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Steric molecular descriptors designed for machine learning (ML) applications are critical for connecting structure-function relationships to mechanistic insight. However, many of these descriptors are not suitable for application to com-plex systems, such as catalyst reactive site pockets. In this context, we recently disclosed a new set of 3D steric molecular descriptors that were originally designed for dirhodium(II) tetra-carboxylate catalysts. Herein, we expand the Spatial Molding for Rigid Targets (SMART) descriptor toolkit by releasing SMARTpy; an automated, open-source Python API package for computational workflow integration of SMART descriptors. The impact of the structure of the molecular probe for generation of SMART descriptors was analyzed. Resultant SMART descriptors and pocket features were found to be highly dependent upon probe selection, and do not scale linearly. Flexible probes with smaller substituents can explore narrow pocket regions resulting in a higher resolution pocket imprint. Macrocyclic probes with larger substituents are more applicable to larger cavities with smooth boundaries, such as dirhodium paddlewheel complexes. In these cases, SMARTpy provides comparable descriptors to the original calculation method using UCSF Chimera. Finally, we analyzed a series of case studies demonstrating how SMART descriptors can impact other areas of catalysis, such as organocatalysis, biocatalysis, and protein pocket analysis. 

Completing a series of nickel-group 13 complexes, a coordinatively unsaturated nickel-boron complex and its derivatives with a H 2 , N 2 , or hydride ligand were synthesized and characterized. The toggling “on” of a Ni(0)–B( iii ) inverse-dative bond enabled the stabilization of a nickel-bound anionic hydride with a remarkably low thermodynamic hydricity of kcal mol −1 in THF. The flexible topology of the boron metalloligand confers both favorable hydrogen binding affinity and strong hydride donicity, albeit at the cost of high H 2 basicity during deprotonation to form the hydride. 

Understanding H 2 binding and activation is important in the context of designing transition metal catalysts for many processes, including hydrogenation and the interconversion of H 2 with protons and electrons. This work reports the first thermodynamic and kinetic H 2 binding studies for an isostructural series of first-row metal complexes: NiML, where M = Al ( 1 ), Ga ( 2 ), and In ( 3 ), and L = [N( o -(NCH 2 P i Pr 2 )C 6 H 4 ) 3 ] 3− . Thermodynamic free energies (Δ G °) and free energies of activation (Δ G ‡ ) for binding equilibria were obtained via variable-temperature 31 P NMR studies and lineshape analysis. The supporting metal exerts a large influence on the thermodynamic favorability of both H 2 and N 2 binding to Ni, with Δ G ° values for H 2 binding found to span nearly the entire range of previous reports. The non-classical H 2 adduct, (η 2 -H 2 )NiInL ( 3 -H 2 ), was structurally characterized by single-crystal neutron diffraction—the first such study for a Ni(η 2 -H 2 ) complex or any d 10 M(η 2 -H 2 ) complex. UV-Vis studies and TD-DFT calculations identified specific electronic structure perturbations of the supporting metal which poise NiML complexes for small-molecule binding. ETS-NOCV calculations indicate that H 2 binding primarily occurs via H–H σ-donation to the Ni 4p z -based LUMO, which is proposed to become energetically accessible as the Ni(0)→M( iii ) dative interaction increases for the larger M( iii ) ions. Linear free-energy relationships are discussed, with the activation barrier for H 2 binding (Δ G ‡ ) found to decrease proportionally for more thermodynamically favorable equilibria. The Δ G ° values for H 2 and N 2 binding to NiML complexes were also found to be more exergonic for the larger M( iii ) ions.