A Visualizable and Widely Applicable Steric Repulsion Descriptor for Guiding Experimental Chemistry

Abstract

While steric effects fundamentally shape molecular behavior and are experiencing renewed interest across chemistry, visualizing where they occur remains challenging. Indeed, steric interactions have traditionally been depicted in a qualitative, often sketchy manner. We present SELF (Steric Exclusion Localization Function), which enables the quantification, atomic resolution, and visualization of steric repulsion in three dimensions (whether between molecules or between fragments of a single molecule) directly from quantum-mechanical calculations. Accessible through the user-friendly IGMPlot software, SELF transforms abstract quantum-mechanical concepts into visual insights that chemists can immediately interpret and apply. We illustrate SELF’s versatility across diverse chemical systems: from understanding atropisomerism in pharmaceutical scaffolds to rationalizing selectivity in catalysis through steric effects of phosphorus ligands in organometallic chemistry. Unlike traditional quantum-mechanical methods which condense the characteristics of steric effects into a single number, SELF provides unprecedented spatial resolution of steric clashes while maintaining rigorous quantitative analysis. This approach bridges the gap between theoretical concepts and practical chemical understanding, making sophisticated quantum-mechanical analysis accessible to the broader chemical community. We hope this tool will prove valuable for chemical design, research applications, and teaching steric effects.