Relative Tetrahedral Stereochemistry
9 Jan 02


Relative Tetrahedral Stereochemistry ("RTS") is a new feature in ChemFinder 7.0.1 which allows more flexibility in storing and searching stereoisomers.  It was developed for, and with the help of, a valued ChemFinder customer.

Previously, given a structure with one or more stereocenters, you could store three different possibilities:

In ChemFinder 7.0.1, with the RTS feature enabled, the following new possibility is available for structures with more than one stereocenter:

This page describes how to use the new feature in ChemOffice 7.0.1.


Specifying Relative Stereocenters in ChemDraw

Relative centers are indicated graphically, using the "thick bond" style available in ChemDraw:   

         

         

Both 6 and 9, which are equivalent, indicate two substituents cis to each other, where 7 and 8 indicate trans.  (If the numbering seems arbitrary, it's because we want the diagrams to match the ID's in the database we use below.)

ChemDraw 7.0.1 supports this representation, but not automatically.  Many ChemDraw users are accustomed to using thick bonds interchangeably with standard hash/wedge bonds, and we want to avoid surprising them with a new interpretation (especially considering that IUPAC specifies that the unwedged hashed bond be used only in the old way).  Thus, in order to activate the RTS feature in ChemDraw, it is necessary to modify a Registry setting as described below.  (Thx to Jonathan for inserting the IUPAC reference).

Once RTS is enabled, what it means is the following.  Normally, when you right-click on a stereocenter and choose Show Stereochemistry from the drop-down menu, the center is assigned a CIP stereo assignment (R or S), as in 2-5

         

         

In ChemDraw 7.0.1, with RTS enabled, when you attempt to Show Stereochemistry on a relative center, you will get no assignment.  Relative centers cannot be assigned an absolute configuration.

To activate the RTS feature in ChemDraw 7.0.1:

Create the following Registry key and DWORD value, and set its value to 1 (on):

HKEY_CURRENT_USER\ Software\ CambridgeSoft\ ChemDraw\ 7.0\ General\ Relative Tet Stereo

When this value is 0 (default), ChemDraw considers thick bonds to be interchangeable with hash/wedge bonds, as it always has.  When the value is 1, the behavior of Show Stereochemistry is modified as described above.  (Note: The installer does not create this key.  It must be created by hand.)


RTS in ChemFinder

Like ChemDraw, ChemFinder by default considers thick bonds to be equivalent to hash/wedge bonds, and has a new Registry value to override this behavior.  For reference, the value is:

HKEY_CURRENT_USER\ Software\ CambridgeSoft\ ChemFinder\ 7.0\ Pro\ Options\ Relative Tet Stereo

but ChemFinder presents this value in the user interface, so editing the Registry is not required.  It is found in a new checkbox on the Stereochemistry Search Preferences dialog (Search > Preferences > Search Details > Match Stereochemistry How...):

When this box is unchecked (default), RTS is disabled; ChemFinder considers thick bonds to be interchangeable with hash/wedge bonds, as before.  When the box is checked, RTS is enabled, so that search behavior is modified as described below.

There is another new Registry value which plays a role here, but it is a more subtle feature and not available through the user interface.  The value ABS_HITS_REL specifies whether a query drawn absolute (hash/wedge bonds) is allowed to hit a target stored as relative (thick bonds).  The default is 0 (NO).

HKEY_CURRENT_USER\ Software\ CambridgeSoft\ ChemFinder\ 7.0\ Pro\ Searching\ SRCH_ABS_HITS_REL


Searching

Relative and absolute configurations may be registered separately in ChemFinder 7.0.1, and can be distinguished by various search options.  The basic ChemFinder search philosophy can be summarized as follows:  a more specific query is a more precise request, and should get fewer hits than a more general query.  If the query represents a particular absolute configuration, it should hit only that; if it represents a mixture, it should hit any of the components.

In order to demonstrate how searching works, we generated a database of nine stereoisomers of the same structure.  Eight are shown above; the ninth is unmarked:

Each structure was used as query, and searched against the entire set repeatedly, varying search options.  The complete results are shown below in the RTS Search Grid.  Each column in the grid shows a different search variation, with  decreasing selectivity from left to right:

Identity search.  This is the most specific search, designed mainly to check for duplicates at registration time.  (Choose Identity from Search > Preferences> Search Types)  In an identity search, a compound hits only itself or equivalent representations of itself.  As the grid shows, each of the nine stereoisomers hits itself only, except for the equivalent pairs 6=9 and 7=8.

The remaining columns are labelled SSS, but results apply to both Substructure and Full Structure searches.

(a): Tetrahedral match = SAME, RTS enabled.  In the stereo search choices, if you choose Same you are requesting that whatever stereochemistry is specified in the query must match that of the target.  If the query has hash/wedge bonds, a hit must have the same configuration; if the query has relative bonds, a hit must have the same relationship between centers.  The grid confirms this: absolute queries 2,3,4,5 hit only themselves; relative query 6 hits both targets with the given relation (2,5), as well as itself and the equivalent 9.

(b): Tetrahedral match = SAME, RTS disabled.  If RTS feature is not enabled, thick bonds are interchangeable with hash/wedge bonds, and relative stereocenters are not recognized.  Thus 2 and 6 behave the same, as do 3 and 7, etc. 

(c): Tetrahedral match = SAME, RTS enabled, ABS_HITS_REL on.  Allowing absolute queries to hit relative targets gives more hits, as shown in the grid.  The average user will not be concerned with this case.

The remaining columns work the same regardless of Registry settings. 

Tetrahedral match = EITHER.  This choice requests that a stereocenter in the query hit a stereocenter in the target, but need not match its configuration.  In this case, every query except 1 hits every target except 1.

Tetrahedral match = ANY.  This choice disregards all stereochemistry in the search.  All queries hit all targets.


MDL File Formats

All bond styles available in ChemDraw are retained in CDX files.  The same is not true of major MDL structure files: MolFiles, SDFiles, RDFiles (see MDL File Formats).  In these formats, only three stereo bond types are available: hash, wedge, or either (squiggly bond); thick bonds are not recognized.  This presents a problem for the ChemFinder user wishing to import or export structures having relative stereocenters.

ChemFinder 7.0.1 addresses this problem by using a proprietary tag in the file, recognized only by ChemFinder.  The tag is BOND_RELS, and is applied to every stereo bond of thick type.  For example, here is an excerpt from the bond table of a molfile for structure 6

...
4 5 1 0 0 0 0
2 6 1 1 0 0 0           <- bond 5, marked as UP
4 7 1 1 0 0 0           <- bond 6, marked as UP
M CFW 5 BOND_RELS       <- overrides type of bond 5 to be UP/THICK
M CFW 6 BOND_RELS       <- same for bond 6

The consequences of having a ChemFinder-only tag are:


RTS Search Grid

Numbers in the grid indicate which ID's are hit when the molecule in the Structure column is used as query.  Columns 3-8 show results under differing search conditions, and are arranged in order of decreasing search specificity.  These data were obtained with ChemFinder 7.0.1.434.

ID Structure Identity SSS (a) SSS (b) SSS (c) SSS SSS
SAME SAME SAME EITHER ANY
1 1 ALL ALL ALL ALL ALL
2 2 2 2,6 2,6,9 2-9 ALL
3 3 3 3,7 3,7,8 2-9 ALL
4 4 4 4,8 4,7,8 2-9 ALL
5 5 5 5,9 5,6,9 2-9 ALL
6 6,9 2,5,6,9 2,6 2,5,6,9 2-9 ALL
7 7,8 3,4,7,8 3,7 3,4,7,8 2-9 ALL
8 7,8 3,4,7,8 4,8 3,4,7,8 2-9 ALL
9 6,9 2,5,6,9 5,9 2,5,6,9 2-9 ALL

Notes

  1. Settings: Options\Relative Tet Stereo = 1 (ON),  Searching\SRCH_ABS_HITS_REL = 0 (OFF)
  2. Settings: Options\Relative Tet Stereo = 0 (OFF), Searching\SRCH_ABS_HITS_REL = (ignored)
  3. Settings: Options\Relative Tet Stereo = 1 (ON),  Searching\SRCH_ABS_HITS_REL = 1 (ON)
  4. Full structure search works the same way as substructure search (SSS).

Summary

The new Relative Tetrahedral Stereochemistry feature in ChemOffice 7.0.1 allows relations between stereocenters to be depicted graphically using thick stereo bonds.  A Registry setting can be made so that ChemDraw 7.0.1 recognizes these bonds, and refuses to assign CIP stereo labels to them.  A checkbox in ChemFinder 7.0.1 determines whether these bonds are recognized; if so, various types of search can distinguish between absolute and relative centers.  ChemFinder 7.0.1 can import and export these bonds using modified MDL file formats.