Recently, Böttcher tried to overcome many shortcomings of the existing scoring systems and devised a new approach based on substructure analysis, intended for the expression of the total molecular complexity. The Böttcher score Cm is inspired by the Shannon entropy, and defines molecular complexity in an additive manner by the consideration of atomic connectivity, the number of valence electrons for atoms, heteroatom diversity, stereogenicity and molecular symmetry. It has generated significant interest, resulting in a rapid increase in its popularity since its introduction, notably by the organic synthesis community. Considering the general interest in this scoring system and apparent improvement over the alternative complexity measures, we explored whether the Böttcher complexity score may also serve as a descriptor that could correlate compound complexity with biological activity and selectivity. In this case it might be employed to rationalize trends observed in the biological analysis of our in-house compound libraries. However, initial analysis using total and size-normalised scores, indicated that although the Böttcher complexity index is intuitive and very applicable in a chemical context, there seems to be no or at best only very limited correlation to biological compound activity and selectivity (see Supporting Information). In light of the recent report by Méndez-Lucio and Medina-Franco investigating the relationship between different complexity measures and selectivity, we concluded that scores, such as the Bertz molecular complexity, also do not seem to be broadly applicable in a biological context. Considering the already proven correlation between Fsp3 and FCstereo indicators and biologically relevant characteristics of compounds, we now propose a new empirical scoring system termed the spacial score (SPS).