Solvent-Guided Dynamical Enantioselectivity


DDCP and its two enantiomeric product channels


Bifurcating PES with a valley-ridge inflection point

It’s been awhile since I’ve done a post… I’ve been in the process of changing home base from San Francisco back to Bristol. But there’s a paper I’ve recently written which I’m excited about. It’s a computational study of a molecule, DDCP (meso-2,3-difluoro-2,3-dimethyl-diazo-cyclopropane), which was identified by my colleague, Professor Barry Carpenter. For the last year or so, Barry has been playing around with the solution phase dynamics code that I’ve been developing. He chose DDCP because it has a very interesting potential energy surface (PES) topology: it exhibits a so-called ‘valley-ridge inflection point’ – i.e., passage over a transition state that bifurcates on the way down toward products. In this case, the bifurcating path leads to products which are distinct enantiomers. The simulations that we ran suggest that enantioselectivity on such a PES topology can in fact be dynamically guided by transient interactions with the surrounding solvent environment in which the reaction takes place. We ran a series of MD simulations in achiral solvents, and (as you might expect) these showed equal ratios of the product (R) and (S) enantiomers. However, by computationally screening a range of different solvents, we “discovered” a chiral solvent which gives a dynamically-guided enantiomeric product excess of 15.2 ± 2.1%. It appears that interactions with the solvent cage in the early stages of the reaction preferentially guide the system down a specific product channel, and that excess vibrational energy is quickly dissipated to the solvent degrees of freedom. The observation of this solvent effect is exciting: it is approximately an order of magnitude larger than experimentally observed excesses where the conversion of products to enantiomeric products occurs over separate transition states, and it makes an exciting target system for experimental investigation!

Post-Doctoral Opportunity!

diamondI’ve recently been awarded EPSRC funding to support a post-doctoral researcher. The project involves an exciting new multidisciplinary collaboration with a talented team of experimental surface spectroscopists in Edinburgh. The primary objectives are: (1) build user-friendly algorithms that automate the process of constructing potential energy surfaces [e.g., using machine learning and/or interactive strategies]; and (2) carry out accelerated classical and semi-classical molecular dynamics simulations to assist the Edinburgh group interpret results from inelastic and reactive scattering dynamics at the surfaces of inert and reactive liquids. This work will build on my group’s expertise using state-of-the-art parallel programming paradigms, new classes of rare event algorithms, and even interactive sampling strategies to explore a range of reaction dynamics in condensed phases. Beyond increasing our fundamental understanding of collision dynamics and energy transfer at liquid surfaces; this project has important practical applications – namely, providing tools and strategies that enable us to model heterogeneous chemical reaction dynamics in earth’s atmosphere (e.g., on the surface of aerosols). Because the radiative forcing of aerosols remains amongst the largest uncertainties in global climate change models, this an area where progress is desperately required.

The anticipated start date of this post is Jan/Feb 2016, with an initial appointment of 1 year, and the possibility for a 2-year extension. Salary is £31,342 – £35,256 (GBP) per year, depending on experience. Feel free to send me an email to make informal inquiries. International applicants welcome. Further application details are available at

Tracking Energy Flow in Liquid Reaction Dynamics


Results from one of the molecular dynamics simulations in the paper, showing a 400-fs time trace of the atomic nuclei. Motion of the liquid is shown in blue, and DF in white. The interlaced starlike shapes arise from significant vibrational excitation in the newly formed DF

Today’s issue of Science contains a report that I wrote along with colleagues at Rutherford Appleton Laboratory (UK) and Heriot-Watt University (UK), providing atomically-resolved detail describing how a chemical reaction happens in a liquid. This is an area that I’ve been working on for awhile now – specifically trying to figure out how atomic and molecular energy transfer works. I first got interested in this stuff a few years back, when I showed that the product yields of the well-known “hydroboration” reaction in organic chemistry are very sensitive to how quickly energy in the reacting molecule dissipates into the surrounding liquid. This result was a surprise for me: all chemical reactions involve energy being deposited into molecules, but it’s generally neglected in descriptions of how chemical reactions in liquids work. The conventional thinking is that molecules can’t hold on to their energy long enough for it to make much of a difference. This study showed that the molecules involved in the reaction were holding onto their energy deposits for long enough to have a profound effect on the identity of the reaction products.

People have known for some time that if you deposit energy into a molecule using a laser light pulse, it can hold onto its excitation for quite awhile, even in a liquid.  But most of the liquid chemistry occurring in nature happens under so-called “thermal” conditions, where there’s no laser pulses involved. Under thermal conditions, the general assumption is that energy deposited in a molecule by way of a chemical reaction is dissipated so fast that it’s not really worth worrying about, and couldn’t possibly affect the reaction outcome. Today’s Science paper combines some very fast time-resolved spectroscopy and state-of-the-art molecular dynamics simulations (that was my role!) to examine a simple chemical reaction in a liquid that produces a DF molecule. The results provide compelling evidence – yet again – that even under thermal conditions, the reaction product holds onto its energy for a rather long time. What’s particularly surprising about this result is that we intentionally chose a so-called ‘strongly coupled’ system, where we expected this not to be the case. But alas, even under these conditions, DF is produced with lots of excitation (nearly three quanta!), and the excitation persists. The simulation framework (run on a massively parallel supercomputing architecture described further in an arXiv paper and implemented in CHARMM and TINKER) showed that the newly formed DF holds onto its energy while it searches out hydrogen bond partners with its neighboring liquid molecules. The simulations also showed that DF’s time-resolved experimental spectra is the result of two effects – loss of energy, and formation of hydrogen bonds – each of which wants to move the spectra in opposite directions, and therefore mostly cancel each other out.

I’m excited about this stuff, especially because I’ve started thinking about whether it transfers over to larger molecules in organic and biochemistry. Results generated using the same simulation framework recently showed that these sorts of effects can actually lead to solvent-induced enantioselectivity for much larger molecules, which is a fascinating result that we’re looking at in further detail.

dS West Coast Premier @Stanford Art Institute

Miyako-postCardLast week, danceroom Spectroscopy made its West Coast premier at the Stanford Art Gallery, and it’s looking beautiful! If you get a chance to check it out, it’s all free – and it will be on from 4 – 20 Sept 2014, open every day from 11am – 6pm. dS itself is set up, in all its glory, along with an accompanying exhibition of photos taken by dS photographer Paul Blakemore over the years. You can find more details at this link.

Handeled during the Messiah


image by artist Becca Rose –


A recent story about my attempts to crowd-surf during a performance of Handel’s Messiah in Bristol (originally published in the Independent) became a national headline in the UK over the weekend. The story in question happened in the summer of 2013, but nearly a year later, it is now going viral across the internet. Seems there’s not much to talk about in classical music over the last 11 months.

The back-story here is as interesting as the image of some science nerd carried away crowd-surfing during Messiah. In 2013, Bristol’s Old Vic theatre ran the ‘Bristol Proms’. The idea was to relax the standard classical rules to reach new audiences. This approach is a result of simple economics: with public arts funding being slashed, art is feeling the heat to generate profit, and classical music is no exception. A classical concert is an expensive affair, and the age distribution of typical classical audiences spells a real risk of the art form drying up. And that’s why Universal Music threw its weight behind Bristol’s Proms. As one of the planet’s largest distributors of classical music, they can see the writing on the wall.

Each night of the Proms, Old Vic theatre director Tom Morris marched out onstage to preach the new paradigm: “Enjoy a beer in the pit, chat when you like, clap when you like, whoop when you like, engage with the music as you like, and no shushing other people.” It was a nod to the music’s roots, given that modern classical audience protocols are less than a century old.

As an international artist with a longstanding interest in cultural theory, I’ve become increasingly fascinated in analyzing how modern power works across societies, institutions, and organizations. One of the most important starting points is to determine whether power is maintained from the top-down, or from the bottom up. Michel Foucault, one of my favorite social theorists, often referred to the so-called Panoptic model of power. He argued that power nowadays is not enforced from the top, but rather from the bottom, with everybody keeping an eye on everybody to enforce the norms. However, the bottom-up system is also more complex, because it requires that the participants internalize the rules in order to enforce them.

So what better chance to examine the mechanics of modern power than at the Bristol Proms? The conditions were perfect: the theatre director had taken it upon himself to establish new rules for an audience that is notorious for its maintenance of rigid norms. How would the audience respond to the director’s new rules? Were the rules any more than a gimmick? Who ultimately did hold the power here, the audience or the director? And to what lengths might audiences go to enforce their rules?

On the final evening, I attended Handel’s Messiah with two friends. The previous night I had been onstage introducing a collaboration undertaken with violinist Nicola Benedetti. Using a system called ‘danceroom Spectroscopy’, the vibrations from Nicola’s violin were analysed in real-time, letting her violin modulate a visualized molecular simulation. During my onstage collaboration at the beginning of the night, I made a joke, “So the rules are a little bit different tonight. I hope to see some crowd-surfing in the pit,” which got a good laugh from the crowd. My artistic contributions with Nicola earned me a complementary seat, but I chose instead to stand in the pit with my friends.

In line with the instructions delivered by the director at the beginning of the show, we permitted ourselves to freely engage with the music. Standing in the pit, the performers were nearby, and we fed off of their tangible emotion and energy. But the audience did not approve. During the Hallelujah (Praise the Lord!) crescendo, I raised my hands in praise and let out a cheer, reveling in the intensity of the 30-strong choir only a few meters away. That’s when I was knocked down by a punch to the kidneys. It wasn’t delivered by venue staff, but by a middle-aged white male audience member – a classical vigilante of sorts. As I fell to the floor, I banged my head on the stage. The man bent down and said something to the effect of, “You shut up and get the hell out of here, asshole.”

My response was simple: “If you want me to leave, then you have to forcibly eject me. I’m following the rules that were given at the start of the show.”

And thus it came to pass that I was forced out of Handel’s Messsiah by two classical audience members during the Hallelujah chorus. The previous night I had been onstage to rapturous applause. Now I’m being assaulted and dragged out. All for praising the Lord.

The Theatre director immediately came out to find me. He offered apologies, and asked whether I wanted to sneak in the back and watch the remainder of the show with him in the director’s seat.

I declined. I was too shaken up and actually in quite a bit of pain. One of my friends, himself a classically trained musician, was speechless.

The post-show response was even more surreal: a steady stream of audience members and performers, having seen my exit, tracked me down to congratulate me for my performance. Brilliant, they said. It seemed so authentic – an excellent bit of staged violence in the pit. Most refused to believe that it was in fact genuine physical assault.

Responses to my cheering are fascinatingly polarized. Several folks, including musicians, thought that it was just the sort of thing that needed to happen, and that it was a good step toward liberating the classical art form; plenty of others were very unhappy at the disturbance.

Nevertheless, my preferred mode of enquiry is the scientific method: formulating and testing hypotheses by conducting experiments both in the lab and beyond. My preliminary results hint at two conclusions related to classical music:

  1. It is the audiences (not the director, and not the performers) that run the show. They have internalized the norms and they enforce the norms. The norms that they have internalized might only be a few generations old, but they are very strong.
  2. The extent of internalization is strong enough to lead to violence in the form of physical assault, an excellent example of how it is actually we the people that perpetuate the very violence that we despise, in line with observations made by theorists like Zizek.

As far as I know, we have yet to see a sustained classical crowd-surf. I took baby steps to pull it off, but didn’t even come close. Shuffling of the feet combined with a little bit of cheering quickly catalyzed enough violence to get me ejected. The image of some science nerd crowd-surfing at a classical concert is simply too good to let go, and I sincerely hope that I do live to see the day when somebody can carry it farther than I managed. The amount of support that I have received over the past few days gives me confidence that I will see this happen.

But beware. This is dangerous territory. Science can be profoundly disruptive, especially with crowds this tough. And you can rest assured, there are even tougher crowds out there.

Hidden Fields Trailer!

Adam Laity has put together an awesome little trailer for the most recent version of Hidden Fields, made using the danceroom Spectroscopy framework. Hidden Fields interprets dancers as fields whose movement creates ripples and waves in an invisible sea of energy. The result is a gentle piece comprised of interactive graphics and soundscapes, both of which respond in real-time to how the dancers use their movement to sculpt the invisible fields in which they are embedded. Enjoy!

Another national outreach award for danceroom Spectroscopy!

DS FESTIVAL -158-compressed

Good news! danceroom Spectroscopy (dS), the interactive molecular dynamics project I started three years ago, has earned its sixth award in the last 18 mos! This one as part of the UK’s national Engage Competition. dS aims to open ways for a greater appreciation of the subtle beauty of the invisible atomic world. dS developed from my research into high-performance computational quantum dynamics: by visualising participants as real-time energy fields, it allows you to step into a real-time, interactive and immersive atomic simulation, where movement generates sound and image. dS has formed a major attraction at cultural and educational settings within the UK and internationally, elegantly merging research in science, technology, high-performance computing, and art to all sorts of people.

dS owes this latest success to the support it has received from number of partners, including EPSRC, the Royal Society, the Royal Society of ChemistryNVIDIAArts Council EnglandStanford University, the University of Bristol, the University of the West of England, and Watershed.