Dial-a-Molecule Network Meeting on Computational Prediction of Reaction Outcomes and Optimum Synthetic Routes

This workshop took place on 10th and 11th September at the Weetwood Hall Conference Centre & Hotel in Leeds, and you can find out more about it on the Dial-a-Molecule website. I was invited to give a presentation on the ligand knowledge base approach, and my contribution title was: “Computational Prediction of Reaction Outcomes and Optimum Synthetic Routes”. Since then, I’ve developed 2 new collaborations with other attendees of the meeting and we’ve successfully applied for some seed-funding from the network – more about this soon.


New Paper Published on Organometallics ASAP

Our latest paper has just appeared on the ASAP page for the ACS journal Organometallics: “Computational Discovery of Stable Transition Metal Vinylidene Complexes”, DOI: 10.1021/om500114u, arising from my collaboration with Dr Jason Lynam at York. The Bristol part of the work was started by two summer students, Ben Rawe (now at UBC) and Tim King (now at Cambridge) and then continued by a final year undergraduate project student, Keshan Bolaky; the rest of the calculations were done by yours truly. In this work we have explored substituent, metal and ligand effects on the thermodynamic preference for the vinylidene tautomer with both experiment and computation. This has allowed us to formulate a “recipe” for the stabilisation of vinylidenes by transition metal complexes. If you don’t have institutional access, I’d be happy to share via ACS Articles on Request, please get in touch!

Table of Content Graphic, Reprinted with permission from {COMPLETE REFERENCE CITATION}. Copyright {YEAR} American Chemical Society.

Table of Content Graphic, Organometallics, Article ASAP, DOI: 10.1021/om500114u. Reprinted with permission from Organometallics. Copyright 2014 American Chemical Society.


2013 Year Review

DSC_1445-copyAlmost spring already! So I have been rubbish with keeping the blog up-to-date, and now the easiest thing seems to be to write a quick review of 2013 and move on. Actually, it seemed that way in January, I just haven’t gotten around to actually doing this until now… No more procrastinating, here is my summary of 2013 highlights:

From January-March 2013, I was involved in a project with Prof. Chris Frost and his PhD student, Will Mahy, as well as Dr Paul Murray from CatScI Ltd., looking at copper-catalysed coupling reactions that showed some interesting experimental results. This collaboration was funded as one of a number of projects aimed at strengthening the links between researchers in catalysis based in Bath, Bristol and Cardiff, and contributed an additional 0.3 FTEs of my time. It still needs a bit more work when I can find the time, but we are hoping to publish some of the results in due course.

In February, I also hosted Dr Jason Lynam, from the University of York, who visited for a couple of days to make progress on our joint publication on transition metal-stabilised vinylidenes. The paper has now (as of early March 2014) been accepted for publication, details to follow soon.

In March, a meeting with Prof. Doug Stephan from the University of Toronto led to a low-level collaboration with Shawn Postle, on of Doug’s PhD student, aimed at establishing whether DFT-calculated parameters can be used in the context of frustrated Lewis pairs. Early results look promising…

April saw the annual Bristol Synthesis Meeting, as well as a visit from Dr Lee Higham from the University of Newcastle. Lee came to give a seminar (“Surprises in Primary Phosphine Chemistry and their Applications in Catalysis and Disease Imaging” and catch up with old friends (he was a postdoc in Prof. Paul Pringle‘s lab many moons ago), but also to discuss LKB parameters for some of his primary phosphine ligands and the introduction of E(SOMO) as a measure of ligand stability to our databases.

York Minster quite early one morning in June 2013

York Minster quite early one morning in June 2013

In May and June, my colleague Dr Jenny Slaughter and I got busy in the background to prepare posts and get the Picture It… Chemistry blog ready for launch.

June also saw my return visit to Jason Lynam in York (still working on the paper…), as well as a chance to catch up with Prof. Laurel Schafer from the University of British Columbia in Vancouver, interrupting her time in Oxford for a short visit to Bristol and give a seminar on “Catalytic Hydroaminoalkylation”. I first met Laurel at the GRC in Newport, RI in 2012, so this was a welcome opportunity to catch up about research and set the world to rights over dinner.

The start of July was taken up with the 20th EuCheMS Conference on Organometallic Chemistry (EuCOMC XX) in St. Andrews, a good opportunity to catch up with Dr Claire McMullin, find out about new developments in computational chemistry and organometallic catalysis, as well as plan a visit by Dr Mie Vilhelmsen to Bristol later in the year.

View of St. Andrews, taken from West Sands Beach

View of St. Andrews, taken from West Sands Beach

This was swiftly followed by the official launch of our Picture It… Chemistry blog on 10th July, attracting around 700 views on its first day and over 1,400 over the course of July. We also accompanied Jenny to Showoff Science, where she spiced up the evening with her talk about chillis.

Dr Jenny Slaughter at Science Showoff (image taken from Picture It... Chemistry Blog, http://chempics.wordpress.com/

Dr Jenny Slaughter at Science Showoff (image taken from Picture It… Chemistry Blog, http://chempics.wordpress.com/

August and September were relatively quiet and taken up with research, holiday and teaching preparation, as well as moving office. However, in late August the Picture It… Chemistry blog was mentioned on the Nature Chemistry Blogroll for Everyday Chemistry, leading to considerable spikes in visits to the blog at an otherwise quiet time of year.

October started with a visit from Dr Mie Vilhelmsen to the Centre for Computational Chemistry, where she gave a seminar on her work in the group of Prof. Stephen Hashmi in Heidelberg, “Cooperative Effects in Dual Gold Catalysis”, with the second slot taken up by yours truly, talking mostly about the project with Jason’s group, “(On the road to) Computational Optimisation of Organometallic Catalysts”. At the end of the month, I travelled to Texas to give a seminar at the Eastman Chemical Company in Longview, followed by 4 further research seminars at research active chemistry departments in the Dallas area (well, I was there already). The (somewhat knackering) 5 seminars in 5 days were as follows:

  • Monday, 28th October, Eastman Chemical Company, Longview, “Computational Tools for the Optimisation of Organometallic Catalysts”
  • Tuesday, 29th October, Texas Christian University, Fort Worth, “Applying Ligand Knowledge Bases to Pd-Catalysed Cross-Coupling”
  • Wednesday, 30th October, University of Texas in Dallas, “Discovery and Optimisation of Organometallic Catalysts: Maps and Mechanisms”
  • Thurday, 31st October, University of Texas in Arlington, “Computational Discovery of Stable Transition Metal Vinylidene Complexes”
  • Friday, 1st November, University of North Texas, Denton, “Computational Tools for the Optimisation of Organometallic Catalysis: P-Donor Ligands in Cross-Coupling and Hydroformylation”

The hospitality I experienced at all 5 sites was excellent and it was great to hear about so much diverse science, but also hear about research life on the other side of “the Pond”. while I’m extremely grateful to everybody who gave up their time to meet with me, I would especially like to thank my hosts, Damon Billodeaux (Eastman), Ben Janesko (TCU), Steve Nielsen and Ken Balkus (UTD), Peter Kroll and Rasika Dias (UTA) and Tom Cundari (UNT) for their hospitality.

The rest of the year was relatively quiet, so there were no more excuses but to knuckle down and write two invited reviews (both now accepted, more about this soon), as well as finish the paper with Jason and work on another paper about Claire’s work while she was a PhD student. Details to come once I have DOI numbers… Things were rounded off nicely when the Picture It… Chemistry blog got another mention from Nature Chemistry, this time showing us at No. 10 of the Top 10 Chemistry Blog Posts for a guest post on Aspirin, leading to a quadrupling of traffic on the blog. Not quite enough compensation for working most of the vacation on a book chapter with Jason and his colleague Dr John Slattery, but nearly…

I promise to try and do better with regular updates on the blog! Behind already, though…


From the archives – GRC on Organometallic Chemistry (July 2012)

View of the coast from Salve Regina University, Newport, Rhode Island

When Hurricane Sandy tore into the eastern seaboard of the US, I actually sought out the local news for Newport Rhode Island, as well as the university sites of several US colleagues to see whether they had been badly hit. I know that travel for conferences and meetings is considered, especially by members of my family, as one of the perks of the job (at which point incredulity is expressed if you mention that you haven’t been to visit all (any) of the highlights of not just the nearest city, but the entire country). And meanwhile, back in the real world, sometimes it just becomes a chore, especially if you haven’t been home for a while, or it’s hot and you end up sitting in lectures and meetings all day, deprived of both sleep and decent food.

View of the coast from Salve Regina University

But both points of view conveniently forget one thing – there is merit in travelling abroad for researchers as it’s often easier to connect with people in person, and that ranges from meeting somebody for the first time to discussing a long-term joint project, as well as from chatting over lunch with a distant colleague to completing a significant publication with your old boss. All of it is much easier (at least for me) if you are actually meeting the other party. So, despite being a fairly grumpy traveller, I tend to pack my suitcase several times every year and put my trust in conference organisers, airlines and hotels, to meet up with colleagues, friends and former students, and to catch up about work. And I usually come back not just with a backlog of work, but also with new ideas, new contacts and sometimes even with progress on papers that have been languishing on somebody’s desk until we had a chance to kick ideas around and get them done. A Skype call just can’t beat that.

I think this is the Columbia, winner of the 1958 America’s Cup

So in July this year, I went to the Gordon Research Conference on Organometallic Chemistry, which takes place every year in Newport, Rhode Island, on the campus of Salve Regina University. If you’ve never been, Gordon conferences have a slightly different format, with talks both in the morning and late afternoon/evening, but a few hours after lunch free for other activities. While it was nice to see the sun (and actually necessary to stave off jet-lag), I passed on football (sorry, soccer) and other sporty activities, and explored the local area on foot instead, as well as networking with colleagues in the breaks. I even managed to go “sight-sailing” – not as good as controlling the boat yourself, but at least an opportunity to get out on the water for a couple of hours. And the best bit – no guilt! No skiving required! And plenty to talk about, as you could always ask about afternoon activities as well as research interests. I even used some of the photos, as well as maps of both areas (Newport, UK and Newport, Rhode Island, USA) in my talk about “Prediction of Ligand Effects on Organometallic Catalysts”, which is all about maps (of ligand space) after all.

View of the bay at Newport, RI

Having made these personal connections with both site and people, I actually wanted to know whether anybody had been badly affected by Hurricane Sandy and whether the Salve Regina site, which is incredibly close to the sea as you can see in the photos, was still standing. So I’ll be dropping a line to some, and listen to the jungle drums about others. But, and this is my point, the important thing is there is now a personal connection, because I’ve been there. It is difficult, especially for students and early-career researchers, to meet colleagues on other continents and so make those broader connections. But it is worth doing because you can’t divide the world neatly into work and private life when work takes up most of your time and passion. Now I just have to remind myself of that next time planes or trains go wrong…

A schooner in the bay, Newport, RI


New Paper – LKB-PPscreen

Schematic showing the variables for bidentate ligands in organometallic catalysis.

As hot-off-the-press as online publishing ever gets, our latest paper has just become available online as a Dalton Transactions Advance Article:

Screening substituent and backbone effects on the properties of bidentate P,P-donor ligands (LKB-PPscreen).
In it, we present a computational exploration of the effect of systematic variation of backbones and substituents on the properties of bidentate, cis-chelating P,P donor ligands as captured by calculated parameters. The parameters used are the same as reported for our ligand knowledge base for bidentate P,P donor ligands, LKB-PP (Organometallics 2008, 27, 1372–1383; Organometallics 2012 31, 5302–5306), but calculation protocols have been streamlined, suitable for an extensive evaluation of ligand structures. Analysis of the resulting LKB-PPscreen database with principal component analysis (PCA) captures the effects of changing backbones and substituents on ligand properties and illustrates how these are complementary variables for these ligands. While backbone variation is routinely employed in ligand synthesis to modify catalyst properties, only a limited subset of substituents is commonly accessed and here we highlight substituents which are likely to generate new ligand properties, of interest for the design and improved sampling of bidentate ligands in homogeneous organometallic catalysis.
AKA the work of one hot summer where we decided to run as many calculations as we could get away with!

October Changes

My EPSRC-funded Advanced Research Fellowship ended at the end of September 2012 and while there are still papers to write up and a final report to complete, things are moving on.

I’m now working on a joint project with CatScI Ltd. to develop an industrial application of computational prediction in homogeneous catalysis. We will develop an improved ligand screening protocol for homogeneous catalysis, integrating fully the computational evaluation of catalyst properties with the company’s high-throughput automated catalyst screening and analysis facilities. In this project we will apply CatScI’s expertise in the development and optimisation of transition-metal catalysed reactions, using both calculated catalyst property descriptors and optimally designed catalyst screening data, to develop novel catalysts in a unique, industry-led project. Focusing on the need to ensure ‘manufacturability’ in the chemical industries, this two-year project aims to deliver efficient, stable and selective catalysts that perform at the right price. It is supported by a Research, Development and Innovation grant from the Welsh Government.

I’m also taking on additional teaching duties, delivering the Physical and Theoretical Chemistry part of the Chemistry 1E course, which aims to teach Chemistry, up to an approximate equivalent of A-level, to students with little or no background in Chemistry or even in Science. My lectures will cover Thermodynamics, Kinetics and Acid Base Equilibria. I’m also supervising and marking in the Level 2 teaching lab and I still have an experiment in the Level 3 teaching lab, which I continue to mark.

Fitting all of this into part-time working (0.4 FTE + teaching) is proving a bit challenging, especially given my plans for new collaborations, grant and paper writing and science communication projects, but it’s early days yet. If you are trying to get hold of me, the best way is still email, as I tend to check that at least once every weekday, with an out-of-office reply on if I expect to be unable to do so for a while.