Reaction Energetics Enumeration Panel

Calculate reaction barriers, enthalpies, and energies of intermediates for a series of related compounds, based on a prototype reaction, which can include multiple transition states and intermediates. The structures for the reactions are enumerated by addition of functional groups to the structures for the prototype reaction.

To display this panel: click the Tasks button and browse to Materials → Quantum Mechanics → Workflows → Reaction Energetics Enumeration.

The following licenses are required to use this panel: MS Maestro, OPLS (optional), MacroModel (optional), Jaguar, MS Force Field Applications (optional)

  • Using
  • Features
  • Additional Resources

Using the Reaction Energetics Enumeration Panel

When studying the effect of substituents on a reaction barrier or a reaction enthalpy, it is useful to have a semiquantitative guide to the relative effects of the substituents at an approximate level before performing full calculations. The more expensive calculations can then be focused on the substituents that are most likely to produce the desired energetics. The semiquantitative results can also be used to construct a QSAR model for the prediction of the barrier or enthalpy for screening of other compounds. The capability to calculate reaction barriers or reaction enthalpies for a series of related compounds is provided in this panel.

The reaction for each compound must be based on a prototype reaction, in which substitutions are made on the structures in the prototype reaction. The structures for the series of compounds are enumerated by addition of functional groups to the structures for the prototype reaction at designated locations. For useful results, the reaction pathway and products should not depend very much on the substituents: the transition states and the products must have similar geometries to those of the prototype structures for the common atoms.

For a successful evaluation of reaction energetics, the quality and preparation of the input structures is critical. In addition, there are some conditions that the structures must meet.

  • The structures that you use in this panel should be close to the reactant, product, intermediate or transition state structures, especially for the transition states. The reactant and product structures should be the minimized pre-reactive and post-reactive complexes. A molecular mechanics minimization (e.g. with MacroModel) of these complexes might be useful as a starting point (but would not be helpful for the transition states or the intermediates). You can perform the geometry optimizations to the minima and transition states of the prototype reaction using Jaguar directly, then import the structures into the panel for the enumeration and energetics evaluation.

  • The atom numbering in all the prototype reaction structures must be the same. This is necessary because the attachment points for the substituents must be on the corresponding atoms in these structures. One way to do this is to start from the reactant structure and build the transition state, intermediate, or product structures in the Workspace with the build tools, breaking and forming bonds without deleting any atoms. To ensure that no automatic deletion of hydrogens is done, deselect Adjust number of hydrogens following additive build operations under Builder – Behavior in the Preferences panel. Structures with a common numbering scheme are also needed if you plan to optimize transition states using the LST or QST methods in Jaguar, before importing them into this workflow.

When you enumerate structures, it is recommended to select Quick-clean substituents. This option performs a force-field minimization of the substituent groups to relieve strain and clashes before doing the quantum-mechanical optimization.

For a faster evaluation of the energetics when doing an enumeration, you can freeze the core atoms and only optimize the substituents, by choosing Core from the Atoms to freeze during optimization option menu. The energetics will be less accurate, but if the substituents do not affect the location of the core atoms significantly, this may be sufficiently accurate for comparison of different substituents. For higher accuracy, you can do a full optimization of the structures, including transition state searches, by choosing None. You can select the atoms to freeze for a balance between accuracy and speed, by choosing Custom and picking the atoms in the Workspace. Transition state searches are only done if you do not freeze any atoms. If you do freeze atoms, a minimization (optimization to lowest energy) is done for the non-frozen atoms.

The energies produced from this panel obviously depend on which atoms are frozen. When no atoms are frozen, the energies of the reactant and product structures are the energies of the pre-reactive or post-reactive complexes. Any frozen atoms are frozen in all structures at their initial coordinates. So to obtain energies with respect to the isolated reactant or product molecules from this panel, for example, you could place the molecules at large distances in the reactant or product structure by (to simulate infinite distance), and freeze at least one atom in each molecule, to ensure that the optimization did not move the molecules toward each other.

To write out the input file and a script for running the job from the command line, click the arrow next to the Settings button and choose Write. For information on command usage and options, see reaction_energetics_enumeration_driver.py Command Help.

All of the enumerated structures are returned in the output Maestro file, along with properties as described in the table below.

Property Description
On reactant only:
Reaction Barrier n kcal/mol Energy difference between reactant and transition state n.
Reaction Step n kcal/mol Energy difference between reactant and intermediate n.
Reaction Enthalpy 1 kcal/mol Energy difference between reactant and product.
On each structure:
Reaction Energetics Moiety Type of structure: reactant, tstate, intermediate, or product.
Reaction Energetics Moiety Index Index of the transition state or intermediate, which is the value of n in the above energy property names.
Reaction Energetics Energy Property Name of the energy property above that gives the energy difference between the reactant and this structure.
Reaction Energetics Step Index The index of this structure in the reaction order: reactant is 1, next structure is 2, and so on.
Reaction Energetics Child Structure False if this is the reactant, True if this is any other structure. Useful for grouping just the structures with energy data.
On transition states only:
Reaction Energetics TS Type Type of transition state search done: general, bond, non_torsion.

Reaction Energetics Enumeration Panel Features

Create steps from option menu and button

Create the reaction steps from a predefined set of structures. Choose the source of the structures, from Selected entries, Workspace, or File. For the first two, click Create to copy the structures and create the steps; for the latter, click Browse to navigate to and open the file that contains the structures.

The first step created is assigned as the reactant structure by setting the Step menu choice to Reactant. The remaining structures are automatically assigned alternately as Transition state and Intermediate. You can change the assignment of any of the structures after the steps are created, and reorder the steps (using the arrow buttons at the top right of the steps).

Replace existing steps option

Select this option if you want to replace the existing steps when you create steps. Otherwise, the steps created are appended to the existing steps. In this case the first structure does not have to be a reactant, but

Reaction step sections

Each step in the reaction is defined in a section that has common controls. The controls are described below.

Step option menu

Select the type of structure loaded for this step. The options are:

  • Reactant—The reactant structure. This must be the first step in the sequence, and must be present.

  • Transition state—Transition state structure. A transition state optimization is performed. The Type option menu is activated so you can choose the type of transition state search to perform.

  • Intermediate—Intermediate structure between two transition states.

  • Product—The product structure. This must be the last step in the sequence, if it is present.

Type option menu

Specify the type of transition state search to perform when optimizing the transition state itself (not just the enumerated substituents). This optimization is only done if there are no frozen atoms (see Atoms to freeze during optimization), The full optimization is based on analytic calculation of the initial Hessian, with a search that follows an eigenvector of the Hessian as determined by the choice made from this option menu:

  • General—Follow the lowest eigenvector of the Hessian to find the transition state.

    (Keyword itrvec=0 in the gen section of the Jaguar input file.)

  • Non-torsion—Follow the lowest eigenvector of the Hessian that does not represent a torsional motion to find the transition state.

    (Keyword itrvec=−1 in the gen section of the Jaguar input file.)

  • Bond-stretch—Follow the lowest eigenvector of the Hessian that represents a bond-stretching motion to find the transition state.

    (Keyword itrvec=−2 in the gen section of the Jaguar input file.)

Load structure from option menu and Load button

Choose the source of the structure for this step from the option menu and load it.

  • Selected entry—Use the entry that is selected in the Project Table. There must be only one entry selected. Click Load to load the entry.
  • Workspace—Use the entry that is in the Workspace. You should ensure that the Workspace contains only one entry. Click Load to load the entry.
  • File—Load the entry from a file. Click Browse to navigate to and open the file that contains the structure (which is taken to be the first structure in the file if it contains more than one).
step management buttons

These buttons perform display and ordering operations on the step. They allow for easy duplication and rearrangement of steps.

    Show or hide the contents of the step. When hidden, only the step number, label (if any) and these buttons are displayed. This is useful when you have a number of steps and want to compare two separate steps, for example.
    Move the step up or down one place in the list.
Duplicate the step. This is useful for creating similar steps with variations on the settings.
Delete the step.

2D structure display area

A 2D representation of the structure loaded for the step is displayed in this area.

Append Step button

Add a new step section to the end of the list.

Define Enumeration button

Set up the substituents to use in the enumeration of structures at each step. The entire reaction energetics are determined for each substituent (if only one position is substituted) or substituent combination (if substituents are added at more than one position). Opens the Define Enumeration Dialog Box, with the reactant as the molecule on which the substituent positions are defined; the reactant molecule is displayed in the Workspace. As the atom numbering must be identical for all structures used for the reaction, the substituents are simply transferred to each structure at each step. When the substituents are defined, click OK in the Define Enumeration Dialog Box.

The bonds that are enumerated must exist in each structure, and must not be reactive bonds, i.e. bonds that are formed or broken in any part of the reaction sequence.

Note: If you subsequently change the reactant structure, the enumeration is discarded, and you will have to redefine the enumeration for the new reactant structure.

Quick-clean substituents option

Clean up the substituents defined in the Define Enumeration Dialog Box, using the OPLS_2005 force field. This is done for each step of the reaction, and relieves clashes and strain resulting from the substitution.

Frozen atoms section

Choose the atoms to freeze during the geometry optimizations. The same atoms are frozen for each step in the reaction sequence. If you freeze atoms, the energy for the non-frozen atoms is minimized for all structures—no transition state search is performed.

Atoms to freeze during optimization option menu

Select an option for the atoms to freeze, from the following:

  • Core—Freeze the atoms defined as the core in the enumeration. Only the substituents are optimized (minimized).
  • None—Do not freeze any atoms, but perform a full geometry optimization of each structure (to a minimum or a transition state as appropriate).
  • Custom—Define the atoms to freeze by picking them in the Workspace. The Workspace must contain one of the structures that was loaded for the reaction steps.
Pick in Workspace option and text box

If you chose Custom from the Atoms to freeze during optimization option menu, select this option and pick the atoms in the Workspace that you want to freeze. The atoms are listed by atom number in the box to the right of this option.

Calculation quality options

Select an option for the quality of the results. The three options represent different levels of theory and basis set, which are shown in the Keywords text box.

Jaguar Options button

Set Jaguar options for the enumeration. Machine learning force fields can be used in place of the quantum mechanics calculations. Opens the Jaguar Options - Reaction Energetics Enumeration Dialog Box. This dialog box also allows you to specify additional Jaguar keywords. The solvent (if any), level of theory, and basis set are shown to the right of the button.

The default options are determined by the Calculation quality option that you selected.

Job toolbar

Manage job submission and settings. See Job Toolbar for a description of this toolbar.

The Job Settings button opens the Reaction Energetics Enumeration - Job Settings Dialog Box, where you can make settings for running the job.

Status bar

The status bar displays information about the current job settings and status for the panel. The settings includes the job name, task name and task settings (if any), number of subjobs (if any) and the host name and job incorporation setting. The job status can include messages about job start, job completion and incorporation.

Use the Reset button to reset the panel to its default settings and clear any data from the panel. You can also reset the panel from the Job toolbar.

The status bar also contains the Help button , which opens the help topic for the panel in your browser. If the panel is used by one or more tutorials, hovering over the Help button displays a button, which you can click to display a list of tutorials (or you can right-click the Help button instead). Choosing a tutorial opens the tutorial topic.

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