Gearing up the Right Thought Process for Solving Problems

The approach behind solving a structure elucidation problem is very similar to attempting a math problem or working on a jigsaw puzzle. This similar mental framework shares a basis, but not limited to, on understanding the basic rules that define the problem, and in some cases the creativity and flexibility to redefine the problem.

When presented with a set of data, an elucidator can recognize that the data is valid and logical, address any problematic areas and explore a strategy to fix or solve it without making too many assumptions. Although various problem solving techniques exist, ultimately, it is experience that goes a long way.

  

The following reference addresses some of the underlying issues described in this blog: J.E. Davidson and R.J. Sternberg. The Psychology of Problem Solving. Cambridge University Press, 2003.

Gearing up the Right Thought Process for Solving Problems

The approach behind solving a structure elucidation problem is very similar to attempting a math problem or working on a jigsaw puzzle. This similar mental framework shares a basis, but not limited to, on understanding the basic rules that define the problem, and in some cases the creativity and flexibility to redefine the problem.

When presented with a set of data, an elucidator can recognize that the data is valid and logical, address any problematic areas and explore a strategy to fix or solve it without making too many assumptions. Although various problem solving techniques exist, ultimately, it is experience that goes a long way.

  

The following reference addresses some of the underlying issues described in this blog: J.E. Davidson and R.J. Sternberg. The Psychology of Problem Solving. Cambridge University Press, 2003.

Considering a Pyridinone Fragment

Chemical shift information offers a clue into an atom’s hybridization state. For example, carbon atoms with a carbon chemical shift greater than 90 ppm are typically considered as sp2 carbons. If 4 sp2 carbons are present, one can infer 2 alkene pairs. Five sp2 carbons and an available oxygen and nitrogen atom suggest the possibility of a pyridinone fragment.

The example below shows a 5 sp2 carbons and 2 sp3 carbons, coloured pink and blue, respectively. The chemical shift at 167 ppm for the quaternary carbon suggests the presence of an amide group.

Using the information described above, a set of 6 possible candidate structures can be pieced together.

Considering a Pyridinone Fragment

Chemical shift information offers a clue into an atom’s hybridization state. For example, carbon atoms with a carbon chemical shift greater than 90 ppm are typically considered as sp2 carbons. If 4 sp2 carbons are present, one can infer 2 alkene pairs. Five sp2 carbons and an available oxygen and nitrogen atom suggest the possibility of a pyridinone fragment.

The example below shows a 5 sp2 carbons and 2 sp3 carbons, coloured pink and blue, respectively. The chemical shift at 167 ppm for the quaternary carbon suggests the presence of an amide group.

Using the information described above, a set of 6 possible candidate structures can be pieced together.

Hampering Data Interpretation

A common misinterpretation of 2D NMR data can occur when dealing with weak correlations. Weak correlations are commonly introduced in how the sample is prepared or how the data is collected or processed. Examining the spectrum down to level of the density matrix can ensure all correlations are picked up.

The 1H-13C HMQC below shows a protonated carbon at 3.2 and 32 ppm. Since the proton multiplet at 3.6 ppm has no carbon correlation, the proton is most likely from an exchangeable group such as NH or OH group.

When the spectrum threshold is lowered to 1 % relative to the most intense correlation, a weak correlation at 2.6 and 41.9 ppm is seen. Therefore, the proton at 3.6 ppm is actually a CH group and not an exchangeable one.

Hampering Data Interpretation

A common misinterpretation of 2D NMR data can occur when dealing with weak correlations. Weak correlations are commonly introduced in how the sample is prepared or how the data is collected or processed. Examining the spectrum down to level of the density matrix can ensure all correlations are picked up.

The 1H-13C HMQC below shows a protonated carbon at 3.2 and 32 ppm. Since the proton multiplet at 3.6 ppm has no carbon correlation, the proton is most likely from an exchangeable group such as NH or OH group.

When the spectrum threshold is lowered to 1 % relative to the most intense correlation, a weak correlation at 2.6 and 41.9 ppm is seen. Therefore, the proton at 3.6 ppm is actually a CH group and not an exchangeable one.

Identifying the Molecular Ion using Dimer Information

A previous blog described how a sodiated ion peak can be used to locate or calculate the molecular ion for an unknown compound. In a similar fashion, the dimer ion peak can be used to identify the mass of the unknown even if the molecular ion is no visible.

The ESI+ MS data below shows 4 ion peaks at m/z 401.0, 422.9, 801.0 and 823.0. Assuming the ion peak at m/z 801.0 is 2M+H+, the weight of the unknown is (801.0-1.007) / 2 = 400.0 Da. The same holds true if the sodiated dimer ion (2M+Na+) is used: (823.0-22.989) / 2 = 400.0 Da.