Hydrogen Atoms in 2D/3D Substructure Searching

Hydrogen atoms can be difficult to locate by X-ray crystallography and hence their coordinates are sometimes missing or incomplete in CSD entries. However, they are always completely defined in the Chemical Diagram that forms the basis for 2D chemical substructure searching, and these searches will proceed accurately under all circumstances, so long as no 3D geometrical parameters are defined. However, if a moiety in a 2D diagram displays an agostic or bridging M-H-CH2-R interaction, the agostic H atom must be defined explicitly to retrieve relevant entries from the CSD (see Automatic Addition of Hydrogen Atoms) and (see Adding Hydrogen Atoms Manually).

 

If H-atoms form part of a substructure and any sort of 3D parameter (atom labels, distances, angles, etc.) is defined, then 3D coordinates must be accessed, and the missing or incomplete set of H-coordinates can cause you to miss hits. For example, if you are looking for structures with S-H bonds in the range 1.0-1.3 Å, you will not locate any structures in which the H atom position is undefined, because it is impossible to compute the S-H distance in these cases.

 

Whether structures are missed may depend on how the hydrogens are defined when drawing the substructure. Hydrogen atoms can be drawn in two ways:

 

•	Implicitly, e.g. by right-clicking on a non-hydrogen atom and selecting the menu item Hydrogens from the pull-down menu; this will be shown as, e.g. SH1. Hydrogens added in this way are terminal atoms i.e. they cannot be used to retrieve hits with bridging H atoms.

•	Explicitly, by actually drawing them; this will be shown as, e.g. S-H. Hydrogens added in this way can be used to define hydrogen bridging positions.

 

If a 3D parameter has also been defined, then these two alternative ways of defining hydrogen atoms will give different results, even if that 3D parameter does not involve the hydrogen atom.

 

Thus:

 

•	If the hydrogen has been defined implicitly, it does not matter whether its coordinates are present or absent.

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If the hydrogen atom has been drawn explicitly, its coordinates must be present in the CSD, otherwise a structure will not be counted as a hit even if it contains the substructure you have drawn. In addition, H atoms are considered to form part of a substructure if they might be present by virtue of an Any atom or a multipick selection: even if you have not defined H atoms explicitly you may obtain unexpected results.