Seasons of Lab

Seasons of Lab

 ♫ “Five hundred, twenty-five thousand, six hundred reactions…”

That song from the musical Rent is in my head as I write this post on seasons. It’s a catchy one that brings back memories of my misspent youth hanging out with people who would sing showtunes at the drop of a hat in perfect four-part harmony!

One of the things I love about working in a chemistry lab and constantly making new compounds as part of my research is the beautiful accidental shapes and patterns molecules can assemble into, given enough time – and how our pattern-seeing brains can ascribe poetic meanings to these patterns based on what we want to see! Two recent examples from my own work caught my eye enough recently to pull out a camera and snap a shot. They tell a chronologically-consistent story of the changing seasons, as the colours of Bern’s horizon have changed from auburn to snowy white this last month, I’ve seen fallen leaves and swirls of snow in the bottom of round-bottomed flasks:

Autumn left behindWinter precipitate

Obviously crystals are some of the most beautiful formations that we can see in the lab, with their sparkle and sharp, defined edges: needles, plates, and more complex symmetries. As chemists, we love large ‘single crystals’ which can be subjected to X-ray diffraction experiments to generate the molecular structures which illustrate the pages of so many research articles these days. I had an old starting-material from much of my work in Trinity College Dublin (2,6-Bis(trimethylsilyl)ethynylpyridine, if you must know), which loved to crystallise. I believe I fished out a crystal of it from a reaction mixture once, hoping it would tell me something about a new exciting product, but alas no. Nonetheless, my colleague Dr Salvador Blasco solved this structure, which, despite not telling us anything new, was pleasingly symmetrical:

2,6-Bis(trimethylsilyl)ethynylpyridine

I often think with wonder about the deep insight of early chemists into the nature of matter that they could be so certain of chemical structures with a small range of tools like melting-points, taste, and a series of tests and probes; we have access to so many techniques nowadays that we take for granted that can show us, atom by atom, how a molecule fits together. So often, the early chemists of a century and more ago were right or close to it based on wisdom intuition and methodical analysis.

With major developments in materials science in recent decades, tools such as Scanning Electron Microscopy and Helium Ion Microscopy have allowed us to look closely at how the surfaces of substances are arranged on a slightly larger scale than single molecules, which can be vital to understanding them. More pertinent to the whimsical theme of of this post is just the fascination you feel when seeing that, on zooming all the way in, the flexible gel-like substance you have made looks like a plate of spaghetti, or a woven cloth. The picture below comes from my Dalton Transactions article, thanks to my collaborators Drs Kotova, Bell and Prof Boland, working at CRANN/AMBER in Trinity College Dublin:

Helium ion miscroscopy of a metallogel

There is beauty and fascination everywhere. It’s just a matter of how far you need to zoom in to see it!

Swiss Chemical Society Fall Meeting

A large contingent from the Albrecht research group in Bern made our way down to Lausanne today for the Swiss Chemical Society’s annual Fall Meeting at EPFL. As always, it was a massive meeting, underscoring the impressive amount of chemistry research that goes on in small-but-mighty Switzerland.

The introductory speaker, Prof Emsley, highlighted some unique aspects of Swiss research, including the strong industrial presence in the country (indicated by the generous sponsorship of every session by pharmaceutical and instrumentation companies), as well as the rich international complexion of the researchers who work at the Swiss Universities and companies. More than a quarter of all researchers are non-nationals – and that is a real strength, allowing for diverse workers and ideas to come together from all over Europe and the world. Mobility and openness, in principle, allow the best people to find the best partners for their research and push forward important developments in science.

One of my colleagues presented his recent results (Angewandte Chemie), while seven of us presented posters over the extended lunchtime session. Lots of interesting conversations were had with researchers at other universities, as well as industrial chemists; in Switzerland industrial chemists are well integrated into the professional society (the SCS), which I think is beneficial to all of us, for focussing our targets and sharing the latest advances. Indeed, in addition to leading academics like Prof Karsten Meyer, we also saw presentations from the likes of Syngenta.

We got to socialise a little and explore the EPFL campus after the talks, and, in the Rolex Building, I was lucky enough to run into old friend Marie Curie! I had a colleague snap this photo of me and the other Marie Sklowdowska-Curie Fellow in the Albrecht group with our mentor! She’s everywhere!

Marie Curie and her fellows

 

Chemistry in the Rising Sun – ICCC in Sendai

Pictures of me presenting at ICCC in SendaiI am just after returning from the 43 (and largest ever) International Conference of  coordintion Chemistry in Sendai, Japan. This year’s ICCC had an awful lot to offer, with 2,500 of us in the Sendai International Centre, and spread over up to twenty parallel session at times, there is clearly a lot happening in inorganic and coordination at the moment. Some highlights included fascinating molecular machines (with an inspiring closing address from 2016 Nobel laureate Jean-Pierre Sauvage), catalytic approaches to the challenges presented by the need to find new fuel sources for a changing world, new pincer and NHC ligands, luminescent diagnostic probes and therapeutic agents and much much more.

Me speaking from the podium in the Exhibition Hall on Thursday morning

I was privileged to get the chance to present my work in Session 38 “Organometallic complexes for synthesis and polymerisation”, to a room full of my peers and leaders in the field, including people I had interacted with during the week and who came along to see what it is I am up to in my current work! My presentation on the catalytic activity of carbohydrate-functionalised N-heterocyclic carbene complexes went very well and there were even a few useful questions that prompted a bit of discussion afterwards.

After Thursday morning, I could relax a bit more and just enjoy attending the sessions without worrying about perfecting my talk! Luckily that afternoon had also been set aside on the programme for sight-seeing, so I wandered around the site of Sendai Castle and the adjacent shrine with a few other chemists. I also got to sample the regional delicacy of beef tongue and make my own chopsticks from scratch. A nice mix of learning, culture and networking.

 

I really enjoyed catching up with old colleagues from Europe and the UK and meeting new people from both hemispheres to share ideas with (as well as a fateful trip to karaoke after the conference banquet wrapped up earlier than necessary) as well as the engaging discussions had at the poster sessions. I’m also getting better at asking questions after lectures, as my confidence in the field grows with experience!

Looking forward to the next one in Rimini!

Thanks, of course, to my Marie Skłodowska Curie Fellowship (GLYCONHC) and the European Commission for funding the work which I presented

From Bern to CERN

From Bern to CERN

It’s always nice to have an opportunity to see behind the curtain, and all the better if you feel like you’re doing it for a good reason. I was fortunate enough to be invited to join the delegation of Irish parliamentarian James Lawless TD on a fact-finding mission to CERN, the particle physics research centre which straddles the Swiss-French border in a way that is a metaphor for how it brings countries together.

 

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Deputy Lawless, Prof Ronan Nulty, Dr Kevin Byrne (both of UCD, Dublin; School of Physics and School of Medicine, respectively), and myself visited the facility and met with leaders and scientists who make it work. The aim of the trip was for CERN to put the case for Irish membership of the body to us, for us to see what benefits would come to the country via participation in the many exciting ground-breaking projects happening, and for Deputy Lawless, as opposition Science and Technology spokesperson on  to bring this back to the relevant Oireachtas committees and lobby for Ireland making room in its 2019 budget for CERN membership.

It was wonderful to tour the sprawling campus of rolling fields which lie no less than 50 metres above the Large Hadron Collider and visit the various experiments set up along its 26.7-km circumference. At ALICE, CMS and LHCb (‘b’ for ‘beauty’, a flavour of quark) we met scientists, enthusiastic to talk about their work in everything from fundamental particle physics, to medicine and data processing. I was particularly interested by some work at ISOLDE using radioactive lanthanide isotopes in medical applications in hospitals near the collider. It was noted that while a few of the staff were Irish, in almost every case they also held another passport, because as a non-member state, our citizens do not have the same access to employment in this project as those from the 22 member states.

What most surprised me, as we looked at Irish-made semiconductors in action, and visited the factory where they design and assemble particle-accelerator parts, was that, while Irish people do make a contribution here, it’s often relying on loopholes or having a unique product that no one else can offer. Membership, however, would ensure us access on an equal footing to all other partners. Importantly this would mean returns to the Irish economy in every sector, allowing Irish firms to tender for contracts in construction, cleaning, catering, office supplies etc. in addition to the obvious high-tech and engineering opportunities. Big optimistic scientific exploration has positive knock-on effects throughout society.

One of the most obvious examples of unexpected by-products of investing in fundamental research is the very technology by which you are reading this post now. The World Wide Web was invented at CERN by Tim Berners-Lee. We were able to visit the office where this revolutionary technology came to life, almost as an afterthought, to share information from this worldwide collaborative research. And even if you don’t think quarks and neutrinos effect your life (they do!), at least the Web is tangible evidence that clever people allowed to create and explore together can do great things!

Where the Web was born

 

I’m calling this photo a Bunsen Byrner

Recently I was lucky enough to get an invite to the 11th CaRLa Catalysis Winter School in Heidelberg, and it was an eye-opening and engaging week, meeting with some of the rising talents within the fields of homogenous catalysis (among others) and hearing from speakers like Mats Tilset (check out his recent article on trans-mutation of gold – a pun I really approve of) and Ilan Marek about their contributions to the field. In particular, I enjoyed having a week to spend time discussing posters with the other attendees; normally this is the most rushed part of any conference, as you try to simultaneously stand by your own poster and see as many others as possible. The Winter School invited flash presentations on all the posters, and gave ample time and coffee over which to really get into the details!

I was able to present my on-going research from my Marie Curie Individual Fellowship (GLYCONHC, MSCA-IF 749549), where I investigate the impact of including carbohydrates in the structure of metal-NHC catalysts. The work is progressing well, and I think I benefited from being able to discuss hurdles in the project with catalysis experts and my peers during the week.

CaRLa (The Catalysis Reasearch Laboratory) is an institute at University of Heidelberg, supported by BASF, a giant of the chemical industry. As a result, the research they undertake is very aligned to real economic and market challenges. We were given a tour of the massive site at Ludwigshafen on the river Rhine, and the scale of production in just the one plant we visited was staggering – round-bottom flasks just can’t compete with building-sized reactors!

One interesting historical note about Heidelberg is that it is where Robert Bunsen did much of his pioneering work in 19th century chemistry and – famously – gifting us with the most widely known (and least widely-used nowadays) apparatus of the chemistry lab. I couldn’t walk past his statue without getting a punny selfie- the “Bunsen Byrner”!

It was great news today to hear the 2016 Nobel Prize in Chemistry was awarded to some pioneers in the field of supramolecular chemistry: Jean-Pierre Sauvage, J Fraser Stoddart and Bernard Feringa. During my PhD studies, I read the work of Sauvage and Stoddart a lot for inspiration; they are constantly producinSauvage's article in Tetrahedron Letters 1983g beautiful and elegant structures from discrete molecular units interacting in controlled ways. While most of my PhD ended up focussing on lanthanide-directed self assembly and luminescent compounds, I was always chasing the goal of interlocked structures and remember being fascinated by Sauvage’s early results describing the first metal-directed catenanes (Tetrahedron Letters 1983), mechanically interlocked rings with no chemical bonds between the two molecular components. This article laid the groundwork for the tiny molecular machines for which the trio were given the prestigious award today. Stoddart’s contributions to controlling rotaxane movement and Feringa’s publication of the first ‘molecular motor’ were remarkable breakthroughs, but the elegance of interlocked systems has fascinated me since I first saw them and I was delighted to finally publish some of my own work on catenanes in Angewandte Chemie this year, contributing in a small way to the ever-expanding supramolecular field.

To end this post, I’ll add a quote from my PhD supervisor Prof Thorri Gunnlaugsson (Trinity College Dublin) talking today about Sir JF Stoddart, a man he greatly admires and who received an honorary doctorate from Trinity a few years ago:

Speaking about the significance of the work that led to him sharing the 2016 Nobel Prize, Professor of Chemistry at Trinity, Thorri Gunnlaugsson, said: This is truly a fantastic day for chemists and specially for those of us who are involved in the development of supramolecular and nano-chemistry. The development of molecules that are functional and can carry out actions such as programmed operations, and can mimic macroscopic function on the nanoscale, such as that of machines, has been at the heart of this area of chemistry.”

“Today’s announcement of the Nobel Prize in Chemistry being awarded to Professors Stoddart, Sauvage and Feringa, for their development of molecular machines, acknowledges the major scientific achievement made to date in this important field.”

 

 

Monosaccharide azides – challenges

I am not a carbohydrate chemist by training. I remember as an undergrad being very intimidated by the chair conformations, Fischer projections and the seemingly endless chiral centres, so I filed that knowledge away as “unlikely to use” and focussed on supramolecular chemistry. In recent times however, I couldn’t help but be drawn back to looking at these natural sources of chirality, particularly as a next direction to turn after my investigations to amino-acid derived triazolyl(pyridine) ligands. Sugars seemed a way to get chirality and solubility all in one go with the potential for biological interactions as a bonus.

oac-n3 sugar scheme

So, I began researching how to make various monosaccharide azides of the above form in a selective way, so that I could very the stereochemical properties at will when making families of compounds. It required a lot of searching to find everything I need, so I will present it here for anyone else who might be interested in making (in particular) tetra-acetylated glucose, galactose and mannose with an azide in the anomeric position, either α or β.

For glucose and galactose, buried in the German-language pages of a paper by Paulsen et al. from 1974 is a Lewis acid catalysed reaction, which selectively gives the β-azide derivative directly from reacting the penta-acetylated sugar (with mixed anomeric configuration) with tin(IV) chloride and trimethylsilyl-azide. This reaction has some nasty components and leaves you with a lot of tin-contaminated water to dispose of. I was delighted, therefore to find that the reaction can also be carried out rather straightforwardly from the commercially-available α-bromo tetra-acetylated compounds (for glucose and galactose) by simply heating overnight with sodium azide in a water-acetone mixture, a methodology that comes from that oft-overlooked source: Journal of Chemical Education (Norris and co-workers, 2012).

With mannose, things are a little trickier! It differs from glucose and galactose, by having the C-2 hydroxyl group in the axial position, and since this is adjacent to the reactive anomeric position, this will influence the outcome. Using tin(IV) chloride, as above, for instance, will yield the α-azide. This is a result of the reaction, as above, favour a 1,2-trans geometry. For the purposes of my research, however, I was really interested in using the β-azide to make a compound which differed from the glucose derivative in only one position. After a lot of hunting, I stumbled upon a two-step reaction in an article by Prof Paul Murphy from NUI Galway (Chem. Eur. J. 2013), which had originated with an early study from University of California. This approach generated an α-glycosyl-iodide in situ and reaction with tetrabutylammonium azide gave the desired β-azide product in good yields. Importantly, this gives β-azides in all cases and allowed me access to the building blocks I need to pursue my current project.