musings on music and life

January 17, 2017

Poromboke Paadal

Filed under: Carnatic Music — sankirnam @ 12:39 pm

This video has been trending on Youtube for the last couple of days:

One cannot fault TMK’s music – the music is beautiful, and his rendition is excellent, as always.

I just find it interesting that he is using Carnatic music as a medium for environmental activism, given that Carnatic music is an extremely niche art form. This may not be the optimal way to reach out to a lot of people with this message.

December 16, 2016

My experiences with learning “Data Science” in 2016

Filed under: Coding, Data Science — sankirnam @ 11:21 pm

Well, 2016 is drawing to a close…

This has been a weird year globally, with the death of a lot of influential people in history (including, among others, Muhammad Ali and lately J. Jayalalitha, the Chief Minister of Tamil Nadu, India), and some other strange political occurrences (Brexit and Trump getting elected). I haven’t posted here much because I have a million thoughts swirling around my mind all the time now, and finding a couple of hours of focused time in order to distill them down into an article on a single topic is a bit challenging. Nonetheless, there is something that I want to discuss today.

Firstly, I had the sobering realization a few days ago that it has been 2 years since I finished my PhD and I have nothing concrete to show for it; I’ve been unemployed for the past two years. Well, I’ve learned some valuable things about life and other topics which I wouldn’t have been able to learn otherwise, but it has been at a rather expensive cost: progress in my career.

In any case, one of the major themes of this year (for me) was that I made major progress in learning programming! I want to share what I learned so that others who are thinking of venturing down this path can learn from my experiences.

Firstly, my motivation in learning to code resulted in me being a little unfocused; I was unemployed and seeing a lot of people around me getting hired for cushy tech jobs with great salaries. Desperation shouldn’t be your only motivation for trying something. I was also unaware of the vast variety of “coding” jobs out there, and they can be quite different; CSS is considered “coding”, but it is vastly different from doing software development in C++, for instance.

I’m all for teaching computer science principles in the grade school level; the basics of control flow are not terribly complicated – it’s just logic, after all. Understanding looping, recursion, iterations, and conditionals does not require a very advanced background in any other subject, and knowing these will take you very far later on in life. I’m a strong believer that everyone should learn to code, given the increasing automation that is threatening all industries today. Those who can code will be the last people to have their jobs automated out of existence, pure and simple.

All this being said, I started my journey down this rabbit hole with Codecademy. I highly recommend this for others who also have no formal background in programming/CS, as it eases you into the relevant concepts of the language of your choice. It’s a great place to learn the higher-level languages (such as JavaScript, Python, and Ruby), but keep in mind that the courses are introductory, and very short (they can be completed in a few hours). They’re designed to give you just enough knowledge so that you can go out and keep learning on your own or from other sources.

After Codecademy, my next stop was FreeCodeCamp. FreeCodeCamp is amazing, and I hope it grows from strength to strength over time. It is the brainchild of Quincy Larson, and it attempts to create a fairly rigorous curriculum in Full-Stack Web Development starting from scratch; no prior knowledge is required, like Codecademy. The first lesson is literally “Hello World!”. It starts off with a comprehensive coverage of the front-end (website building with HTML and CSS), and also covers responsive design using Twitter’s Bootstrap API. It then progresses into JQuery and vanilla JavaScript, and it has you also do some pretty challenging algorithm challenges, which reinforce your understanding of all the methods and properties in JavaScript. The bonus with FreeCodeCamp is that it also has you working on projects, which can be incorporated into a portfolio so that you have something to show to prospective employers.

Web Development has the lowest barrier to entry among all the different types of programming, and that’s why places like FreeCodeCamp thrive. It was after doing it for a while that I realized webdev wasn’t for me, however; I don’t have the patience to mess around with DOM elements and get that alignment juuuuust right; if I really had to choose, I would be more comfortable doing back-end stuff.

I continued working on JavaScript and FreeCodeCamp while applying to programming bootcamps in April-May 2016, and eventually ended up taking a “Data Science” bootcamp by Logit in Hollywood. I wrote about it earlier,  so there’s no need to reiterate what’s already been said. I felt like “Data Science” would be the best fit, given what I had experienced with programming thus far, and also (naively) thought it would give me the best ability to leverage my PhD.

I used the word “naively” in the previous paragraph; here’s what I learned:

  1. Getting a job after a bootcamp is all about how strong your resume is prior to the bootcamp. Now, that may not seem fair, as people want to go to bootcamps to “reset” their careers and get a fresh start, but the reality is that you really can’t learn much in just 12 weeks. And now that bootcamps are getting more popular, employers are looking for other ways to distinguish you from the hundreds or thousands of other people who are also taking bootcamps. Sure, you took a JavaScript bootcamp, but what else stands out? Do you have an advanced degree (MS/PhD) or did you go to a top university (Harvard/Stanford/MIT/Caltech/CMU etc.)? Do you have relevant prior work experience?
  2. In “Data Science”, degrees in CS, math, statistics, computational fields (e.g. computational biology), biostatistics, or physics are extremely sexy. If you have one, flaunt it as much as you can! Any other degree (including my PhD in Organic Chemistry, as I discovered) is worthless in this context. That’s because “Data Science” is a poorly defined field and a lot of employers still don’t know what they want. If you look at job descriptions, most will require knowledge of a scripting language (R or Python), Java, a lower-level language (C or C++), thorough understanding of SQL, and Bash scripting (on Linux). These are not things you can pick up in a few weeks at a bootcamp.
  3. The “Data Science” market is cooling off right now. A few years ago, there was a massive hype surrounding “Data Science”, and there were numerous articles talking about how there was a critical shortage of “Data Scientists” in the country. My experiences have shown the opposite, however – it took one of my friends in my cohort (who has a PhD in physics, one of the “sexy” subjects I mentioned above), about 4 months to land a job after the bootcamp.

So – what useful, actionable advice can I give after all this? What I can say is that if you want to learn “Data Science”, all the material is available online for free. The advantage with a bootcamp is that it gives you a roadmap of what to study, as well as connections – to your classmates, instructors, and other people who the organization is affiliated with. Out of all the courses I’ve seen and taken online regarding “Data Science”, this progression is probably the best, and most logical (feel free to leave comments if you have other suggestions):

  1. Start with Codecademy if you have 0 programming experience. If you want to get into Web Development, complete the JavaScript, HTML, CSS and related tracks, and then dive right into FreeCodeCamp. Otherwise, if you think you may want to do Data Science or want to have a broader understanding of CS fundamentals, stick with Python.
    N. B. Something to keep in mind: if you have no prior experience with programming, don’t worry about R. R is a specialized language for statistics; it is written by statisticians for statisticians, and the syntax is very challenging even for experienced programmers.
  2. Once you’ve completed Codecademy, the next course I would take is MIT’s 6.00.1x Intro CS course on EdX. I have taken this course myself and I have written about it. This course gives you a fantastic intro to the fundamentals of computer science at a fairly rigorous academic level, and it uses Python as well, so that should give you more practice with programming in vanilla Python. The follow-up course 6.00.2x is also good and covers more advanced topics including algorithms, random walks, and other topics, which should put you in a good position to learn more about “Data Science”.
  3. HarvardX’s PH526x course on EdX is a good follow up to this sequence, since it introduces a lot of the popular Python packages for “Data Science” including numpymatplotlib, Pandas, and others. I also just finished the course earlier this week and will put my thoughts on it in a separate post here.
  4. Microsoft DAT210x on EdX is also highly recommended, and I also wrote about it after completing the course. This course gives plenty of practice with machine learning, and will put you in a good position to learn more about any of the algorithms in the course (K-Means, KNN, SVM, Random Forest, and others).

So – after taking all of these courses, THEN you can think about joining a bootcamp to further your knowledge. I wish I had done all the above courses before I did the “Data Science” bootcamp this summer; I would have been in a better position to learn, absorb, and better assimilate the material. But what’s done is done, and I’m continuing to learn Python, Machine Learning, and “Data Science” concepts at my own pace. I’m continuing to practice vanilla Python on Hackerrank, and you can follow my progress on my github – I’m trying to make github commits on a regular basis so that it makes a favorable impression on whoever happens to stumble across it! Interestingly, some of my repositories are getting a fair bit of traffic….so, you never know!

I sincerely hope that this rather “stream-of-consciousness” post helps you, if you do decide to venture down this path!

 

December 9, 2016

More recordings!

Filed under: Carnatic Music — sankirnam @ 8:15 pm

Shameless plug for a thani I played in a concert a few months ago here, on Diwali:

In retrospect, the sound quality is not bad, considering that I was playing without mikes – this audio is directly spliced from the video recording of the concert.

November 23, 2016

Dr. M. Balamuralikrishna

Filed under: Carnatic Music — sankirnam @ 12:54 am

I just heard the news today that the renowned musician Dr. Mangalampalli Balamuralikrishna passed away. I’m not referring to him as a “Carnatic vocalist” or “Carnatic musician” here, because his music transcends such classifications. My Facebook news feed today was full of people writing posts on this theme, and I figured I could write something a little longer here.

Dr. Balamuralikrishna (I’ll refer to him from here on as “BMK”) was probably the first Carnatic musician (!) to achieve celebrity status, and I’ve heard stories about the kinds of crowds he was able to pull not just at concerts, but just by being in a certain area; one of my friends told me about how he once traveled with BMK in a train in India, and at every stop, there would be hordes of people at the station waiting with garlands for an opportunity to see their favorite musician!fphotograph12

BMK with M. Chandrashekaran (violin) and Umayalpuram K. Sivaraman (mrudangam) – one can see that the year is 1959, and the writing looks like Kannada, so this was probably in Bangalore? EDIT: Thanks to KV Ramprasad and others on Facebook, the sign is actually in Telugu, and reads “Sri Tyagaraja Sangeetha Sabha Anantapuram, established 1959”.

There’s not much I can add to all that has been written about this legendary musician – fortunately his legacy will live on in the numerous recordings that exist of his concerts, as well as the countless commercial albums that he has released, and his movies. Like most of the top musicians of his generation, BMK was a child prodigy, and was adept not just in vocal music, but also in viola and mrudangam.

This is a particularly interesting clip of BMK accompanying the doyen Semmangudi Srinivasa Iyer on the viola – not the usual violin. You can tell it is noticeably bigger than a violin would be. In audience shots, you can see several of today’s top musicians in attendance, including Sanjay Subrahmanyam, T. M. Krishna, and R. K. Sriram Kumar, among others.

Dr. BMK was gifted with a golden voice, which is partly what made his music so great. It is not only resonant, but very fluid – he was able to span 3 complete octaves with ease, and the middle to lower octaves have a very bassy quality that nobody else has. Of course, having a great voice is one thing, and being able to harness it’s full potential is quite another; great musicians with both qualities literally only come once or twice a generation. I do consider myself fortunate that I was able to hear him live just once, in a concert in Sydney organized by Pallavi.

This Kalyani from a concert in Bombay in 1963 demonstrates not just the potential of BMK’s voice, but also his creativity – he employs sruthi bedham (modal shift of tonic) several times not just in the raga alapana, but also in the kalpana swaram, which is much more rare (in fact, I have not heard anyone do it since). Of course, Lalgudi Jayaraman is able to follow effortlessly, and his replies also garner applause several times! I mentioned this particular thani by Umayalpuram Sivaraman sir in a previous post, and it is worth rementioning; the UKS stamp is clearly present from the araichapu phrases to the signature mohara and final korvai in tisra nadai.

Dr. Balamurali’s legacy also lives on in the numerous compositions he authored – he has created numerous thillanas and varnams, in addition to composing krithis in all the 72 melakartha ragams. He also created new ragams such as Mahathi, Lavangi, and others, which did land him into some controversy with vidwan Dr. S. Balachander, who disputed whether those scales could be considered complete ragams at all, since they only had 3 or 4 notes.

This is BMK’s pancha gathi bedha thillana (set to 5 nadais) in 5 “-priya” ragams, as announced in the beginning. This rendition is particularly famous among collectors as it is from his Sangita Kalanidhi concert at the Madras Music Academy, December 1978. This concert also deserves further mention, as the main piece in that concert is an RTP in Kalyani set to a new thalam – Panchamukhi Adi thalam. BMK describes it as doing “gathi bedham” (changing the counts per beat) on the “sashabdha kriyas” (the ‘sounded’ beats when putting the thalam). In other words, only modifying the 1st, 5th, and 7th beats in Adi thalam (those beats are ‘sounded’ since they are downward slaps) to have 2.5 aksharams. Panchamukhi Adi thalam therefore has 12.5 beats. The pallavi set to this thalam is really simple and yet charming, and UKS sir plays a brilliant thani to this new thalam, with his usual razor control. I didn’t upload it because my Soundcloud account is getting full, but it is circulating among collectors. On an interesting side note, I also heard that M. G. Ramachandran (the Chief Minister for Tamil Nadu at the time) was in attendance at that concert!

This is the same pallavi from a different concert with B. V. Raghavendra Rao and Bangalore V. Praveen.

BMK has explored this concept, and sung pallavis in the related trimukhi Adi thalam and navamukhi thalam – in fact, he sang an RTP with the latter in Gamanashrama (53rd melakartha) in the Music Academy in 1980. Gamanashrama is an extraordinarily difficult ragam to sing, as it only came about with the invention of the melakartha scheme in the 17th century. The janya ragams associated with it (Hamsanandi and Purvikalyani) predate it by a long time, and so it is difficult to sing the ragam and maintain its identity unique to Purvikalyani.

EDIT: As pointed out to me yesterday, Hamsanandi is probably younger than Gamanashrama, and upon reflection, this makes sense; the trinity (Thyagaraja, Muthuswami Dikshitar, and Shyama Sastri) did not have any krithis in Hamsanandi. Most of the popular krithis we know in that ragam are actually from more recent composers, such as Harikesanallur Muthaiah Bhagavathar, Papanasam Sivan, and others.

I had mentioned earlier that BMK had acted in a few movies; his Wikipedia page has the complete list (and the fact that his wiki page is so long and detailed is a testament to his fanbase). This song, Oru Nal Podhuma (“is one day enough?”) is one of his hit Tamil cine songs from the movie Thiruvilayadal. This recording is from a concert on 15/2/1985, in Bahrain, and the mrudangam is by none other than Thanjavur Upendran sir. BMK and Upendran sir were extremely close friends, and they had performed thousands of concerts together, including a tour to the US in the 80s. Upendran sir was also one of the people who convinced Balamurali early on to settle in Chennai in other to further his career in Carnatic music.

I’ll leave it here for now. I realized that I had not written any posts on the broad topic of Carnatic music (excluding me making shameless plugs of my clips/concerts) in a while, and this sad news prompted me to write something.

November 18, 2016

Realtalk

Filed under: Chemistry Jobs — sankirnam @ 10:43 am

Please see this video if you want a realistic perspective on the field of chemistry today. He touches on very important topics that I have discussed here in the past, such as:

  • The fact that it is hard to get realistic, accurate information on chemistry employment. Chemjobber remains the most accurate, up-to-date source available online, even if people may find it depressing. ACS information or BLS data is either inflated or not representative of the general population (due to selection bias).
  • Money, unfortunately, IS EVERYTHING. The people who say otherwise are those who have plenty of money, a decent income, and are well off. Being poor limits your opportunities, and as pointed out, lands you in a vicious rut which is difficult to break out of.
  • The flooding of graduate programs. As correctly pointed out, chemistry graduates usually end up in graduate degree programs, whether it is pharmacy, medicine, or chemistry graduate school. This is a structural issue that needs to be resolved at a more fundamental level; the chemistry B.S. needs to be reworked and maybe become more rigorous so that it is worth more.

November 17, 2016

Classics in Organic Chemistry, Part VIII

Filed under: Classics in Organic Chemistry — sankirnam @ 3:46 pm

This paper was further down on my list, but I’ve decided to bump it up and cover it today.

Modern practitioners of organic synthesis or medicinal chemistry will no doubt be aware of how hot fluorine chemistry is now; every issue of JACS, JOC, Organic Letters, Angewandte Chemie, or Chemical Science has at least one paper on the development of new fluorination methodologies. But this was not always the case. Fluorine chemistry used to be considered very esoteric, primarily because of the reagents required (F2, HF, SF4, among others), which also necessitated special reaction conditions and apparatus. This limited the accessibility of fluorinated compounds, and research in this area was primarily done by groups in academia (such as Olah, Seppelt, Christe, Bartlett, Rozen, Haszeldine, Barton) or industry (DuPont, 3M) that had the infrastructure in place to carry out this chemistry.

One of the long-standing challenges in organofluorine chemistry was the development of a mild, effective method to introduce the trifluoromethyl (-CF3) group into organic molecules. I had briefly discussed the challenges in isolating the trifluoromethide anion earlier; this is why the development of nucleophilic trifluoromethylation methods only came about recently. It is necessary to use reagents that act as “pseudo-anions”, and can do a transfer of the -CF3 group under certain conditions.

Prakash and Olah were motivated by their desire to study carbocations that had an electron-withdrawing group α to the cation, such as the ones below:coc_8_1

The synthesis of the precursors for these cations is rather interesting – each involves a different type of chemistry. The α-nitro cation above is prepared by ionizing the gem-dinitro compound (which was synthesized from benzophenone oxime and N2O4), while the α-fluoro cation is prepared from gem-difluorodiphenylmethane, which can be prepared from benzophenone and SF4. The α-cyano cation is prepared by ionizing benzophenone cyanohydrin, which can be easily prepared using a procedure developed by Prof. Paul Gassman with TMSCN and ZnI2.

The α-CF3 cation can be prepared from 2,2,2-triphenylacetophenone and phenylmagnesium bromide, but substituted derivatives are more challenging to prepare; you’ll need substituted derivates of 2,2,2,-triphenylacetophenone which are either challenging to synthesize, of limited commercial availability, or expensive. The easier route would be to start from benzophenone and add a -CF3 to the carbonyl. This was elegantly solved by Prakash, Olah, and Krishnamurti in 1989. They demonstrated that the compound TMSCF3 could undergo nucleophilic trifluoromethyl transfer to carbonyls very readily, under fluoride-ion catalysis. TMSCF3 had first been prepared by Prof. Ingo Ruppert (Germany) a few years earlier, but he had not demonstrated any potential reactions with it.

coc_8_2

This is the proposed mechanism; interestingly, fluoride is not necessarily the only catalyst that can initiate this reaction – Dr. Prakash later showed that carbonates and amine-N-oxides can also act as catalysts. I’m not sure if DMF/imidazole can also initiate this reaction (as they do Corey’s TBS protection), but I’m sure that should also work. One big challenge that still has not been solved is to do this transfer asymmetrically; in other words, a facially-selective trifluoromethyl transfer to carbonyls is still lacking.

This has led to a whole slew of developments which are simply too numerous to list here, leading to TMSCF3 being called the “Ruppert-Prakash reagent”, after the chemists who first synthesized it (Ruppert) and demonstrated its synthetic utility (Prakash). The commercial availability of TMSCF3 also opened up trifluoromethylation to all organic chemists (the original synthesis (adapted from Ruppert’s work) uses CF3Br, which is now banned under the Montreal Protocol). Recently, a postdoc in Prakash’s group (who used to work next to me) came up with an improved synthesis of TMSCF3 from CF3H, which is a byproduct of Teflon manufacturing, and therefore much cheaper and more readily available than CF3Br.

Many, many other types of trifluoromethyl transfer reagents have been developed, and almost all of these use TMSCF3 in their synthesis. The electrophilic trifluoromethylating reagent developed by Togni is illustrative of this. Melanie Sanford has also conducted very nice work in organometallic chemistry studying the reductive elimination of -CF3 from Pd(IV); I particularly remember a very interesting set of papers she had published that showed that “F+” reagents were the only compounds capable of oxidizing the Pd(II) to Pd(IV) and selectively inducing the reductive elimination of the -CF3, because the energy of reductive elimination of -F was greater than that of -CF3. It’s not much though; I think it was 5 kcal or less! Of course, all of these trifluoromethylated metal complexes were synthesized with TMSCF3 as the -CF3 source.

Stephen Buchwald (MIT) also published a couple of papers using TMSCF3 and Pd/Cu complexes for doing -CF3 transfer to a variety of systems.

CuCF3 and AgCF3 are also receiving increased interest now; I talked about CuCF3 earlier. Both of these complexes can be generated in situ from TMSCF3 and appropriate metal salts, and can be used for a variety of transformations, including Sandmeyer-type reactions. I remember that I and my labmates had tried to implement this reaction without much success, and when we saw Goossen’s paper, it seems that the copper counterion is very significant; the reaction only works with CuSCN, which we did not have on hand.

As mentioned earlier, the challenge with developing organometallic reagents for nucleophilic -CF3 transfer (such as LiCF3 or CF3MgBr) is that the CF3 anion is kinetically unstable and tends to undergo fast α-defluorination to yield difluorocarbene. This can be a nuisance, but depending on your needs, can also be synthetically useful. Difluorocarbene can also undergo the usual carbene reactions, such as 2+1 additions to olefins to give gem-difluorocyclopropa(e)nes, as well as insertions into weak bonds, such as S-H or Sn-H. Some friends of mine in Prakash’s group were able to use this to develop useful chemistry – one nice example is the insertion of CF2 carbene so generated into the Sn-H bond of Bu3SnH to make Bu3SnCF2H, which proved to be a useful reagent for -CF2H transfer.

coc_8_3

There was a paper published a couple of years ago by a group in Russia describing the synthesis of TMSCF2H from TMSCF3 by a simple reduction using sodium borohydride. This allows improved access to TMSCF2H (which was otherwise difficult to prepare) and related analogues (such as TMSCF2D, TMSCF2Cl, and others). The challenge with TMSCF2H is that it is more difficult to activate compared to TMSCF3 (it is speculated that the reactive species that does the actual -CF3 transfer is a pentavalent siliconate), accounting for the limited substrate scope (with ketones) in this paper by Jinbo Hu.

Anyway, this is a brief overview of trifluoromethylation chemistry, and I hope the huge impact that Dr. Prakash’s initial paper had is evident – TMSCF3 is now the major source of -CF3 in organic chemistry; most research chemists will not think about how it is produced! This is by no means exhaustive, and numerous reviews (such as this one) are being published about this area of chemistry all the time; check those out if you want more details.

October 31, 2016

Review of MITx 6.00.1x

Filed under: Coding, education — sankirnam @ 12:53 pm

just finished the above course – I just completed the last problem on the final exam and completed the exit survey a few minutes ago, so I figured I would write my thoughts on the course while they’re still fresh.

My impressions of the course are unanimously positive. I just finished the current iteration of the course (Aug – Nov 2016), and I found it to be excellent. I just finished writing an email to Prof. Grimson (the professor conducting the course), thanking him for all his efforts in preparing such high-quality materials!

Keep in mind that the title of the course is “Introduction to Computer Science and Programming using Python”, and so it is aimed to be an intro CS course of sorts. Nonetheless, it does serve as a very good introduction to the Python language, and covers fundamental CS concepts while teaching the Python language, including the various data structures (lists, tuples, and dictionaries), functions, and classes. The course isn’t intended to teach Python specifically, and so doesn’t cover a lot of the things unique to Python (such as lambda functions, list comprehensions, and other topics).

In retrospect, I wish I had taken this course before taking the “Data Science” bootcamp this summer – I would have been better prepared and would have had at least a rudimentary understanding of the CS fundamentals. Anyway, what’s done is done, and I’m glad that I was able to take this course.

The problem sets were very well crafted. They were appropriately challenging, and I probably did spend around the recommended 15 hours/week or so on them, and they weren’t too difficult where I would have ended up throwing my computer out the window and quitting in frustration. The bonus is that I ended up also learning how to use my computer better – since this course uses Python 3, I ended up using Anaconda to install that (so that I could manage that alongside my existing Python 2 install). I also ended up using Spyder as my IDE of choice for the course, and I’ve come to like that a lot.

As always, if you want to take a look at the problem sets, exercises, and my solutions, I’m posting everything to my github.

Proof of completion (I blacked out my username and email to dodge spambots):mitx6001x

Anyway, onwards to the sequel course, 6.00.2x! I started this course and it’s proving to be MUCH tougher, since the barrier is no longer the Python language, but abstractly developing algorithms before implementing them in Python.

October 18, 2016

Still on the job search

Filed under: Chemistry Jobs — sankirnam @ 4:09 pm

It has been about 20 months since I got my PhD in chemistry, and I’m still on the search applying for my first job. It’s been a really emotionally draining, tough ride. Before I graduated, I had heard horror stories from others about the chemistry job market and how brutal it is…but there’s nothing like experiencing it firsthand yourself. There are several major hurdles, which I’ll try and document here.

  • Applying online. The major portal for job applications is now online. This is convenient for both job seekers and employers; job seekers can electronically send applications for positions (which normally include a cover letter, resume and/or supplemental information such as a research summary) from the comfort of their home or office. With the internet, employers and recruiters also have a larger talent pool. The process is still time-consuming, however; I would estimate that it takes me on average about 45 minutes to fill out an online application; this includes filling out the information in the online forms (I always end up having to manually do this since the resume parsing never works), making edits to my resume to tailor it for the position, and writing a cover letter. I put in all this work, only to be greeted with:
  • The cone of silence. This is the most frustrating aspect of the job search. You’ll submit your application online, and usually within 1 minute receive an e-mail saying “Thank you for your application, it has been successfully received, and will be reviewed by our team”. This will be followed by….. silence. You won’t hear anything for weeks, or even months on end. I have a list of all the jobs I have applied to, and at least 85% of them have a note saying “Status: No reply”. I would follow up… if I knew who to follow up with! The internet is only so helpful in this regard, and its not always possible to find out who the particular recruiter or hiring manager is for a particular position.
    Case in point: I recently applied to 3 positions in Allergan in August, and still have not heard anything back. The recruiter for the position (as listed on LinkedIn) was unresponsive to my e-mails, and it was only by following up with a friend of a friend in the company that I was informed that yes, they had my application and that it was still under consideration. The funny thing is, these positions are still being listed on job boards and are still accepting applications!
  • The insane saturation of this particular job market. Don’t listen to the politicians – we don’t have a shortage of scientists in this country. We have a massive, massive, glut, and anyone who does any kind of scientific hiring will be able to corroborate this. It’s especially bad at the PhD level – back to my example at Allergan, I was discreetly informed not to get my hopes up since they received 500+ applications for 1 opening in medicinal chemistry. Plus, I did happen to have some nice chats with senior executives at [unnamed pharma companies], and they (somewhat condescendingly) told me to stop wasting my time, because pharma hiring is focused on pedigree; if you don’t have a degree from Harvard/Stanford/MIT/Caltech, etc. your application will be immediately discarded. The irony is that these executives did not have degrees from those schools.

That being said, it seems to me that there’s really only one surefire way to get a job out of school, and that is through campus recruiting. Unfortunately no companies in my area of study (chemistry) came to hire at my university, so that ruled out that approach. The other way is to join a position through a friend’s referral, which works for smaller companies and startups. Applying to big companies is seemingly slower, since the application has to go through several stages – a recruiter (who may or may not know the subject and understand your resume), followed by an interview with the hiring manager (who will be knowledgeable in the domain), and further interviews. I have been told that ‘80% of jobs never get advertised’ and other statistics like that, but those are only relevant for experienced job seekers looking to move laterally; it’s not relevant for fresh graduates looking for their first job. For your first job, you need to play by the company’s rules for applications. Once you get experience and make contacts, then you can get your friends to backdoor you into positions at other companies.

At least, that’s my observation. I don’t know what other avenues there are for gaining employment (I should specify that I mean relevant employment that would utilize my education and background; I could always go and be a cashier at a grocery store, but that would be a massive waste of my education and also the taxpayer money that went into funding that education). If anyone has any ideas, let me know!

The other question that comes up is “so, what about Data Science?”. Yes, that is still on the table; I’m still working with recruiters from Harnham, but nothing has panned out yet. To be honest, I’m not totally thrilled. After doing some soul-searching, I have realized that I don’t necessarily have the mentality to go into “Data Science” or software development. It’s one of those things that I am simultaneously overqualified (I have a PhD, after all) and underqualified (PhD in a irrelevant subject) for. I don’t have years of software development experience or deep knowledge of a lower-level language (e.g. Java, C, C++), or a degree in math, statistics, computer science, or physics (which are considered sexy in this field). I have actually been advised that maybe I should hide my PhD in organic chemistry since it is irrelevant to Data Science. At the same time, I’m glad I took that bootcamp – I can now study the material at my own pace, and the knowledge of programming and computational thinking is becoming increasingly critical today, what with the amount of time we spend interfacing with digital devices in the form of laptops, cellphones, tablets, and other computers.

So….I’m still looking for my first job in chemistry! If anyone has any leads, please do let me know.

I forgot to include this gem as an example to illustrate my point:
I applied to this position at BBraun in Irvine in March – on paper, it is a typical Analytical chemist position, and one that I am reasonably well-suited for. The only weird thing is that they explicitly want “Pharmaceutical industry or a relevant post-doc experience of 3-6 years for PhD”, which doesn’t make much sense (but can be chalked up to “credential inflation” in this over-saturated job market). In any case, I was swiftly rejected by the company, but to my surprise, the position is still up, over 6-7 months later! Stuff like this just really infuriates me. Companies like these waste so much time searching for the perfect “purple unicorn” candidate, and then raise a hue and cry about a “STEM shortage” when they’ve rejected everyone for the most random reasons.jackie-chan-wtf

I know people are curious, so here are the stats:

Jobs applied to: 1465
Interviews: 9

EDIT (10/26/2016): This morning, I was greeted with this e-mail from Merck: “Thank you for your interest in Merck.  We appreciate you taking the time to pursue career opportunities with us.  We have chosen at this time to suspend the search for this position and may reopen the search at a later date”. I applied to this position 2 months ago (August 25, 2016, to be exact), never heard anything back, and then received this notification. Seriously, something is screwy in hiring – has this happened to other people, or is it just me? Also, I honestly think there should be less of a stigma against unemployment – just look at how much time elapses in the job search! The companies are the ones that are slow in getting back to job seekers; in other words, the rate-determining step in the job search is waiting to hear back from companies, which means that individuals should not be held completely responsible for long periods of unemployment if they are applying aggressively.

2ND EDIT (11/16/2016): Yesterday, I got this email from Eli Lilly: “Thank you for your recent inquiry for the Research Scientist-Small Molecule Design and Development-Developability position, requisition #28370BR.

The position in which you originally expressed interest has unfortunately been cancelled and was not filled. Please feel free to review current openings and submit your interest accordingly”. At least this position didn’t leave me hanging for that long – I applied to it on 10/13/2016. I’m just completely nonplussed here…

October 13, 2016

NMR data in papers

Filed under: Chemistry — sankirnam @ 1:42 pm

As someone who has written several papers in organic chemistry, and is currently in the process of writing another one, I just had this thought:

Why can’t journals require authors to include the .fid files of NMR spectra in the supplemental information, as opposed to spectral data lists or printouts of the spectra?

Including printouts is a holdover from a bygone era; thanks to the internet, everything is now digital, and storage space is no longer an issue for most people (or companies). Journals should make authors include the .fid files of any NMR spectra required to accompany a publication! At best, they get up to 50-70 MB (for 2-D NMR spectra), which in this day and age is not that big.

Making authors include .fid files has several benefits:

  1. Writing papers becomes a lot less tedious. Yea, its not fun to sit at your computer and adjust the magnification, aesthetics, and other aspects of a spectrum when all you’re really interested in is the data. Yes, I know you want to make it look like a piece of art, but really, if you have pride in your skills as a scientist, and if you have any ethical integrity at all, you should be willing to stand behind the raw .fid files of any NMR spectra of your compounds.
  2. It’s actually easier for other people. Let’s face it – a lot of the times, the integral values and peak numbers are not very visible on a printout. Also, if you have a very complex spectrum (such as from a natural product), then including multiple zoomed-in regions or going into detail on every single multiplet is a hassle. Also, if someone is trying to reproduce your procedure, doing a .fid-to-.fid comparison is a lot easier than looking at printouts.
  3. It reduces the risk for fraud. The Bengü Sezen case could have been partly avoided if she had been forced to submit .fid files for the NMR data of her products, as opposed to doctored NMR spectra. It’s much, much harder to manipulate a raw .fid file than photoshop an NMR printout.

If only journals accepted .fid files – I could just put them all in a folder, upload it, and be on my way! But unfortunately, most journals do not. JOC (Journal of Organic Chemistry) still requires a list of spectral data for synthesized compounds in the experimental section of the manuscript as well as printouts of the spectra in the Supplemental Information. I guess manually entered spectral data is still required because NMR processing software is still not very good at identifying multiplets and picking peaks (it’s especially bad when they overlap). A trained eye will know what to look for, but a computer will not.

These are some of the challenges that lie in bringing organic chemistry to the 21st century!

October 12, 2016

Classics in Organic Chemistry, Part VII

Filed under: Classics in Organic Chemistry — sankirnam @ 6:04 pm

Ok, let’s keep the train rolling here…

This next topic is related to an ill-defined project I worked on early in my PhD, where I was investigating synthetic reactions related to isocyanide synthesis using TMSCN. One of the first places my advisor told me to look was at an intriguing 1982 JACS communication by Prof. Paul Gassman. To preface, it is well-established that the cyanide ion is ambident and can react from either the or the C position; the conditions employed can influence whether a nitrile or isonitrile will be obtained as the product. Gassman’s paper revisited this topic using epoxides as the electrophile, and he demonstrated that by intelligently choosing the right Lewis Acid (ZnI2 in this case), one can obtain β-isocyano alcohols as the product upon ring-opening with TMSCN (followed by desilylation with KF).

cyanide1

Now that I reflect about the background for this paper, it is actually not as serendipitous as I had used to think as a first/second year grad student. Gassman had previously published a few papers, including an Organic Syntheses procedure, for converting ketones to cyanohydrins; the conditions employed in the above reaction are pretty much identical, save for switching out the ketone for an epoxide.

The utility of this reaction lies in the fact that isocyanides are extremely valuable synthons – there are a family of extremely useful multicomponent reactions based on isocyanides, including the Ugi Reaction and the Passerini Reaction. These reactions succeed because the isocyanide is a rare example of a (1,1)-amphoteric molecule; the same atom (the R-carbon) establishes a connection with both the nucleophile (carboxylic acid) and electrophile (aldehyde or imine). The Ugi reaction was developed by Prof. Ivar Ugi (no surprise), and I discovered a cool fact about him when I happened to check out his book Isonitrile Chemistry from the library, and I saw that it said “Prof. Ivar Ugi, University of Southern California”. Apparently he was a faculty member at USC for a short time (around a year or two) in the early 70’s, before Prof. Olah came to USC.

In any case, the next question is, how does this isocyanation work? In my mind, the mechanism is pretty straightforward; it’s simply a variant of the Ritter reaction with TMSCN, avoiding the use of aqueous acids to prevent hydration of the intermediate nitrilium ion or isocyanide to an amide. This reaction has seen a slow stream of contributions – you can see the references for a list of papers that describe the conversion of various types of compounds to isocyanides or amides. Recently, Ryan Shenvi (Scripps) revisited this chemistry and somehow got a paper in Nature; I don’t understand why this was selected for publication, because as you can see here, there’s nothing truly original about it, and the conditions are not really practical:

A solution of trifluoroacetate 13 (32.0mg, 0.1 mmol) in TMSCN(0.1ml) was cooled to 0 ℃ and treated with a solution of anhydrous Sc(OTf)3 (1.5 mg, 0.003 mmol) in TMSCN (0.1 ml). […]”

The reaction is carried out neatusing TMSCN as the solvent! Not really scalable, and only for the truly desperate.

If you ask me, the cyanation reactions are more intriguing, because the mechanism is more unclear. Prof. Weber (who used to be at USC) demonstrated a complementary reaction to Gassman’s reaction above; when Et2AlCl is used as the Lewis acid instead of ZnI2nitriles are obtained instead. The mechanism invoked by Prof. Weber involves a little more hand-waving, however:

cyanide2

The first step involves the interconversion of TMSCN with its isocyano isomer. It’s not far-fetched on paper, and you can certainly defend this using the Curtin-Hammett principle. However, the literature support for this is rather weak; detailed spectroscopic studies of triorganosilyl cyanides gave no evidence for the presence of the isocyano form. However, another Japanese group studied this set of reactions with more Lewis Acids, and what seems apparent to me is that soft Lewis acids seem to promote formation of the isocyanide, whereas hard Lewis acids promote formation of the cyanide. Thus, two different mechanisms are at play depending on the Lewis acid involved. With reactions involving cyanide, the nitrogen preferentially attacks hard electrophiles (i.e. carbocations, giving the Ritter reactions, as well as other electron-deficient species). My proposal is that the first step would be a nitrilium ion formed from TMSCN attacking the aluminum atom; this species would be the active cyanating agent. If anyone is up for it, it may be possible to characterize this species; Melanie Sanford recently wrote about rapid-injection (RI)-NMR being used to characterize transient Cu(III) intermediates, and the same technique could possibly be used here. In contrast, other Lewis acids (ZnI2, Pd salts, etc.) activate the epoxide for nucleophilic ring-opening by attack of the nitrogen in TMSCN, which is drawn to the nascent carbocation by Coulombic forces.

do have some ideas for new synthetic reactions based on this chemistry, but that will have to be explored once I can get back in a lab.

References:

  1. Gassman, P. G.; Guggenheim, T. L. J. Am. Chem. Soc. 1982104, 5849 
  2. Spessard, G. O.; Ritter, A. R.; Johnson, D. M.; Montgomery, A. M. Tetrahedron Lett. 198324, 655 (This paper was published independently and at the same time as Gassman’s paper above, and describes the same results)
  3. Gassman, P. G.; Talley, J. J. Org. Synth. 198160, 14  (Gassman’s 1981 prep for converting aldehydes/ketones to cyanohydrins with TMSCN)
  4. Okada, I.; Kitano, Y. Synthesis 201124, 3997 (Refs. 3-9 cover converting various functional groups to isocyanides)
  5. Kitano, Y; Chiba, K.; Tada, M. Tetrahedron Lett. 199839, 1911
  6. Kitano, Y.; Chiba, K. Tada, M. Synthesis20013, 437
  7. Kitano, Y.; Chiba, K. Tada, M. Synlett19993, 288
  8. Kitano, Y.; Manoda, T.; Miura, T.; Chiba, K.; Tada, M. Synthesis 20063, 405
  9. Pronin, S. V.; Reiher, C. A.; Shenvi, R. A. Nature 2013501, 195
  10. Mullis, J. C.; Weber, W. P. J. Org. Chem. 1982 47, 2873 (Weber’s conditions for the ring-opening of epoxides and oxetanes with TMSCN + Et2AlCl)
  11. Seckar, J. A.; Thayer, J. S. Inorg. Chem. 1976 15, 501 (Detailed spectroscopic study on the interconversion of the iso- and normal forms of triorganosilyl cyanides)
  12. Hickman, A. J.; Sanford, M. S. Nature2012484, 177 (Review in which various methods for characterizing transient high-valent metal intermediates are discussed, including RI-NMR)

This is by no means an exhaustive list; I have many more papers with me on this topic. If you want them, let me know.

Finally, I have to include this link to Prof. Andrei Yudin’s blog, which got this whole discussion started in my mind.

« Newer PostsOlder Posts »

Blog at WordPress.com.