Locating Transition States: Part 1

Tutorial Created with Software Release: 2024-4
Topics: Catalysis & Reactivity, Energy Capture & Storage, Organic Electronics, Thin Film Processing
Methodology: Molecular Quantum Mechanics
Products Used: AutoTS, Jaguar, MS Maestro

Tutorial files

1.8 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

 

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Abstract:

 

In this tutorial, we will demonstrate several methodologies for locating transition states with Maestro Materials Science.

 

Tutorial Content

  1. Introduction to Locating Transition States

  1. Creating Projects and Importing Structures

  1. Locating the Transition State via a Manual Guess

  1. Locating the Transition State via AutoTS

  1. Conclusions and References

  1. Glossary of Terms

1. Introduction to Locating Transition States

The transition stateThe structure corresponding to the highest energy on a one-dimensional reaction pathway. In multi-dimensional reaction schema, the structure corresponds to a saddle point, making going through the structure the lowest energy reaction pathway. , or activated complex, corresponds to a first order saddle point on the potential energy surfaceA multi-dimensional surface that describes the energy of a structure as different features, such as bond lengths, change (PES) that describes a reaction with an energetic barrier, as shown in Figure 1. The transition state is both the highest energy point in one direction on the surface and the lowest energy in the perpendicular direction. These directions correspond to possible reaction pathways for the system being studied. Reactants are statistically favored to follow reaction pathways that run through this transition state as they transform into products.

Figure 1: An example of a potential energy surface.

Locating a transition state is essential for computing the activation energy of a reaction, and thereby the rate, i.e. via the Arrhenius equation. As a result, finding transition states is useful in many materials science applications: predicting reactivity, understanding reaction mechanisms, catalyst design and optimization, predicting outcomes of various competing reactions and more. However, as transition states are momentary, even on chemical time scales, they can only be studied computationally. To confirm that the simulated transition state is a good model, one can calculate the vibrational frequencies of the transition state structure and see if the negative frequency vibrational mode matches the motion that is expected to happen in that step of the modeled reaction, as will be shown in this tutorial.

There are several approaches to searching for a transition state with Jaguar:

1) Using the Jaguar - Transition State Search panel, this tool is explored in Section 3

2) Coordinate Scan: scanning along a distance, angle, or dihedral assists in finding an optimal starting guess to be used in combination with other transition state tools, see the Rigid and Relaxed Coordinate Scans and the Dynamic Relaxed Coordinate Scans tutorials for more information

3) AutoTS: an automated workflow in which reactants and products are input and interpolation is used to search for the transition state with minimal user intervention, explored in Section 4

4) Reaction Network Profiler: an automated workflow for analyzing full reaction landscapes with minimal user intervention, see the RxnProfiler for Polyethylene Insertion tutorial for how to use this tool

Searching for a transition state is typically a difficult task in molecular modeling. Unlike an optimization to a minimum (see: Introduction to Geometry Optimizations, Functionals and Basis Sets), the search for a transition state highly depends on the quality of the initial guess. So if an initial attempt at finding the transition state structure does not yield expected results, modify the initial guess geometry before attempting another calculation. Occasionally you will find that a transition state that you have found is actually connected to minimum energy structures that are different from the structures you intended to be reactants and products, which may indicate a multi-step process with another transition state.

To explore the Jaguar - Transition State Search and AutoTS tools, we will model the transition states for the Diels-Alder reaction between ethene and cyclopentadiene. A follow up tutorial, Locating Transition States: Part 2, describes how to use a known reaction transition state to find the transition state for a similar reaction.

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.

  1. Double-click the 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 input and results files are included for running jobs or examining output. Download the zip file here: schrodinger.com/sites/default/files/s3/release/current/Tutorials/zip/qm_transition_states.zip If you are working on Windows OS and are having trouble unzipping the files, please try to unzip the files using 7-zip or another file archiver.
  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 QM_transition_states_tutorial, click Save
    • The project is now named QM_transition_states_tutorial.prj

In order to compute the energy of the transition state structure that we can compare to the energies of the reactant and product molecules, we will need to perform a geometry optimization on the reactants and products at the same level of theory as the transition state. Optimizing the reactant and product geometries also serves the purpose of being helpful (though not required) for locating the transition state. Performing a frequency calculation along with the optimization can help confirm that the structures are minima, as they should have no negative frequencies, unlike a transition state which will have one. Thus, we recommend performing a geometry optimization and frequency calculation on all reactants and products before searching for the transition state if you are interested in a reaction profile. For geometry optimization examples, see the Introduction to Geometry Optimizations, Functionals, and Basis Sets tutorial.

In this case, the structures of the reactants and products have been built in advance, and geometry optimizations and frequency calculations have been performed at the B3LYP-D3/LACVP** level of theory. The subsequent step will guide you to import those outputs. If you are interested in building and optimizing the reactants and products yourself, feel free to do so.

Figure 2-3. Imported reactant and product structures in the entry list.

  1. Go to File > Import Structures
  2. Navigate to where you downloaded the tutorial files (presumably in your working directorythe location where files are saved), and select reactants_products_optimized.maegz. Click Open
    • A new entry group titled optimized_reactants_products (3) appears in the entry list, containing four entries associated with the reactants and products of our reaction of interest

Note: You can confirm that these molecules have been geometry optimized by opening 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. There you can see the level of theory for the optimizations as well as the energies, among other properties

3. Locating the Transition State via a Manual Guess

We will now begin our search for the transition state. The first method that we will demonstrate is finding the transition state using the Jaguar - Transition State Search panel. This method is excellent if you know approximately what structure the transition state will have. If you do not know what structure your transition state is likely to have, see Section 4 for another method for finding transition state structures or the Rigid and Relaxed Coordinate Scans tutorial to see how to find a good transition state geometry guess.

Figure 3-1. Creating a merged entry.

The manual transition state search method requires that we create a starting ‘guess’ of the transition state geometry. To do so, we will merge the reactants into one entry, and align them in a geometry that we suspect is similar to the transition state geometry.

  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 both ethene and cyclopentadiene
  2. With both 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, right-click and select Merge
    • A new entry titled cyclopentadiene ethene is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion

Note: We are arbitrarily merging the reactant structures. In this case, we could just as easily start from the product structures. If you suspect that the transition state resembles the reactants or products more closely, then you should start with those structures.

Figure 3-2. Selecting and including the merged entry.

  1. Click, hold and drag this new entry to the bottom of the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  2. 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 entry in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed
    • A structure appears in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed in which the molecules are overlapping

Figure 3-3. Preparing the transition state guess.

We will try to orient the molecules in a way that we expect them to appear after the Diels-Alder reaction occurs, see the Figure:

  1. Select the ethene molecule and use the 3D Builder panel to move the ethene molecule away from the cyclopentadiene ring, similar to the Figure
    • The distances do not need to be exactly the same, but the molecules should be separated by a little over one C-C bond length (~1.5 Å)

Note: In cases where the transition state structure is more complex or more difficult to optimize, you can also adjust the bond lengths in the molecule to further improve the guess structure of the transition state.

Figure 3-4. Loading the transition state structure guess.

  1. Ensure that the cyclopentadiene ethene 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
  2. Go to Tasks > Materials > Quantum Mechanics > Molecular Quantum Mechanics > More Molecular QM Tasks > Transition State Search
  3. Keep Standard as the Search method
  4. Click Load next to the Use structures from dropdown. This should load our cyclopentadiene ethene structure from the workspacethe 3D display area in the center of the main window, where molecular structures are displayed

Figure 3-5. Loading the transition state structure guess.

We can identify the bonds expected to break or form during the reaction as “active constraints” to help guide the transition state search:

  1. Go to the Optimization tab
  2. Under Add new constraint, change the Type dropdown to Distance and check the box next to Pick, keep the option in the dropdown to atoms
  3. Keeping the panel open, return to the workspacethe 3D display area in the center of the main window, where molecular structures are displayed and select the six atom pairs associated with the relevant forming and breaking bonds, noting that the numbering may be different and that the order does not matter
    • The atom pairs are added to the constraints table in the panel
    • Spring icons appear in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed associated with the selected distances

Figure 3-6. Set constraints as active constraints.

  1. Once the six pairs are in the panel, check Set constraints as active constraints

Figure 3-7. Defining the Basis set.

  1. Return to the Transition State tab
    • Some of the parameters have been automatically updated, in particular the Search along option is now updated to the Active coordinate eigenvector associated with our active constraints
  2. Change the Basis set to LACVP maintaining the ** Polarization
    • This is the same basis set that was used to optimize the reactant and product geometries

Figure 3-8. Adding the frequency calculation and running the job.

  1. Finally, go to the Properties tab
    • For more information about the other property options see the documentation for the Properties Tab
  2. Check Vibrational frequencies
    • This will add a frequency calculation after the optimization step, which is essential for confirming the transition state as well as for allowing us to calculate free energy in the end
  3. Change the Job name to TS
  4. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in about 30 minutes on a 8 CPU host
  5. If you would like to run the job yourself, click Run. Otherwise, import the pregenerated Section_03 > TS > TS.01.mae file
  6. Close the Jaguar - Transition State panel

Here are some additional considerations when working with the Transition State Search panel:

  • There are two other search method options: linear synchronous transit (LST) and quadratic synchronous transit (QST). For more about these methods see the documentation, they are not covered in this tutorial.
  • In the Optimization tab you can also add fixed constraints (as opposed to the active constraints used herein), which can be useful for searching for a transition state while minimizing degrees of freedom. A subsequent calculation should always be performed without constraints.
  • Solvent can be defined via several implicit solvation models on the Solvation tab. Note that this example is a gas-phase search.
  • If constraints are not defined, there are other options in the Search along menu that are dependent on the Search method, see the documentation for more information

Figure 3-9. Output from the transition state job.

When the job is complete (or after importing) a new entry is incorporated titled cyclopentadiene ethene

  1. Change the name of the entry to manual_TS by double-clicking on the entry name
    • Notice that the vibration viewer () appears in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion because we ran a frequency calculation

Figure 3-10. Visualizing the transition state.

We can verify the transition state by analyzing the frequency calculation:

  1. Open the Vibrations directly from the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion by double-clicking on the button ()
    • The table that appears is automatically sorted by ascending frequencies. Notice that there is one negative frequency. A transition state should have exactly one negative frequency, and this vibrational mode should be associated with the bond breaking and/or forming process
    • If you do not see the button next to the generated entry and you ran the previous calculation yourself, make sure you followed step 16.
  2. Visualize this vibration by clicking the play button at the bottom of the menu
    • We can see that the vibration resembles the expected reaction pathway, which is very good evidence that this is the transition state of interest
  3. Close the Vibrations pop up

Figure 3-11. Reaction profile for the Diels-Alder reaction.

You can create a plot of the energy of the system over the course of the reaction via the Reaction Profile Viewer panel. To see the steps for how to create this plot for a similar example, those shown in the Locating Transition States: Part 2 tutorial, see the Calculating Reaction Energetics for Molecular Systems tutorial.

4. Locating the Transition State via AutoTS

We will demonstrate another method for locating the transition state, AutoTS. AutoTS is an automated way of finding transition states for reactions with energetic barriers and works particularly for reactions with a single transition state. Its workflow requires only the structures of the reactants and the products as input, and then automates the rest of the process:

  1. Optimize reactant and product geometries
  2. Determine which bonds are breaking and forming
  3. Establish correspondence between atoms in the reactants and the products
  4. Generate a transition state guess (either from a template or using an interpolated reaction path)
  5. Launch a transition state search with Jaguar
  6. Begin validating the transition state
  7. Run frequency calculations
  8. Connect the transition state with the reactants and the products using an intrinsic reaction coordinate (IRC) algorithm
  9. Create output files and create a transition state structure in the workspace

We will once again use a Diels-Alder reaction to show the functionality of this panel.

Figure 4-1. Sketching reactants and products in the AutoTS panel.

  1. Go to Tasks > Materials > Quantum Mechanics > Molecular Quantum Mechanics > More Molecular QM Tasks > AutoTS
  2. 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 both ethene and cyclopentadiene in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  3. In the panel, click Import > From Project Table in the Reactants section
    • If you are starting with unoptimized structures, you could have also used Sketch to draw the molecules
    • Since we already have the optimized structures, we are going to use them here
  4. 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 DA_product in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  5. Under Products, click Import > From Project Table
    • Your inputs should match the Figure

Figure 4-2. Naming and running the job.

  1. Go to the Advanced Settings tab
  2. Change the basis set to LACVP**
    • This matches the settings in the last section so that we can directly compare the results
  3. Change the Job name to AutoTS
  4. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in about 2 hours on a 12 CPU host
  5. If you would like to run the job yourself, click Run. Otherwise, we can import pre-generated outputs in the analysis stages
  6. Close the AutoTS: Perform Calculations panel

Note: The Preview Reaction Complex tab can be used to generate reactant and product complexes (merged structures) and to see a guess at the reaction path. Adjustments can be made as needed.

While the job is running, we can take a closer look at the settings in the panel:

  • The Preview Reaction Complex tab allows the user to generate a guess at the reaction pathway and reaction complexes and modify them as needed. This tool is particularly useful with complicated reaction pathways. The generated structures will appear in a new group in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion. This group can be renamed by changing the Reaction Name at the top of the panel.
  • In the Reaction Options section:
    • The spin multiplicity of the reacting system needs to be given, it cannot be interpreted from the spin multiplicities of the reactants and products. The default value is 1, which happens to be the value needed in this example.
    • The AutoTS panel uses reaction templates to construct transition state geometries and reaction pathways, if the inputs are similar to one of the saved templates.
    • Computing the energies at infinite separation returns the energies for the molecules as if they were isolated. This is only done for the reactants and products unless the Compute reaction free energies with molecules at infinite separation is also selected.
    • For more about Intrinsic Reaction Coordinates, see the documentation.
    • Additional Jaguar keywords can be used for special Jaguar settings that are not available directly in this panel. See The gen Section of the Jaguar Input File for more information.
    • Special Options allows the user to include keyword settings in the script the panel generates.
  • The Level of Theory section allows one to specify functionals and basis sets, similar to other quantum mechanical calculations.
  • The Path Options section allows the user to have finer control over how the panel generates the reaction pathway.
  • The Molecular Comparison section determines how the panel compares the different structures in the intrinsic reaction coordinate.

Figure 4-3. Importing the results of the AutoTS calculation.

When the job is complete, we can view the results in the AutoTS: View Results panel. The AutoTS calculation assesses various paths without any additional user input

  1. If you did not run the job yourself, go to File > Import Structures
  2. Select the AutoTS > AutoTS_AutoTS >  AutoTS_full_path.mae file and click Open
    • An entry group including the reactant, transition state and product structures is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  3. Use the Workflow Action Menu (WAM) button () to access the Results panel      

Alternatively, go to Tasks > Materials > Quantum Mechanics > Molecular Quantum Mechanics > More Molecular QM Tasks > AutoTS Results and load the AutoTS_full_path.mae file via the Import button

Figure 4-4. AutoTS results.

The AutoTS: View Results panel contains the energy diagram associated with the reaction.

To have the results be comparable to our transition state calculation in Section 3, change the Type of Energy Property to Infinitely Separated.

If you are interested in viewing the vibration associated with the transition state, use the vibration viewer () in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion and animate in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed

Results from the standard transition state search.

Results from the AutoTS calculation.

Above we have included the results from both transition state search methods. The energetics are almost the same between the two, showing that both methods found the same transition state.

5. Conclusions and References

In this tutorial, we learned how to locate a transition state for a Diels-Alder reaction. We confirmed the transition states with frequency calculations. Finally, we learned to use the AutoTS workflow to complete the entire procedure in one automated process.

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.

If you are interested in running Jaguar calculations from the command line, please visit the documentation for example files and guidance.

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

For further reading:

6. Glossary of Terms

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

Potential Energy Surface - A multi-dimensional surface that describes the energy of a structure as different features, such as bond lengths, change

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

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

Transition state - The structure corresponding to the highest energy on a one-dimensional reaction pathway. In multi-dimensional reaction schema, the structure corresponds to a saddle point, making going through the structure the lowest energy reaction pathway.

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