NMR Spectra Prediction

Tutorial Created with Software Release: 2024-4
Topics: Catalysis & Reactivity, Consumer Packaged Goods, Organic Electronics, Pharmaceutical Formulations
Methodology: Molecular Quantum Mechanics
Products Used: Jaguar, Jaguar Spectroscopy, Jaguar, MS Maestro, Maestro

Tutorial files

51 MB
This tutorial is written for use with a 3-button mouse with a scroll wheel.
Words found in the Glossary of Terms are shown like this: Workspacethe 3D display area in the center of the main window, where molecular structures are displayed

 

Tip: You can hover over a glossary term to display its definition. You can click on an image to expand it in the page.
Abstract:

 

In this tutorial, we will learn how to predict NMR spectra for individual molecules, solid state systems, and molecules within an amorphous system.

 

Tutorial Content

  1. Introduction to NMR Spectra Predictions

  1. Creating Projects and Importing Structures

  1. NMR Spectrum Prediction of Phthalaldehydic Acid using Jaguar

  1. NMR Spectrum Prediction of Crystalline Cysteine using Quantum ESPRESSO

  1. NMR Spectrum Prediction of Dimethylacetamide in Chloroform using the Amorphous Properties Panel

  1. Conclusion and References

  1. Glossary of Terms

1. Introduction to NMR Spectra Predictions

Nuclear Magnetic Resonance (NMR) spectroscopy is an incredibly useful tool in the determination of molecular and crystal structures. The peaks on a spectrum are called chemical shifts and the location of the shifts are specific to atoms and sensitive to their chemical environment, meaning that the spectra can be used to differentiate between similar structures or show that certain functional groups are present in a system. The shifts are at different locations because unique chemical fragments have different electron configurations that surround the nucleus and create their own electromagnetic fields. These fields interact with the applied magnetic field and are said to shield the nucleus and thus change the resulting chemical shiftFrequency of the resonance expressed by an atom with a magnetic nuclei, reference to a standard compound is needed to make the resonance values meaningful, otherwise, only the relative distances between shifts are comparable between spectra.

Figure 1: Overview of the tools covered in this tutorial.

Predicting Molecular NMR Spectra

Molecular NMR spectra can be used to determine the structure of various systems, most notably of organic compounds. The predicted spectra obtained from calculations - like those described in this tutorial - can thus be used to help ensure the synthesis of a new molecule was successful. NMR uses a strong magnetic field to align the nuclear atomic spins. This is why NMR spectrometers are meant to observe atomic isotopes with magnetic nuclei of 1H, 13C, 19F, etc. 

Here, we use Schrödinger’s quantum mechanics engine, Jaguar, to predict molecular NMR by performing a conformational search on a given system, calculating the chemical shifts for each conformer, and then using Boltzmann averaging as the results for the final spectra. The Jaguar Spectroscopy panel can be used to predict 1H, 13C, 15N, 19F, and 31P NMR spectra for a molecule in the gas phase. For more information on this panel please visit the help documentation.

Predicting Solid State NMR Spectra

Solid-state NMR spectroscopy is a powerful technique for crystal structure determination and refinement, especially in conjunction with powder X-ray diffraction (XRD) spectroscopy. Solid-state NMR data can readily provide direct insights on a variety of structural properties that may augment the process of structure determination from powder XRD data, including: (i) assessing the phase purity of a polycrystalline sample, (ii) determining the number of crystallographically independent molecules in the asymmetric unit, (iii) establishing the existence of disorder in the crystal structure (for example, static positional disorder or dynamic disorder), (iv) providing insights on the conformational properties or the tautomeric form of the molecules present in the crystal structure, and (v) revealing the nature of specific intermolecular interactions that exist in the crystal structure, including quantitative determination of specific inter-nuclear distances. See Jonas, E. and Kuhn, S. J. Cheminform. 2019, 11, 50. The anisotropic nature of NMR shifts that is lost in more common solution-state NMR spectra can also be seen in the solid state. However, this information comes at the expense of broader peaks and the lack of a solution peak that can be used to align different spectra.

The Quantum ESPRESSO Calculations panel and the associated NMR Viewer panel can be used to predict solid state NMR spectra for comparison to experimental data.

Predicting the NMR Spectra of Molecules in Amorphous Systems

Using the Amorphous Properties panel allows for the prediction of NMR shifts of a molecule whose immediate environment could have an impact on its surroundings. The nature of the panel also allows for the calculation of separate NMR spectra for different molecular species in the same system. The molecule(s) of interest for the NMR spectra can be selected, and the resulting spectator atoms can be treated at a lower level of theory for a less expensive calculation. The engine that calculates the NMR spectra is Jaguar, the same as for the first panel mentioned.

2. Creating Projects and Importing Structures

At the start of the session, change the file path to your chosen Working Directorythe location where files are saved in MS Maestro to make file navigation easier. Each session in MS Maestro begins with a default Scratch Projecta temporary project in which work is not saved, closing a scratch project removes all current work and begins a new scratch project, which is not saved. A MS Maestro project stores all your data and has a .prj extension. A project may contain numerous entries corresponding to imported structures, as well as the output of modeling-related tasks. Once a project is saved, the project is automatically saved each time a change is made.

Structures can be built in MS Maestro or can be imported using File > Import Structures (or drag-and-dropped), and are added to the Entry Lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion and Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data. The Entry Lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion is located to the left of the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed. The Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data can be accessed by Ctrl+T (Cmd+T) or Window > Project Table if you would like to see an expanded view of your project data.

OR

  1. Double-click the Maestro or Materials Science icon

Figure 2-1. Change Working Directory option.

  1. Go to File > Change Working Directory
  2. Find your directory, and click Choose
  3. Pre-generated files are included for running jobs or examining output. Download the zip file here: https://www.schrodinger.com/sites/default/files/s3/release/current/Tutorials/zip/nmr.zip
  4. After downloading the zip file, unzip the contents in your Working Directorythe location where files are saved for ease of access throughout the tutorial

Figure 2-2. Save Project panel.

  1. Go to File > Save Project As
  2. Change the File name to nmr_tutorial, click Save
    • The project is now named nmr_tutorial.prj

Figure 2-3. Importing the starting molecule structures.

Throughout the rest of the tutorial we will be studying three systems to explore the capabilities of the different NMR spectra prediction tools. These structures have been provided in the tutorial files:

  1. Go to File > Import Structures
  2. Navigate to where you downloaded the tutorial files and select starting_structures.mae and click Open
    • A new entry group containing three molecules is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion

Figure 2-4. The entry list after importing.

Optional: You can prepare the structures yourself:

3. NMR Spectrum Prediction of Phthalaldehydic Acid using Jaguar

In this section, we will use the Jaguar Spectroscopy and Spectrum Plot panels to predict and visualize the NMR spectra of a single molecule, phthalaldehydic acid, also known as 3-hydroxyisobenzofuran-1(3H)-one.

Figure 3-1. Phthalaldehydic acid is selected and included in the workspace.

  1. Make sure the phthalaldehydic acid entry is selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includedthe entry is represented in the Workspace, the circle in the In column is blue.

 

Feel free to use the style toolbox to change the view of the molecule, we have changed it to a ball-and-stick representation here.

Figure 3-2. The Jaguar Spectroscopy panel.

  1. Go to Tasks > Browse All > Jaguar > Spectroscopy Workflows or search for Spectroscopy Workflows in the search bar
    • The Jaguar Spectroscopy panel opens
    • Ensure that the Use structures from: dropdown shows ‘Project Table’ (1 selected entry)

Figure 3-3. Settings for the calculation on phthalaldehydic acid with no solvent.

  1. In the Calculate Spectra: dropdown menu select NMR
  2. Keep the checkbox next to Use conformational search selected
    • This allows the calculation to average the predicted chemical shifts across different conformations of the molecule, weighted by the stability of the conformer, for a more accurate result.
    • Allowing for conformational searches is particularly needed to obtain accurate spectra for molecules with high degrees of conformational freedom
  3. Click on NMR Options and ensure 1H and 13C are selected
  4. Do not change any of the default options in the Conformational Search Options menu or in the Jaguar settings

Figure 3-4. Running the calculation to predict the NMR spectrum of phthalaldehydic acid.

  1. Change the Job name to nmr_phthalaldehydic_acid_none
  2. Adjust the job settings () as needed.
    • With 8 threads the job takes about 20 minutes
  3. If you would like to run the job yourself, click Run. Otherwise, go to File > Import Structures, navigate to where you downloaded the tutorial files, and Open Section_03 > nmr_phthalaldehydic_acid_none > nmr_phthalaldehydic_acid_none > nmr_phthalaldehydic_acid_none_nmr-out.mae 

Figure 3-5. The Entry List after the job finishes.

When the job is incorporated, you should see an entry with the minimum energy conformer and a subdirectory containing the conformers used in the calculation. All three of these structures will have corresponding NMR files.

 

  1. Go to Tasks > Materials > Quantum Mechanics > Molecular Quantum Mechanics > Plot Spectra

Figure 3-6. Spectrum Plot panel.

The plot spectrum panel allows one to visualize the 1H, 13C, or 19F NMR spectra. In this tutorial we will only study the 1H NMR spectra results, but the results from the previous calculations can be used to study the 13C NMR spectra of phalaldehydic acid in a similar manner. An additional example is included at the end of this section that will have a 19F NMR spectra.

  1. Click on the Type dropdown menu and select NMR 1H
  2. Ensure the Plot option shows Spectra for Selected Entries (3)
    • We will load the NMR spectra for all three output structures, the two conformers and the minimum energy conformer
  3. Click Load

Figure 3-7. The Spectrum Plot panel after the results of the phthalaldehydic acid in chloroform calculation have been loaded.

  1. Select the Normalize checkbox
    • The scale of the plot is adjusted so that the maximum absolute value of the displayed intensity of 1, this is suggested when the predicted NMR is being compared to experimental spectra.

 

Take some time to compare the overlaid plots.

Let’s explore some of the features of this panel:

  • The table of calculated shifts:    

This table shows the calculated shifts for the minimum energy conformer and the csv file that it is pulling the values from is shown above the table. The file can be changed by using the Spectrum dropdown at the bottom of the plot:

 

 

The table also shows any other atoms that may be contributing to the spin and spin coupling Boltzmann values. A user can select a row or multiple rows in the table and use the Label Selected Shifts button to label the selected shifts on the plot with the chemical shiftFrequency of the resonance expressed by an atom with a magnetic nuclei, reference to a standard compound is needed to make the resonance values meaningful, otherwise, only the relative distances between shifts are comparable between spectra value.

  • Options for viewing multiple plots:
    • Overlaid:    
    • Stacked:    
    • Hide/show individual plot:     Using the Remove button will unload the plot, but it can be loaded again using the Load button at the top of the panel.The Hide button switches to Show when the file in the Spectrum dropdown is currently hidden from the panel.

Figure 3-8. The Spectrum Plot panel with the spectra of only the minimum energy conformer of phthalaldehydic acid.

  1. Hide or Remove the two spectra for the conformers using the menu at the bottom of the panel
  2. In the Plot option menu select Other Experimental Spectrum and click Browse
    • To show an example of this functionality, let us compare our calculated spectra to an experimental spectrum from Kagan, J. J. Org. Chem. 1967, 32, 12.
    • You can compare to an experimental spectra if you have the data saved in a CSV file. Note that for experimental data files, the first column of the table should be the frequency data in ppm, the second column should be the intensity of each shift.

Figure 3-9. Comparison of predicted phthalaldehydic acid spectrum to an experimental spectrum.

  1. Navigate to where you downloaded the tutorial files and select Section_03 > phthalaldehydic_acid_experimental.csv
    • If an error message appears click OK this will not impact loading the spectrum

 

From this we can tell that the predicted spectrum aligns fairly well with the experimental spectrum.

Additional example: Mitragynine

Try to repeat the steps in this section to predict the 1H and 13C NMR of mitragynine. The starting structure has been included with the tutorial files: Section_03 > mitragynine.mae > nmr_mitragynine.maegz

 

If you would like to see the output files without running the calculation they have been provided with the tutorial files: Section_03 > nmr_mitragynine > nmr_mitragynine > nmr_mitragynine_2_nmr-out.mae
Here is the resulting spectrum:

 

This can also be compared to the experimental spectrum taken from L. Flores-Bocanegra et al. J. Nat. Prod. 2020, 83, 2165−2177 in which the calculated spectrum is in good agreement. Mitragynine_experimental.csv is provided in Section_03 of the tutorial files for comparison using the Spectrum Plot panel.

 

4. NMR Spectrum Prediction of Crystalline Cysteine using Quantum ESPRESSO

Solid State NMR (ss-NMR) spectroscopy is distinct from the molecular NMR. It is usually performed on the crystal powders with the objective to analyze the local crystalline environment and thus to predict or validate the crystal structure.

Quantum Espresso GIPAW is an essential tool for interpreting and understanding experimental solid state NMR of crystalline systems. It is based on the extension to the augmented-wave (PAW) method for pseudopotentials by Blöchl Phys. Rev. B 1994, 50, 17953  with a gauge correction introduced by C. J. Pickard and F. Mauri, Phys. Rev. B 2001, 63, 245101  and references therein)]  Calculations can be performed for the experimental crystal structure, theoretically predicted (or optimized) crystal structure, or at instantaneous “dynamic” geometry.  Also molecular NMR can be calculated for the molecule in the periodic box. In this tutorial we shall learn how to run calculations and visualize the results of atomic chemical shifts and relate them to the crystal structure.     

Figure 4-1. Creating a full unit cell based on the initial cysteine structure.

  1. Select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includethe entry is represented in the Workspace, the circle in the In column is blue cysteine in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed

 

Feel free to style the structure, for this tutorial we have applied the ball and stick representation

  1. Open up the Periodic Structure Tool window by click on the green button at the bottom right-hand corner of the workspacethe 3D display area in the center of the main window, where molecular structures are displayed ()
  2. Hover over Build Cell to bring up the menu
  3. Check the box next to Create new entry
  4. Click Apply

Figure 4-2. Full cysteine unit cell.

A new structure should automatically be selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includedthe entry is represented in the Workspace, the circle in the In column is blue in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed. This structure should have 4 cysteine molecules, as shown in the Figure, and represents a full unit cell for a solid cysteine crystal.

  1. Click on the entry in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion and rename it as cysteine_unit_cell

 

To learn more about the crystal building tools in Maestro and MS Maestro see the Building and Manipulating Crystal Structures tutorial and the documentation page on Workspace Tools for Periodic Structures

  1. Make sure this entry is selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries

Figure 4-3. The Quantum ESPRESSO Calculation panel.

  1. Go to Tasks > Materials > Quantum Mechanics > Quantum ESPRESSO > Quantum ESPRESSO Calculations
  2. Make sure the Use structures from: dropdown shows Project Table (1 selected entry)
    • If the dropdown does not show this, make sure you have selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries the cysteine_unit_cell_entry from the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  3. In the Geometry section choose Optimize atomic positions and cell
    • If you have an already optimized structure, choosing Frozen will result in a faster calculation as no geometry optimization steps will need to be performed
  4. Deselect all options from the Property menu except for NMR
  5. Click on the Pseudopotentials… button

Figure 4-4. Choosing the folder that contains the pseudopotentials needed for this calculation

NMR predictions using Quantum ESPRESSO utilizes the GIPAW pseudopotential method to describe core electrons.  We already have downloaded the pseudopotentials for use in this tutorial, they were included with the files downloaded for the tutorial.

  1. Click Browse next to the Path textbox
  2. Navigate to where you downloaded the tutorial files and select Section_04 > Pseudopotentials

 

Figure 4-5. The Quantum ESPRESSO Calculations - Pseudopotentials panel after the pseudopotential files have been loaded.

We will use the norm-conserving pseudopotentials for the PBE functional with GIPAW reconstruction. Note, GIPAW type pseudopotentials are required for the ss-NMR calculations, and no other pseudopotentials will work. See the Further Reading section at the end of this tutorial for more information on GIPAW pseudopotentials and NMR.

  1. Double check that all of the file endings are .pbe-tm-new-gipaw-dc.UPF
  2. Click OK
    • If a warning about energy cutoffs appears click OK
    • To learn more about energy cutoffs in the context of pseudopotentials see the resources listed in the Further Reading section

Figure 4-6. Changing the job name and submitting the calculation in the Quantum ESPRESSO Calculations panel.

We will not change any of the other settings. If you are curious about the other tabs click on the question mark at the bottom of the Quantum ESPRESSO Calculations panel and/or hover over the question mark to see other tutorials that use this panel.

  1. Change the job name to ssNMR_cysteine
  2. Adjust the job settings () as necessary
  3. Click Run and close the panel
    • With 8 threads and at most 1 simultaneous subjob on a CPU host this calculation takes about 3 hours

Figure 4-7. Workspace after cysteine NMR calculation files have been loaded.

When your calculation finishes or you have imported the provided output files, you should see two new entries in your workspacethe 3D display area in the center of the main window, where molecular structures are displayed:

  • ssNMR_cysteine_cysteine_unit_cell_0_vc-relax_0
  • ssNMR_cysteine_cysteine_unit_cell_0_gipaw_1

 

These files are also available for importing from the provided tutorial files: Section_04 > ssNMR_cysteine > ssNMR_cysteine.maegz

 

The first output is the result of the optimization, the second is the result of predicting the NMR spectra of the optimized system. Note that even if you choose Frozen in step 10 you will still have two outputs after running the calculation.

  1. Includethe entry is represented in the Workspace, the circle in the In column is blue only the second entry, ssNMR_cysteine_cysteine_unit_cell_0_gipaw_1, in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed
  2. Use the WAM button to open up the NMR Viewer
    • Alternatively, go to Tasks > Materials > Quantum Mechanics > Quantum ESPRESSO > NMR Viewer
    • This will open the NMR Viewer panel that will allow us to analyze our results

Figure 4-8. NMR Viewer panel after the solid-state NMR results for our cysteine unit cell have been loaded.

  1. The results will automatically populate the viewer if the panel was opened via the WAM button, if not click Import
    • The text next to the import button should automatically populate with the title of the file it is reading from: ssNMR_cysteine_cysteiene_unit_cell_0_gipaw_1

Let’s take a closer look at some of the features in this panel. You can find out even more by clicking on the blue question mark at the bottom right hand corner of the panel or going to the related documentation page.

 

  • Atom specification language (ASL) dialog box

 

 

You can use the atom specification language to select a subset of shifts to show on the viewer. You can use the green buttons on the left side of the dialog box to save the selection, select all atoms, or use ASL presets, respectively. You will see an example of using this dialog box in the next step of the tutorial

  • Calculated shift table:

 

 

The first column shows the atoms the shifts correspond to. These labels are the same as the atom labels on the structure. The shifts that are highlighted in yellow are those shown in the viewer, if they are white they are hidden from the viewer.

  • Viewing ellipsoids

 

 

ssNMR atomic chemical shifts are anisotropic in nature as they depend on the local atomic environment. Chemical shifts are represented by a tensor, however, the table of calculated shifts displays only the isotropic part of the tensor (i.e. σ_iso=1/3Tr(σ) ). This tool allows one to view the anisotropic nature of the shifts via ellipsoids on the structure in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed. The less spherically symmetric the ellipsoid is, the more anisotropic character it has. Checking the “Show ellipsoids” box draws these ellipsoids on the atoms in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed for the atoms selected in the NMR Viewer panel.

  • Viewing multiple spectra:     Open New Viewer opens a new empty viewer that a spectra can be loaded into. Open Viewers for Selected Entries opens multiple viewers for any entries selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed, provided they have solid-state NMR spectra files.   

Figure 4-9. Atom Selection panel, in this example we are selecting all the carbon atoms in the system.

  1. In the Select atoms: menu, click on the green plus sign () to show the Atom Selection panel
  2. Click on Select at the bottom of the menu that appears
    • This will open the Atom Selection panel
  3. In the left-hand menu select Element
  4. In the middle Element menu select C
  5. Click Add to make the selection
  6. Click OK to pass the selection to the NMR Viewer panel

 

Figure 4-10. Only the carbon peaks from the predicted solid-state NMR spectra of cysteine.

The viewer updates to now only include the carbon shifts for the predicted solid-state NMR of cysteine.

 

You could now compare this structure to an experimental solid state NMR spectrum or to a solvated 13C NMR spectrum, like the one given in Ruks, T., et. al. Langmuir. 2019, 35, 767-778.

 

Note: The viewer visualizes the absolute shifts. For direct comparison with the experimental spectra, the relative shift with respect to a reference compound must be considered.

Note: The ssNMR viewer does not account for peak broadening and line shape factors typically observed in the experiment.

 

5. NMR Spectrum Prediction of Dimethylacetamide in Chloroform using the Amorphous Properties Panel

Generally molecular NMR shifts may be affected by the solvent in two different ways:

  1. Change of molecular conformation
  2. Formation of the specific solvation shell around the molecule

The explicit influence of the solvent can be addressed using the Amorphous Properties Panel utilizing QSite quantum mechanics - molecular mechanics (QMMM) approach. In this section, we will use a system of dimethylacetamide (DMAc) molecules dissolved in chloroform to explore the capabilities of these tools via the use of the Amorphous Properties panel.

Figure 5-1. Accessing the Amorphous Properties panel.

  1. Select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includethe entry is represented in the Workspace, the circle in the In column is blue the dimethylacetamide_in_chloroform system that was imported in Section 2
  2. Go to Tasks > Materials > Quantum Mechanics > Workflows > Amorphous Properties

Figure 5-2. Settings for the NMR prediction of DMAc in chloroform.

  1. Check Limit active molecules to those of type:
  2. In the corresponding dropdown menu select C4H9NO Mols:10
    • This specifies that we are only interested in calculating the NMR of the DMAc molecules
  3. In the Treat spectator atoms as: dropdown select ESP Charges
  4. For Molecule subset: select Random and increase the number of molecules to 2
    • Two of the active molecules are studied here to show that different molecules will give similar, but not identical, NMR spectra
  5. Keep the Property: set to NMR and the Bonds to optimize set to None
  6. Change the job name to amorphous_NMR_DMAc_ESP
  7. Change any job settings () as necessary
    • This job requires a CPU host
    • With 8 CPUs the job can be completed in about 5 minutes
  8. If you would like to run the job yourself, click Run. Otherwise go to File > Import Structures, navigate to where you downloaded the tutorial files and Open Section_05> amorphous_NMR_DMAc_ESP > amorphous_NMR_DMac_ESP-out.mae
  9. Once the job has been submitted, Close the Amorphous Properties panel.

While the calculation is running let’s explore the features of the panel that are relevant for NMR spectra predictions. More information about the panel can be found in the associated documentation page.

  • Specifying which molecules in the system to study:  

 

In this example we are studying a system of DMAc dissolved in chloroform so we can use this setting to specify that we want to only study the DMAc molecules at a high level of theory.

  • Treatment of spectator atoms:  

 

This specifies how the non-active molecules are to be treated in the calculation. For more information about the options in the dropdown menu see the documentation. The basis set specification allows the user to specify how accurately to represent the spectator atoms. While all basis set options available in Maestro can be chosen, a smaller basis set choice is typical to result in a faster calculation.

  • Further specifying which molecules to study:  

 

While there is already an option to limit what is considered an ‘active’ molecule, however this menu allows the user to further specify if they want NMR spectra for all molecules of a specific type, a random subset of those molecules, or specific molecules given by their molecule number. If one opts not to limit the active molecule type, this menu can still be used. Now the subsets can include molecules of several different types. Note: This only changes which molecules the selected property will be calculated for, it does not change what level of theory other molecules are treated at.

  • Optimization options:  

 

We did not run an optimization as part of the NMR predictions from this tutorial because the starting structure was taken from an optimized system. If the system was not already optimized or if the user wants to optimize all the bonds or just the hydrogen bonds to account for the different levels of theory that might be used in the NMR prediction this menu should be used.

Figure 5-3. Output of the NMR property prediction.

The output includes the full system of DMAc molecules dissolved in chloroform. If we had chosen to optimize the system as part of the calculation this would be the optimized structure. The other outputs are the specific molecules that NMR spectra were predicted for.

There is no viewer panel for the outputs of this NMR predictor, but the calculated shifts are in the output files for each ‘cluster.’

Figure 5-4. Example of the chemical shift information given by the Amorphous Property NMR prediction. This data is taken from Cluster_503.out

To view the chemical shifts:

  1. Navigate to the folder amorphous_NMR_DMAc_ESP
  2. Open one of the files that begins Cluster and ends with .out
    • If you are using the provided tutorial files this would be Cluster_503.out or Cluster_504.out
    • These files can be viewed with any text editor
  3. Scroll down to see the chemical shiftFrequency of the resonance expressed by an atom with a magnetic nuclei, reference to a standard compound is needed to make the resonance values meaningful, otherwise, only the relative distances between shifts are comparable between spectra information for each atom, an example of this information is shown in the Figure
  4. Do the same for the other cluster and compare the calculated shifts
    • You should find that the shifts are similar in value for the different elements but that small structural differences between the molecules have impacted the spacing between them

Figure 5-5. Experimental spectrum of dimethylacetamide.

  1. Compare the predicted hydrogen shifts to the experimental spectrum shown in the figure

 

Note: Similar to the solid-state NMR results, the viewer visualizes the absolute shifts. For direct comparison with the  experimental spectra, the relative shift with respect to a reference compound must be considered.

 

6. Conclusion and References

In this tutorial, we learned how to generate predicted NMR spectra using three different tools in the Schrödinger Materials Science Maestro suite.

For further learning:

For introductory content, focused on navigating the Schrödinger Materials Science interface, an Introduction to Materials Science Maestro tutorial is available. Please visit the materials science training website for access to 70+ tutorials. For scientific inquiries or technical troubleshooting, submit a ticket to our Technical Support Scientists at help@schrodinger.com.

For self-paced, asynchronous, online courses in Materials Science modeling, including access to Schrödinger software, please visit the Schrödinger Online Learning portal on our website.

For some related practice, proceed to explore other relevant tutorials:

 

For further reading:

7. Glossary of Terms

Chemical Shift - Frequency of the resonance expressed by an atom with a magnetic nuclei, reference to a standard compound is needed to make the resonance values meaningful, otherwise, only the relative distances between shifts are comparable between spectra

Entry List - a simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion

Included - the entry is represented in the Workspace, the circle in the In column is blue

Nuclear magnetic resonance spectroscopy - often abbreviated as NMR spectroscopy, an analytical chemistry technique that uses the interactions between strong magnetic fields and magnetic nuclei (1H, 13C, 19F, etc.) to help elucidate the structure of chemical systems

Project Table - displays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data

Pseudospectral approximation - simplifies the description of the motion of electrons in the core of an atom to reduce the computational cost of chemical calculations

Recent actions - This is a list of your recent actions, which you can use to reopen a panel, displayed below the Browse row. (Right-click to delete.)

Scratch Project - a temporary project in which work is not saved, closing a scratch project removes all current work and begins a new scratch project

Selected - (1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries

Shielding - The magnetic field used in NMR spectrometers induces opposing magnetic fields for the magnetic nuclei in the system, different nuclei in different environments will oppose the magnetic field in different strengths leading to different chemical shift values

Working Directory - the location where files are saved

Workspace - the 3D display area in the center of the main window, where molecular structures are displayed