Closer examination of the screening results reveals a key requirement to elicit optical response: ortho hydrogen bond donors installed on π-conjugated scaffolds. Non-catechols can be tolerated if they satisfy these two criteria (e.g., RR, O). Changing the position of the hydrogen bond donors from ortho (T) to meta (1) leads to loss of optical response. Interestingly, compound 4 elicited a response, even though the hydroxyls are closer than the van der Walls radii on ortho-substituted aryls. This suggests that conjugated systems with hydrogen bond donors less than ~3.1 Å 31 apart could be effective sensor substrates. Loss in response also occurs if the hydrogen bond donors are unconjugated (e.g., BB, G) or replaced with an acceptor (e.g., FF, 6, GG, H, P, Q). Sterically bulky compounds meeting these criteria were well tolerated in producing responses (e.g., 4, TT, UU, W). This suggests that the binding pocket of interactions is likely to be shallow or is at least very accessible.