Is polymorphism crystal clear? Nicola Nugent asks Ashwini Nangia...

Ashwini Nangia is a professor of chemistry at the University of Hyderabad, India and he is a member of the editorial board for CrystEngComm. His research interests are focused on crystal engineering and supramolecular chemistry.

How did you become interested in chemistry?
Organic chemistry sparked my interest - I had a good teacher at school. Also, I was fascinated with the periodic table - it's a blend of patterns and order on one hand, and then a bundle of exceptions on the other. This combination of method and madness in the same subject is what made me interested in chemistry.

What kind of research do you do now?
When I first joined the University of Hyderabad, I worked on organic synthesis. About that time, several articles appeared by Dieter Seebach, Fraser Stoddart and George Whitesides. These articles, combined with inspiration from my colleague, Gautam Desiraju, who is a pioneer in crystal engineering, made me look beyond the making of molecules and look at how molecules self-assemble. Since, my research group has looked at several topics, including host-guest inclusion compounds. We have studied the Cambridge Structural Database to look for recurring patterns and used them in our crystal design approaches. Now, we are focusing on polymorphism and pseudo polymorphism, which is not only an academic challenge, but has great relevance for the pharmaceutical industry.

What are some of the applications of crystal engineering?

Crystal engineering has two broad streams - metal-organic frameworks and pure organics. Both of them have a very clear application lined up for them. Metal-organics are important in terms of materials, gas-storage devices, non-linear optics and so on, because they have the strength and robustness which is desired in a material. The organics are ideally suited for applications in drug polymorphs, pigments, dyes and agrochemicals. It's becoming increasingly clear that polymorphs are not just a curiosity. They have very definite and different chemical properties.

Is polymorphism becoming more predictable?
I think we are still very far away from predicting polymorphism. We have a better understanding within families of structures, but not globally. Even the simplest of molecules can be polymorphic, while the most complex structure you can design, based on your logic driven ideas of what should be polymorphic, will turn out to have only a single form. If we start from the basics, a pathway may evolve from which we will understand why certain molecules are polymorphic or how many forms will exist. It goes back to the point I mentioned at the beginning - there is a method, but then there are exceptions, and that's what fuels the curiosity.

What do you think will be the next big breakthrough in your field?
The major challenges today are: polymorphism, crystal structures with multiple Z' (number of molecules in the asymmetric unit) and crystal structure prediction. We are blending experiment with computation. The blending of these ideas will help us understand what really goes into crystallisation, because it's essentially a one step process - you start with a compound, dissolve it and the next morning, if you are lucky, you get good single crystals. We know the beginning and end of the process, but like any reaction mechanism, we want to know the middle. There have been several recent studies in this area. Hopefully in the next five to ten years we'll have a better understanding of what crystallisation really is and how it proceeds.

Much of what I'm saying is focussed on organic crystal engineering area, but similar puzzles face the metal-organic framework field as well. Although the advantage there is that you have one strong and highly directional interaction - the metal to ligand bond. That makes the job a little easier, because at least the primary interaction can be predicted with a good degree of reliability. In organic crystals you are dealing with a large number of interactions which have very similar energies - the hierarchies are not so well defined in the organic world. That's what makes it complex and difficult to predict a priori what's going to happen.

What was the most groundbreaking discovery in polymer science in the 20th century?
The most important contribution was by Staudinger - he was trying to persuade his contemporaries that polymers differed from the rest of chemicals by being very large molecules, and that was the only difference. Until then, many thought that the properties of rubbers and what we now call polymers were the consequence of ill-defined secondary interactions rather than large molecules that got entangled with each other.

What is the secret to running a successful research group?
I think the success of any research group, anywhere in the world, is down to the students. You can have a lot of good ideas, but what drives the idea to reality, at least for experimental chemists, is the student who implements the idea. I have a good group of research students who are able to see the plan or vision that I have when I suggest a problem. Like all research plans, I will be frank enough to admit that many of them don't see reality, but the students are able to get the sense that if one thing doesn't work, something else has to be tried.

What is the most rewarding aspect of your work?
It has always been my dream to work in a contemporary area of research. Being realistic about the facilities in my department, it's pleasing that we are able to do something close to where the latest developments in crystal engineering are happening. I may have been able to do a different type of chemistry, perhaps more instrument based chemistry, if I was working overseas, but it makes me very happy to do the research and produce our results in India.

What challenges face researchers in India?
The main challenge is the issue of attitude. The school system puts a lot of emphasis on achieving good grades rather than encouraging innovative thinking and risk taking. The students are wedded to the fact that whatever they do should work, and the first setback they face in research is that most things don't work. But a negative result is not always a bad thing in science. One negative result today may lead to a positive result tomorrow. A shift in thinking is really the biggest challenge.

What advice would you give to a young scientist?
For any scientist at any point in their life, the most important thing is to do something innovative and challenging. And most of all, whatever you do, you should enjoy it. If you're not enjoying it, you cannot do it for a lifetime. You should do something that comes from your heart.