A Markush structure is a description of compound classes by generic notations. They are often used for patent claims and for combinatorial libraries.
R-groups, atom lists, position variation and repeating units with repetition ranges are commonly used features in the representation of Markush structures.
An R-group can describe a set of derivatives in one single structure (substitution variation).
To add attachment points for the R-definitions, you can use menu Atom > R-group Attachment from the menu (or R-group Attachment from the popup menu), or alternatively, when you draw the R-definitions and the mouse cursor still shows "R1", clicking on an atom of the definition will toggle the attachment point on that atom. (Please note that divalent R-groups must have two attachment points defined.).
To change the order of the attachment point select an the attachment point and set the new number using the R-group Attachment Order option from the contextual menu (or Atom > R-group Attachment Order menu item).
You can define additional conditions, such as occurrence, rest H, and if-then expressions to R-groups in the R-logic dialog window.
To do this, select menu option Structure > R-logic. After setting the conditions in the R-logic dialog window, press the OK button to apply the changes.
R-logic can be visualized by switching on the View > Advanced > R-logic menu option.
R-groups can be formatted as all other atom labels. For more details click here.
Please note that the R-logic is not applicable for R0.
Move the cursor to the atom where you would like to place the R-group. (In this example, we place R-groups in place of the terminal carbon atoms.)
When the atom is highlighted (blue circle around the atom label), type 'R1' (or the other required R-label) on the keyboard.
Alternative solution is selecting the R-label from R-group sub-menu of the popup menu by pressing right mouse button over the atom.
Draw an alternative ligand with an R-group connection:
Move the cursor to an empty place on the canvas (take care that nothing is selected) then type the next R-group label (R2 in this case). The "in hand" object changes to the ID of the R-group (R2). (In this example, we add a ligand to terminal oxygen atom.)
Click the terminal oxygen, then drag the mouse. You will see that the new bond is displayed and its orientation follows the cursor. Release the mouse button when the bond stands in the right direction.
Click with the left mouse button on atoms where you would like to place the attachment points. Repeat this operation on the other two members in the R1-definition. (In this example, at the third molecule, we select the left oxygen atom for attachment.) Alternatively, you can define R-group attachment points via the popup menu by selecting the R-group attachment option on an atom of an R-group definition.
Create the R2-definition by repeating the last two steps on the two remaining fragments.
In case of one attachment point, the connections are not numbered, only marked by a wavy line on the substituent side.
In case of more than one attachment point, the connections are marked by numbers on the root structure (the so called ligand order). Connection points on the substituents are marked with a wavy line, and the order is indicated by numbers (except for the first one).
The ligand order on a bond can be changed using the Bond > Ligand order menu item. Simply select the bond in question and go to this menu option (also available upon mouse-over in the context menu). Selecting another ligand order option in the offered list will transpose the two affected ligand order numbers. The example below demonstrates a case where we want to change ligand order on a bond which connects two R-groups.
MarvinSketch allows you to add Atom List and NOT lists query atoms to your molecule.
An Atom List is a user-defined list of elements included in a structure.
A NOT List is a query atom that allows you to define a list of elements that should not be included in the structure.
Atom List and NOT list can be edited using the Atom label editor tool. For more details click here.
You can create a variable point of attachment (postion variation) to represent a variable connection point to a group of atoms.
The representation is similar to the above mentioned multi-center bonds.
The alternative attachment points are displayed with grey shadow. If you move the cursor to the center (the bond ending in the ring) the represented atoms are highlighted (blue circle around the atom labels).
The simplest way is to insert homology groups is creating a pseudo atom with the homology group name using the Atom Label Editor tool.
Alternatively, homology groups can be inserted from the Periodic Table's Advanced tab.
Select the homology group and right-click. Choose Edit Properties... Set the group properties in the dialog box.
Here is an example of the property dialog window for a cycloalkyl group:
By default, the atom and homology group properties are not shown. You can switch it on by checking the View > Advanced > Atom Properties menu.
A sequence of ranges to specify the repetition can also be used in a special group called repeating unit with repetition ranges.
Here the repetition range is "3,5-7". The repetition count for the included structure can be: 3,5,6 or 7.
The repetition ranges consist of ranges and/or numbers separated by commas. E.g 3, 5-7
You can draw link nodes using the contextual popup menu in two ways:
The Link Node submenu can be reach fro the Atom menu as well.
If it is not possible to create a link node for the specified configuration (for example at ring fusions) an error message is thrown.
Outer (non-repeating) bonds will be denoted by brackets crossing them, and the repetition numbers will be put on the atom.
All portion of the molecule connected to the link atom through non-outer bonds are supposed to repeat together with the atom.
See examples below.
|Molecule with link node||Meaning|
To edit a link node repetition number or change outer bonds, repeat the drawing steps above.
To make a link atom ordinary atom again, select Off from the Link node submenu or more simply, it can be overwritten.