An Additive Definition of Molecular Complexity

Area of Science:

• Computational chemistry
• Chemical informatics
• Drug discovery

Background:

• Assessing molecular complexity is crucial in chemistry, particularly for drug design.
• Current methods for calculating molecular complexity can be complex and lack universal applicability.

Purpose of the Study:

• To establish a novel framework for quantifying molecular complexity based on information theory.
• To introduce a simple, additive complexity index (Cm) that is sensitive to various molecular features.

Main Methods:

• Developed a complexity index (Cm) derived from information content and atomic microenvironments.
• Utilized an additive approach for calculating molecular complexity.
• Evaluated the index's performance against existing methods and correlated it with antibiotic parameters.

Main Results:

• The complexity index (Cm) is derived from information theory and chemical knowledge.
• Cm is calculated simply and additively on a per-atom basis.
• The index is sensitive to stereochemistry, heteroatoms, and symmetry, providing universal assessment.
• Consistent values for large molecules and chemical reactions were obtained.
• Correlations between antibiotic molecular complexities and compound-specific parameters were demonstrated.

Conclusions:

• The established framework provides a universally applicable tool for assessing molecular complexity.
• The additive nature of Cm simplifies comparisons of molecules and reactions.
• This complexity index shows potential utility in medicinal chemistry for drug design and lead optimization.