Daniella Goldfarb talks to Colin Batchelor about her dreams for electron spin resonance

Daniella Goldfarb is the Erich Klieger chair in chemical physics at the Weizmann Institute of Science, Rehovot, Israel. Her research interests in electron paramagnetic resonance range from metalloproteins to zeolites. She has been a member of the Physical Chemistry Chemical Physics editorial board since the start of 2007. Daniella Goldfarb was recently awarded the Bruker BioSpin Lectureship by the RSC's electron spin resonance group at their 40th annual international meeting.

What are you working on at the moment?
I concentrate on electron spin resonance - the older and smaller brother of nuclear magnetic resonance. It deals with compounds that are paramagnetic, with one or more unpaired electron. We use it to learn about structure and dynamics in different systems, but we are involved in developing the spectroscopy and instrumentation. We not only use commercial instruments but we build our own spectrometers too, so we can do things that are out of the ordinary, but will hopefully turn into routine experiments.

What does EPR tell us that other methods can't?

Let's look at a metalloenzyme where the metal centre is paramagnetic. In this case NMR has difficulties because the lines of nuclei near the metal are usually very broad. X-Ray crystallography is great, but only if I have crystals. Even if I have crystals it tells me where the atoms are, but it doesn't tell me about the electronic structure, the oxidation state, charge distribution etc. In metalloenzymes these are very important because these really determine the activity of the site. Having the structure is the beginning, so you know where the atoms are and you can start working out what they do. For this you need spectroscopy. And for paramagnetic centres EPR is often the method of choice.

A lot of Israel's GDP goes on fundamental research - why do you think Israel does this?
We complain that it's not enough! When Israel was really young and the standard of living was much lower, more money was going into education and research than now, so although it looks a lot, it's going down. When times were really tough (economically) the government realized that the only resource that Israel has is its people, and you have to invest in education. Maybe our politicians don't understand that the successes we've had with Nobel Prizes in the past few years were based on work done years ago.

What started you on magnetic resonance problems?
After my B.Sc. I knew I would go into physical chemistry. I was looking for a PhD position and spoke to different people at several universities: you have to think about the advisor, though you know your general area of interest. I was lucky to talk to the one who 'fathered' the field of magnetic resonance in Israel, which has a long tradition. If you look at the number of people who do magnetic resonance in the Weizmann Institute you realize the stature is relatively high for a small country. I started with NMR and once you're in the field of magnetic resonance it requires a lot of expertise, mastering both the theory and the experimental method Once you achieve it, you don't move out so easily so I guess I'd always stay doing magnetic resonance, but I can apply it to new fields.

Are there any exciting new applications you'd like to follow up?

So far we've worked on metalloprotein systems in the resting state, characterizing the active site and aiming at relating its structure to what its function. What we'd like to do is follow the metal active site during a reaction, to quench the reaction and trap intermediates and unravel the reaction mechanism. I'd like to see a movie of the reaction - right now with standard freeze-quench instrumentation you have a resolution of 5 ms, which is enough for certain reaction. So, in principle, you can follow the time evolution of hyperfine coupling parameters and distances between paramagnetic centres. This will give a movie based on experimental results, not molecular dynamics simulations.

What's the big obstacle?
You just have to feel comfortable with the more advanced techniques. For conventional frequency EPR there is no problem. For high-field EPR the sample is in a very tiny capillary and to do this freeze-quench you have to rapidly freeze the reaction, then inject it into this tiny capillary. There is a group that has managed to do this and we'll find a way too. Another problem for biological samples is that the concentrations are low. EPR is still not as sensitive a technique as fluorescence. I believe that in a year or two we'll manage. Once the sample is frozen in the spectrometer it doesn't matter whether it's an intermediate or a stable state. This direction will keep us busy for the next ten years.

If you could work on a scientific problem in any field, what would it be?
I would like to stay in EPR spectroscopy, but apply it to nanostructures and single molecules. The problem is sensitivity right now. I'd like to go smaller, not to stay in the bulk, but to look at surfaces or single nanostructures. This is more of a dream than a new direction, but I'd like to look at a molecular machine at work. The problem is always resolution vs sensitivity; you have high sensitivity and low resolution or low sensitivity and high resolution.