Compound Fragmentation Tool

[bbkf]

I am relatively new to LC-MS. I am developing a method that I got from the literature with some additional compounds added to it.

Does anyone know of a program or tool that can predict fragmentation patterns of compounds? Or do i just need to buff up on my organic chemistry? I'd prefer the first suggestion

Or can anyone direct me to a book where I can learn how compounds are fragmented in an MS/MS system.



ps - I'm new so be gentle

[lmh]

There are tools out there, such as Mass Frontier. I heard a rumour that the developers of Chemdraw were thinking about adding such a feature, but it was only a rumour.

Frankly, from an LC-MS perspective, I am unimpressed by tools so far, and also by what little I've seen of textbooks. For GC-MS, the textbooks are better.

There are instrument-related reasons why LC-MS fragmentation differs between instruments, which doesn't help, but the main difficulty is chemistry. GC-MS fragmentation, by EI, is highish-energy. Generally the mechanism is that a load of energy is put into a molecule, and shuffles itself about amongst the available bonds. If one happens to get more energy than its bond energy, it breaks. This is called Quasi Equilibrium Theory (QET). The transition states are simple, and there are many of them, so once there is enough energy to make it possible, it happens rapidly. But it doesn't happen at low energy.

CID in LC-MS systems is low-energy. Here, only reaction mechanisms with low-energy transition states can apply. These are usually intra-molecular reactions where parts of the molecule have to interact, so the molecule needs to be in a particular conformation. This is statistically unlikely, so it's slow, and dominates only at low energy.

But the important bit is that these low-energy intramolecular reaction fragmentations are very dependent on the exact geometry of the molecule, and which groups can interact with which others. They are therefore much harder to predict than EI fragmentations.

(footnote: there are, of course, some EI mechanisms that depend on specific conformations, e.g. the famous McLafferty rearrangement, but they seem few enough to be documented! Correct me if wrong...)

[orcicdejan]

While there are a few books dealing with LC-MS, I would suggest you to try finding research papers about your compounds (or something similar enough) giving typical fragmentation patterns. If you specify what do you want to analyze, maybe I could recommend some papers. And, yes, some organic chemistry knowledge definitely comes handy (though a lot of reactions during the fragmentation tend to be a bit... unusual).

As for the software, ACDLabs do have an application called ACD/MS Fragmenter, which supports both EI-MS (for GC-MS systems) and APCI, ESI, CI, FAB (for LC-MS). However, I cannot say I was overly impressed (at least for my ESI spectra). I've tested it for several compounds, and it generated a lot of fragments that were absent in my spectrum, while some of the major peaks were absent in it's list.

[lmh]

just a small addendum: one reason why fragmentation chemistry looks unusual is that it occurs in a vacuum, so there are no solvent effects. Solvents make a big difference to how a group or molecule behaves.