Predictive Models for Ligand Effects on a Reactive Al-Containing Radical Intermediate from Multivariate Linear Regression Analysis

Our lab has studied a complex with an Al–Fe bond capable of cooperative substrate activation processes. This reactivity was previously found to depend on Al–Fe homolytic bond dissociation followed by substrate coordination to the Al^III center of the resulting redox noninnocent radical intermediate. The current study investigates ligand influences on the Al–Fe bond dissociation free energy (BDFE_Al–Fe) and the Gibbs free energy of H₂O coordination at aluminum (ΔG_OH2) for a series of variants with systematic changes in their ligand substitution patterns. DFT calculations combined with multivariate linear regression analysis provided predictive models for ligand effects on both BDFE_Al–Fe and ΔG_Al–OH2 for three synthetically tunable positions in the molecular architecture when using appropriate electronic (σ_para, σ_meta) and steric (wSterimol, %V_bur) descriptors. Chemical interpretations of the predictive models were facilitated by the use of these intuitive descriptors. Linear scaling relationships relating BDFE_Al–Fe and ΔG_OH2 provided further insight. We expect our findings to inform designs of future Al-containing heterobinuclear complexes for small molecule activation processes and cleavage reactions of strong or inert bonds.