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Updated: Jul 17, 2025

Spatial Separation of Molecular Conformers and Clusters
Published on: January 9, 2014
Spacial Score─A Comprehensive Topological Indicator for Small-Molecule Complexity
Adrian Krzyzanowski1,2, Axel Pahl3, Michael Grigalunas1
1Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
Abstract:
The fraction of sp3-hybridized carbons (Fsp) and the fraction of stereogenic carbons (FCstereo) are two widely employed scores of molecular complexity with strong links to biologically relevant features. However, they do not comprehensively express molecular topology, and they often do not match the chemical intuition of complexity. We propose the spacial score (SPS) as an empirical scoring system that builds upon the principle underlying Fsp and FCstereo and expresses the spacial complexity of a compound in a uniform manner on a highly granular scale. The size-normalized SPS (nSPS) can differentiate distributions of natural products and synthetic compounds and is applicable in the analysis of biological activity data. Analysis of the ChEMBL database revealed general trends of increasing selectivity and potency with increasing nSPS. SPS can also be used advantageously in planning and analysis of synthesis programs for direct comparison of chemical transformations and intermediates in reaction sequences.
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