides for nonlinear optical imaging
Anjul Khadria, Yovan de Coene, Przemyslaw Gawel, Cécile Roche, Koen Clays and Harry L. Anderson
DOI: 10.1039/C6OB02319C


Victoria Corless is currently completing her Ph.D. in organic chemistry with Prof. Andrei Yudin at The University of Toronto. Her research is centred on the synthesis of kinetically amphoteric molecules, which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.

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Outstanding Reviewers for Organic and Biomolecular Chemistry in 2016

Following the success of Peer Review Week in September 2016 (dedicated to reviewer recognition) during which we published a list of our top reviewers, we will continue to recognise the contribution that our reviewers make to the journal by announcing our Outstanding Reviewers each year.

Outstanding Reviewers for Organic and Biomolecular Chemistry in 2016, as selected by the editorial team, have been chosen based on the number, timeliness and quality of the reports completed over the last 12 months.

A big thank you to those individuals listed here as well as to all of the reviewers that have supported the journal, helping us to get decisions to authors in under 3 weeks, on average. Each Outstanding Reviewer will receive a certificate to give recognition for their significant contribution.

Professor Kyo Han Ahn, Pohang Univeristy of Science and Technology

Professor Barry Carpenter, Cardiff University

Dr Justin Chalker, Flinders University

Dr Bobo Dang, University of California

Professor Concepción González Bello, Universidade de Santiago de Compostela

Dr Alakananda Hajra, Visva-Bharati University

Dr Charles Heath, CSIRO

Professor Colin Suckling, University of Strathclyde

Professor David Yu-Kai Chen, Seoul National University

Professor Jian Zhou, East China Normal University

We would also like to thank the Organic and Biomolecular Chemistry boards and the organic chemistry community for their continued support of the journal, as authors, reviewers and readers.

If you would like to become a reviewer for our journal, just email us with details of your research interests and an up-to-date CV or résumé.  You can find more details in our author and reviewer resource centre

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