Several explanations could account for the observed dependence of sensor response on the electron donating or withdrawing character of the substituents. One possibility is that electron donating substituents enhance the π-stacking stability of the aryl ring on the nanotube surface, consistent with wellknown substituent effects on π-interaction between aromatic rings. This stable stacking may more efficiently displace water molecules from the nanotube surface, transiently reducing the surface dielectric constant and thereby increasing optical output. This hypothesis is supported by previous findings, where we showed that dopamine binding outcompetes sodium cholate binding to nanotube surfaces in ssDNA-SWCNT conjugates. Another potential explanation is that stably bound and electron rich aryl motifs could coordinate with deleterious surface defects, locally and transiently altering nanotube bandgap, which could increase optical output. Alternatively, electron rich substituents themselves, instead of the πstacked aryl group, may be responsible for displacing water or transiently mitigating the effect of surface defects, thus enhancing the nanotubes' brightness. These potential mechanisms highlight the complexity of interaction between analytes and ssDNA conjugated nanotubes, suggesting that multiple factors contribute to sensor response. In conclusion, our findings indicate that optical responses in ssDNA-SWCNT conjugates depend both on molecular bindings events, similar to traditional optical sensors, and the chemical properties (structure, charge, electron density) of the analyte, similar to activity-based sensing models. These findings may offer avenues for tuning the performance of existing sensors or guiding the development of new ones through designed ssDNA modifications that improve analyte binding.