Ann Valentine talks to Elizabeth Davies about bioinorganic chemistry, titanium and avoiding rust

              

Ann Valentine is an assistant professor of inorganic and biophysical chemistry at Yale University, US. Her research explores the use of metals in nature and the development of potential titanium-based anticancer drugs. She was awarded the American Chemical Society PROGRESS/Dreyfus Lectureship Award in 2007 and the Paul D Saltman Award for Metals in Biology in 2009.

 

Who or what inspired you to become a scientist?

My parents, grandparents and four siblings certainly encouraged me to be anything I wanted to be, and supported me all along. A really life-changing moment was when a high school biology teacher, Ada Margaret Hutchison, judged my junior high science fair project. She approached me afterwards and I was terrified, but she said, 'You did a good job. I hope to see you in the science club next year.' It's amazing what an encouraging word at just the right moment can do. 'Miss Hutch' was my mentor for the next four years. I learned that science was this great collective enterprise to belong to, complete with a special language and mysterious secrets. 

What motivated you to specialise in bioinorganic chemistry?

That would be another mentor - my PhD advisor, Steve Lippard. I came to grad school sure that I hated biochemistry. I wanted to be an inorganic chemist and make beautiful complexes that would never leave the glove box.  Steve showed me that nature is an incredibly good inorganic chemist. My graduate work was about an enzyme that bacteria use to convert methane to methanol using oxygen as the oxidant. We humans would love to be able to do that reaction efficiently and the bacteria have already figured it out. I was hooked.

What projects are you working on at the moment?

Right now we are working on a protein called nicatransferrin. It's a monolobal transferrin which is a primitive form of the two-lobed version that carries iron around in our serum. It comes from an organism called an ascidian or sea squirt. Ascidians are invertebrate chordates - they're right on the evolutionary boundary between invertebrates and vertebrates. They are favourites of inorganic chemists because some species sequester shockingly high concentrations of metals. We think that nicatransferrin may help us understand how nature developed the ability to manage hydrolysis-prone metals like iron in an environment containing oxygen. We also work on titanium, which is a somewhat weird thing for a bioinorganic chemist to do but which is my scientific obsession.

What's hot at the moment in your field?

Two things spring immediately to mind: bioinorganic materials chemistry and metal sensors. The chemistry of biomineralisation is being described in wonderful molecular detail, and chemists are figuring out how to use biomineralisation (or bio-inspired mineralisation) to make useful materials. New tools for imaging metals will let us answer so many important questions: what are metal concentrations in cellular environments and how do they vary under different conditions? Of course, there's still a lot to do in other bioinorganic areas like small molecule activation, metal transport and trafficking and development of spectroscopic methods - expanding the toolbox is always good! 

What's the secret to being a successful scientist?

One key to doing well is to filter out the people who try to discourage you: 'Organic chemistry is impossible', 'Graduate school is just a grind', 'Junior professors are miserable'. Why do we like to scare young aspiring scientists this way? If you love what you're doing, the rewarding aspects outweigh the down side. If they don't, then you're doing the wrong thing with your life and it's completely fine to go do something else.

What do you find to be the most rewarding aspect of your career?

My colleague Bob Crabtree says our most important products are not molecules but people and he's totally right. My favourite moments are when my students come up with some experiment I didn't think of or some way to make an experiment work that hadn't occurred to me. As scientists, we learn the answer to some question nobody's ever answered before and understand something new - that's a total rush.

Do you remember your first experiment?

Sure, my science fair project in the 8th grade. I poured increasing concentrations of salt water on bean plants to see how much it would take to kill them. All of my early science fair projects focused on plant death by various means. 

If you weren't a scientist, what would you do?

I would probably be a teacher. I really enjoy this aspect of my job. I'm so grateful to be able to do both research and teaching. I think one reinforces the other and makes me better at both.

Collaborations form a large part of modern scientific research. Which scientist, past or present, would you really like to work with?

A real guru of aqueous inorganic coordination chemistry was Arthur Martell, who passed away in 2003. I'm pretty sure that some of the problems we really puzzle over, he could have knocked out in a good afternoon. He wrote wonderful books that we're guided by, but I sure wish he were still working.

What characteristics do you see as necessary for your position?

I think there are as many ways to succeed as a scientist as there are successful scientists. Perseverance certainly helps, and a deep love of science. Creative and energetic people have an advantage. 

Your group motto is 'Avoiding rust and paint since 2001' - how successful are you at this?

Some days better than others - but we're definitely much better at it now than when we started! Both iron and titanium, the metals in which we specialise, hydrolyse in water to make insoluble oxides (Fe₂O₃ or rust for iron, TiO₂ or paint for titanium). In my lab, when you see that orange or white precipitate, you know it's time to start over. We're figuring out ligand systems to control this hydrolysis by taking clues from nature which has already worked this out.

Could your work on titanium have therapeutic implications?

In the wake of the fantastic success of the platinum anticancer drugs in the 1960s and '70s, there was a new enthusiasm about metal-based medicines. Two that were really promising, but that stalled in clinical trials, were based on titanium: titanocene dichloride and budotitane. There are problems with formulation and dose-limiting toxicities for these compounds, related to their propensity for hydrolysis. We hope that, by doing better inorganic chemistry, we can make molecules that are better behaved in solution but still reach and kill cancer cells. Our work in this area is sponsored by the American Cancer Society, whose support we really appreciate.

Can you tell us a little known fact about yourself?

I was a four year varsity swimmer at the University of Virginia - distance freestyle and butterfly.

What do you like to do in your spare time?

I mostly spend time with my husband, Mike Lawlor, who's a chemist at a pharmaceutical company, and with our son, Joe, who's one and a half. So I spend a lot of my leisure time playing with wooden trains.