Around the same time, Hartenfeller et al. published a paper presenting robust organic synthesis reactions, encoded as SMIRKS patterns, that could be useful for in silico compound design. This publication, and its subsequent companion paper analyzing to what degree products generated with these chemistries would cover the bioactivity-relevant chemical space , sparked a number of projects that based large virtual libraries on these "Hartenfeller reactions." Numerous other projects involving virtual and tangible chemistry spaces and reaction prediction tools have emerged in the recent past and have been reviewed in the literature , as have projects of using such ultra-large libraries for virtual screening. We felt, however, that SMIRKS patterns do not contain, and cannot easily be annotated with, any algorithmically usable chemistry knowledge for the reaction's successful application in the laboratory. For example, does the SMIRKS for the Sonogashira coupling ,