The algorithm that calculates “Chemical Space” fails when using extended smiles or molfiles that contain extended information.
An example extended smiles that would fail is: “CO©[H]N1C=CC=C1 |c:5,7,H:3.2|”
Regular SMILES does work, but will also fail if a null/undefined record is encountered. Both issues are a problem for users with irregular or sparse compound datasets.
Please see documentation at this URL for Chemxon’s extended smiles format: https://docs.chemaxon.com/display/docs/chemaxon-extended-smiles-and-smarts-cxsmiles-and-cxsmarts.md#:~:text=Chemaxon%20Extended%20SMILES%2FSMARTS%20is,or%20use%20them%20as%20comment.