Conformational sampling was performed using CREST version 3.0 with the GFN-FF force field and the GFN2-xTB semi-empirical level of theory with xTB version 6.7.0 (Figure Step II). SMILES (Simplified Molecular Input Line Entry System) text representations of each NCB can be found at and in the supplemental information and were converted to xyz-coordinate files using OpenBabel version 3.1.1. For structures in our library, CENSO version 1.2.0 31 was used to further refine the ensemble before clustering into 10 or fewer representative structures. Transition state conformers were generated using constrained CREST conformational sampling without CENSO to refine the ensembles. More details can be found in section 4 of the supplemental information. Density functional theory (DFT) calculations were performed using Gaussian 16, Revision C.01 (Figure Step III). All geometry optimizations used PBE0-D3(BJ)/6-31+G(d)/SMD(water) as the level of theory. Vibrational frequency analyses at the geometry optimization level of theory confirmed the nature of transition structures and ground state structures based on the presence of only one imaginary normal mode or none at all, respectively. Intrinsic Reaction Coordinate (IRC) calculations also used this level of theory to ensure the nature of transition structures during the mechanistic study. Additional single-point energy corrections with larger basis sets were used to obtain more accurate energies. For the calculation of all barrier heights, we used ωB97M-V/def2-TZVP/SMD(water) to obtain these energies. Calculations which used the ωB97M-V functional were done using Orca version 5.0.3 with support from libXC version 5.1.0. Energy corrections for structures in our library and the newly-designed NCBs were performed with PBE0-D3(BJ)/def2-TZVP/SMD(water). Free energies were calculated and potential energy surfaces constructed using Goodvibes version 3.2. Natural bonding orbital (NBO) program version 7.0.5 was used to obtain atomic partial charges.