In this scientific commentary, we revisit the problem of defining and characterizing Lewis-type interatomic interactions in a physically disciplined manner. Although identifying a “nucleophile” (or “Lewis base”) and an “electrophile” (or “Lewis acid”) is, in principle, pathway-dependent and therefore partly arbitrary, a characteristic feature of such noncovalent and metal-coordination interactions is that the atom acting as a Lewis base provides its electron pair (or an analog thereof) to the internuclear binding region, thereby directing it toward an electron-deficient site in the valence shell of the neighboring atom, which serves as a Lewis acid. Accordingly, the information sufficient to discriminate between the Lewis-basic and Lewis-acidic sites in a given noncovalent or metal-coordination Lewis-type interaction can be obtained from the distribution of appropriate electron-pair localization descriptors, such as the readily accessible Laplacian of the electron density, \(\nabla^2 \rho(\mathbf{r})\) , as a measure of local (de)concentration of negative charge within the electron cloud and—more incisively—the exchange charge density \(q_{x}(\mathbf{r})\) , which reflects the (de)condensation of electron-pair density in the many-electron cloud. By contrast, we argue that the prevalent \(\sigma\) -hole/ \(\pi\) -hole notation is inapplicable to an established interaction and instead pertains only to arbitrarily chosen reference (precursor) species. We therefore recommend shifting the primary interpretive focus to rigorously defined interatomic charge transfer, that is, the charging of chemically bound atoms, as a more fundamental concept than Lewis acidity/basicity or ill-defined electrophilicity/nucleophilicity, and we propose a minimal extension of widely employed element-based interaction labels by explicitly indicating the role of the Lewis-acidic atom in the interatomic charge transfer (e.g., electron-donating versus electron-accepting variants of element-named bonds). In addition, the covalent character of a polar interatomic interaction can be assessed by the degree to which the quantum chemical response is realized. Moreover, in its conventional definition based on electrostatic-potential mapping, the \(\sigma\) -hole/ \(\pi\) -hole concept does not explicitly account for electron correlation, most notably Fermi correlation. Instead, we call attention to the Slater total static potential felt by an electron in a many-electron multinuclear system, \(\varphi_{\text{em}}(\mathbf{r})\) , as an operational gauge of electrophilicity (Lewis acidity): within this convention, lower values of the Slater average potential imply a more pronounced electrophilic character.
