Note: This post has been written by Scott Campbell, Chief Scientist at Sierra Analytics

Many high performance mass spectrometers have sufficient resolving power and mass accuracy to determine the elemental composition of mass peaks in a spectrum. High resolving power may be required to separate two or more components at a similar m/z value, otherwise the unresolved m/z value does not represent a single component. The resolving power required is a function of the exact components present and cannot be predicted in advance, but typically a resolving power of 5,000 to 10,000 might be necessary. High mass accuracy is also needed, on the order of a few parts per million. For masses up to about 500 Da, this level of mass accuracy will often result in very few possible chemical formulas. This capability is provided within MestreNova: Mass Analysis – Elemental Composition.

There are several parameters, also called constraints, involved in elemental composition analysis. The picture below shows the constraints pop-up with the default values.

1. Element ranges – the table shown above is the set of elements to be considered in the analysis. By default, C, H, N, O, and S are enabled as shown in the table. To add additional elements, one clicks on the “+” sign button. To remove an element, one can click on its row and then click the “X” button. Or, the minimum and maximum values can be set to zero.
2. Tolerance – as mentioned above, high mass accuracy, a small ppm or mDa value, is required. In the case that’s shown below, at m/z 353.078, allowing carbon, hydrogen, nitrogen and oxygen with ranges shown in the table above, and from 0 to 2 chlorines and no sulfur, there are 13 possible molecular formulas within 5 ppm. If the higher mass accuracy tolerance of 10 mDa was used, there would be 76 molecular formulas within the tolerance.
3. Adduct – if we choose, we can specify an adduct, in this case protonation, and also display in the results the unadducted molecular formulas.

The correct formula, since it’s known in this case, is the formula for griseofulvin, C17 H17 O6 Cl, which is fourth in the list.  At this point, there are two refinements to the constraints that can be made.  The molecular ion region of the spectrum is shown below.

Since the ionization mode of the spectrum is ESI with protonation, the molecular ion will be an even electron ion.  Thus, we can select “even” for electron mode (as opposed to “odd” or “both”).  The constraints pop-up at this point follows.

Now the results table shows a list of seven results, down from thirteen, since odd electron ions are excluded.

The final consideration is the molecular ion isotope cluster, shown below.  It is quite apparent that the molecular formula contains a single chlorine (or a large number of sulfurs, which is unlikely).  This is reflected in the “cluster match” column above, which is a measure of the similarity of the computed isotope clusters of each formula vs. the acquired spectrum.  Only the third and fourth formulas match to a high degree, 0.999 and 1.000.  The other cluster match values of about 0.85 indicate a significant difference in the computed vs. acquired clusters.

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Assigning spectral peaks to the right atoms in your structure has been a routine practice for NMR spectroscopists since NMR was used in chemistry over half a century ago. For small molecules, depending on the goal of the analysis, people may have a single 1H spectrum with a known structure, or several 1D or 2D spectra (typically, a 1H, HSQC, and HMBC) with a more complex structure that the user is not sure whether it is completely right or not. In the latter case, the assignment is usually a process to verify the validity of the proposed structure, and find hints to the right structure.

It is interesting to see that, while people no longer use a pen and paper when they write a manuscript, many are still using hardcopies of spectral plots, and write their assignments on them. This is weird, but the main reason is that there are were no software tools handy and accessible enough to replace this old way of paper-based peak assignment.

We have a good news: Mnova 7.0 has the right tools for you! Whether you have just a 1D spectrum or any combination of the routinely used 1D and 2D spectra, you can just drag and drop the NMR raw data into Mnova to open them together, open the structure (either by a .mol or .sdf file, or copy and paste the structure from ChemDraw, Isis/Draw or ChemSketch), and you are ready to do that assignment just like (and probably more convenient than) on your spectral plots.

Assignments with just a spectrum

If you just have a 1D 1H spectrum, do a multiplet analysis to group the multiplets if you want, and next click A key to switch to the interactive assignment mode, and click on an atom in the structure, and click on the multiple label to assign it to that atom. The assignment is displayed on the peak and in the multiplet label, and the atom label’s color is changed to green by default:

What if you don’t want to do multiplet analysis at all? That’s OK. After click on the atom to assign, then you can simply click-and-drag to cover the multiplet to assign, or just click on a peak top, and the region or peak location is assigned to the atom.

Let the fun begin: Assignmetns with multiple spectra

If you have multiple spectra, the real fun begins. Any assignments done in a 1D, is automatically carried to the 2D spectra with the same observed nucleus, and vice versa. For example, after you have assigned the multiplet (doublet of doublet) at 8.37 to atom 6, you will see this marked in the HSQC spectrum:

Now you just need to click atom 6, and then click on that HSQC peak, and the C6 is assigned to the chemical shift in F1. Of course, the 13C assignment is carried to C-13 spectrum and HMBC etc.

After assigning some peaks that are easily identified in HSQC, now you can superimpose your HSQC and HMBC spectra, and assign the remaining peaks:

Once you are done with 1H assignments, it is a good time to look at your NOESY spectrum to assign those NOE correlations that may help you determine the stereochemistry of the structure:

All the results are book-kept in the Assignments Table (choose View > Tables > Assignments to display it). The table talks with the structure and the spectrum: you can click a line in the table and the corresponding peak and atom will be highlighted.

Want to report or publish your assignments? Choose Scripts > Export > Assignments to export such results into a report like the following:

What about the price?

Finally, you would imagine that we are selling this assignment package with a fancy new name and a scary price tag – you are wrong! It’s FREE! It is just one of the tons of new features that we have added to Mnova NMR during each new release.

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So finally we have released version 7.0 of Mnova! This is a very exciting release for us, with what I think is a lot of very major functionality additions and improvements. The team in Santiago have been working very hard on this version for the last few months, and they have done a really great job!

The new functionality for peak picking, integration and multiplet analysis, which finally exploits the power of GSD, is a major change with very positive consequences. However, I know Carlos has already bloged about that, so I am going to focus this post on a very major addition to our product line. ..

The Mnova Spectral DB.

This is another area we have been working on for a while now, and finally we are in a position to release the first version of this product. I am very excited about this. With Mnova, our users can now handle their NMR and LC/GC/MS data in one single tool. Now, with the database, they can also store, share and mine that data, and leverage the knowledge that has been built in their company, department, research group, etc. From a Graphical User Interface perspective, we have made a huge effort to make sure that all this functionality is seamlessly integrated in Mnova.

So, imagine that you run some data for a sample. Let’s say it is an unknown and that you run 1H, 13C, HSQC and HMBC, as well as LCMS, including MSMS. When you get your data, the first thing you can do is to search the database to ask: Has anyone in my company/research group ever run anything like this before? You can select peaks, multiplets or isotopic clusters of interest from any of the experiments, and just run a search on the DB, looking for other datasets run in the past which show the same features. Any hits that you get will immediately tell you a lot about the chemistry you are looking at.

Of course, this is just one of many use cases which are possible with this database. You can have impurity databases, parent compound databases, screening compound databases, ligand databases, etc., storing the analytical data corresponding to anything you have ever characterized so that it can be easily found. You can also store and search molecular structures (exact match and substructure search), text fields, tables, etc.

The idea is to move the analytical knowledge base at your company, group or department from the head of the people who worked up each specific dataset to a tool everyone can easily access and use. You can say good bye to that ‘I know someone else here must have worked with something like this before but, who, when, what did it turn out to be?’ feeling.

The presentation you can see in this video will tell you a lot about the things you probably want to know about this databasing tool. And, should you want to give it a try, all you have to do is get in touch with us at support@mestrelab.com to get full instructions on how to set up our trial.

Give it a go!!

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I think the best way of answering this question is by saying that pretty much anything people want to do in batch can be done, given the flexibility and power afforded by our RICA Engine, but most of these applications are not straight out of the box and require a bit (or a lot) of custom work.

So, if you think you have an application for batch quantitation, this is what you should do:

1. Send us to support@mestrelab.com a sample of your data and your data structure (where in your disks are the spectra and molecular structures, in what formats, and how are they organized).
2. A short outline of your current workflow, basically explaining the operations you would like to automate, or the workflow you want to be able to do in batch mode.
3. An example of your desired output, or an explanation of what this should be. What information would you like the automatic quantitation analysis to give you, what it should look like and in which format it should be.

With this information, we can prepare a detailed specification for you and a quote for what it would take to carry out the necessary work, so that you can decide whether this is something you want to do.

We are looking forward to hearing from you!

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Many of our users have been asking us for solutions for quantitation, and in particular for concentration and assay calculation. Whilst this is something that more often than not the NMR spectroscopist will do in an organization, many of them tell us that they would really like to give this to the chemists, so that they can calculate concentrations themselves.

However, a continuous challenge for spectroscopists and analytical facilities managers is to keep the software simple for their users, as most synthetic and medicinal chemists don´t want to spend a lot of time learning analytical softwares or carrying out complicated workflows.

This is where the RICA scripting engine in Mnova comes into its own. This is a very powerful engine which allows our users to automate most routine workflows achieving huge interface simplification and time savings.

We have developed a couple of scripts which will allow any user to calculate concentrations with minimum effort and interaction.

• The first script is qNMR_Basic script, which calculates concentration based on an internal reference after being manually given the integral regions of interest by the user.
• The second does something similar, but allows you to compare alternative integration methods (analog integration and GSD) and to use internal or external references.

Below you can watch a video of how these scripts work, and here you can read more about them, or buy them if they interest you.

Also, if you have a specific need to automate further the calculation of concentrations in your organization, get in touch with us. Our Mestrelab Services and Scripting group can implement custom scripts for you to make your life much easier! Just think what you could do, things like batch calculate concentrations or assay strengths for whole libraries, populate your own databases with the results, etc. Think what your ideal workflow would be and get in touch with us to find out if it can be implemented for you!

We plan to build more application oriented scripts such as these ones in the near future so, if you have any ideas of things you would like us to do, please let me know through the comments in the blog or write to support@mestrelab.com.

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It is really easy to sort traces of your arrayed datasets: click on the ‘Setup Stacked Spectra’ icon to display the applicable dialog box. Then click on the number of the spectrum to change its location and drag it to the desired position.

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• Greatly simplify the workflow of the analytical data users they are supporting in their organization
• Significantly improve efficiency in the handling, processing and analysis of analytical data within their organizations.

The fact is that at these conferences we hear the words: ´Could I…´very often, and the answer now is, most of the times, yes. If you are wondering how these Mnova tools could help make your analytical department a more effective place, you can start by taking a look at this graphic below, which I will discuss in more detail in the next post, but which shows how you can take the majority of your analytical data from acquisition to its final goal (be it registration, publication, or any other) with a very streamlined workflow which imposes minimal time and interaction demands on your users.

This is just an example of what an automated workflow would look like after combining several of the Mnova plugins and a some scripting

And this next graphic shows what this would look like from the point of view of the final user, i.e., the chemist, who is looking for optimum results and maximum information from minimum interaction:

From the final user view point, 4-5 clicks can result on the whole handling of an analytical dataset and its corresponding proposed structure!

And how easy is it to achieve this with the current Mnova? Very! You can even ask us to do the work for you, but more on that on my next post!

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When you buy an annual or perpetual license for any of Mnova’s plugins, you are entitled to one year of minor and major updates as well as free technical support (throughout the one year period from date of purchase).

If you’re not sure when your annual or your perpetual license’s Update&Support package will expire, you can actually find this information within the application: simply run Mnova and go to ‘Help/License Manager’.

Let’s see an example of a perpetual license:

In this particular case, the Update&Support package for the NMR plugin has expired, meaning that I won’t be able to install any updates which have been released by up to 30 days ago (see the column ‘Update Days= -30′ in red). However I will be able to use the last version I updated to because my license is perpetual (never expires).

To find out all of Mnova’s release dates, please take a look at this link at the download page.

Alternatively, you can take a look at our summarized list of releases below (click here to see what features you are missing if you are running an old version of Mnova):

• Mnova 6.1.1 – Apr 13th, 2010
• Mnova 6.1.0 – Mar 22nd, 2010
• Mnova 6.0.4 – Jan 20th, 2010
• Mnova 6.0.3 – November 17th, 2009
• Mnova 6.0.2 – October 9th. 2009
• Mnova 6.0.1 – September 15th, 2009
• Mnova 6.0.0 – September 15th, 2009
• Mnova 5.3.3 – August 31st, 2009
• Mnova 5.3.2 – June 4th, 2009
• Mnova 5.3.1 – April 3rd,  2009
• Mnova 5.3.0 – December 23rd, 2008
• Mnova 5.2.5 – October 7th, 2008
• Mnova 5.2.4 – August 7th, 2008
• Mnova 5.2.3 – June 20th, 2008
• Mnova 5.2.2 – May 15th, 2008
• Mnova 5.2.1 – April 3rd, 2008
• Mnova 5.2.0 – February 29th, 2008
• Mnova 5.1.0 – November 10th, 2007
• Mnova 5.0.3 – July 27th, 2007

After the one year period from the original purchase, Update&Support packages can be purchased at 20% of the current cost of the equivalent licence. These will include all minor and major updates throughout the one year period after purchase and free technical support for one year. Please note that the prices quoted are net of all taxes. All taxes due in the country where the customer is based are the sole responsibility of the customer.

If you are interested in the renewal of your Update&Support package just visit our webstore or email us at sales@mestrelab.com

Of course, normally the Updates&Support package for an annual license will expire on the same day as the license, and the software will stop working unless you buy a new license.

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Update: Mnova MS 25% off price list for existing Mnova customers. Check the promo at our webpage

On a previous post of a few days ago I wrote:

It is clear that the LC/GC/MS market is at a juncture which I think the NMR market has already been at. Too many vendors with too many software data systems for the average user, and a significant interest in a transparent visualization / post processing / analysis tool for LC/GC/MS data. It seems that Analytical Departments are currently split down the middle, with many quite happy to give LCMS or GCMS spectra to their chemists in PDF or even hard copy, and many expecting to give them more, and expecting more from them. For the latter, of course, the Mnova MS plugin could be the ideal tool. Over the next day or two, I will blog more on the arguments for this second approach.

Now is the time to elaborate on this. Imagine a typical customer who has in their lab NMR spectrometers from 2 different manufacturers and LC/MS or GC/MS from 4 major manufacturers.  I am sure you would agree this is fairly typical. This customer has streamlined its operation to gain productivity by operating the lab in open access, allowing all organic/synthetic/medicinal chemists (hereon chemists for convenience, as opposed to analytical chemists, I hope I don’t upset any purists) to submit samples directly for experiments and run a routine set of experiments (just a standard 1H-NMR and an LCMS, for example).

The customer then has 2 options:

1. They can analyze the results, verify the samples match the structures proposed by the chemists, annotate the analytical data and prepare a report in the analytical group. This will result in the time of the analytical group being tied up in a lot of routine work and in the chemists having to wait for longer to get their results and continue with their drug design (or otherwise) work.
2. They can make the data available to the chemist who submitted the sample (by placing it on a repository on a server, by emailing to the chemist, etc.) and let the chemists do the analysis, annotation and report preparation. The chemists can then revert to the analytical department for problems, difficulties, for situations when the expected structure cannot be confirmed, etc. The work of the analytical department will then be more focused around problem solving, elucidation, controlling instruments, implementing new experiments and, potentially, doing research. How liberating. As for the chemists, they will get their results quicker and will be able to get on with their work, for those cases where everything goes well.

Option 2, I think, has a few advantages: It is more productive, it allows the customer to get more high-end value out of the analytical chemists and to have a more satisfied analytical chemistry group, with more interesting jobs and more scientific output.

This seems to have become accepted by most companies and institutions when it comes to NMR. In the great majority of cases, when I speak to or visit potential customers, the chemists are the ones doing the post-processing of data and report preparation. However, in the case of LC/GC/MS, the balance seems to be very different, with most analytical departments doing the verification work and reporting to the chemists either on paper or pdf. Paper, of course, has the limitation of being harder to move around, harder to take with you, etc., so a lot more cumbersome from a logistics point of view, not to mention the fact that it does  not work as part of an electronic environment where Electronic Lab Notebooks or other data management tools are being used. Not to mention, of course, the environmental impact of manufacturing all this paper and printer cartridges, recycling of the cartridges, etc.  (you cannot have a serious blog post these days without at least one mention to the environment). PDF is better from those points of view, but still results in a lot of information loss. The chemist gets a result which does not tell him/her much about their data, other than what they were looking for, and that can result in lost opportunities or, if the result is negative, a lot of coming and froing between chemist and analytical chemist, until more is learnt about the failure. This is an inefficient workflow.

Of course, up until now, giving the chemists the ability to run LC/GC/MS in open access was fraught with difficulty (or, at least, hampered by a significant hurdle) for multivendor labs, in that potentially the chemists would have to learn several software packages to handle their data, all of them with different paradigms, different behaviour and, often, inflexible and expensive licensing.

By combining NMR processing and analysis within Mnova, we have aimed to eliminate these difficulties and to allow our customers to run in the second scenario outlined above, with the productivity and satisfaction advantages already outlined, but keeping a very important concept in mind: simplicity and consistency of use of the software and minimal learning curve. This could work something like:

NMR and MS Workflow. Click to see full-size

So, in this scenario, the chemists are doing their own validation and producing high quality reports, ready for submission to registration and other corporate systems, or to publication, or to be potentially included for thesis write up. This does not require involvement from the analytical group, so this group does not become a bottleneck, overloaded by many routine requests from many chemists. The analytical group then get the tough jobs and can focus on those, remaining an analytical group and not a report preparation group.

But, in order to run in open access, it makes sense to ask chemists to learn one single software package, as learning a series of analytical packages would be too time consuming and detract from their ‘day job’. This is where Mnova comes in, offering a fully integrated environment for the chemist to work in, and with the following, highly summarized, capabilities:

Mnova NMR

• Read and process automatically:
  • Bruker, Varian, JEOL, etc.
  • 1D and2D NMR
• Phase and baseline correction
• Peak Picking, Integration, Multiplet Analysis
• Many advanced tools: Deconvolution, data analysis, array handling, etc.
• Reporting, annotations, easy exporting to MS Office, Open Office, PDF, PNG, JPG, EPS, etc

Mnova MS

• Read and process automatically:
  • Agilent, Bruker, Thermo, Waters,  etc
  • LCMS, GCMS
• TIC peak picking and integration
• MS peak picking
• Structure confirmation – match TIC to proposed structures
• Molecular formula elucidation: present possible formulae for a molecular ion
• Reporting, annotations, easy exporting to MS Office, Open Office, PDF, PNG, JPG, EPS, etc

My question is: Has your company / university tried to run with NMR and MS in open access? If you haven’t  yet, you should consider it. And, to facilitate that process, Mestrelab would be delighted to give you a temporary site or campus license so that you can evaluate the potential of implementing this setup. All you have to do is contact us on support@mestrelab.com, or via our website or this blog.

Below you can see a typical report easily generated with Mnova NMR and MS.

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I start with an apology. I  realize the blog has been quiet for a while. This is due to how crazily busy things are with Mestrelab (this is a good thing, I am not complaining) but it makes it hard to keep up with the mailbox and, of course, with the blogs.

So, a couple of weeks ago we spent a few days in Washington DC showcasing our software and giving demos. I want to take the opportunity to thank all those who visited our booth, more than 70 people all together, to get demonstrations of both the NMR and MS plugin.

MS plugin.

The good news is that the MS plugin appears to be well liked by potential users, particularly by organic and medicinal chemists and those supporting them. This probably responds to the software concept, which is very much targeted at the workflow and interest of this specific user profile. Did I make what I planned to make? If I did not, what did I make? So here is what the MS plugin allows you to do easily, implementing a very significant use of automation, and how we see it being used:

1. Transparently open data coming from Agilent, Bruker, Thermo and Waters equipment as well as data in mzXML and mzData format (this is our way of supporting formats we don’t have converters for yet, as these are good intermediate formats)
2. Read in the TIC on the fly, pick peaks and integrate fully automatically, report this information in tables.
3. Display different MS traces by easy mouse interaction, apply background subtraction fully automatically, display TICs for base peaks or for specific Mass ranges and many other visual manipulation features.
4. Compute potential elemental compositions for  a given molecular ion, based on a set of user defined constraints, and report these findings.
5. Match libraries of compounds to LC/MS or GC/MS data, therefore allowing for fast structure verification

This is a very cursory summary and I will follow on my next post with a Powerpoint presentation outlining further detail.

We have, of course, not forgotten NMR. Not at all. Our users were very excited by the possibilities opened by our new deconvolution algorithm, GSD, and also by the Data Analysis and Curve Fitting modules.

ACS Conference

I also represented Mestrelab in the Young Chemists Conference Fun Run. I know, I know. I am not young and I am not a chemist! On the other hand, let me tell you, it was not fun. Well, it was, really, but only after I finished in a very reputable 6th place, it was certainly not fun whilst doing it! If you feel like a laugh, you can check out a photo in C&E News, luckily it was taken at the beginning and not at the end of the race, when things would have looked even much worse!

I was impressed with Washington DC. Particularly, the free museums (great place to take your kids for a few days, as Chen did) and the amazing parks, which join all the main monuments in one single run. This is particularly impressive at night, specially the Capitol and the Lincoln Memorial. I also swang by the Pentagon, which is impressive in its size, and spent an evening walking around Georgetown, which is a nice, European-like town with plenty of good restaurants.

More on the MS plugin and IMSC over the next few days, I promise.

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