Nucleophilicity & Electrophilicity

Identify electrophilic and nucleophilic sites in a molecule and compute methyl anion affinities (MAA) and methyl cation affinities (MCA) using the ESNUEL methodology (Jensen group).

from atomiverse import Atoms, NucleophilicityElectrophilicity
from atomiverse.levels import GFN2_XTB

water = Atoms.from_smiles("O")

job = NucleophilicityElectrophilicity(
    atoms=water,
    charge=0,
    multiplicity=1,
    level_of_theory=GFN2_XTB,
)
job.submit()

result = job.require_result()
for site in result.electrophilic:
    print(f"Electrophilic site {site.site_index} ({site.site_name}): "
          f"MAA = {site.affinity_kjmol:.2f} kJ/mol")
for site in result.nucleophilic:
    print(f"Nucleophilic site {site.site_index} ({site.site_name}): "
          f"MCA = {site.affinity_kjmol:.2f} kJ/mol")

Inputs

atoms is the starting molecular geometry (3D coordinates).

charge (default 0) and multiplicity (default 1) describe the electronic state.

level_of_theory selects the computational method used for both geometry optimisation and single-point energy evaluation.

smiles (optional) provides a SMILES string for more robust site identification. When omitted, bonds are perceived from the 3D structure.

Results

result.electrophilic lists all identified electrophilic sites with:

• site_index: Atom index in the input molecule
• site_name: Functional-group label
• product_smiles: SMILES of the methylated product
• affinity_kjmol: Methyl anion affinity (MAA) in kJ/mol

result.nucleophilic lists all identified nucleophilic sites with:

• site_index: Atom index in the input molecule
• site_name: Functional-group label
• product_smiles: SMILES of the methylated product
• affinity_kjmol: Methyl cation affinity (MCA) in kJ/mol

result.methyl_anion_ref_kjmol is the reference energy of CH3- in kJ/mol.

result.methyl_cation_ref_kjmol is the reference energy of CH3+ in kJ/mol.

result.reactant_energy_kjmol is the energy of the reactant in kJ/mol.

Thresholds

When interpreting MAA and MCA values, the following qualitative thresholds can be used as a guide:

Affinity (kJ/mol)	Classification
< 0	Unfavourable
0 – 50	Weak
50 – 100	Moderate
100 – 200	Strong
> 200	Very strong

These thresholds are general guidelines; absolute values depend on the level of theory chosen.

Important Notes

• The workflow site identification uses a set of SMIRKS reaction patterns ported from the upstream ESNUEL project (MIT licensed).
• Each methylated product is geometry-optimised and evaluated with a single-point calculation at the chosen level of theory.
• More negative affinities indicate stronger reactivity (MAA for electrophilic attack, MCA for nucleophilic attack).
• The reactant geometry is also optimised before energy evaluation.

Compute Resources

CPU cores and memory are determined automatically based on the molecule size. The walltime estimate accounts for one optimisation + SPE for the reactant plus additional calculations for each identified reactive site.