Ways to control interactions of a molecule by varying amounts of fluorine atoms, a manipulation that holds out promise in biochemistry
Naresh Patwari & team, Department of Chemistry, IIT Bombay
Scientists have always been interested in understanding the mechanisms of interactions between different molecules when brought in contact with each other. Over the years, they have gained good insight into how molecules behave and react with one another, and how they attach themselves to form bonds.
An understanding of these molecular interactions at the most basic level has helped nearly all branches of the physical sciences. But a lot is still not very well understood, especially in biology and biochemistry, where very complex and chaotic structures and systems are observed. But incremental advancements are being made almost on a routine basis.
The work of Naresh Patwari and his team at the department of chemistry at IIT Bombay promises to throw some new light on molecular interactions that have important implications for protein structure and function in biology.
Patwari has been studying molecular interactions for over 15 years now. For the last few years, he has been concentrating on a phenomenon called fluorine substitution in hydrogen-containing compounds.
Fluorine has some special properties, and its size and structure are such that it can be used to replace hydrogen in certain organic compounds, with very interesting end results. Patwari describes teflon-coated cooking ware as an illustration. Teflon is an organic polymer with lots of fluorine atoms thrown in. The non-sticking property of teflon comes from the fact that the fluorine atoms become so hard that they are in no position to react with the food items being heated or cooked.
The “hardness” of fluorine atoms in certain conditions is a property that can be exploited for some interesting and useful manipulations. Patwari and his team have studied these in detail. They have altered the quantity of fluorine atoms in different compounds and noticed a change in their ability to interact with other molecules.
This capability to control the interactions of a molecule by varying the amounts of one of its constituent atoms gives scientists a powerful handle to make modifications to a material to obtain desired objectives. Patwari and his team used the compound phenylacetylene for their experiments. With a combination of laboratory experiments and computer simulations, the researchers have shown that fluorine offers much better control and flexibility to scientists as compared to other atoms.
Patwari says this opens up some exciting possibilities for manipulations in biochemistry. The susceptibility of human beings to certain kinds of diseases involves chemical interactions. If these interactions can somehow be stopped — just like fluorine in teflon-coated cookware prevents interaction with food items — some resistance to diseases can be induced. Specifically, Patwari is looking at fluorine substitution in some amino acids which make up the proteins.
Already, there is quite a lot of interest regarding fluorine in biology, but the results he has obtained with other chemicals puts Patwari in a unique position to exploit this situation.
To be sure, fluorine substitution is not random. Nor is it a simple substitution of one atom with another. It is a very targeted exercise. Random substitution can change the compound altogether, altering its properties. Patwari says finding the right places in the molecule to introduce the substitution is critical to it success. It is for this reason that the substitutions are made at places that are more important for the structure of the molecule, not so much for its functions. This way the original character of the molecule is maintained while imparting it fresh properties due to the presence of fluorine.
There are about 20 amino acids that make up all the proteins in the human body. Patwari says fluorine substitution does not work in most of them. But there are two or three amino acids where this process can introduce exciting properties. Patwari is still to begin experimenting with bio-molecules but says his work so far gives him hope that there could be important lessons for drug delivery and drug targeting as well.
For his work on molecular interactions, Patwari was named one of the winners of this year’s Shanti Swarup Bhatnagar prize, the highest scientific honour in the country for scientists below the age of 45 years..