After training a regression model to predict NCB stability, we used that information to design NCBs with substituent groups outside the scope of those previously identified. To do this, we further examined the descriptors which were used in training the DFT-level model by examining the relationship between each descriptor and the NCB stability. In Figure , we show a subset of these relationships and label the data according to substituent positions to highlight how certain descriptors can discriminate by substituent identity. Examining the relationship of f(-) at the C4H atoms with stability (Figure ), there are two substituents which yield higher stabilities, corresponding to R1 substituents E and J. Each of these substituents have an aryl substituent bound directly to the N atom in the 1,4-dihydropyridine ring. Furthermore, the two most stable NCBs in our library are E4b and J4b, suggesting that aryl R1 substituents are a favorable design component to enhance NCB stability (Table ). This suggests that alterations to an aryl R1 substituent could be a viable path for further NCB chemical space exploration. Other substituent identities also impact stability, but not to the extent of that seen from R1 aryl substituents. We performed a similar analysis of the R2 substituent (Figure ), showing that the aldehyde moiety (4) tends to have higher stability than the other functional groups represented in our library at this position. The five most stable NCB structures in our library, and fifteen of the twenty most stable, have 4 as the R2 substituent. We hypothesize that this trend is due to the highly electronwithdrawing nature of aldehydes. Though 4 is not a substituent previously evaluated in literature, we added it to our library as an additional substituent to determine if the electron-withdrawing characteristics made a large impact on NCB stability. Based on these data, this is a key design feature in optimizing stability in NCBs. The next most stable substituent, 2, is also highly electronwithdrawing as a nitrile, which has been evaluated previously.