Chemical Communications Blog

ChemComm Milestones – Sílvia Osuna

30 Jul 2020

We’re celebrating researchers who published their first independent article with ChemComm. Professor Sílvia Osuna published her first article in 2017: Computational tools for the evaluation of laboratory-engineered biocatalysts. We wanted to find out more about Sílvia and her research – Read more below.

What are the main areas of research in your lab and how has your research progressed since publishing your first article?
The main research areas in my lab are the application and development of computational tools for evaluating laboratory-engineered enzymes, with the final goal of rationally designing new enzymes. The Feature article published in Chem. Commun. in 2017 focused on providing an overview of the available computational strategies that can be used to evaluate laboratory-engineered enzymes. Since then, we have computationally evaluated a variety of enzymes mostly through extensive Molecular Dynamics simulations (monoamine oxidase, tryptophan synthase, and alcohol dehydrogenases, among others) to unveil the role exerted by distal active site mutations on the enzyme conformational landscape. Most importantly, we have also developed new computational tools for predicting active site and distal mutations for enhanced activity (Shortest Path Map tool), which we are currently applying for altering the conformational dynamics of different enzymes. The key role exerted by remote mutations on the active sites of enzymes suggests that allostery (i.e. regulation of enzyme function by distal positions) might be an intrinsic characteristic of enzymes, which we are exploiting for enzyme evolution. Therefore, our research is now more focused on applying the developed tools to rationally design new enzyme variants rather than evaluating and explaining the enhanced activities of previously reported laboratory-engineered enzymes.

What do you hope your lab can achieve in the coming year?
I hope in the coming year we can further validate our computational tools for predicting distal active site mutations. Due to the broad sequence space of enzymes, the computational prediction of such distal mutations has been proven to be extremely challenging. However, our new tools developed open the door to new protocols based on the introduction of active site and also distal mutations. This is totally unprecedented in the computational enzyme design field, and I hope in the coming year we can further demonstrate that our developed computational tools can be successfully applied for enzyme design.

Describe your journey to becoming an independent researcher.
I received a PhD in 2010 from the University of Girona (UdG) at the Institut de Química Computacional (IQC) under the supervision of Prof. Miquel Solà and Prof. Marcel Swart. I worked on the computational study of the chemical reactivity of carbon-based compounds, such as (metallo)fullerenes and carbon nanotubes. In October 2010 I moved to the group of Prof. Houk at the University of California, Los Angeles (UCLA) thanks to the IOF Marie Curie fellowship. At that time, I started to work in the computational design of enzymes of medical and pharmaceutical interest. In December 2013, I rejoined the Institute of Computational Chemistry and Catalysis (IQCC) at the University of Girona with a postdoctoral Juan de la Cierva position. I was also awarded a Career Integration Grant (CIG) project for developing a computational protocol for designing new enzymes, and also an I+D MINECO Project together with Prof. Swart. In 2015, I obtained a European Research Council – Starting grant project (ERC-StG) to apply network models for the computational design of efficient enzymes (NetMoDEzyme), and also a 5-year Ramón y Cajal position from the Spanish government. In 2018, I was promoted to the current permanent ICREA position I currently hold. My group is now funded by the ERC-StG project, an I+D MINECO project, and a Human Frontier Science Program project.

What is the best piece of advice you have ever been given?
My grandmother used to tell me a Catalan saying “De pressa i bé, mai s’avingué”, which I believe the English equivalent would be “Slow and steady wins the race”. There are of course exceptions to the saying, but I believe it is a generally good advice that also applies in scientific contexts.

Why did you choose to publish your first article in ChemComm?
I received an invitation to submit a Feature article to ChemComm a few months after being awarded the ERC-StG project. I decided this was an excellent idea as I had already done an extensive bibliographic search for writing the ERC project. Most importantly, I like ChemComm, its published Feature articles, and its broad readership. I was also really happy to see that our published Feature article was included in the most downloaded articles of 2017 in physical and environmental chemistry. When I received a second invitation to contribute with a second Feature article in 2018, I didn’t hesitate to accept the invitation.

Sílvia received her PhD in 2010 from the University of Girona (UdG) at the Institut de Química Computacional (IQC) under the supervision of Prof. Miquel Solà and Prof. Marcel Swart. In 2010, she moved to the group of Prof. Houk at the University of California, Los Angeles (UCLA). In 2012, she rejoined the Institute of Computational Chemistry and Catalysis (IQCC) at the University of Girona with a postdoctoral Juan de la Cierva position, which was followed by a Ramon y Cajal contract, and her current permanent ICREA research professor position. Sílvia’s research lies at the interface between computational chemistry and biology. Her research focuses on the study of biochemical processes mainly related to enzyme catalysis.

Read more from our ChemComm1st authors in ChemComm Milestones – First Independent Authors

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Controlling chirality at an osmium centre

29 Jul 2020

By Samantha Apps, Web Writer.

Chirality is the concept of non-superimposable mirror images. A simple example of chiral objects are our hands, and in chemistry, molecules are chiral if they have a stereogenic (or asymmetric) centre. Like our hands when it comes to writing or dextrous tasks, chiral compounds are ubiquitous in chemistry, where often only one enantiomer (a chiral isomer) is selective for binding or reactivity. Chiral transition-metal complexes are also desirable for asymmetric catalysis, where the majority of systems have chiral ligands to impart chirality in the complex. The alternative ‘chiral-at-metal’ approach imparts chirality at the metal centre by the selective arrangement of asymmetric, achiral ligands, allowing the metal centre to act as both the stereogenic centre and the reactive centre for catalysis.

Figure 1: General structure for chiral-at-metal complexes using chelating, achiral ligands (above), and the specific structures of the enantiomers for the new osmium system Os1 (below)

Researchers in Germany have adopted this chiral-at-metal approach for asymmetric catalysis, previously reporting Ir(III), Rh(III), Ru(II) and Fe(II) systems, and have now translated this to the first example of a chiral-at-osmium complex (Figure 1). A new octahedral osmium(II) complex was synthesised (Os1), with two bidentate phenanthrolinium ligands (plus carbonyl and bound acetonitrile ligands) that are coordinated in a non-C₂-symmetric fashion to create the stereogenic osmium metal centre. Complex Os1 was initially synthesised as a racemic mixture (rac-Os1), in which the researchers were able to resolve to the individual enantiomers using a chiral auxiliary ligand. This method involved replacing the labile acetonitrile ligand with a chiral auxiliary ligand, (S)-2, to form a mixture of diastereomers Δ-(S)-Os2 and Λ-(S)-Os2, which were separable by solubility. Δ-(S)-Os2 precipitated out of the reaction solution, and was isolated and purified by filtration and washing in a >99:1 diastereomeric ratio (d.r.), and the Λ-(S)-Os2 that remained in solution was purified by column chromatography in a >99:1 d.r. The separated diastereomers were then treated with acid in an acetonitrile solution to replace the chiral auxiliary ligand back to the bound acetonitrile, to give the separated enantiomers Δ-Os1 and Λ-Os1, with >99:1 enantiomeric ratios (Scheme 1).

Scheme 1: Synthesis of Os1, starting with formation of the racemic mixture, followed by enantiomeric resolution using a chiral auxiliary ligand (S)-2

The researchers then tested the catalytic activity of the separated enantiomers of Os1 with respect to intramolecular C(sp³)–H aminations that proceed via transition metal nitrenoid intermediates. Δ-Os1 showed catalytic activity for the amination of various nitrene precursor reagents, such as the conversion of sulfonylazides (3) to cyclic sulfonylamides (4) and azidoformates (5) to 2-oxazolidinones (6), tolerating various substrate functional groups (a-c) (Scheme 2). Significantly, the chiral osmium catalyst gave high catalytic yields and enantiomeric purities, particularly in comparison to the previously reported ruthenium analogue (see Scheme 2 for comparative ratios).

Catalysis using chiral-at-osmium complex

Scheme 2: Catalytic C(sp3)-H aminations using Δ-Os1, with comparisons in activity and enantiomeric purity to the previous ruthenium analogue

Overall, this new chiral-at-osmium complex has shown superior catalytic activity with greater enantiomeric selectivity for intramolecular C(sp³)–H aminations, additionally providing the first examples of catalytic enantioselective ring-closing C-H amination of 2-oxazolidinones. This catalytic activity can be attributed to the labile acetonitrile ligand of Os1, which also proved beneficial for allowing enantiomeric resolution of the initial racemic mixture by substitution with a chiral auxiliary ligand.

To find out more, please read:

Asymmetric Catalysis with Chiral-at-Osmium Complex

Guanghui Wang, Zijun Zhou, Xiang Shen, Sergei Ivlev and Eric Meggers*

Chem. Commun., 2020, 56, 7714-7717

About the blogger:

Dr. Samantha Apps is a Postdoctoral Research Associate in the Lu Lab at the University of Minnesota, USA, and obtained her PhD in 2019 from Imperial College London, UK. She has spent the last few years, both in her PhD and postdoc, researching synthetic nitrogen fixation and transition metal complexes that can activate and functionalise dinitrogen. Outside of the lab, you’ll likely find her baking at home, where her years of synthetic lab training has sparked a passion in kitchen chemistry too.

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ChemComm – Welcome to our new Advisory Board members

22 Jul 2020

By Harriet Kent, Editorial Assistant.

This year, we have welcomed twenty new members to our Advisory Board. Learn about each member below.

Brendan Abrahams, University of Melbourne, Australia. Professor Abrahams graduated with a PhD in 1989 working in the area of cadmium and mercury coordination chemistry. He was appointed to ongoing teaching-research position within the School of Chemistry at the University of Melbourne in 2004. In addition to coordination polymers his current interests include supramolecular chemistry and crystal engineering.

	Raffaella Buonsanti, EPFL, Switzerland. Professor Buonsanti’s group works at the interface of materials chemistry and catalysis; they focus on developing a fundamental understanding of the chemistry behind the formation of colloidal nanocrystals and they use them as controlled and tunable electrocatalysts for the conversion of small molecule into value-added chemicals
	Jyotirmayee Dash, Indian Association for the Cultivation of Science, India. Professor Dash’s research interests are synthesis of natural products, the self-assembly of nucleobases and the recognition and regulation of nucleic acids.
	Sujit Ghosh, IISER Pune, India. Professor Ghosh’s major research areas include Luminescent MOFs, Chemical sensors, Pollutants capture, Ion exchange materials, hydrocarbons separation etc. suited for potential applications in the chemical industry and environmental issues.
	Robert Gilliard, University of Virginia, USA. The Gilliard laboratory focuses on understanding structure-function relationships in main-group thermochromic, luminescent, and radical materials, as well as the structure and reactivity of low-valent main-group organometallics.
	Shaojun Guo, Peking University, China. Professor Guo holds a BS in Materials Chemistry from Jilin University and a PhD in Analytical Chemistry from Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His current research interests are nano/sub-nano/atomic materials for catalysis and energy applications.
	Amanda E. Hargrove, Duke University, USA. Professor Hargrove earned her Ph.D. in Organic Chemistry from the University of Texas at Austin followed by an NIH postdoctoral fellowship at Caltech. Professor Hargrove’s laboratory focuses on developing small molecule probes to investigate the structure and function of RNA molecules relevant to human disease.
	Ilich A. Ibarra, National University of Mexico, Mexico. Professor Ibarra moved in 2014 to Universidad Autónoma de México working as an Assistant Professor. In 2017 he was promoted to Associate Professor. In 2019 he was awarded with the “Young Investigators Award in Exact Sciences”, UNAM, Mexico.
	Silvia Marchesan, University of Trieste, Italy. Professor Marchesan’s research interests lie at the interface between chemistry, biology, and materials science for the development of innovative solutions through the design of nanostructured systems with an eye to the environment (www.marchesanlab.com).
	Alexander J. M. Miller, University of North Carolina at Chapel Hill, USA. Professor Miller’s research group takes a mechanism-guided approach to the design and discovery of molecular catalysts for sustainable chemical and fuel synthesis.

	Ellen Sletten, University of California, Los Angeles, USA. Professor Sletten began her independent career at UCLA in 2015 and has established an interdisciplinary research program that leverages the tools of physical organic chemistry to create new therapeutic and diagnostic technologies.
	Mizuki Tada, Nagoya University, Japan. Professor Tada was appointed full professor at Nagoya University in 2013. Her research interests are the areas of heterogeneous catalysis, coordination chemistry, three-dimensional imaging of solid materials using hard X-ray spectroscopy.
	Judy Wu, University of Houston, USA. Professor Wu’s research interests span physical organic chemistry, photochemistry, and supramolecular chemistry. Judy was the recipient of an NSF CARERR award, an NIH-MIRA award, and a Sloan Research Fellowship.
	Yi Xie, University of Science and Technology of China, China. Professor Xie is a recipient of several awards, including L’Oréal-UNESCO for Women in Science Awards, TWAS Prize for Chemistry, IUPAC Distinguished Women in Chemistry/Chemical Engineering, Nano Research Award. Her research interests focus on the design and synthesis of inorganic functional solids with efforts to modulate their electronic and phonon structures.
	Qiang Zhang, Tsinghua University, China. Professor Zhang’s current research interests are advanced energy materials, including dendrite-free lithium metal anode, lithium sulfur batteries, and electrocatalysis, especially the structure design and full demonstration of advanced energy materials in working devices.
	Wenwan Zhong, University of California, Riverside, USA. Professor Zhong’s research is devoted to develop innovative bioanalytical techniques to advance the understanding on how biomolecules function and to improve disease diagnosis and treatment.
	Eli Zysman-Colman, University of St. Andrews, UK. Professor Zysman-Colman’s research program focuses on the rational design of: (I) luminophores for energy-efficient visual displays and flat panel lighting based on organic light emitting diode (OLED) and light-emitting electrochemical cell (LEEC) device architectures; (II) light harvesting dyes for dye-sensitized solar cells (DSSCs) and organic photovoltaics; (III) sensing materials employed in electrochemiluminescence; and (IV) photocatalysts for organic reactions.
	Appointed but not pictured: Lifeng Chi* and Arindam Chowdhury

Read the collection of high-impact articles from our new members: https://rsc.li/advisoryboard2020 Free to access until 21st August.

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ChemComm Milestones – Han Xiao

15 Jul 2020

By Harriet Kent, Editorial Assistant.

We’re celebrating researchers who published their first independent article with ChemComm. Dr Han Xiao published his first article in 2018: A noncanonical amino acid-based relay system for site-specific protein labeling. We wanted to find out more about Han and his research – Read more below.

What are the main areas of research in your lab and how has your research progressed since publishing your first article?
Understanding complex biological systems and developing novel therapeutic approaches requires explorations at the interface of chemistry and biology. The focus of our research is the development of various chemical tools that allow us to precisely probe and manipulate biological systems. We are interested in (1) adding new building blocks with novel chemical, biological, and physical properties into different biological systems; (2) enhancing the performance of chemical biological tools for a variety of applications; (3) using these tools to better understand and ultimately control various biological processes; and (4) exploring the therapeutic utilities of these tools in the context of cancer, autoimmune, and metabolic diseases. My program has a strong translational focus, seeking to initiate new clinical opportunities, and contribute to advances in chemical biology, glycobiology, and cancer immunology.
Our article demonstrates the first application of autonomous cells with the endogenous ability to biosynthesize different noncanonical amino acids and incorporate them into proteins. Noncanonical amino acid, p-amino-phenylalanine, was biosynthesized in E. coli, followed by site-specific incorporation into a specific protein residue. The resulting protein was ready for functionalization using an oxidative conjugation reaction. We are continuing cells utilizing a 21st amino acid and further examine their utility in protein evolution and therapy development.

What do you hope your lab can achieve in the coming year?
Although I have been building my independent research profile at Rice, I am actively exploring new research directions by collaborating with researchers in different fields. I hope we can tell you more of these exciting works in the coming year.

Describe your journey to becoming independent researcher.
My academic training and research experience have provided me with a broad background in multiple disciplines, which is critical for me to build up my independent research program. As an undergraduate, I supported Dr. Liu-Zhu Gong’s group (USTC) by developing flexible routes to synthesize chiral amines in alkaloid nature products. As a graduate student, I joined Dr. Peter G. Schultz’s lab at the Scripps Research Institute (TSRI). My graduate work was mainly focused on expanding the technique of genetically incorporating noncanonical amino acids in both prokaryotic and eukaryotic organisms and applying this technique for better cancer therapeutics. To further my goal of becoming a professional scientist, I started my post-doctoral research career in Prof. Carolyn R. Bertozzi’s laboratory at Stanford University, whose lab has extensive experience in studying cancer-associated glycosylation. I learned a lot from my previous advisors about how to carry out projects as well as run a lab. The different training experiences from these labs laid the foundation for the interdisciplinary program I would like to build up at Rice University.

What is the best piece of advice you have ever been given?
The best advice was given to me by my parents: Prepare for the Future.

Why did you choose to publish your first article in ChemComm?
ChemComm is a renowned journal with a large readership from all chemistry disciplines as well as interdisciplinary fields. I am very happy to publish our first work in ChemComm.

Biography
Han Xiao is an Assistant Professor of Chemistry and Biosciences at Rice University. Han obtained his undergraduate degree from the University of Science and Technology of China (USTC) where he graduated with a B.S. in chemistry and an honors degree in physical science. He conducted undergraduate research in Prof. Liu-Zhu Gong’s group, focusing on organic methodology and synthesis of natural products. After graduating from USTC in 2010, Han joined the Ph.D. program at the Scripps Research Institute (TSRI). His thesis work with Prof. Peter G. Schultz focused on expanding the technique of genetically incorporating unnatural amino acids in both prokaryotic and eukaryotic organisms and applying this technique for better cancer therapeutics. In 2015, Han joined the laboratory of Prof. Carolyn R. Bertozzi as a Good Ventures Postdoctoral Fellow of the Life Science Research Foundation at Stanford University. In his postdoctoral work, he was engaged in the development of novel cancer immune therapy targeting the cell-surface glycans axis of immune modulation. In July 2017, Han started his independent research at Rice University. Find him on Twitter: @Han_Xiao2016

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ChemComm Milestones – Hiroshi Yamagishi

03 Jul 2020

By Harriet Kent, Editorial Assistant.

Hiroshi Yamagishi recently published his first independent research article with ChemComm. We wanted to celebrate this exciting milestone by finding out more about Hiroshi and his research. Check out his #ChemComm1st article: Facile light-initiated radical generation from 4-substituted pyridine under ambient conditions

We asked Hiroshi a few questions about his experience in the lab and working with ChemComm. Read more below.

What are the main areas of research in your lab and what motivated you to take this direction?

After receiving the PhD for the synthesis and fundamental structural investigation of supramolecular porous fibers and crystals, I was motivated to expand this research topic in regard to their functionality. Our group in University of Tsukuba is now focusing on the synthesis of molecular porous aggregates and investigating their host–guest chemistry and optical functions.

Can you set this article in a wider context?
The host porous crystal, Pyopen, is an attracting and counterintuitive compound. Although the constituent organic molecules are bound together via labile van der Waals-like forces (C–H···N bonds), the porous framework exhibits high thermal stability. Distinct from the conventional MOFs, COFs, or HOFs, the stability of Pyopen is based on the packing mode or the interdigitation of the molecules. We expect that the difference in the bonding regime should result in novel outcomes, and we are now investigating a series of chemical and physical characters of such molecular porous crystals sustained by van der Waals crystals. This article highlights one of the intriguing optical and chemical features of the van der Waals crystals.

What do you hope your lab can achieve in the coming year?

One of the fundamental yet challenging topics in the field of van der Waals porous crystal is to establish a molecular design strategy. Distinct from the MOFs, COFs, or HOFs, the prediction or designing of van der Waals porous crystal is yet to be established due to the extremely low bonding energy and the low directionality of van der Waals force. This topic is what I am now trying to overcome in the coming year.

Describe your journey to becoming independent researcher.

In the course of the PhD, I fortunately received an offer as a researcher from a chemical company and was really willing to join after I got the PhD. However, when I visited the UK as a guest researcher for half a year before joining the company, I occasionally met with a colleague in the University of Tsukuba there, who also visited UK for Sabbatical and proposed to me a position in University of Tsukuba. Through this experience, I understood from the heart the meaning of the sentence: “Nobody knows the future”.

What is the best piece of advice you have ever been given?

An advice from a colleague of mine was indeed impressive and encouraging to me. In the course of a discussion about a research result, he said “I hate the word ‘failure’. You did not fail, but revealed a novel fact that the reaction proceeded in a different way from what you expected”.

Why did you choose to publish in ChemComm?

ChemComm is a renowned journal that covers the diverse chemical sciences. Chemical Science is also attractive to me, but I prefer the communication format for publishing our results with urgency. Therefore, I chose ChemComm.

I am an Assistant Professor in Department of Materials Science, University of Tsukuba since 2018. I was educated at the University of Tokyo, gaining a PhD in 2018 for the development of intricate nanoporous organic and metal¬–organic architectures with distinct structural flexibility. I am currently focusing on optical resonators based on supramolecular aggregates with a view to realizing flexible lasers, displays, optical circuits and sensors. Compounds of interest covers organic linear and dendritic polymers, organic and metal–organic crystals, and organic liquid.

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Bacteria vs. bacteria: studying small molecules for microbial competition

30 Jun 2020

By Samantha Apps, Web Writer.

Antibiotic resistant bacteria, and the subsequent diseases caused by their infection, are of serious global concern. As more and more bacteria develop antibiotic resistance and jeopardise the current treatments for serious infections, there is a strong imperative to both develop new medicines and to understand these bacterial pathogens. Pseudomonas aeruginosa, Staphylococcus aureus and species from the genus Burkholderia are all such antibiotic resistant bacteria that contribute to various human diseases, and they can pose a serious threat to cystic fibrosis patients through chronic lung infections. These are often polymicrobial infections, meaning that the different bacteria interact by association and can alter the impact of the resulting disease.

P. aeruginosa and Burkholderia generally interact competitively with S. aureus, reducing its viability. This is achieved by the secretion of small molecule respiratory toxins which include 2-alkyl-4(1H)-quinolone N-oxides (AQNOs) by P. aeruginosa or 3-methyl-2-alkyl-4-quinolone N-oxides (MAQNOs) by Burkholderia (see Figure 1). Researchers in Germany and Austria sought to understand the antagonistic interactions of these bacteria and have now reported the synthesis of various representative AQNOs and MAQNOs and investigated their action against S. aureus.

Quinolone derivatives secreted by bacteria

Figure 1: Structures of the quinolone derivatives produced by P. aeruginosa and Burkholderia that act against S. aureus

The researchers approached the synthesis of the AQNOs and MAQNOs by starting with the preparation of the corresponding quinolones, and then converting them to the quinolone N-oxides. They focussed on the C₉ nonyl-/nonenyl- derivatives, NQNOs and MNQNOs, as previous studies showed this alkyl chain length proved the most active against S. aureus. Mass spectrometry and fragmentation was primarily used to characterise the synthesised compounds, and the researchers were able to establish a new library of standards to be used for the identification of quinolones and quinolone N-oxides. This therefore allowed the researchers to quantify the specific quinolone derivatives produced by certain strains of P. aeruginosa and Burkholderia using this standard library, as shown in Figure 2.

Figure 2: Quantification of the quinolones (AQs and MAQs) and quinolone N-oxides (AQNOs and MAQNOs) secreted by P. aeruginosa (strains PAO1 and PA14) and Burkholderia thailandesis using calibration against the established standard library

The researchers then investigated the possible activity of these quinolone derivatives against S. aureus. The activity of S. aureus was measured using a chromogenic assay, by varying concentrations of the quinolone derivatives until a minimum inhibitory concentration (MIC) was reached, with complete respiratory inhibition of the bacteria. The C₉-quinolones (before N-oxidation) showed no inhibition against S. aureus at the highest concentrations tested, but the corresponding quinolone N-oxides (NQNOs and MNQNOs) showed activity against the bacteria. More specifically, unsaturated derivatives were more active, and the MNQNOs, with 3-methylation of the quinolone core, showed the greatest antibiotic activity against S. aureus. These results suggest that the methylated quinolones produced by species of Burkholderia, as well as unsaturared quinolones produced by P. aeruginosa, have an important role in competitive interactions against S. aureus in polymicrobial infections.

To find out more, please read:

Profiling structural diversity and activity of 2-alkyl-4(1H)-quinolone N-oxides of Pseudomonas and Burkholderia

Dávid Szamosvári, Michaela Prothiwa, Cora Lisbeth Dieterich and Thomas Böttcher

Chem. Commun., 2020, 56, 6328-6331

About the blogger:

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Studying Anticancer Agents with XFM

23 Jun 2020

By Alessia Millemaggi.

It turns out that rhenium-based compounds have been showing some promising anticancer activity as they’re stable, allow for real time imaging, structurally diverse, and have low off-site toxicity. The most commonly studied complexes are based around a Re(I) tricarbonyl core with the other three binding sites occupied by ligands of varying complexity. Researchers in the US and Australia developed a tricarbonyl Re isonitrile polypyridyl complex fac-[Re(CO)3(dmphen)(para-tolyl-isonitrile)]+, where dmphen = 2,9-dimethyl-1,10-phenanthro-line, called TRIP for short. TRIP showed promising cytotoxicity and can be imaged using confocal fluorescence microscopy, taking advantage of the emissive metal to ligand charge transfer (MLCT) state. The persistence of the emission indicates that the ligands remain bound to the Re even within cells. The complex’s cytotoxicity stems from its inducement of cells to accumulate misfolded proteins, resulting in apoptosis from the unfolded protein response (UPR). UPR induced cell death is relatively uncommon and led the researchers to find a method to characterize the speciation of TRIP in vitro. They used synchrotron X-ray fluorescence microscopy (XFM) to probe the cellular uptake and distribution of TRIP and an iodo-derivative I-TRIP by looking at elemental signals.

Figure 1. Chemical structures of TRIP and I-TRIP

I-TRIP is particularly well-suited to this type of study, as the iodine provides an additional spectroscopic handle on the isonitrile ligand absent in TRIP. Of course, the researchers had to confirm that I-TRIP possessed similar cytotoxicity and working mechanism to TRIP. Various assays and biological studies showed evidence of comparable cytotoxicity and mechanism, demonstrating that altering the substitution of the isonitrile ligand doesn’t significantly impact the bioactivity of the complex. With that settled, the experiments could move to the synchrotron to probe elemental distributions.

Figure 2. XFM elemental distribution maps of HeLa cervical cancer cells treated with either DMSO (control), TRIP, or I-TRIP.

Cells treated with both TRIP and I-TRIP show a clear Re signal, confirming that they can enter and persist in cells. Critically, the colocalization of the Re and I maps for I-TRIP samples indicate that the isonitrile ligand remains bound as a part of the Re complex inside the cells. This strongly suggests that the Re complex is intact while it induces cell death, adding to the developing mechanistic understanding of their activity. This work shows the utility of XRM as a technique to study the distribution of organometallic complexes in living cells. Additionally, the tunability and stable bioactivity of the Re complexes shows that they’re amenable to study by a wide range of techniques that will allow for further mechanistic probing.

To find out more, please read:

X-Ray fluorescence microscopy reveals that rhenium(I) tricarbonyl isonitrile complexes remain intact in vitro

Chilaluck C. Konkankit, James Lovett, Hugh H. Harris and Justin J. Wilson

Chem. Commun., 2020, 56, 6515-6518

About the blogger:

Dr. Beth Mundy is a recent PhD in chemistry from the Cossairt lab at the University of Washington in Seattle, Washington. Her research focused on developing new and better ways to synthesize nanomaterials for energy applications. She is often spotted knitting in seminars or with her nose in a good book. You can find her on Twitter at @BethMundySci.

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Virtual issue on Aggregation-induced Emission (AIE)

22 Jun 2020

By Harriet Kent, Editorial Assistant.

We’re celebrating the upcoming 20th anniversary of aggregation-induced emission (AIE), a term which was first coined in 2001. We’ve put together a collection of key AIE articles published in RSC journals. Here are the articles in the collection from ChemComm, including the very first AIE article!

Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole
Ben Zhong Tang et al
Chem. Commun., 2001, 1740–1741

A conical intersection model to explain aggregation induced emission in diphenyl dibenzofulvene
Quansong Lia and Lluís Blancafort
Chem. Commun., 2013, 49, 5966

Diarylboryl-phenothiazine based multifunctional molecular siblings
Kalluvettukuzhy K. Neena, Pakkirisamy Thilagar* et al.
Chem. Commun., 2017, 53, 3641-3644

Aggregation-induced emission in precursors to porous molecular crystals
Zhenglin Zhang, Ognjen Š. Miljanić* et al.
Chem. Commun., 2017,53, 10022-10025

A cyanine-based fluorescent cassette with aggregation-induced emission for sensitive detection of pH changes in live cells
Mingxi Fang, Haiying Liu* et al.
Chem. Commun., 2018,54, 1133-1136

AIE-active micelles formed by self-assembly of an amphiphilic platinum complex possessing isoxazole moieties
Takehiro Hirao,Takeharu Haino* et al.
Chem. Commun., 2020,56, 1137-1140

A self-delivery DNA nanoprobe for reliable microRNA imaging in live cells by aggregation induced red-shift-emission
Zhe Chen, Leilei Tian* et al.
Chem. Commun., 2020,56, 1501-1504

A light-up probe with aggregation-induced emission characteristics (AIE) for selective imaging, naked-eye detection and photodynamic killing of Gram-positive bacteria
Guangxue Feng, Bin Liu* et al.
Chem. Commun., 2015, 51, 12490-12493

Rational design of substituted maleimide dyes with tunable fluorescence and solvafluorochromism
Yujie Xie, Rachel K. O’Reilly et al.
Chem. Commun., 2018,54, 3339-3342

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A precious pairing

18 Jun 2020

By Samantha Apps, Web Writer.

Understanding metal-metal interactions is of fundamental interest to chemists, especially in the design of new materials or catalysts. Heterometallic metal-metal bonding is particularly fascinating, since the unique properties of each metal can be combined or even manipulated, to enhance structural, electronic or even photochemical effects. Gold and platinum are one such pairing of interest and there have already been several applications of AuPt clusters reported for catalysis. However, well-defined, homogeneous AuPt complexes are comparatively under explored, but there is a huge potential for these heterodinuclear complexes to catalyse useful chemical transformations. Research in Germany by Butschke and co-workers now describes the first example of an AuPt complex with a bound olefin, as a valuable, formal Au^+IPt⁰ precursor for further reactivity and chemical transformations (Figure 1).

Figure 1: The new AuPt heterodinuclear complex with Pt-bound olefins (right), and existing examples in the literature with Pt-bound phosphines (left and centre).

The new cationic AuPt complex described in this report differs from the existing literature by the presence of weakly bound olefin ligands (in this case, norbonene/nbe) coordinated to the platinum. The other existing examples have only strongly σ-donating phosphine ligands coordinated to the Pt centre, which increases the overall stability of the complexes and renders them unreactive for further chemistry. In contrast, the nbe ligands are more weakly bound, and have a much lower dissociation energy, creating a more reactive complex which is therefore a valuable precursor to other formal Au^+IPt⁰ complexes. This increased reactivity is reflected in the preparation and subsequent manipulations of the complex, which had to be conducted at low temperatures to prevent decomposition.

Figure 2: The X-ray crystal structure of the new AuPt complex.

The new AuPt heterodinuclear complex prepared in this report was characterised by a range of spectroscopic and structural techniques. Single-crystal X-ray diffraction confirmed the molecular structure of the complex, as shown in Figure 2. A rearrangement of the three axial nbe ligands was observed in the new AuPt complex compared to the [Pt(nbe)₃] platinum precursor; the three olefin ligands are arranged in a spoke-wheel geometry with the bridging methylenes of nbe all pointing in the same direction away from the gold (an ‘up-up-up’ configuration, in comparison to an ‘up-up-down’ arrangement as in the Pt precursor). NMR spectroscopic characterisation also helped to elucidate and confirm the structure. The ¹⁹⁵Pt-NMR resonance of the AuPt complex was particularly noteworthy, showing a similar chemical shift to that of the Pt precursor, which indicates little to no electronic change at Pt⁰ in the new AuPt complex. This was also reflected in the ¹³C NMR resonances for the olefinic carbons, which again, were similar in the AuPt complex and the Pt precursor.

Figure 3: Comparing the new AuPt complex (3) to other systems with fewer bound olefins, in terms of the Au-Pt bond dissociation energy (x-axis) and the overall charge transfer between the Au and Pt (y-axis), according to three different calculations.

The authors then further probed the binding of the gold centre to the platinum, and why there was no apparent significant change in the electronics between the new AuPt complex and the Pt precursor. A comparison to the existing AuPt complexes reported revealed that these are often assigned formally as Au^-IPt^+II, where there is a dative interaction between the Lewis base (Pt) and the Lewis Acid (Au). In contrast, the new AuPt complex in this report is formally assigned as Au^+IPt⁰, where there is considerably less charge transfer in the metal-metal bonding, as shown by DFT calculations (see Figure 3). This formal Au^+IPt⁰ assignment ultimately results in the coordinated nbe olefin ligands having a low dissociation energy (i.e. they are highly labile and susceptible to ligand substitution), which is further supported by DFT calculations and is reflected in the lack of an identifiable electrospray-ionisation mass spectrometry peak for the [M]⁺ ion. Therefore, this new AuPt complex is a desirable precursor for the preparation of other formal Au^+IPt⁰ complexes, which will allow for future reactivity studies on these unusual heterodinuclear systems.

To find out more, please read:

A heterodinuclear, formal Au^+IPt⁰ complex with weakly bound alkene ligands

Lukas D. Ernst, Konstantin Koessler, Andreas Peter, Daniel Kratzert, Harald Scherer and Burkhard Butschke

Chem. Commun., 2020, 56, 5350-5353

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ChemComm Milestones – Malte Fischer

17 Jun 2020

By Harriet Kent, Editorial Assistant.

Malte Fischer recently published his first article as a corresponding author with ChemComm. We wanted to celebrate this exciting milestone by finding out more about Malte and his research. Check out his #ChemComm1st article: B(C6F5)3- and HB(C6F5)2-mediated transformations of isothiocyanates.

We asked Malte a few questions about his experience in the lab and working with ChemComm. Read more below.

What are your main areas of research and what motivated you to take this direction?

I would like to summarize the research I am doing and I am interested in, simply under the term “synthetic chemistry”. Specifically, I mean research within the interfaces of organic chemistry, main group chemistry and organometallic chemistry. I am enthusiastic about the progress – especially in recent years – in synthesis, method development and in the search for applications for new molecules. I am convinced that there will always be a need for effective synthesis routes to access unusual and new molecules and I very much hope that I can contribute to this.

Can you set this article in a wider context?

The article is settled in main group chemistry. During my PhD I became more and more interested in this exciting field of research. Based on the reported results I will continue the research in this field.

What do you hope you and your research can achieve in the coming year?

Despite this difficult time, I am simply looking forward to going back to the laboratory at some point to continue having fun in doing research.

Describe your journey to becoming an independent researcher.

I think the moment when I was able to synthesize and characterize my first molecule unknown in literature (happened during my bachelor thesis) inspired me so much that since then I have had the goal of doing independent research and realizing my own ideas. I am definitely still in the beginning of becoming an independent researcher and I am currently working on laying the foundation for it – and this work has given me a lot of pleasure so far.

What is the best piece of advice you have ever been given?

The best advice was given to me by my parents and I try to live by it as much as possible: Pursue what interests you most and captivates you – the rest will come naturally.

Why did you choose to publish in ChemComm?

ChemComm simply stands for publications of the highest quality and with a large readership from all chemistry sub-disciplines. I am immensely pleased to have become a small part of this journal with my first publication as the corresponding author.

Malte’s Bio:

The publication ‘B(C6F5)3- and HB(C6F5)2-Mediated Transformations of Isothiocyanates’ originates from the phase as a research scientist within the group of Prof. Beckhaus in Oldenburg.

05/2019 – 02/2020 Research Scientist/ PostDoc – Carl von Ossietzky University Oldenburg, Germany. Supervisor: Prof. Dr. Rüdiger Beckhaus

10/2015 – 05/2019 PhD in Chemistry. Carl von Ossietzky University Oldenburg, Germany. Supervisor: Prof. Dr. Rüdiger Beckhaus

10/2013 – 10/2015 Master of Science in Chemistry

10/2010 – 10/2013 Bachelor of Science in Chemistry

Find Malte on Twitter: @FiMalte

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