Intriguingly, the keto emission for 5 diminished in the TTR□/TTR■ mixture (Fig. ). This observation is consistent with a lower affinity for the TTR□/TTR■ mixed interface relative to the A108G TTR■ homo-tetramer. Of course, the TTR□/TTR■ mixture still contains a statistical population (25%) of TTR■/TTR■ homo-interfaces within the mixed tetramers. Thus, binding of 5 to this smaller fraction of A108G TTR■ homo-interfaces likely contributes to the observed keto emission signal. Alternatively, 3 did not display any notable selectivity or change in enol versus keto emission intensity across any of the TTR tetramers (Fig. ). This result is unexpected given the structural similarities of 3 and 5 (differing only in the position of the carboxylic acid). For example, tafamidis (1) can bind the WT TTR□ binding pocket with C2 symmetry (i.e. The CO2H group can orient towards either the 'top' or 'bottom' interface, PDB 3tct). Thus, it is surprising that the subtle regioisomerism of the CO2H between 5 and 3 can lead to significant differences across the TTR tetramers in Fig.