Oligo(ethylene glycol) (OEG) and alkoxy chains contain oxygen atoms that increase hydrophilicity, polarity, and chain flexibility compared to hydrophobic alkyl side chains. Conjugated materials bearing OEG or alkoxy side chains exhibit different morphologies and electronic properties compared to their alkyl side chains counterparts. To investigate the role of side chain chemistry and composition on molecular charge transport, we synthesized a series of terphenyl derivatives with OEG and alkoxy side chains using automated synthesis (Fig. ). In general, molecules with OEG/alkoxy chains show higher conductance and reduced molecular adsorption behavior compared to their alkyl side chain counterparts (Fig. , Supplementary Figs. ). Enhanced intramolecular conductance for molecules with OEG/alkoxy chains likely derives from two aspects. First, oxygen atoms in the side chain generally increase HOMO energy levels, which results in slightly better alignment with the Fermi energy level of Au electrodes (Supplementary Table ). Second, molecules with oxygen-containing side chains generally show more planar backbone conformations, which enhances charge transport (Supplementary Table ). We further hypothesize that the reduced adsorption behavior for molecules with OEG/alkoxy chains is related to side chain flexibility. Prior work reported that introducing oxygen atoms into linear alkyl chains decreases the barriers to rotation around the corresponding single bonds, thereby increasing degrees of freedom for the linear chains. More flexible oxygen-containing side chains side chains may incur a greater entropic cost upon surface immobilization. The increased protein binding affinity of macrocyclic small molecules relative to their linear counterparts is attributed to a similar phenomenon. To test this hypothesis, we synthesized a series of molecules with the same side chain length but varying levels of side chain oxygenation (O3, RO7, and R8). In the case of RO7 (side chains with a single oxygen atom), the high conductance peak appears prominently at 10 mM compared to 0.1 mM for R8 (Fig. ). On the other hand, O3 (containing three oxygen atoms) did not show a prominent high conductance peak up for concentrations up to 10 mM (Fig. and Supplementary Fig. ). These results are consistent with increased oxygenation of side chains increasing chain flexibility and suppressing side chain-mediated adsorption (Fig. ). Moreover, it is possible that aliphatic chains form stronger van der Waals interactions with the electrode surface than their oxygenated counterparts. In this work, we use automated synthesis and single-molecule experiments to investigate the effect of side chain chemistry on the charge transport properties of terphenyl derivatives. Broadly, these results deepen our understanding of structure-function relationships in organic electronic materials and highlight the need to fully understand the effect of substitution position, side chain chemistry, backbone identity, and side chain functionalization on charge transport. Importantly, our work demonstrates the utility of automated chemical synthesis to enable efficient and systematic exploration of chemical space for organic electronic materials. Overall, this work opens new avenues in combining automated synthesis with single molecule characterization to aid in the design of new materials for organic electronics.