Reimagining the geometry of transition states (in PRL!)

I'm excited to report that my former graduate student, Dr. Galen Craven, and I just published an article in Physical Review Letters (PRL). The critical question in determining the rate between chemical reactants and products relies on knowing when exactly the reactants become products. This is like asking yourself when did you get sick? You might remember when you were healthy and you know when you definitely have a cold, but do you know when you transitioned from being healthy to sick? Presumably, if you could know when this transition happens, then you would know when to take medicine or when not to. For example, if you start feeling a little off but you haven't hit the transition to being sick, you might still not get sick at all and so there would be no need to take a pre-emptive medication. In the same way, chemists need to know when molecular reactions really take place and when exactly they did so. Transition state theory then provides a way to use that transition to obtain the rate of a reaction. And that's also useful because then we know if it will take place in the same time scale as other events such as being fast enough to finish while you are on a quick break or so slow that it won't happen before the universe has ended.

Specifically, we discovered a new way for obtaining the structure of the transition state between reactants and products when the reaction is in a complex solvent. All of the previous methods had obtained this surface by optimization (using variational transition state theory) or through successive approximations (using perturbation theory).The key is a mathematical tool, called the Lagrangian descriptor, that had been developed earlier by Wiggins and his colleagues in the area of fluid mechanics.We were able to use the Lagrangian descriptor to obtain the transition state geometry directly without either optimizing the rate or employing perturbation theory. And this means that we now have a new tool for obtaining reaction rates in nonequilibrium systems.

As with most articles in PRL, it was a tortuous path through the reviewing process. We were pleased that nearly all of the reviewers (and we had 6 in the end!) saw the work as novel and potentially game-changing. The full reference of the article is: G. T. Craven and R. Hernandez, "Lagrangian descriptors of thermalized transition states on time-varying energy surfaces," Phys. Rev. Lett. 115, 148301 (2015). (doi:10.1103/PhysRevLett.115.148301) I'm happy to acknowledge the support from the Air Force Office of Scientific Research (AFOSR).

Sustainable Nanotechnology - Designing green materials in the nanoparticle age

The birth control pill turned 50 recently, and it was a reminder of the great power of a chemical compound, estrogen, to affect social and political change. A little less attention was given to the role that estrogen levels in our water streams have had on fish in water streams. (See for example, a Scientific American article from 2009 on the possible implications of estrogen in waterways. ) There’s some debate as to where the leading sources of estrogen come from. While most studies indicate that the birth control pill is not the major contributor to its presence in the waterways, there is no doubt that estrogen pollution exists. Regardless, when the birth control pill was introduced, I suspect that few even considered the possibility that estrogen would be a factor in the health of fish in waterways such as the Potomac and Shenandoah rivers.

In this century, there is little doubt that nanoparticles comprise a class of chemical compounds that are revolutionizing nearly everything that we touch, see or smell. Indeed, I am tempted to argue that this century might be called the “nanoparticle age” in the same way that history named the last century as the “industrial age.” The challenge to chemists (and material scientists) is not just designing nanoparticles to solve particular problems, but to do so with materials that have no unintended consequences. Anticipating such unknown unknowns is a grand challenge, and the solution requires a team of scientists with expertise in making, measuring, and modeling the nanoparticles in the upstream design side and in biology and ecology on the downstream side. The Center for Sustainable Nanotechnology (CSN) is taking this challenge head-on. I’m happy and exited to say that I have joined the CSN as part of the modeling team!

Please also check out the announcement of the start of the 5-year effort of the CSN through an NSF CCI Phase II grant CHE-1503408. 

May the ducks quack for you (A Tip for Conference Organizers)

Every two years since 2001, I have been co-organizing a workshop in Telluride on “Chemical Dynamics in Complex Environments” (Chem-DiCE). It's a great venue that attracts scientists (and their families) to attend and return. In our particular workshop, we focus on challenges to address molecular behavior (such as reactions) occurring in solvents that are heterogeneous and far from equilibrium. It turns out that this problem is common to many different chemical phenomenon. We therefore invite researchers that are are facing this challenge in different milieu, such as colloidal dispersions, renewable energy generation, proteins, and confined liquids.  We also aim to split the participants equally across theory/computing and experiment. For many of our participants, this meeting is the only time they see each other, let alone be exposed deeply to the research in their respective fields. The net effect is that our workshop gives rise to a cross-pollination of ideas and solutions across broad areas of research. I'd like to think that this is the main reason for the success of our workshop.

However, perhaps the real reason for our success is the organization structure:  Everyone who speaks gets an hour. That is, exactly an hour. At that point the ducks quack (on our timer), and the speaker is finished. It’s not uncommon for speakers to go through only one-quarter to one-third of the material they prepared. That’s because the audience is so interactive that many questions come to the surface, allowing us all to probe the material that is covered much more deeply. It also allows for consideration of questions or issues that someone from outside of a field might naively ask but which, in running counter to the established dogma, requires a profound new direction or solution to address. No speaker ever gets to the end, and they are invariably unhappy that they were unable to do so. But everyone is happy that all the other speakers are stopped at exactly an hour. In the eight workshops that we have run so far, only once was someone allowed to speak beyond that hour. In that case, the speaker wanted to answer a question that had been raised as the ducks were quacking. He pleaded to continue, and I concurred only after the entire group voted unanimously in favor. Thus the structure of talks is very egalitarian, and provides an opportunity for all to learn something new. That’s why I think that my colleagues keep coming back!

Sustainable Nano on Open Access Sustainably

(This article is a cross-post between EveryWhereChemistry and Sustainable-Nano!)

Sustainability’s future is now. Our recent article was just published in an all-electronic journal, ACS Central Science, which is among the first of the American Chemical Society (ACS) journals offered without a print option. It therefore embodies sustainability as it requires no paper resources, thereby limiting the journal’s carbon footprint to only what is required for maintaining the information electronically in perpetuity. It is also completely Open Access, which means our article is available for all to read. Does this equal accessibility (called “flat” because there is no hierarchy in levels of access) amount to yet another layer of sustainability? More on that question in a moment. Meanwhile as the article itself is about sustainability, it embodies the repetitive word play in the title of this post.

But there is another double meaning in the publishing of this work: The flatness underlying the vision of Open Access is also at play in how the work was done. ELEVEN different research groups were involved in formulating the ideas and writing the paper. This lot provided tremendous breadth of expertise, but the flatness in the organizational effort allowed us to merge it all together. Of course, it wouldn’t have happened without significant leadership, and Cathy Murphy, the paper’s first author, orchestrated us all magnificently. While flatness in organizational behavior isn’t typically considered part of sustainability, in this case it provided for the efficient utilization of resources (that is, ideas) across a broader cohort.

So what is our article about? Fifteen years into the 21st century, it is becoming increasingly clear that we need to develop new materials to solve the grand challenges that confront us in the areas of health, energy, and the environment. Nanoparticles are playing a significant role in new material development because they can provide human-scale effects with relatively small amounts of materials. The danger is that because of their special properties, the use of nanoparticles may have unintended consequences. Thus, many in the scientific community, including those of us involved in writing this article, are concerned with identifying rules for the design and fabrication of nanoparticles that will limit such negative effects, and hence make the particles sustainable by design. In our article, we propose that the solution of this grand challenge hinges on four critical needs:

1. Chemically Driven Understanding of the Molecular Nature of Engineered Nanoparticles in Complex, Realistic Environments
2. Real-Time Measurements of Nanomaterial Interaction with Living Cells and Organisms That Provide Chemical Information at Nanometer Length Scales To Yield Invaluable Mechanistic Insight and Improve Predictive Understanding of the Nano−Bio Interface.
3. Delineation of Molecular Modes of Action for Nanomaterial Effects on Living Systems as Functions of Nanomaterial Properties
4. Computation and Simulation of the Nano−Bio Interface.

In more accessible terms, this translates to: (1) It’s not enough to know how the nanoparticles behave in a test tube under clean conditions as we need to know how they might behave at the molecular scale in different solutions. (2) We also need to better understand and measure the effects of nanoparticles at contact points between inorganic materials and biological matter. (3) Not only do we need to observe how nanoparticles behave in relation to living systems, but to understand what drives that behavior at a molecular level. (4) In order to accelerate design and discovery as well as to avoid the use of materials whenever possible, we also need to design validated computational models for all of these processes.

Take a look at the article for the details as we collectively offer a blueprint for what research problems need to be solved in the short term (a decade or so), and how our team of nanoscientists, with broad experience in making, measuring, and simulating nanoparticles in complex environments, can make a difference.

The title of the article is "Biological Responses to Engineered Nanomaterials: Needs for the Next Decade.” The work was funded by the NSF as part of the Phase I Center for Sustainable Nanotechnology (CSN, CHE-124051). It was just released at ACS Central Science, XXXX (2015) as an ASAP Article. The author list is C. Murphy, A. Vartanian, F. Geiger, R. Hamers, J. Pedersen, Q. Cui, C. Haynes, E. Carlson, R. Hernandez, R. Klaper, G. Orr, and Z. Rosenzweig,

It’s available as Open Access right now at http://dx.doi.org/10.1021/acscentsci.5b00182

The Analytics of FaceBook and what it says about you (and others)

There’s no way that I could possibly go into all that FaceBook (and Google) knows about me from the amalgamation of all the sites I have visited and the content that I have produced, not to mention what they gather from the data of all of my friends and acquaintances about me through their own links and hits to my material. But I do want to hit on one crazy connection that intrigues and scares me at the same time.

FaceBook presumably tracks the degree to which each of my posts has been clicked in any way by my friends, whether they simply read it, clicked on the forwarding link, liked it, commented on it, shared it, etc. (Note that while I may not know who lurked it, FaceBook does!) That means that there is a way for FaceBook to tell me what aspect of my on-line personality is of interest to each of my friends. Presumably each of these faces is different and is somehow a reflection not just of myself but also that of my fB friend. There’s clearly some statistical error and noise among these faces because each is contingent on the overall activity of a given fB friend and their strategy for digesting fB content. Nevertheless, it seems nearly unfathomable that fB has a way to access the degree of my multiple personalities by way of running statistics on these faces. In turn, such data would presumably be possible for me to obtain a better understanding of what I really have in common with a given friend. Chances are that knowing this would make the relationship weaker rather than stronger as I might be tempted to zero in on only the known overlaps rather than the discovery of new commonalities. But how will I or you actually respond to this type of information when fB eventually gives us this (new) feature (whether free or charged)?

Stretching proteins and myself into open access (OA)

I'm not sure where to side on the Open Access (OA) publishing business. On the one hand, paying for an article to be published is a regression to the days of page charges albeit without the double-bind that readers are also required to pay. On the other hand, it does flatten access to the article, and often panders to enlightened self-interest by way of increased exposure and citations. Indeed, a strong argument in favor of OA for articles, data and code was just published in the Journal of Chemical Physics by my friend, Dan Gezelter. (Fortunately his Viewpoint is OA and readily available.) Regardless, publishers need to cover their costs, and here lies the challenge to the scientific community. The various agencies supporting science do not appear to be increasing funding to subsidize the fees even while they are making policy decisions to require OA. Libraries love OA because it might potentially lower their skyrocketing journal costs, though no substantial lowering appears to have yet occurred. Long story short, my group is now doing the experiment: We recently submitted and just published our work in PLoS (Public Library of Science.) Props to them for being consistent as they also required us to deposit our data in a public site. I was also impressed by the reviewing process which did not appear to be lowered in any way by the presumed conflict-of-interest that a publisher might have to accept papers (and associated cash) from all submissions. The experiment continues as I'll watch to see how our OA article fares compared to our earlier articles on ASMD in more traditional journals.

Meanwhile, we are excited about the work itself. My students, led by outstanding graduate student, Hailey Bureau, validated our staged approach (called adaptive steered molecular dynamics, ASMD) to characterize the energies for pulling a protein apart. The extra wrinkle lies in the fact that the protein is sitting in a pool of water. That increases the size of the calculation significantly as you have to include the thousands (or more) of extra atoms in the pool. The first piece of good news—that we had also seen earlier—is that ASMD can be run for this system using a reasonable amount of computer time. Even better, we found that we could use a simple (mean-field) model for the water molecules to obtain nearly the same energies and pathways. This was a happy surprise because, for the most part, the atoms (particularly the hydrogens) on the protein appear to orient towards the effective solvent as if the water molecules were actually there.

Fortunately, because of OA, you can easily read the details online. The full reference to the article is: H. R. Bureau, D. Merz Jr., E. Hershkovits, S. Quirk and Rigoberto Hernandez, "Constrained unfolding of a helical peptide: Implicit versus Explicit Solvents," PLoS ONE 10, e0127034 (2015). (doi:10.1371/journal.pone.0127034) I'm also happy to say that It was supported by the National Science Foundation.

Monthly Status Reports (A random walk through how I run my lab, Item 4)

In the business world, or in "Office Space," everyone has seemingly heard of the TPS that must be submitted to your boss at arbitrary (but far too often) frequency. More annoyingly, the TPS often appears to remain unread serving only to occupy one's time with busy work. So it is with ironic amusement that I rediscovered this tool so as to improve the efficiency of my lab. After all, theorists are out-of-the-box thinkers who don't want to be constrained by the mundane, right? And yet this monthly task is exactly the extra structure my students needed to maximize their progress, liberating them to not even see the "box."

For nearly two years, I have asked my students to submit a Monthly Status Report (MSR). It includes only four components: accomplishments, accountability, goals, and pain-points. The goals include not just what is to be done in the next month, but also their overarching plans. In accountability, they summarize what was performed with regards to the previous month's goals. If they succeeded with all of their goals, then that serves to calibrate a more ambitious plan for the following month! The pain-points provide a quick summary of which items I might need to help them with or which I am overdue on. (Yes, I also need help keeping all the balls in the air!) The MSR needs to include items regarding their educational plan, and not just their research projects. To this end, I ask them to include a running clock of the time spent as a graduate student or postdoc. The clock increments by one month each time, of course. The total number, though, reminds us to track professional development activities appropriate to the student's educational timeline. The key to insuring that this is not a totally pointless exercise is that the MSR is followed by a 1:1 thirty-minute meeting discussing progress and charting out meetings and tasks for both student and me to follow up on. I've found that this "meta" meeting is critical to ensuring that both the student AND her or his projects succeed. When I had a smaller group, the MSR wasn't necessary, but now it's critical. I have found it to be more effective than the annual Individual Development Plan (IDP), if the latter is done exclusively, because the IDP is yearly and that feedback isn't often enough. Indeed, the MSR makes the IDP easy for students to complete and increases the effectiveness of the IDP.

Again, the MSR is a simple tool from business school 101, but don't scoff it if you want to help your students increase their productivity and maximize what they learn in graduate school. The key is to use it as a vehicle to hold a frequent and periodic conversation between you and every one of your students!

Balls of ice cream

When you go to your local ice cream shop, you likely ponder the question of how many scoops you wish to order. I, on the other hand, prefer to order balls of ice cream. The scoop corresponds to the void that is to be filled, but a ball corresponds to the filling. It seems to me that I'd rather order balls of ice cream rather than empty space. My wife suggests that this is just a matter of my literal mistranslation of "bolas de helado" rather than any deeper significance over the ontology of balls verses scoops. As an optimist, I certainly prefer for them to be more than half-filled, and hence naturally prefer balls of ice cream to voids, that is scoops.

This argument extends to the nanoscale. Are the properties of a particle driven by itself or by the space which it occupies? If the latter, then its properties are independent of the nanoparticle aside from its shape. As a chemist, this is a disappointing possibility because I would like to tailor the properties of the particles, such as how they assemble, by changing the atoms or molecules at the surface (and the interior). The good news is that such control can be exercised. That is why we have been studying so-called Janus particles and other patchy particles. In our rendering, they look like ice cream balls made of blueberry and strawberry ice cream halves or layers.  The blueberry faces like to face the strawberry faces (because they correspond to charges and opposites attract), and this gives rise to their interesting patterns and response to changes from the outside.

Check out our some of our recent papers on Janus and striped particles and stay tuned for the next ones!

M. C. Hagy and R. Hernandez, "Dynamical simulation of electrostatic striped colloidal particles," J. Chem. Phys. 140, 034701 (2014). (doi:10.1063/1.4859855)
M. C. Hagy and R. Hernandez, "Dynamical simulation of dipolar Janus colloids: Dynamical properties," J. Chem. Phys. 138, 184903 (2013). (doi:10.1063/1.4803864)
M. C. Hagy and R. Hernandez, "Dynamical Simulation of Dipolar Janus Colloids: Equilibrium Structure and Thermodynamics," J. Chem. Phys. 137, 044505 (2012). (doi:10.1063/1.4737432)

Controlling chemical reactions by kicking their environs

Chemists dream of controlling molecular reactions with ever finer precision. At the shortest chemical length scales, the stumbling block is that atoms don’t follow directions. Instead, we “control” chemical reactions by way of putting the right molecules together in a sequence of steps that ultimately produce the desired product. As this ultimate time scale must be sufficiently short that we will live to see the product, the rate of a chemical reaction is also important. If the atoms don’t quite move in the right directions quickly enough, then we are tempted to direct them in the right way through some external force, such as from a laser or electric field. But even this extra control might not be enough to overcome the fact that the atoms forget the external control because they are distracted by the many molecules around them.

In order to control chemical reactions at the atom scale, we are therefore working to determine the extent to which chemical reaction rates can be affected by driven periodic force. Building on our recent work using non-recrossing dividing surfaces within transition state theory, we succeeded in obtaining the rates of an albeit relative simple model reaction driven by a force that is periodic (but not single frequency!) in the presence of thermal noise. It is critical that the external force is changing the entire environment of the molecule through a classical (long-wavelength) mode and not a specific vibration of the molecule through a quantum mechanical interaction. The latter had earlier been seen to provide only subtle effects at best, but the former can be enough to dramatically affect the rate and pathway of the reaction as we saw in our recent work. Thus while our most recent work is limited by the simplicity of the chosen model, it holds promise for determining the degree of control of the rates in more complicated chemical reactions.

This work was performed by my recently graduated student, Dr. Galen Craven, in collaboration with Thomas Bartsch from Loughborough University. The tile of the article is "Chemical reactions induced by oscillating external fields in weak thermal environments."The work was funded by the NSF, and the international partnership (Trans-MI) was funded by the EU People Programme (Marie Curie Actions). It was just released at J. Chem. Phys. 142, 074108 (2015).

Blog Post #100 - Looking Back & Looking Forward

This is my 100th post. The first 99 posts have already received over 31,000 page views. The rather eclectic mix of my posts is visible in the top 5 viewed posts:

* 924 views:   Keep your outline to yourself! (A random walk through... (Jan 27, 2014)
* 634 views:   6. The blurring of physical chemistry and chemical... (Aug 14, 2013)
* 419 views:   Chemistry is Everywhere (My first post on Apr 27, 2013!)
* 412 views:   Advancing Science Through Diversity #OXIDE #Telluride... (Jun 24, 2013
* 356 views:   Soft materials made up of tricked-up hard particles... (Jun 18, 2014)

As traditional publishers have long known, how-to books and articles do well, and my post giving tips for delivering better scientific presentations is at the top. On the other hand, a historical view of physical chemistry and chemical physics also found an audience. A post reporting on our recent theoretical and computational research work has done well. Our discussion of diversity also found an audience. There is no telling how well such page views correlate with each other. For example, are readers of the diversity-related articles interested in my science publications or in my off-beat observations about the underlying science of a rock?

All of these analytics are catnip for scientists who crave hard data to support the impact and importance of our work. The h-index (named after Jorge Hirsch), for example, attempts to quantify the impact of a scientist’s oeuvre through a cumulative but tempered accounting of the citations that their work has received. It’s of practical use because it’s very hard to compare different scientists. On the other hand, the h-index is wrought with confounding factors… The larger the field, the more citations every paper within it receives; membership in groups of prolific scientists who happily follow each other’s work gives a happy boost to all; advances in “hot” areas will necessarily receive more attention; the Matthew effect; the longer the scientist's career, the higher the h-index; and the list goes on. Such factors, though seemingly giving some scientists advantages over others, are not necessarily positively uncorrelated with their impact. And the h-index has become a metric that nearly every scientist detracts, but simultaneously follows with equal interest.

So looking at the analytics of my posts, I am simultaneously humbled and dismayed. I never expected that there would be, on average, more than 300 page views per post. This number is likely more than what my scientific articles receive. The latter have been peer-reviewed and have advanced science, but have they directly touched nearly as many lives as my posts? On the other hand, 300 page views pales in comparison with some of the more established science bloggers, and is far surpassed by anything that LeBron James or Taylor Swift tweets by a factor of, like, infinity. So I’ll keep posting, if only because thankfully you, dear reader, are still reading, and hopefully I’m providing you with some outside-the-box perspectives not available elsewhere.

The Sight and Sound of Science

How do you process music? Do you let the music flow over you? Do you translate the sound to notes? Do you look at the fingering and movement of the player? The answers perhaps depends on your level of knowledge and talent in the instruments that generate the music. The beauty of music is that you can enjoy it at any or all of these levels. I would argue that it is the same for science. Whether the details are in the equations or in the instrumental apparatus, you can still enjoy the phenomenon. 

When you look at the sky during the day or at sunset what do you see? It’s likely you’ve noticed that the sky is blue, and sunsets are red. I see that too, but I also think about the jumble of collisions between photons and the particles in the sky. The red photons are less likely to be back scattered than the blue ones… So in the end, the red ones get jumbled less, and reach my eye directly as the sun is setting. The blue photons scatter more and spread across the sky. Each of those trajectories involves equations describing the motion of the photons and one could try to follow them too. But actually, there are so many that no one can really follow them all. Instead, it is their emergent behavior that can be tracked in some collective way. You might think that that emergent dance of photons is all of the beauty in and of itself. You, like me, might find all the fun in determining the governing equations and finding their solution. Or you might remain steadfast that the beauty lies in a visually arresting sunset as if it were a painting. Regardless, the beauty comes out from science!