J Chem Inf Model. 2016 Mar 28;56(3):462-70. doi: 10.1021/acs.jcim.5b00723. Epub 2016 Feb 22.
Journal of chemical information and modeling
Thomas Böttcher
PMID: 26857537 DOI: 10.1021/acs.jcim.5b00723
A framework for molecular complexity is established that is based on information theory and consistent with chemical knowledge. The resulting complexity index Cm is derived from abstracting the information content of a molecule by the degrees of freedom in the microenvironments on a per-atom basis, allowing the molecular complexity to be calculated in a simple and additive way. This index allows the complexity of any molecule to be universally assessed and is sensitive to stereochemistry, heteroatoms, and symmetry. The performance of this complexity index is evaluated and compared against the current state of the art. Its additive character gives consistent values also for very large molecules and supports direct comparisons of chemical reactions. Finally, this approach may provide a useful tool for medicinal chemistry in drug design and lead selection, as demonstrated by correlating molecular complexities of antibiotics with compound-specific parameters.
