Wednesday, September 17, 2014

The challenge of writing books on water

Biman Bagchi has just published a new book,
Water in Biological and Chemical Processes: From Structure and Dynamics to Function 

Cambridge University Press sent me a complimentary copy to review. I am slowly working through it and will write a detailed review when I am done.

I think this is a very challenging subject to write a book on for at least three reasons. First, the scope of the topic is immense. Furthermore, it is multi-disciplinary spanning physics, chemistry, and biology, with a strong interaction between experiment, theory, and simulation. Second, although there have been some significant advances in the last few decades there is real state of flux, with a fair share of controversies, advances, and fashions. Finally, which audience do you write for? Experimental biochemists or theoretical physicists or somewhere in between.

Although this is an incredibly important and challenging topic few authors have taken up the challenge. One who has is Arieh Ben-Naim

Molecular Theory of Water and Aqueous Solutions, Part I: Understanding Water (2009)

Molecular Theory of Water and Aqueous Solutions Part II: The Role of Water in Protein Folding, Self-Assembly and Molecular Recognition (2011)

This was a topic of great interest to my late father. He wrote two comprehensive reviews with John Edsall, published in Advances in Biophysics

Water and proteins. I. The significance and structure of water; its interaction with electrolytes and non-electrolytes (1977) [does not seem to be available online]

Water and proteins. II. The location and dynamics of water in protein systems and its relation to their stability and properties (1983)

Classic earlier books include:

The Structure and Properties of Water
 by David Eisenberg and Walter Kauzmann
(1969, reissued in 2002 by Oxford UP in their Classic Texts in the Physical Sciences)

A seven volume series, Water: A comprehensive treatise, edited by Felix Franks

At the popular level there is
Life's Matrix: A Biography of Water 
(2001) by Philip Ball

Monday, September 15, 2014

An efficient publication strategy

Previously I posted about my paper submission strategy.
A recent experience highlighted to me the folly of the high stakes game of going down the status chain of descending impact factors:
Nature -> Science -> Nature X, PNAS -> PRL, JACS -> PRB, JCP.

Two significant problems with this game are:
1. A lot of time and energy is wasted in strategising, rewriting, reformatting, and resubmitting at each stage of the process. Furthermore, if there are multiple senior authors each stage can be particularly slow.
2. Given the low success rates the paper often ends up in PRB or a comparable journal (J. Chem. Phys., J. Phys. Chem.) anyway!

I have followed this route and it has been a whole year between submission and publication.

In contrast, on 28 July I submitted a paper as a regular article to J. Chem. Phys. and it appeared online on 10 September!
Six weeks!
I have also had papers published in PRA and PRB much faster than in PRL.

Why is speedy publication valuable?
  • The sooner it is published, the sooner that some people, particularly chemists, will take it seriously.
  • The time and mental energy that is saved can be spent instead  doing more research and writing more papers.
  • A few months can be the difference so you can list the paper as published on the next job application, grant report, or grant application.
  • The sooner it is published the sooner it will start getting cited. 
Furthermore, in the long run, the value of the science carries the day. If the research is valuable and significant it will have a real impact, regardless of where it is published. Papers make the impact not the journals. If I look at my own publication list [particularly on the 5+ years time scale] there is not a lot of correlation between journal impact factor, real scientific impact [the most desirable citations] and total citation numbers.

Saturday, September 13, 2014

Reflecting on teaching evaluations

Getting feedback from students via formal evaluations at the end of a course can be helpful, encouraging or discouraging, frustrating, satisfying ...

A few weeks ago I got my evaluations for a course I taught last semester. Here are my reflections. First, given there were only 5 they should be taken with a grain of salt! They were very positive which was quite encouraging. They aren't always...

I was particularly encouraged that students noticed and appreciated several things I worked on and increasingly emphasise.

One student pointed out how my treatment of semiconductors was not as clear at the earlier material. I agree! This was the first time I had taught that part of the course. In contrast, most of the other material I have taught 5-10 times before. Some of it relates closely to my research and I have thought about deeply. This shortcoming  also reflects that I am still not comfortable with the semiconductor material. I can "say the mantra" of how a p-n junction works but I still don't really understand it. I am not surprised that the students picked up on this.

Over the years I have co-taught courses with colleagues who have varied significantly in experience, ability, enthusiasm, effort, ...
I have noticed that my evaluations correlate with those of my co-teacher. Students make comparisons. If I co-teach with an experienced gifted teacher students are more critical of me and my evaluations go down. On the other hand if I co-teach with a younger less experienced colleague or an older colleague who has no interest in teaching my scores go up.
The take home point is not to get too discouraged in the former case and not to let it go to my head in the latter case.

The evaluations also seem to correlate with the ability, background, attitudes, expectation levels, and motivation levels of the students. Do they see me as an ally or an adversary? Given what I have observed during the semester I am usually not too surprised by the evaluations.

Thursday, September 11, 2014

When is water quantum?

Many properties of bulk water, including its many anomalous properties, can be described/understood in terms of the classical dynamics of interacting "molecules" that consist of localised point charges. However, there is more to the story. In particular, it turns out some of the success of classical calculations arise from a fortuitous cancellation of quantum effects.

Properties to consider include thermodynamics, structure, and dynamics. Besides bulk homogeneous water, there is water in confined spaces, at surfaces, and interacting with ions, solutes, and biomolecules.

Distinctly quantum effects that may occur in a system include zero-point motion, tunnelling, reflection at the top of a barrier, coherence, interference, entanglement, quantum statistics, and collective phenomena (e.g. superconductivity). As far as I am aware only the first two are relevant to water: they involve the nuclear degrees of freedom, specifically the motion of hydrogen atoms or protons. A definitive experimental signature of such quantum effects in seen by substitution of hydrogen with deuterium.

Although there have been exotic claims of entanglement, from both experimentalists and theorists, I think these are based on such dubious data and unrealistic models they are not worthy of even referencing. More positively, there may also be some collective tunnelling effects involving hexagons of water molecules, as described here.

When are quantum nuclear effects significant? 
What are the key physico-chemical descriptors?

I believe there are two:
the distance R between a proton donor and acceptor in a hydrogen bond and
epsilon, the difference between the proton affinity of the donor and the acceptor.

Quantum nuclear effects become significant when both R is less than 2.6 Angstroms and epsilon is less than 10 kcal/mol.
In bulk water at room temperature the average value of R is about 2.8 Angstroms and epsilon is of the order of 20 kcal/mol and so quantum nuclear effects are not significant for properties that are dominated by averages. However, there are significant thermal fluctuations than can make R as small at 2.4 Angstroms and epsilon smaller, for times less than hundreds of femtoseconds. More on that below. Furthermore, when water interacts with protons, to produce entities such as the Zundel cation, or with biomolecules, the average R can be as small at 2.4 Angstroms and epsilon can be zero.
This way of looking at quantum nuclear effects is discussed at length in this paper.

[Image from here]

What are the key organising principles for understanding quantum nuclear effects?

I proposed before these two.

1. Competing quantum effects: O-H stretch vs. bend

Hydrogen bonding changes vibrational frequencies and thus the zero-point energy. As the H-bond strength increases (e.g. due to decreasing R) the O-H stretch frequency decreases while the O-H bend frequencies increases. These changes compete with each other in their effect on the total zero-point energy. Also, the quantum corrections associated with the two types of vibrations have the opposite sign reducing the total quantum effects.
I think this idea was first clearly stated by Markland, Habershon, and Manolopoulos.

2. Dynamics dominated by rare events

For example, consider proton transfer in water. When R is at the average value of 2.8 Angstroms the energy barrier is very large. However, if there a very short fluctuation in R so that it reduces to 2.4 Angstroms the barrier disappears and the proton transfers.

What are the implications of these two organising principles for computer simulations?

Pessimism and caution!

1. Subtracting two numbers of about the same size can be error prone.
Suppose that we can calculate the quantum effects of each of the vibrational modes to an accuracy of about 10 per cent. Then we add the contributions (picking some representative numbers):
100 - 50 - 30 = 20. The problem is that the total error is about +/-20.

2. The probability of the rare events is related to the tails of the nuclear wave function. The problem is that this is very sensitive to the exact form of the effective potential energy surface (PES) for the nuclear motion. Tunneling is very sensitive to the height and shape of energy barriers. The problem is that is very difficult, particularly for hydrogen bonding, to calculate these PES accurately, especially at the level of Density Functional Theory. These issues are nicely illustrated in a recent paper by Wang, Ceriotti, and Markland.

This post is motivated by preparing to be part of a working group on quantum water at a Nordita workshop.

My questions are:
Is the picture above valid? Is it oversimplified? Are there exceptions?
Are the two organising principles valid and important? Are there other relevant principles?

Wednesday, September 10, 2014

Double proton transfer rates vs. distance

There is a nice paper
Tautomerism in Porphycenes: Analysis of Rate-Affecting Factors
Piotr Ciąćka, Piotr Fita, Arkadiusz Listkowski, Michał Kijak, Santi Nonell, Daiki Kuzuhara, Hiroko Yamada, Czesław Radzewicz, and Jacek Waluk

They look at nineteen different porphycenes, which means that R, the distance between the nitrogen atoms that donate and accept a proton varies.
[This is a testimony to the patience and skill of synthetic organic chemists to produce 19 different compounds.]

The rate of tautomerization [i.e. double proton transfer] can be measured my monitoring the time dependence of the fluorescence anisotropy because the transition dipole moment of the two tautomers is in different directions, as illustrated below, in the graphical abstract of the paper.

The key result is below: the rate of tautomerization [i.e. double proton transfer] versus R. Note the vertical scale varies by three orders of magnitude.

For single hydrogen bonds many correlations between R and observables such as bond lengths and vibrational frequencies have been observed.

The natural explanation for this correlation is that as R decreases so does the energy barrier for double proton transfer. At least at the qualitative level this is captured by my simple diabatic state model for double proton transfer [which just appeared in J. Chem. Phys.]. However, my model only predicts a correlation is the ratio of the proton affinity of the donor with one and two protons on the donor does not change as one makes the chemical substitutions that change R.

(I think) all these experiments are done at room temperature in a solvent.
Two open questions concern whether the double proton transfer is sequential or concerted, and whether it is activated or involves tunnelling. At low temperatures in supercooled jets there is evidence of tunnel splitting and concerted transfer.

Monday, September 8, 2014

A few tips on getting organised

I would not claim to be the most organised person. I know I can do better. But, I also know I struggle less than some. Here are a few things that help me to avoid chaos. I don't do all of them all the time, but they are good to aim for.

Just say no.
The more responsibilities you take on and the busier you get and the harder it is to juggle everything, keep up, think clearly, set priorities, avoid the tyranny of the urgent....

A clear desk
I am more relaxed, focused, and productive, if the only thing I have on the desk in front of me is what I am actually working on. Move the piles of other stuff somewhere else, out of view.

Google Calendar
I have a work calendar and a personal one. I include all my weekly meetings and obligations.
Everyone I work with can see the work calendar and knows what I am up to. They can also see "busy" if there is something in the personal one. My family sees both.

Keep the schedule
Once something is in the calendar it is more or less fixed. Only in exceptional circumstances do I reschedule.

Papers for Mac
Any paper I download goes in there. Mostly I only print it if I am going to read it now. Papers is great for searching and finding stuff.

The paperless office
Sorry, I can't do it. Anything that requires a detailed and thoughtful reading I have to read in hard copy. But, ...

The paper recycling bin is your friend
I only save papers I am likely to read again. All the admin stuff goes in a box below my desk that then ends up in the recycling bin.

A moratorium on buying new bookcases and filing cabinets
I already have too many, both at work and home. So, if I buy more books or file more papers I have to get rid of some existing ones.

Turn it off. Try to only look at it a few times a day.
I have folders I do occasionally file stuff in.
I have not yet managed to use tags such as to remind me to act on certain things.

to do list
I have a long one on the computer, and so it is easily edited and updated.
I don't look at it often enough, out of guilt and frustration. But it is a useful reminder and it does feel good to cross stuff off.
On busy days I do hand write a schedule for the day.

Mobile phone
I don't use one.

I could do a lot better. I welcome others to share what they have found helpful.

Friday, September 5, 2014

The challenge of coupled electron-proton transfer

There is a nice helpful review
Biochemistry and Theory of Proton-Coupled Electron Transfer 
Agostino Migliore, Nicholas F. Polizzi, Michael J. Therien, and David N. Beratan

Here are a few of the (basic) things I got out of reading it (albeit on a long plane flight a while ago).

There are a diverse range of biomolecules where coupled electron-proton transfer plays a key role in their function. The electron transfer (ET) and proton transfer (PT) are usually spatially separated. [See blue and red arrows below].

There are fundamental questions about whether the transfer is concerted or sequential, adiabatic or non-adiabatic, and how important the protein environment (polar solvent)  is.

Often short hydrogen bonds are involved and so the nuclear degrees of freedom need to be treated quantum mechanically, in order to take into account tunnelling and/or zero-point motion.

Diabatic states are key to understanding and theoretical model development.

Although there are some "schematic" theories, they involve some debatable approximations (e.g. Fermi's golden rule), and so there is much to be done, even at the level of minimal model Hamiltonians.