Saturday, December 13, 2014

Dynamic NMR

When a nucleus moves between two (sometimes more) chemical states we have Dynamic NMR.  Common examples are: the equilibrium between conformers; complexes that can have two different structures, etc. "Chemical Exchange" is the expression that encompasses everything. The principle is so general, that the kind of chemical bonds that are created and destroyed is not relevant. What matters is the rate of exchange between the two states. If the exchange is slow, you see nothing in 1-D, but you see a cross-peak in the EXSY spectrum (another name for the more familiar NOESY). If the exchange is a little faster, you see two broad signals in 1-D. Warm the sample and the exchange becomes faster and faster: you see a single signal, but quite a broad one. At higher rates the single signal is so sharp that we don't mention Dynamic NMR anymore.

More exactly, the appearance of the spectrum depends both on the rate of exchange and on the difference (in Hz) between the two peaks. If we increase the magnetic field, the effect is similar to cooling.

To calculate the rate, we perform Lineshape Analysis, that is we compare a simulated spectrum with the experiment. At the fastest and slowest extremes, even a drastic change in the rate has little effect on the spectrum. At coalescence, instead, even a small change in the rate has a dramatic effect. This is when the signal is the broadest and when the rate of exchange can be calculated with the highest accuracy.

A few years ago I wrote a tutorial on a complex between a ligand with two nitrogens and a platinum ion. The ion could move between the two nitrogens. There were also six hydrogens in the molecule: A exchanging with A', B with B' and C with C'. The very nice thing was that the three frequency differences (A-A', B-B', C-C') had different values. We could therefore see three temperatures of coalescence and measuring the exchange rate was easy. The similarity between the simulation (black) and the experiment (red) was really OK: 

In the first days of DNMR, acronym for dynamic NMR, only the singlets were studied. Not only the signals were stronger, but also easy to understand. Simple formulas, valid at coelescence only, were used instead of lineshape analysis. Partly because of this simplicity, results were not consistent. In the late 60s Binsch showed that coupled systems, just because they were very complicated, were also a much more accurate probe than singlets. Binsch also wrote the theory to simulate the coupled systems and the first computer program for the task, called "DNMR".

A great expert, today, is prof. Alex Bain. His suite of programs (open source) is called MEXICO. Another great expert is Hans Reich, who wrote WinDNMR. If you want a cheap alternative, I have written iNMR. You can try the Windows version for free for two months.

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Friday, April 19, 2013

Teaching iNMR

iNMR is available for Windows Vista (ot higher) and for Mac OS 10.6 (or higher). NMR classes in academic institutions can ask a free, full-functional, copy for each participant. With the program you can open files coming from any spectrometer and you can also simulate a spectrum. Sample files are also available.
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Friday, March 22, 2013

10 Good Reasons to Choose iNMR

  1. iNMR is a single application that includes a multitude of specialized modules. When you buy a license you get everything. Most of our competitors, instead, give you the basic functionality only and then ask you more money for the additional modules and the yearly upgrades. With iNMR you just pay once and receive years of upgrades and support.
  2. You are not locked in. iNMR always works with the original spectrometer files. Any additional information that you generate is stored into short and readable XML files that you can open with countless external applications. Your experimental data remain readable by all other NMR software in circulation.
  3. You'll receive email support directly from the author, 360 days per year, from 8 AM to 12 PM (Central European Time, UTC+2 from April to October, UTC+1 otherwise). If necessary you can receive a patched or customized version in a matter of hours. This is what you pay for when you buy a license.
  4. You can further extend the functionality of iNMR with your own scripts, thanks to the embedded Lua interpreter. Lua is a first-class programming language which is the ideal in terms of versatility and speed. Only two NMR programs include a Lua interpreter: CARA and iNMR. If you don't know the language we'll write the scripts for you. Gratis.
  5. iNMR is a native Windows application that directly calls the traditional Windows APIs, something unique in the NMR field. iNMR is written in C/C++ and takes for itself only a minimal amount of disc space and memory. You can't say the same thing about other NMR programs, which are built upon several intermediate layers of software.
  6. Microsoft explicitly recommends to embrace Direct2D as the drawing API for new applications. iNMR is the only NMR program to follow the advice and the results are amazingly clear plots, fast drawing of large matrices and assured support by future versions of Windows.
  7. The graphic interface is the simplest and the tidiest. More screen estate is available for spectroscopic contents, you are not distracted by unnecessary widgets. The optional keyboard shortcuts are easy to memorize and increase your productivity.
  8. The same license is valid for many kinds of computers. iNMR is available for the last 3 major versions of Windows and 6 versions of Mac OS, which means 59% of the active computers. Any PC built in the last 8 years is good.
  9. As a working tool, iNMR has already been successfully tested by thousands of Mac users since 2005 and hundreds of Windows users since 2012.
  10. For industrial customers iNMR represents by far the cheapest offer on the market. Figures speak for themselves.

Saturday, February 04, 2012

Campus License

iNMR is offering annual campus subscriptions at an aggressive price. The program is available for both Windows and Mac. Check it through.

Monday, January 30, 2012

Role Reversal

In the beginning computers were computational tools with no graphic interface. From the user's point of view CW-NMR and FT-NMR were equivalent, because both of them plotted the results on paper and the analysis only began after printing. People ignored that FT spectrometers contained a computer and a program. Things changed with the structural determinations of biopolymers by Wüthrich and others. The 80s were a period of economical growth, protein NMR was a promising new field, Bill Gates was becoming the richest man in the world with his software company, so combining NMR with software was a risky but potentially lucrative investment. There was money and there were people looking for it. Not forgetting that you really needed a good software to process 2-D NMR. The first generation of stand-alone NMR software (separated from a spectrometer) was written with biopolymers in mind: Felix, Triad, etc…
In the 90s personal computers became moderately fast and were finally able to complete a FT operation in a matter of seconds or minutes, instead of hours. A new concept was possible: off-line processing. Basically it means working far from the spectrometer. Gates had already created Windows, and Bruker created a program for it, called Win-NMR. In theory it was a good idea, because Windows offered a graphic interface that was unknown on the spectrometers of the epoch. In practice it didn't work too much, for a number of reasons. Computers weren't so widely available as today, chemists didn't want to come out of the spectrometer room without a plot (and after having it, they didn't ask for more), writing software was not something Bruker was celebrated for, the price was absurdly high.
A few years later the web arrived everywhere and with it free software: RMN, SwaN-MR, Mestre-C, SpinWorks for the small molecules; NMRPipe, PROSA and Gifa for the big molecules; never the twain shall meet. Free software is not forever: the organizations that fund the projects gets soon tired of spending money, in a matter of years. Computers evolve in the meanwhile, old software doesn't run on new machines and it needs to be recompiled. The source code is often non available but, even when it is, a lot of hard work is required. See for example how long it took for the Vespa team to revive PyGAMMA. Eventually people understood that freedom comes from money: you pay for your copy and the programmer keeps working on the product, no dependance from big sponsors. Gifa became NMRNoteBook, Mestre-C became MestreNova, SwaN-MR became iNMR.
While free software was going commercial, commercial software became free. Jeol began giving away Jeol Delta. That was quite natural too. In theory the company makes money with the hardware, so they can afford to renounce to the revenues from software, if this helps to make them more popular and Jeol always needs because they are, historically, the no. 3. For similar reasons I suppose, ACD did not ask money for their drawing program ChemSketch. For every person that knows the name "ChemSketch" there are probably 1000 that know "ChemDraw"… So you may think that Bruker and Agilent should do the same: give the software for free and make money with the hardware, because you can duplicate software at no cost and, in their case, the program was born as a part of the spectrometer, it has already been paid for. I have the impression that the contrary is true. It's like with printers and cartridges, or with razors and blades, or with espresso machines and coffee, etc… Bruker and Agilent compete with each other, they must keep the price of the spectrometers as low as possible and make the revenues with service and accessories, like software.
Things changed again two years ago, when ACD decided to give away the NMR Processor for free (for non commercial use). Apparently, the rationale is: they sell many products. In the field where they have a monopoly, they can keep the price absurdly high. In the field where there is competition, they lower the price to zero, so the competitors will soon starve to death and a new monopoly is created. Another possible rationale is: they have lost their battle against the competition and this is their revenge. Whatever the reason, it unleashed a chain reaction. After another year the Notebook became free too (for non commercial use, etc…). To tell the truth, I remember that, many years ago, searching with Google, I landed on a page where they hosted a beta version of the program, which was freely available. When, after a few months, the expiration date arrived, the "expired" tag appeared, but the program was still full-functional.
The model is common nowadays: the basic subscription is free, the premium subscription is so expensive that compensates. The equivalent of the premium subscription are the additional modules that add functionality to the basic program. Around the same time, last summer I received an invitation from Bruker: "Come visit our booth and we'll install TopSpin for free on your Mac. The program will last for 3 years". After another week, Agilent invited me saying: "We'll give you our program not just for the Mac, but for any OS and it will never expire". This is really a bad thing to see. First they ask you 10 thousands euro. After a few years, when people realize that other programs, which cost 30 times less, are actually better, they lower the price to zero but never admit the defeat nor apologize with the old customers (or give them the 10 thousands euro back…).
There's a difference between free and commercial software. When you need help, in the latter case you know whom to call. In the former case you write into a forum and the chances that you receive the proper answer are rather small. With the multitude of available programs it's rare to find an expert into any of them. NMR is just a technique that is used in conjunction with other ones. Most of the users of NMR software are expert in other fields. The number of people who needs explanations is much higher than the number of people who can provide them. It happens that, when a feature is only available in free software, people desire it to be included into commercial software. Can't you believe it? Here is a case.