ARTICLE ON NMR SPECTROSCOPY AND CONFORMATION IN IIT-DELHI MAGAZINE

A short holiday break and a rather protracted bout of the flu have kept me from blogging. So I will link to an article of mine that just got published in the magazine of the Chemical Society of (IIT Delhi. The article is written for the layman and talks about the importance of realizing that most molecules of practical interest, such as drugs, have multiple conformations (flexible structures). While the powerful technique of Nuclear Magnetic Resonance (NMR) spectroscopy has traditionally been used to probe this flexibility, NMR alone cannot provide knowledge of these multiple structures. The article mentions why.

In the article, I describe NAMFIS (NMR Analysis of Molecular Flexibility In Solution), a joint computational-NMR approach partially developed and applied in our lab, which can derive a thermodynamic population for flexible molecules in aqueous solutions such as blood. This information can be very useful for deducing, for example, the protein-bound structure of a drug. Such knowledge can aid in modifying the structure of the molecule to make it into a better therapeutic, since most drugs act in the body by binding to key proteins involved in disease. More detail in the article. Comments, criticism and questions are of course always welcome.

THE NEGATIVE IQ PEOPLE AT THE STATE DEPARTMENT

This is really ridiculous. We are writing a paper with a friend and collaborator of mine who is a NMR (Nuclear Magnetic Resonance Spectroscopy) specialist at a prominent university in the US. He just came back from India after a stay of more than two months. He said that his original trip was planned for only a month. So why did it take so long?

Apparently, his visa was delayed. The fine folks at the US State Department saw the dreaded word “nuclear” in his job description. Alarm bells went off in their experienced minds. Nuclear Magnetic Resonance? Surely this is suspicious. Off they went doing a background check for more than a month. In the end of course they found nothing. But my friend had to stay for an extra month, delaying his work here, not to mention our own work.

This is outrageous. NMR is one of the most important techniques ever in chemistry, biology, materials science and drug discovery. For crying out loud, life-saving MRI is based on it (although not incidentally, they took the word “nuclear” out of MRI because it would make people uncomfortable). Every single day, hundreds, if not thousands of papers are published in journals worldwide that involve the use of NMR in one way or the other. Four Nobel Prizes have been awarded to NMR scientists. My own PhD. thesis is mostly based on the interpretation of results obtained using NMR (I have mentioned about it here) NMR has nothing remotely to do with atomic bombs.

But the bull-headed rocks at the State Department cannot even distinguish between the “nuclear” in NMR and that in “nuclear weapons”. Why can’t they hire specialists who actually know something basic about science (and common sense) instead of randomly spouting gut reactions and going ballistic every time they see the word nuclear? In some ways, it would give people like me sadistic pleasure to think of all those floor scrubbers in the department running around trying to find out if I have a Jihadist background. But as everyone knows, unfortunately in the end the person who will lose the most will be me.

Despicable, and it reminds me of Goverdhan Mehta’s shoddy treatment at the American consulate. But considering the ultimate authority they answer to, we can trust them not to look at trivial things like facts and details.

At least now I know what word to not include in my job description when I file for a Visa. “Magnetic Resonance” will have to do. Sigh.

Least favourite NMR solvent, but a swell liquid nonetheless

Coronene has a poll on what everyone’s least favourite NMR solvent is. I have not used all the solvents on the list, but among the ones I have used, DMSO was probably my least favourite, as it also seems to be for others taking the poll.

In my case, the reason was specific. I needed to do NOESY spectroscopy on a degassed, sealed sample. And even ice kept freezing up the DMSO when we were connecting it to the vacuum. For CDCl3, we could happily use lig. N2 and be happy, but not so for DMSO; we had to patiently do the degassing for almost half an hour. In addition, DMSO is viscous and radically changes the tumbling of molecules, causes aggregation and hydrogen bonding etc. Needless to say, one has to re-experiment with his/her NOESY parameters.

On the other hand, it is instructive to see what a great molecule DMSO is for biological applications. It can be used as a drug-delivery vehicle, although this use is debated. DMSO is widely used as a cryo-protectant, and the serine protease inhibitor PMSF is dissolved in DMSO as it will naturally get inactivated in water.

Ronald Breslow and the late Charlotte Friend also discovered that this simple molecule can induce cell differentiation and later, it was found to be a HDAC (histone deacetylase) inhibitor, a class of molecules that’s heavily researched these days. Interaction with HDACs intimately interferes with transcription. For example, the recent celebrity ‘wine molecule’ resveratrol is purported to increase expression of the HDAC protein SIRT1, possibly affecting longevity.
Incidentally, Breslow’s latest paper is an article in Nature Biotechnology, in which DMSO is used as the starting lead to develop SAHA, a HDAC inhibitor which is now in Phase 2 clinical trials as an anticancer agent.

DMSO also “enters the cell and kills the herpes virus”. Apparently, this is an ‘indisputable fact’, and seems to be the basis of scented DMSO creams as the picture above shows. More interesting talk for the cocktail party; guys, beware of the DMSO girl.

A remarkably simple molecule with some remarkable (and occasionally annoying) properties, this DMSO.