This can be thought of as pH setting the baseline brightness, F0, and ligand addition determining the final brightness, F. However, the maximum brightness induced by some benezene-1-2-diol derivatives in our screen was significantly higher than the brightness of nanotubes at high pH, suggesting that pH-induced brightness saturations and consequent lowering of sensor dynamic range cannot explain sensor pH dependencies (Fig. , fig. ). Indeed, the diminution of ∆F/F as a function of pH showed a different trend in all the species whose optical responses were measured as a function of pH, with some analytes undergoing rapid decrease in their ability to generate optical response (e.g., F, Fig. ), while other substrates exhibited broader pH tolerance (e.g., DA, Fig. ). Since the same ssDNA-SWCNT complex is used for all analytes, the pH dependencies we see are unlikely to be driven by changes in the photophysical properties of nanotubes and their conjugated ssDNA. We hypothesized that these differences are intrinsic to the analytes. Importantly, pH-dependent trends correlated with deprotonation of the analytes, as predicted by the pKA of the substituents on the aryl group. This suggests that the deprotonated species may interact with ssDNA-SWCNT conjugates differently from the parent species (Fig. ). We therefore conclude that optical modulations in ssDNA-SWCNT conjugates generated by benzene-1,2-diol and its derivatives exhibit a sensitivity to molecular charge, in addition to correlations with electrochemical properties we presented in the foregoing analysis. This result suggested that the dynamics of interaction between analytes and ssDNA-SWCNT supramolecular complex, mediated by a combination of molecular structure and charge, likely play a key role in coordinating the optical response process in molecules that have favorable electrochemical profiles (eHOMO). While we used (GT)6-SWCNTs conjugates for this study, similar results were obtained using (GT)15-SWNCTs for a subset of compounds (fig. ), suggesting that the results can be generalized to the (GT)N-SWCNT family of sensors. We next employed molecular dynamics (MD) simulations to rationalize our experimental findings and gain detailed atomic and molecular insight into molecular interactions in ssDNA-SWCNT conjugates, and how these correlate with experimentally observed optical modulations. We focused on a subset of 14 analytes using MD simulations (Methods). Dopamine (DA) was selected as the key model analyte for our computational studies, consistent with our experimental approach. The remaining analytes spanned the full spectrum of experimentally observed optical responses. Specifically, the simulated molecules included the analytes F, C, and O which elicited stronger fluorescence responses than dopamine, and analytes T and 1, which showed weaker responses. Analyte Y, which had a roughly similar response to dopamine, was also included. To explore pH effects, we modeled additional molecules in their dominant protonation states at selected pH values (fig. ). These included F + (at pH = 5), RR (at pH = 7), RR + (at pH = 3), YY + (at pH = 7), O (at pH = 7), O + (at pH = 3), 5 + (at pH = 7), and C -(at pH = 11). We determined molecular charge using ChemAxon Chemicalize 44 modeling of pKA, matched to the pH conditions used during experimental measurements. Each simulated system contained six molecules of the selected analyte, which were allowed to diffuse freely and interact with 4 nm segment of (9,4)-SWCNT chirality wrapped by three strands of (GT)6 ssDNA oligonucleotides, immersed in 0.10 M aqueous NaCl solution (Methods). The systems were simulated for 6 μs to observe multiple binding and unbinding events of analyte molecules on the ssDNA-SWCNT conjugate surface. We began by cataloging all the predominant binding modes observed when the selected analytes interacted with ssDNA-SWCNT molecular complexes. Figure shows representative snapshots of the preferred binding modes of the 14 selected analytes studied. The observed binding modes fall into two categories: analytes either stacked either directly on top of ssDNA nucleotides functionalizing the SWCNT or stacked on the exposed segments of the SWCNT surface. Specifically, the molecules C, C -, T and RR were primarily observed stacking on the ssDNA nucleotides, while molecules F, DA + , RR + , O, O + , 5 + , 1 and YY + stacked on both ssDNA and SWCNT surface. Interestingly, F + favored a distinct insertion mode rather than stacking, although brief instances of sideway stacking on ssDNA bases were occasionally observed (Fig. ). Lastly, analyte Y did not exhibit a single predominant binding mode but rather interacted with ssDNA-SWCNT through a combination of binding modes.