Fields, Local Reactivity and Sterics
Electronic and Steric Descriptors
Compare three-dimensional fields and local descriptors for reaction selectivity in terms of definition, input, interpretation, and limitations.
1. Choosing a descriptor
Select descriptors for the chemical hypothesis being tested, not simply because they are available. Steric shape, electrostatics, orbital interaction, density deformation, and local reactivity are distinct concepts.
| Descriptor | Primary information | Key caution |
|---|---|---|
| Electron density ρ(r) | Electron distribution and molecular boundary | Nonnegative; distinct from orbital amplitude |
| ESP | Electrostatic potential for a test charge | Fix the evaluation surface, units, and sign |
| MO / LUMO field | Orbital phase and local amplitude | Match orbitals and global phase |
| Fukui / dual descriptor | Local response to electron-number changes | Define charge state, spin, and relaxation |
| RDG and sign(λ2)ρ | Low-density, low-gradient regions | Not an interaction energy |
| IGMH and IRI | Interfragment, bonded, and nonbonded regions | Depends on fragments, isovalue, and grid |
| Sterimol and %Vbur | Directional steric occupancy | Depends on axis, center, radius, and conformer |
2. Electron density and electrostatic potential
Electron density describes electron distribution, while ESP is the potential produced by nuclei and electrons. Compare ESP on the same density isosurface or spatial points and fix units and color range.
3. Orbitals and frontier fields
Local HOMO or LUMO amplitude can suggest orbital-interaction regions, but orbital ordering may change between calculations. Match by energy, symmetry, and overlap and align the global phase before field comparison.
4. Fukui functions and the dual descriptor
Finite-difference densities and frontier-orbital approximations are not identical. Keep geometry, spin, occupations, and grids consistent across N, N+1, and N-1 systems and state the sign convention.
5. NCI, IGMH, and IRI
These real-space functions visualize interaction regions. Do not convert surface presence, area, or color directly into an interaction energy; combine them with transition-state energies, EDA, substituent effects, or experiments.
6. Conversion to machine-learning features
- Align molecules in a common coordinate system.
- Use identical grid origin, axes, shape, and spacing.
- Mask or integrate chemically relevant regions.
- Preserve scale and sign.
- Control dimensionality with PCA, regularization, and grouped validation.
Last reviewed: August 4, 2026