Generally it is accepted by chemists that the energy of a molecule and the barrier of a reaction is related to the steric and electronic properties of the molecules involved. Most chemists, however, would prefer to identify and think about the most important steric or electronic descriptor of a molecule for determining barriers/energies.
Here is a list of a few descriptors that may relate to reactivity
- HOMO/LUMO gap – easily calculated from a single point calculation in qchem (with wave-function analysis turned on)
- Charge on reactive atoms – can be computed using a number of formalisms
- Mulliken, Löwdin, CHELPG, Hirsfeld charges – computed during a wave-function analysis in qchem. Unless certain $rem variables are set, only Mulliken charges are printed
- NBO charges – can be calculated using the qchem as an interface for the nbo 7 program
- Volume of functional groups adjacent to reactive atoms – this can be calculated by using Sterimol parameters or % Buried Volume
- Improper torsion (as a measure of planarity in a molecule)
- Heat of reaction, ∆Erxn – the Evans-Polanyi principle states that the barrier of reaction is related to the heat of the reaction. Look at Josh’s paper to see a discussion of the Evans-Polanyi relationship and its limits.
- Forward and Backward charge flow (backbonding) – particularly relevant for metal-ligand complexes to probe π/sigma bonding frameworks. Can be performed easily with ALMO analysis in qchem. To see which orbitals are responsible for charge transfer, use COVP analysis during ALMO.
- Spin density on reactive atoms – calculated when a wavefunction analysis is performed with an unrestricted wavefunction
- Coordination number of reactive atoms and atoms near reactive atoms – this can be done visually, or using open babel using SMILES inputs. Ask around for a script.
- Ionization energy –
- Functional group electronegativity – can be approximated using ALMO analysis in chem (by looking at how much charge is transferred to a functional group during bonding)
- Hammet parameter of functional groups near reactive atoms – approximates the withdrawing and donating effects of functional groups. Not typically calculated.
- pKa of of hydrogens on reactive atoms – calculations may depend on a few factors but here is one paper that calculated pKas – look up papers of systems relevant to yours to see how best to perform pKa calculations
- proton affinity of groups bound to reactive atoms – useful for probing the basicity of groups on a molecule
- Homolytic/heterolytic bond dissociation energy :
- via Single Ended Growing String – if the bond dissociation proceeds with a barrier, as is the case when there are bulky substituents around bond, then SEGSM can give an optimized transition state as well as ∆Grxn (equal to the BDE). Requires use of unrestricted waveunctions.
- via ALMO analysis – can give the BDE of single bonds easily, ans is shown to work well with carbon-metal and metal-metal bonds. Requires use of unrestricted waveunctions.
- Nucleophilicity and electrophilicity