In order to interrogate the mode of stereochemical transfer from point to helical chirality, we performed a computational study of assemblies 12ba and 12oa, as well as the previous assembly 8 (Figure ). Given the presumed importance of both proximal and distal steric effects revealed by MLR modelling, 12oa was selected because it had an ortho substituent on the A-ring, while 12ba was para-substituted. Additionally, 12oa and 12ba were the best and worst-performing assemblies tested during model construction respectively and would, therefore, reflect the limiting cases. Assembly 8 was selected as it would provide a benchmark into the origin of the impact of hemiaminal-ether stereo-chemistry on the CD response. For each assembly analyzed, both aminal epimers were subjected to a gas-phase molecular mechanics-based conformational search using the OPLS3e forcefield. From this, five distinct conformers were identified for 8 while the conformationally flexible 12ba and 12oa resulted in numerous conformers (92 -145 per epimer). To limit computational resources, the latter two were clustered (17 -32 clusters per epimer) based on atomic RMSD and one representative conformer was selected from each cluster. All conformers from 8 and the selected conformers from 12ba and 12oa were then refined via DFT calculations. Geometry optimization was conducted using the B3LYP functional with the 6-31G(d,p) basis set in Gauss-ian16. Single-point corrections were then carried out with the M06-2X functional and def2-TZVP basis set. Solvation effects of acetonitrile were considered using the PCM solvation model. The lowest-energy structures of both (P, S)-8 and (M, S)-8 (Figure ) were analyzed revealing a large energy difference between the (M) and (P) configurations (DGM/P = 2.2 kcal/mol). This likely stems from the difference in orientation of the alkoxy group between the (P) and (M) conformers. (P, S)-8 positions the C-O bond of the alkoxy group (highlighted in blue) downward with respect to the N-Zn bond (highlighted in red). This positioning of the alkoxy group is termed axial and likely benefits from minimized steric interactions with the pyridine motifs. In contrast, the alkoxy group is projected roughly perpendicular to the Zn-N bond in the (M, S)-8 conformer. This placement of the alkoxy group, termed equatorial, is likely disfavored due to energetically unfavorable repulsive interaction with the pyridine rings. The substantial energetic preference for one terpyridine configuration is consistent with the notion that the hemiaminal ether stereocenter controls the helicity. We next considered the computed structures for 12ba, the worst-performing assembly tested during model generation (Figure ). While we investigated both hemiaminal ether epimers, we will discuss (R)-12ba as it was calculated to be more stable than (S)-12ba (not shown) by ca. 1.8 kcal/mol. It was noted that the 30 conformers assessed at the DFT level of theory could all be categorized into two distinct conformational ensembles: one with (M) and one with (P) terpyridine configurations. We then compared the energies and structures of the lowestenergy conformer from each ensemble. As was the case for 8, the configuration of the terpyridine dramatically impacted the orientation of the alkoxy group for (R)-12ba. In this case, the (P) and (M) configurations coincide with the alkoxy group being placed equatorial and axial, respectively. Unlike 8, however, the energy difference between (P, R)-12a and (M, R)-12a were comparatively small (DGM/P = 0.1 kcal/mol). The low energy difference between helical conformers is consistent with the modest CD-signal observed experimentally. Finally, we turned our attention to 12oa, the best-performing assembly assessed in this study (Figure ). Once more, we will only discuss the lowest-energy hemiaminal ether epimer, which was (S)-12oa. All conformers could again be categorized into two distinct conformational ensembles, each with an opposite pyridine helicity. The (M)-terpyridine configuration resulted from the equatorial alkoxy orientation while the (P)-configuration favored the axial alkoxy positioning. Unlike both 8 and 12ba, in which the axial alkoxy orientation was favored, the conformer with the equatorial orientation of the alkoxy group (M, S)-12oa was preferred, now by 2.7 kcal/mol. This comparatively large energy difference likely results in a substantial enrichment of the (M) terpyridine configuration and is consistent with the large CD-signal observed for 12oa. Our combined computational and statistical modeling efforts suggest that attractive p-p interactions as well as London dispersion forces, play a key role in controlling CD-signal intensity by modulating DGM/P (Figure ). For assembly (R)-12ba, we observed attractive NCIs that stabilize both the (P)-equatorial and (M)-axial conformations. Londondispersion contacts can be seen in the former between the g-phenyl ring and both the pyridine rings and the A-ring ortho-protons (see NCI plots, Figure ). 50,51 However, long-range dispersive interactions between the alkoxy chain and the A-ring para-substituent also stabilize the (M)axial conformation. The presence of distal dispersive contacts (i.e., the 4-bocamino group), therefore, stabilizes (M,R)-12ba relative to (P,R)-12ba and attenuates DGM/P. In contrast, more significant attractive NCIs were observed for the (M)-equatorial conformer of (S)-12oa than in the (P)-axial conformer (Figure ). In addition to extensive dispersion interactions, the former benefits from a T-stacked interaction between the A-ring ring ortho-proton and the g-phenyl moiety (see dark blue attractive T-stacking interaction in the inset, Figure16C). The limited rotation enforced by the ortho isopropyl group results in an increased dihedral angle of the biaryl which, in turn, enhances this Tstacked interaction.