Changing Molecular Topology

In general, to change a component of a molecule from one type to another, select the component and then select the appropriate tool for changing it. For example, to change a single bond to a double bond, select the single bond and click the Double Bond tool in the toolbox. To change an oxygen to a nitrogen, select the oxygen and then select N in the Periodic Table. Keyboard shortcuts also are available for selecting elements and bond types.

More information:

To change atoms to other elements or substituents
To change a bond from one type to another
To change the display style of a bond in the 2D workspace
To add atoms and substituents
To add bonds (close rings) in the 2D workspace
To delete components from molecules
To change stereochemistry

To change atoms to other elements or substituents

Select the atom or atoms to be changed in either workspace. (To change a hydrogen to something other than what is currently selected in the Periodic Table, select it with the middle mouse button or region-select it.)
In the Periodic Table, select the element or substituent to which the selected components are to be changed. Hydrogens are added and deleted as necessary.
When you change an element to another element, the selected components change and remain selected, as shown in the illustration below. When you change elements to substituents, the selected element becomes the substituent and the currently selected element in the Periodic Table becomes active again. That is, you can place a substituent such as a ring selected from those under Rings in the Period Table once, and then the currently selected element in the Periodic Table becomes active again.

Keyboard shortcuts

Keyboard shortcuts for element selection

With the cursor in either the 2D or 3D workspace, you can use keystrokes (as an alternative to the cursor) to select or change the most commonly used elements. The keyboard shortcuts for Periodic Table selections are:

Periodic table selection	Equivalent keystroke
carbon	c
nitrogen	n
oxygen	o
fluorine	f
phosphorus	p
sulfur	s
hydrogen	h

Select the atom to be changed, then press a key to change it to a different element. Or, with nothing selected in the workspace, press a key, and the currently selected element in the Periodic Table changes.

Keyboard shortcuts for bond selection

With the cursor in either the 2D or 3D workspace, you can use keystrokes to select or change bond types. The keyboard shortcuts for bond type selection are:

Toolbox selection Equivalent keystroke

single bond - (hyphen)

double bond = (equals sign)

triple bond # (hash sign)

Select the bond to be changed, then press a key to change it to a different type. Or, with nothing selected in the workspace, press a key, and the currently selected bond type in the toolbox changes.

Toolbox selection	Equivalent keystroke
single bond	- (hyphen)
double bond	= (equals sign)
triple bond	# (hash sign)

Keyboard shortcut for Erase tool

If you make a mistake, such as accidentally adding a molecule or substituent or accidentally changing a hydrogen to something else in the 3D workspace, you can correct the mistake by pressing the <Backspace> or <Delete> key or by clicking the Erase tool in the toolbox while the unwanted components are still selected. Catalyst deletes the selected items in the workspace, and if necessary, restores the appropriate hydrogens.

SMILES keyboard shortcuts

You can write SMILES strings for all compounds in the workspace into the Catalyst journal and the History Window by pressing the <F12> key. If any fragments have not been saved, they are designated Unnamed-1, Unnamed-2, etc.

To change a bond from one type to another

Select the bond to be changed.
In the toolbox, select the bond type. The available bond types are single, double, and triple. The selected bond changes, and the number of hydrogens is adjusted as appropriate.

To change the display style of a bond in the 2D workspace

Select the bond for which you want to change the display style.
In the toolbox, select the new bond style. (Available bond display styles are simple, dashed, hashed, hashed wedge, thick line, wedge line, and wiggly line.) Some bond style changes affect stereochemistry: if a stereochemical inversion can be unambiguously determined, a change in style changes the stereochemistry. The display style of the selected bond changes in the 2D workspace. For example:

Changing the alignment of double bonds in the 2D workspace

To select one of the 2D orientations for double bonds (shown in the illustration below), select the double bond in the workspace and then select the Double Bond tool. Click the Double Bond tool to cycle through three different placements of the lines representing the double bond. You also can cycle through the orientations by selecting the double bond and then pressing the equals (=) key several times to display each of the alternatives.

To add atoms and substituents

Assure that nothing is selected in the workspace, then select the element or substituent that you want to add to your molecule. If you select a substituent from one of the Periodic Table's menus, the cursor changes to the red R shown below. You can place the substituent once, and then the currently selected element in the Periodic Table becomes active again.
In the 2D workspace, click the atom to which to bond the new atom or substituent, then click nearby in the workspace to add the new object.
The new component is added to the molecule, and hydrogens are eliminated or added as necessary. In the example below, deselect everything, select O in the Periodic Table, then click in the 2D workspace to add an oxygen atom.

Closing rings

Which hydrogens are eliminated when closing rings?

When you add a bond between two atoms in a molecule to create a ring, Catalyst eliminates the closest extra hydrogens. This means that if you add a bond between atom A and atom B, Catalyst eliminates the hydrogen on atom A that is closest to atom B and vice versa.

When closing rings, if it matters to you which hydrogens are eliminated, you can use the Measure tool to measure the exact distances between atoms, and then dynamically model the molecule in the 3D workspace to get the appropriate hydrogens into position.

To add bonds (close rings) in the 2D workspace

Select an atom to be at one end of the new bond. A rubber band appears.
Click the atom at the other end of the new bond. The bond is drawn, and hydrogens are eliminated as necessary.
Use the Tools/2D Beautify menu item to clean up the appearance of the molecule, if desired.

To add bonds (close rings) in the 3D workspace

Select the atom to be at one end of the new bond.
Extend-select (middle-mouse click) the atom to be at the bond's other end.
In the toolbox, select the type of bond to add between the two selected atoms. The bond appears. Hydrogens are eliminated as necessary.

To delete components from molecules

In either workspace, select the components to delete. (See To make selections in a molecule for information on making selections.)
Select the Erase tool in the toolbox or press the <Backspace> or <Delete> key.

The selected components disappear, and hydrogens are added as necessary. For example:

Stereochemistry tools

To change stereochemistry

The Set Stereochemistry tool lets you change the stereochemistry of a chiral center, specify a cis or trans double bond, specify axial or equatorial atoms in a ring, and specify relative and unknown stereochemistry.

Select the appropriate atom, atoms, or bond in either workspace.
In the toolbox, click the Set Stereochemistry tool.
From the menu that appears, select one of the stereochemistry tools shown below.

See Rules for designating stereochemistry configurations for information on how Catalyst names stereoisomers.

Items in the Set Stereochemistry menu

	Toggle R-S. Switches stereocenters between R and S configurations. Selecting the entire molecule and then selecting this tool produces an enantiomer, since all the chiral centers are inverted. For additional information, see Inverting bridgehead stereochemistry.
	Set R Chirality. Specifies R chirality for the selected stereocenter.
	Set S Chirality. Specifies S chirality for the selected stereocenter.
	Toggle Known-Unknown. Switches the stereochemistry of the selected stereocenter between known and unknown. The label shows the current stereochemistry displayed in 3D, followed by a question mark (?) to indicate that, although displayed as chiral, the stereochemistry is really unknown. See Known/Unknown stereochemistry for more information.
	Set Relative Stereochemistry. Specifies that the relationship between two or more selected stereocenters is relative to one another. (Currently Catalyst supports only one set of relative stereocenters per molecule.) For more details, see Relative stereochemistry.
	Toggle Axial-Equatorial. Switches carbon bonds in a ring between axial and equatorial stereochemistry. For additional information, see Inverting bridgehead stereochemistry.
	Toggle Cis-Trans. Switches exocyclic double bonds between cis and trans configurations.

Known/Unknown stereochemistry

Unknown stereochemistry

The 3D workspace represents the actual structural characteristics of the molecule displayed in it. If you modify the molecule in such a way that a stereocenter becomes distorted, Catalyst sets its stereochemistry to unknown and labels it (R)? or (S)?. The (R) or (S) indicates the displayed stereochemistry, and the ? (question mark) indicates that the actual stereochemistry is unknown.

Situations that can create a stereocenter with unknown stereochemistry include:

Importing molecules with missing stereochemical data from a MOL, TPL, CHM, HIN or SMILES file or pasting such molecules from the clipboard.
Adding hydrogens. Catalyst adds hydrogens as necessary when de-aromatizing a ring, converting a double bond into a single bond, or breaking a ring. Hydrogens cannot always be oriented so that the local geometry is correct, and this causes distorted centers. If adding hydrogens produces chiral compounds, Catalyst sets their stereochemistry to unknown.
Deleting hydrogens when forming rings. When making a ring between two atoms A and B, Catalyst removes the hydrogen on A that is closest to B, and vice versa. The bond is created exactly as it appears in the 3D workspace. This can result in a distorted bond length and also distorted geometries, especially at bridgehead atoms, for example:

To set unknown stereochemistry to known

To restore a distorted stereocenter to known stereochemistry, do one of the following:

Remove any distortion by selecting the Tools/3D Minimize menu item. When Catalyst minimizes a molecule, it finds the local energy minimum closest to the initial structure. Usually molecules with distorted centers are strained, and the closest energy minimum corresponds to an undistorted structure.
or:
Extend-select the stereocenters to select them, and then select the Toggle Known/Unknown tool from the Set Stereochemistry menu to convert the stereochemistry to known.

Conformer generation for molecules with unknown stereocenters

During conformer generation, Catalyst generates specified stereochemical forms of a molecule and conformers in R and S configurations for unknown chiral centers according to the following rules: Catalyst creates up to n/2m conformers for each stereoisomer, where n is the value specified in the Maximum Number of Conformers box, and m is the number of stereocenters in the compound. However, it will create at least one conformer for each stereoisomer. Since there is a total of 2m possible stereoisomers, if you specify an upper limit of n conformers and n is less than 2m, Catalyst cannot explore the entire conformational space. Instead, it returns either 1 or n/2m conformers, whichever is larger, for each stereoisomer, and some stereoisomers are left unexplored. Therefore, for best coverage you should try to limit unknown stereocenters, specifying the chirality of as many as possible.

To make an enantiomer

To make the enantiomer of a molecule, do the following:

Display the molecule in the workspace.
Double-click some part of the molecule to select the entire molecule.
Select the Set Stereochemistry tool in the toolbox.
From the menu that appears, select the Toggle R-S tool.

All R stereocenters change to S, and vice versa, creating the enantiomer of the original molecule.

Relative stereochemistry

If you do not know the absolute configuration of two or more atoms in a molecule, but you know their relative stereochemistry, you can specify that they are members of a relative stereochemical set. (Catalyst supports only one relative set of stereocenters per molecule.)

If you set or change the stereochemistry of an atom that was already included in a relative set, that atom is removed from the relative set. The conformer generation process in Catalyst generates conformers for the molecule as specified. If the molecule has one set of relative stereocenters, the conformer generation process produces conformers that fulfill the requirements for the relative set. For example, if the relative set contains three stereocenters, A, B, and C labeled as A(S)*-B(S)*-C(R)*, the generation process produces conformers with A(S)-B(S)-C(R) and A(R)-B(R)-C(S) configurations if you specify a large enough value in the Maximum Number of Conformers box.

The procedure for declaring relative stereochemistry is:

Assure that the molecule displayed in the 3D workspace represents one of the diastereoisomers.
Select the centers that have relative stereochemistry.
Select the Set Stereochemistry tool in the toolbox, then select the Set Relative Stereochemistry tool.
Catalyst labels a selected stereocenter with an asterisk (*), indicating that it has relative stereochemistry.

Note: You cannot specify relative stereochemistry for a distorted stereocenter.

Inverting bridgehead stereochemistry

You can change the stereochemistry of one or both bridgehead atoms in a single operation. For example, for a bridgehead atom that has R stereochemistry that you want to change to S, select the atom to be changed, then click the appropriate Toggle R-S or Toggle Axial-Equatorial tool from the Set Stereochemistry menu in the toolbox. The stereochemistry at the selected atoms is switched, and the new configuration and designation are displayed.

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