Molecular Formula from a ‘Spot On’ Ion Peak

With a well-tuned and calibrated, high resolution MS instrument, a molecular formula(e) can be devised from the m/z for an ion peak. In cases where more than one molecular formula fits, knowing the accuracy of the MS instrument can help in narrowing down the choices.

The first step is to identify the molecular ion peak and its ionization, e.g. [M+H]+, [M+Na]+, etc. so as to take into account any additional adduct information in fitting a molecular formula. Secondly, use common elements with likely valences such as C, H, O, N (III, IV, V) and S (II, IV, VI) to try to fit a molecular formula.

An ESI+ mass spectrum for an unknown organic compound is shown below. The cationized peak at m/z 216.1749 corresponds to an [M+H]+ and is accurate up to four significant decimal places. The following table illustrates how a mass tolerance of 0.001 Da can assist in narrowing down the list of molecular formulae.

 

#     MF                 Mass (Da)     Difference

1 C15H21N1         215.1674         0.0003

2 C12H25N1S1      215.1708         0.0037

3 C10H21N3O2     215.1634         -0.0037

Molecular Formula from a ‘Spot On’ Ion Peak

With a well-tuned and calibrated, high resolution MS instrument, a molecular formula(e) can be devised from the m/z for an ion peak. In cases where more than one molecular formula fits, knowing the accuracy of the MS instrument can help in narrowing down the choices.

The first step is to identify the molecular ion peak and its ionization, e.g. [M+H]+, [M+Na]+, etc. so as to take into account any additional adduct information in fitting a molecular formula. Secondly, use common elements with likely valences such as C, H, O, N (III, IV, V) and S (II, IV, VI) to try to fit a molecular formula.

An ESI+ mass spectrum for an unknown organic compound is shown below. The cationized peak at m/z 216.1749 corresponds to an [M+H]+ and is accurate up to four significant decimal places. The following table illustrates how a mass tolerance of 0.001 Da can assist in narrowing down the list of molecular formulae.

 

#     MF                 Mass (Da)     Difference

1 C15H21N1         215.1674         0.0003

2 C12H25N1S1      215.1708         0.0037

3 C10H21N3O2     215.1634         -0.0037

Coincidental 13C peaks on an HMBC Spectrum

When interpreting data from a 1H-13C HMBC without a high-resolution 1D 13C NMR, there is the possibility to miss coincidental overlapping carbons. As such, always consider a missing carbon or two as part of the structure elucidation for an unknown.

The 1H-13C HMBC below—note the lack of a high-resolution 1D 13C NMR spectrum—exhibits a 2-3J correlation between a proton at 8.1 ppm (H1) and a carbon at 128 ppm (C2).

Using the fragment information below, a quick structural assumption is that the unknown contains a 5 membered ring. Another possibility is that 2 coincidental carbon peaks are overlapping at 128 ppm. As such, a 6 membered ring is also possible.

 

Coincidental 13C peaks on an HMBC Spectrum

When interpreting data from a 1H-13C HMBC without a high-resolution 1D 13C NMR, there is the possibility to miss coincidental overlapping carbons. As such, always consider a missing carbon or two as part of the structure elucidation for an unknown.

The 1H-13C HMBC below—note the lack of a high-resolution 1D 13C NMR spectrum—exhibits a 2-3J correlation between a proton at 8.1 ppm (H1) and a carbon at 128 ppm (C2).

Using the fragment information below, a quick structural assumption is that the unknown contains a 5 membered ring. Another possibility is that 2 coincidental carbon peaks are overlapping at 128 ppm. As such, a 6 membered ring is also possible.

 

The Facets of Structure Elucidation

I would like to begin the new year with a weblog that summarizes the components of an elucidation process. Each component, shown as a Venn diagram below, can blend in with the next until a conclusion is reached. The goal for the elucidator is to exhaust all aspects of each possible component thus ensuring that nothing is overlooked.

Collect/Process/Organize Data

Dereplication/Database/Library search

Peak matching

Fragment assembly

Verification

Publish/Report/Present/Store

   

The Facets of Structure Elucidation

I would like to begin the new year with a weblog that summarizes the components of an elucidation process. Each component, shown as a Venn diagram below, can blend in with the next until a conclusion is reached. The goal for the elucidator is to exhaust all aspects of each possible component thus ensuring that nothing is overlooked.

Collect/Process/Organize Data

Dereplication/Database/Library search

Peak matching

Fragment assembly

Verification

Publish/Report/Present/Store

   

Verify Twice, Publish Once

The message behind an old carpenter’s adage ‘measure twice, cut once’ can be applied to the process of structure elucidation as ‘verify twice, publish once’. Committing the time to double check a candidate structure against the experimental data can save a lot of hassles and embarrassment from a mistake being published/presented/stored/reported. Without picking on a specific case, journals are littered with examples of incorrect structures.

As the holidays approach, Philosophy to Chemistry to Elucidation blogging will be taking a short break and will resume in the new year. In the meantime, the following link is an interesting read on the importance of shape within the field of Chemistry: Angew. Chem. Int. Ed. Engl. 30 (1991)1-16.