musings on music and life

May 31, 2016

Next concert, 6/12/2016

Filed under: Carnatic Music — sankirnam @ 1:09 pm


As always, if you are in town, please do come! All are welcome.

May 21, 2016

This week in The Economist, 5/21/2016

Filed under: The Economist — sankirnam @ 2:16 pm

Here are a few articles of interest from this week’s issue:

  1. The grim prospect” – antibiotic resistance seems to be getting a lot of attention lately; I have seen several articles on this topic this week alone. Derek Lowe has covered a paper published recently by Andy Myers (whose work I wrote about earlier), and this was also covered in The Verge.
  2. Beef consumption is on the decline in France. Oddly enough, I wouldn’t have pegged the French as massive beefeaters, especially since horse meat, which is a substitute good (to my limited knowledge as a vegetarian) is not taboo in France.
  3. The economics on the supply and demand of quinoa. While it was initially thought that the rumors about the overconsumption of quinoa by Western countries affecting poor farmers in Peru and Bolivia was overblown, it seems there may be merit to that argument after all.

May 18, 2016

Musiri Chamber Concerts, 5/2016

Filed under: Carnatic Music — sankirnam @ 9:24 am

This concert took place in Chennai on Saturday night (Sunday morning in the US):

It’s by my friend Kunnakudi Balamuralikrishna. This features an absolutely riveting Naaganandhini (melakartha 30), with Thyagaraja’s Sattaleni Dhinamu. The ragam starts at 0:37:30 and the krithi and kalpana swarams go till 1:22:00 or so. Singing a vivadi ragam so elaborately is not trivial, and it demonstrates Balamurali’s creativity and the effort he has put in to master this unusual ragam. I don’t need to gush over Narayanan sir’s mrudangam performance in this concert; his anticipation of Balamurali’s sangathis and swara phrases always leaves me in awe, and the thani shows an intellectual approach to music, rather than raw power and speed.

The potential of vivadi melakarthas (like Naaganandhini, Yaagapriya, Kosalam, Chitrambari, and others) was first demonstrated by Vidwan Thanjavur S. Kalyanaraman. There is a recording that he released where he has sung krithis in all of the melakarthas along with ragam and swaram; these serve as prototypes on how the vivadi melakarthas can be approached.

May 17, 2016

On learning to code

Filed under: Coding, Data Science, education — sankirnam @ 11:05 am

Last week, the following article was published in TechCrunch: Please don’t learn to Code. This was swiftly followed by Quincy Larson’s reply, Please do learn to code.

For those who don’t know, Quincy Larson is the founder and director of FreeCodeCamp, an online programming education website that is disrupting the traditional paradigm of teaching programming/ CS. I’m going through it myself, and highly recommend it for anyone who wants to learn programming – the front-end web development curriculum is very well done, and it walks you through HTML, CSS (including responsive design with Bootstrap), JQuery, and JavaScript. Even if you do not necessarily want to go into webdev, this is a good place to start; it has you make projects to really cement your knowledge. Until I did this program, I had no idea how to make a website from scratch with HTML and CSS!

In any case, with regards to the articles I linked at the beginning, I am siding with Quincy Larson on the issue. Computers and digital devices are ubiquitous in our lives nowadays, and we spend at least 5 hours or more (a very conservative estimate) a day interacting with computers, whether it is in the form of desktop computers, servers, laptops, tablets, or mobile smartphones. Knowing how to use these devices is one thing, but that is the bare minimum; if you want to be truly productive in today’s society, you need to be able to get these devices to work for you, and that is where a knowledge of programming comes into the picture. In addition, with the rise of machine learning and increased automation, we’re beginning to see an increased number of jobs that were traditionally done by humans now being done by computers. This automation is beginning to seep into areas that are considered “high-skill”, such as organic synthesis. Thus, it’s like I say nowadays:

You don’t want to lose your job because someone else automates your position, right? You would rather be in a position where you automate someone else’s job. The only way to ensure that you are in the latter position is to learn programming/computer science.

The beauty of the field of programming/computer science is that it is extremely egalitarian, compared to other fields. In the programming arena, people care only about what you’ve done, what you’ve accomplished, and whether you know your stuff or not; educational pedigree is largely irrelevant. Contrast this to a field like organic chemistry, where if you do not have a degree from MIT/Caltech/Harvard/Stanford/Berkeley your resume will be swiftly thrown in the trash. This is why, in CS, it is now accepted that a GitHub profile is the new resume.

In other news, I have been applying to bootcamps for the last few weeks, in order to have something do this summer given that the job situation in organic chemistry continues to remain abysmal. I know I have been scornful of bootcamps and “data science” in the past, but my reason for applying to these places is simple. I could learn the material on my own for free (or a significantly reduced cost), but it would take a long time – at least a year or two. If I can accelerate the process and learn everything in 12 weeks, then it is worth the extra cash, and after all, time is the most valuable asset we have in our lives. This video explains it pretty well:

After interviewing at several places, I was accepted to Codesmith, Logit Data Science, and Dev Bootcamp. I’ve decided to go with Logit Data Science simply because it makes more sense given my background; going into full-stack web development is orthogonal to my past education. There are pros and cons to all decisions; Logit is cheaper, but I’m going to be in the first cohort, so it remains to be seen how good the program is going to be. Also, given that my CS, math, and statistics backgrounds are very minimal, I’m anticipating that this is going to be extremely challenging. But sometimes, succeeding in life is all about risks and taking that first leap of faith! Codesmith is a little better established; they’ve been around for a year. I visited their campus/office a couple of weeks ago in Playa Vista, and was very impressed. The atmosphere is quite relaxed, but I did feel the “work hard, play hard” spirit there. The CEO, Will Sentance, is one of the main instructors there, and his teaching style is absolutely fantastic. He explains all the concepts thoroughly and clearly, and his enthusiasm for the subject is infectious. If you’re considering joining a full-stack bootcamp, I highly recommend Codesmith – do check them out! They are up there with Hack Reactor in terms of quality of instruction and overall experience.

May 16, 2016

Classics in Organic Chemistry, Part IV

Filed under: Classics in Organic Chemistry — sankirnam @ 12:41 pm

And now for our next topic, Sir D. H. R. Barton’s Gif Chemistry.

Derek Barton was another one of the “rockstars of organic chemistry” along with esteemed individuals such as R. B. Woodward, E. J. Corey, Professor G. A. Olah, Prof. K. B. Sharpless, and others. Like Einstein, Ernst Rutherford, and a few others, Derek Barton was particularly famous because his most famous work was not what he received the Nobel Prize for! Derek Barton contributed to an extremely wide range of research areas, including radical chemistry, hypervalent bismuth and selenium chemistry, fluorine chemistry, and of course, his last work involved the oxidation of saturated hydrocarbons under mild conditions – a class of reactions dubbed “Gif chemistry”.

The name is derived from the place where this type of chemistry was first studied, Gif-sur-Yvette in France. At the time, the functionalization of saturated hydrocarbons (alkanes) was a hot topic in the organic chemistry community; it still is today, although it has taken on the sexier name of “C-H activation”. I initially learned about this class of reactions when I was reading Iron Catalysis in Organic Chemistry: Reactions and Applications during the course of my PhD. Iron catalysis remains a topic of personal interest, as it focuses on one aspect of the question “can we substitute 3d metals for the precious 4d metals (Ru, Rh, Pd) as catalysts in organic synthesis?”.

In any case, the overall premise of the Gif reactions is the oxidation of saturated alkanes (by air or other oxidants) using iron as the catalyst. In all cases, adamantane was chosen as the substrate for “its non-volatility, which would make good mass balances feasible, and its symmetry, which simplifies the problem of product identification. In addition, adamantane is a nice mechanistic probe. It has 12 equivalent secondary C-H bonds and four equivalent tertiary C-H bonds”.


Conceptually, this is not terribly difficult to understand; the terminal oxidant in both reactions above is O2 from the air, and the solvents involved are pyridine, acetic acid, and water (in the GifII reaction). Pyridine is necessary because you need an organic solvent to dissolve something as nonpolar as adamantane (or any alkane), and acetic acid is employed as an anion once the iron is also in solution. The surprising observation is that this alkane oxidation takes place in the presence of hydrogen sulfide, which is much easier to oxidize than any alkane; in fact, it turned out that the presence of a sulfide (or phosphine) was necessary for the oxidation to proceed.

Historically, oxidative chemistry using Fe is well known in the literature, and the earliest example is probably Fenton’s reagent, which is well over 100 years old. That being said, there is still a lot of uncertainty regarding the mechanism of the Gif reactions, and unfortunately interest in these investigations waned with Derek Barton’s demise in 1998. The main question was whether this reaction proceeded via radical intermediates (like the Fenton system), or did it involve the intermediacy of a high-valent Fe(IV) or Fe(V) species? One of the arguments against the involvement of radicals is the observation that the reaction proceeds in the presence of hydrogen sulfide; the S-H bond is known to quench carbon radicals readily by HAT (hydrogen atom transfer). Another is the regioselectivity of the reaction; since tertiary radicals are more stable than secondary radicals, one would expect the tertiary product (1-adamantanol) to dominate if radicals were really involved. But, as one can see from the figure above, the secondary products are obtained in greater yield.

Barton and his coworkers were able to isolate a soluble black crystalline complex from the dissolution of iron powder in acetic acid and pyridine; it was found that when this complex was employed in the reaction instead of iron powder, better yields and selectivities could be obtained. Barton’s theory was that a high-valent Fe(V) or Fe(IV)-oxo or -hydroxo species was responsible for the oxidation, as that would also account for the selectivity to secondary positions based on steric arguments. There is some precedence for this, as it is believed that high-valent Fe(V)/Fe(IV) is involved in biological oxidations using cytochrome P450.Barton_gif_2

This catalyst or cluster would be considered “primitive” by today’s standards, as the synthesis is pretty trivial, and the ligands are extremely simple. And yet, it is able to do some pretty impressive transformations!

Barton had this to say about how the reactions work:

“The only way that we can explain these results is by a hypothesis that the reagent that oxidizes the hydrocarbon is present in a dormant form (Sleeping Beauty) until it collides with the saturated hydrocarbon (the Prince) and reacts with a saturated C-H bond (the kiss) to form the real reagent, which immediately gives the iron-carbon bond […]. So, the hydrocarbon on contact with the iron species activates and reacts with the activated iron species without separation. The hydrocarbon should be inducing in the (formally) FeV=O species a change that makes possible such an unusual reaction. There is evidence in the literature for this sort of agostic interaction between nonactivated carbon-hydrogen bonds and organometallic species”.

Funnily enough, this chemistry has been rediscovered recently by Prof. M. Christina White (UIUC). I remember reading her papers and wondering in confusion why it was being published in top journals when there was a distinct lack of originality…all she was doing is repackaging the work Barton had done with Gif chemistry! For instance, in this paper, she has almost the same complex that Barton has described above, except that the ligands have been tweaked a little. Instead of using simple pyridine, she is using PDP (2-({(S)-2-[(S)-1-(pyridin-2-ylmethyl)pyrrolidin-2-yl]pyrrolidin-1-yl}methyl)pyridine). Of course you’re going to improve the selectivity, lifetime, and TOF of the catalyst by making it better defined, but you’re not inventing a new reaction paradigm here. It should be no surprise that the catalyst therefore has an even greater preference for primary or secondary sites over tertiary sites than Barton’s original systems. I would not consider this work Science-worthy by any means, but hey, what do I know?



For those interested, you can read more on these topics in the references below:

  1. “The Selective Functionaliztion of Saturated Hydrocarbons: Gif Chemistry” Barton, D. H. R.; Doller, D. Acc. Chem. Res. 199225, 504
  2. Barton, D. H. R. Tetrahedron 199854, 5805
  3. Barton, D. H. R.; Doller, D. Pure & Appl. Chem. 199163, 1567
  4. Barton, D. H. R.; Boivin, J.; Gastiger, M.; Morzycki, J.; Hay-Motherwell, R. S.; Motherwell, W. B.; Ozbalik, N.; Schwartzentruber, K. M. J. Chem. Soc. Perkin Trans. I 1986, 947
  5. Barton, D. H. R.; Chabot, B. M. Tetrahedron 199753, 487

May 11, 2016

Review of DavidsonX D001x

Filed under: Chemistry, education — sankirnam @ 11:49 am

I recently completed the above course on EdX; the full title is:

DavidsonX: D001x Medicinal Chemistry: The Molecular Basis of Drug Discovery

I have taken biochemistry and medicinal chemistry/drug discovery courses several times in the past during my undergrad and graduate studies, but the quality and coverage of the topics in this course was far, far better than anything I had taken to date. Major kudos to Prof. Erland Stevens (the instructor) for doing a fantastic job. I highly recommend this course to anyone with an interest in medicinal chemistry or drug discovery (even if you’re not interested in doing it for a career).

The course starts from the basics and assumes a basic knowledge of organic chemistry and algebra/arithmetic. The organic background is required just so you know the basic rules of structural organic chemistry; there are no complex synthetic schemes or mechanisms in this course. As far as reactions are concerned, the only reactions really touched upon were those involved in oxidations by the liver.

The math required is tedious but not terribly overcomplicated; the majority of the questions involved calculations with Michaelis-Menten and Lineweaver-Burke plots, or using IC50 values and the Cheng-Prusoff equation. These can all be done with Excel or Google spreadsheets, and Prof. Stevens demonstrates clearly how to do it, but that still doesn’t reduce the tedium of going through the calculations. The main thing to watch out for when doing calculations is that the EdX system only gives you 1 or 2 opportunities to input the answer before closing it off, so you have to make doubly sure to check your math and make sure the answer is correct!

This was my first proper exposure to the concepts of ADME (Absorption, Distribution, Metabolism, Excretion), which is central to pharmaceutical science. Each of these concepts was covered in detail; for absorption, the main methods of delivery that were covered were the IV bolus and oral ingestion, although one should keep in mind that these are only 2 out of the many ways of getting a compound into the body (others include suppositories, inhalation, transdermal diffusion, etc.). Distribution covered the basic “one-compartment” and “two-compartment” models, different ways of thinking about how a compound gets around the body. In this case, the bloodstream can be thought of as a “compartment”, and the fatty tissues as another compartment, both with different volumes, and so the concentration of the compound in each will be different. The blood-brain barrier was not touched upon in this course; this is a topic of personal interest to me, and it can be thought of as a barrier that divides one of the compartments.

In the context of drug discovery, Prof. Stevens gave an overview of the major approaches used in the industry today, such as combinatorial chemistry, HTS, peptidomimetics, fragment-based and phenotype-based screening, and natural products. Functional group replacements and isosteres were also discussed, common ones being replacement of a -CH3 group by a -Cl and tetrazole for a carboxylic acid. As an organofluorine chemist, I know that it is common to use -F substitution in this regard, but this was not really touched upon. The lecture on SOSA (Selective Optimization of Side Activities) was a little confusing; Prof. Stevens used the classic example of the discovery of Viagra’s ability to treat erectile dysfunction to illustrate this, but I remember being misled by the associated questions. This could be improved in future iterations of the course.

The cool thing about the course was the Virtual Lab component, and this really brings to life the concepts taught in the course, allowing the students to see the challenges that medicinal chemists face. Using the “bioactivity predictor” feature of Molinspiration, one can input the structures of small organic compounds and conduct a rudimentary screen against some receptors, and further details can be interrogated with the admetSAR website. The challenge in these labs was to design molecules with an affinity for a certain receptor (as predicted by Molinspiration), but still having good ADME properties. This is really fun to play with, as it gives a sense to the interplay between organic structure and function (which is what structure-activity relationships (SARs) are all about).

This course is a great introduction to medicinal chemistry, and I highly recommend taking it in the future, if it is offered again. After this, one can dive into the medicinal chemistry literature (e.g. Journal of Medicinal Chemistry or BMCL) and gain a deeper understanding of the topics covered in the course and how they are actually being used right now.

May 9, 2016

Next concert, 5/21/2016

Filed under: Carnatic Music — sankirnam @ 11:51 am


As always, if you’re in the area, please do come! All are welcome.

EDIT (5/24/2016): Video of the concert

May 8, 2016

This week in The Economist, 5/7/2016

Filed under: The Economist — sankirnam @ 12:43 am

Not much caught my eye this week, apart from the big coverage of Trump’s clinching of the Republican nomination with his decisive victory in the Indiana caucus.

This article covers a trending topic: the creator of the cryptocurrency Bitcoin. Who is Satoshi Nakamoto?


May 7, 2016

Someone give this man a medal

Filed under: Uncomfortable truths — sankirnam @ 12:55 pm

From Chemjobber yesterday, this gem (in response to a post about the Army Research Laboratory offering a $100,000 (!!!!!) postdoctoral position):

“At least it isn’t being spent to do industry’s research for free (especially when they escape so much tax already). Something about people bending over backwards to “work with industry” or “demonstrate industrial relevance” on NIH/NSF projects while industry continues to downsize-to-nothing internal R&D boils my blood. Do your own god damn research.”

THIS. This. A thousand times this.

I’m honestly surprised that more people aren’t up in arms about the current state of R&D in the United States. Companies here, especially big pharmaceutical companies, are all attempting inversion mergers in order to evade US corporate tax rates, but still want the benefits of NIH/NSF funding and a supply of cheap, well-trained labor on the government’s dime.

The model of pharmaceutical R&D seems to have shifted over the last decade or so; now, a lot of drug discovery research is done by startups rather than Big Pharma, and if any of the leads in the libraries of the startups is particularly promising, they get bought out by a Big Pharma company. Big Pharma gets all the benefits without the cost or the risks of doing research. I emphasize that last statement to highlight the ludicrousness of the situation; companies based on doing research don’t want to do research any more. This is also leading to another nascent bubble in startups and VC-funded companies, which I will talk more about later.

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