Using Automated Synthesis to Understand the Role of Side Chains on Molecular Charge Transport
The development of next-generation organic electronic materials critically relies on understanding structure-function relationships in conjugated polymers. However, unlocking the full potential of organic materials requires access to their vast chemical space while efficiently managing the large synthetic workload to survey new materials. In this work, we use automated synthesis to prepare a library of conjugated oligomers with systematically varied side chain composition followed by single-molecule characterization of charge transport. Our results show that molecular junctions with long alkyl side chains exhibit a concentration-dependent bimodal conductance with an unexpectedly high conductance state that arises due to surface adsorption and backbone planarization, which is supported by a series of control experiments using asymmetric, planarized, and sterically hindered molecules. Density functional theory simulations and experiments using different anchors and alkoxy side chains highlight the role of side chain chemistry on charge transport. Overall, this work opens new avenues for using automated synthesis for the development and understanding of organic electronic materials.
<!>Automated synthesis of terphenyl derivatives with varying alkyl side chains<!>Role of alkyl side chain length on molecular charge transport<!>Molecular adsorption behavior in amine-terminated terphenyl derivatives<!>Role of side chain chemistry on molecular charge transport<!>Supporting Information<!>Notes
<p>The development of high-performance organic electronic devices critically relies on a fundamental understanding of intra-and intermolecular charge transport. 1,2 Organic electronic materials are typically designed for high charge-carrier mobilities and generally have highly delocalized conjugated backbones, with common building blocks including acenes, fluorenes, phenylene vinylene derivatives, thiophene derivatives, diketopyrrolopyrrole, isoindigo and their donor-acceptor copolymers. 1,2 Strong pi-pi interactions in these systems significantly decrease their solubility in organic solvents, which hinders solution processing. To overcome this issue, flexible side chains such as alkyl, fluoroalkyl, and oligo(ethylene glycol) chains are appended to pi-conjugated backbones to enhance solubility, facilitate solution processing, and tune intermolecular packing. 3,4 In recent years, side chain engineering has been pursued for organic electronic materials, which highlights the importance of side chain length, bulkiness, branching, substitution, and chain-end functionalization on charge transport in conjugated polymers. 3,4 However, the majority of prior work has focused on understanding the role of backbone composition and side chain chemistry on the macroscopic or device-level properties of these materials. Despite recent progress, the role of side chain chemistry on the molecular charge transport properties of conjugated organics is not fully understood.</p><p>Unlocking the full potential of organic materials relies on accessing their vast chemical space, but the synthetic workload to make large numbers of new compounds presents a practical barrier to properly survey conjugated organic derivatives. In recent years, automated iterative coupling has emerged as a promising avenue to achieve precise sequence control and enable highthroughput synthesis of oligomeric small molecules. 5 Recent efforts have leveraged general Suzuki cross-coupling reactions using stable and accessible chemical building blocks in the development of an automated small molecule synthesizer. 6 In this way, automated synthesis platforms have emerged as powerful tools to advance our understanding of functional materials properties, but these methods have not yet been widely applied to the field of organic electronics. In general, we lack a full systematic understanding of structure-property relationships for organic electronic materials due to the tedious and challenging nature of chemical synthesis.</p><p>In this work, we systematically investigate the role of side chain chemistry on the charge transport properties of conjugated oligomers using a combination of automated synthesis and single-molecule charge transport experiments. A library of terphenyl derivatives with different side chain compositions and anchors was synthesized using automated iterative Suzuki coupling.</p><p>Following synthesis and chemical characterization, a scanning tunneling microscope-break junction (STM-BJ) technique was used to directly characterize the charge transport properties of these molecules. STM-BJ methods provide an ideal approach for understanding charge transport at the molecular level, thereby enabling quantitative structure-property relationships for organic materials. [7][8][9] Our results show that molecular junctions with long alkyl side chains exhibit a bimodal conductance distribution with an unexpectedly high conductance state upon increasing concentration. Systematic control experiments using asymmetric, planarized, and sterically encumbered molecules indicate that the high conductance state results from surface adsorption and molecular planarization facilitated by long alkyl side chains. Our results further show that the choice of chemical anchors and side chains directly affects molecular adsorption, and density functional theory (DFT) simulations are in reasonable agreement with experiments. Taken together, these results highlight the use of automated chemical synthesis to understand molecular charge transport for the development of new organic electronic materials.</p><!><p>We used automated iterative Suzuki-Miyaura cross-coupling to prepare a library of terphenyl derivatives using stable and easily accessible molecular building blocks containing methyliminodiacetic acid (MIDA) boronates and dihalide groups (Supplementary Information, Sections S.1 and S.2; Supplementary Figs. S15-S80). Building blocks contained phenyl rings with pre-installed alkyl side chains and terminal anchor moieties to facilitate STM-BJ experiments.</p><p>Building on the first-generation automated small molecule synthesizer designed by Burke and coworkers, 6 we developed a second-generation small molecule synthesizer capable of parallel runs of deprotections, couplings, and purifications (Fig. 1a). Briefly, the synthesis strategy relies on the MIDA protecting group rendering boron unreactive until deprotected with mild aqueous base, analogous to the Fmoc group in iterative peptide synthesis (Fig. 1b). The new automated synthesis instrument leverages advances in hardware and software to enable up to 12 fully parallelized, simultaneous preparative-scale iterative Suzuki reactions. Importantly, the increased throughput allows for screening of large regions of chemical space in a single automated synthetic run. Using this approach, a library of symmetric terphenyl derivatives with different alkyl side chains (Rn) and an asymmetric target molecule (R6-H) were prepared using two automated procedures in conjunction with the standard building block set (Fig. 1c).</p><!><p>We began by studying the molecular conductance properties of Rn (Fig. 2a) using a custombuilt scanning tunneling microscope break-junction (STM-BJ) instrument, as previously described. 10,11 STM-BJ has been used in prior work to study single-molecule charge transport as a function of backbone length, 10,12 chemical substituents, 13,14 molecular conformation, 15,16 and anchor-electrode contacts. 17 Prior work has shown that alkyl side chains alter backbone conformation, 16 thereby affecting molecular conductance. Here, we used STM-BJ to systematically understand the role of side chain length and composition in the molecular library generated by automated synthesis. Using this approach, we determined the molecular conductance of Rn in a nonpolar solvent (1 mM solution in 1,2,4-trichlorobenzene) at 0.25 V applied bias. Onedimensional (1D) (Fig. 2b-2c) and two-dimensional (2D) (Fig. 2d-2e and Supplementary Fig. 1) molecular conductance histograms were determined for Rn, such that each histogram is generated from a large ensemble of > 4000 individual traces. Interestingly, molecular conductance in these terphenyl derivatives shows an unexpected dependence on alkyl chain length. In particular, R0-R2 only show a single prominent conductance peak, and molecular conductance decreases upon increasing the alkyl chain length (Fig. 2b). The average molecular displacement for R0-R2 is constant (≈ 0.8 nm) because the alkyl side chain does not significantly affect molecular end-to-end distance for terphenyl derivatives with short side chains (Fig. 2d and Supplementary Fig. 1). In contrast, R3-R12 exhibit two dominant and well-spaced conductance states (high G and low G).</p><p>Interestingly, the conductance of the high G state (10 -3 G0) is more than one order of magnitude larger than the low G state (≈10 -4 -10 -5 G0). The molecular displacement corresponding to the high G state is approximately 0.4 nm, and the molecular conductance of the high G state is independent of the alkyl side chain length for R3-R12 (Fig. 2b and Supplementary Fig. 1).</p><p>Alkyl side chains are known to change the twist angle between planar conjugated units in molecular backbones, which affects electronic properties. 15,16 To understand the role of backbone conformation on molecular conductance, we performed molecular modeling of conductance in terphenyl junctions with varying twist angles. Terphenyl junctions with different conformations (Fig. 3a) were modeled using DFT calculations performed on Spartan'16 Parallel Suite using the B3LYP functional with a 6-31G (d,p) basis set. Following determination of geometry-optimized structures, transmission functions were calculated using nonequilibrium Green's function-density functional theory (NEGF-DFT) via the Atomistix Toolkit package (Fig. 3b and Supplementary Figs. 2-3). Our results show that the transmission values close to the Fermi energy decrease with cos 2 θ (between θ = 0 o and 90 o ), where θ is the dihedral angle between the first two phenyls. The simulated conductance is ≈10 -2.9 G0 for terphenyl junctions with full planar conformations and ≈10 -4.5 G0 when the dihedral angle is close to 90 o , which is in good agreement with the experimentally observed high G and low G states, respectively (Fig. 2b). To further validate these results, we synthesized two control molecules with planar (R1-planar) and twisted (R1-twisted) conformations (Fig. 3a). The experimentally measured conductance values for these molecules are in reasonable agreement with results from NEGF-DFT simulations (Fig. 3b and Supplementary Fig. 4). These results suggest that the low G state derives from twisted conformations and depends on backbone dihedral angles, whereas the high G state is likely associated with a planarized backbone but is only observed for long alkyl side chains (n ≥ 3). However, the molecular displacement corresponding to the high G state is » 0.4 nm, which is significantly smaller than the expected displacement of an extended molecular backbone for a terphenyl derivative. To fully understand the molecular origin of the high G state, we performed a series of singlemolecule conductance experiments using R3-R12 at different concentrations (100 nM -1 mM) (Fig. 3c and Supplementary Fig. 5). Surprisingly, our results show that the emergence of the high conductance state depends on the solution concentration of R3-R12. R3 exhibits a single peak (low G state) at relatively low concentrations (< 1 mM) and dual peaks (high G and low G states) at high concentrations (1 mM). Interestingly, the onset concentration for the emergence of the high G state decreases from 1 mM to 0.1 mM upon increasing the length of the alkyl side chain (Supplementary Fig. 5). Moreover, R3-R12 do not exhibit dual peaks at very low concentrations at 0.01 mM (Fig. 3d and Supplementary Fig. 6), whereas R2 and R3-iPr (containing the isomeric isopropyl side chain) do not exhibit a high G state at very high concentrations (10 mM) (Supplementary Fig. 7), suggesting that a minimum linear alkyl side chain length is required for the emergence of the high conductance state. In addition, we analyzed correlations between the high G and low G states for R3-R12 by determining a 2D covariance histogram (Fig. 3e and Supplementary Fig. 8). These results show a clear negative correlation between the high G and low G states, indicating that these two conductance states occur independently.</p><p>Recent work has reported that additional conductance states may arise from in-backbone molecule-electrode linkages, 9,[18][19][20][21] in situ dimerization, 17,[22][23][24] or intermolecular interactions. [25][26][27] To investigate the origin of the high G state, we synthesized the non-C2-symmetric terphenyl derivative R6-H containing only one terminal anchor using automated iterative cross-coupling (Fig. 1c). Single-molecule characterization using STM-BJ shows that R6-H cannot form stable molecular junctions and therefore does not exhibit a high G state (10 -3 G0) at 0.1 mM (Supplementary Fig. 9). These results suggest that the high G state does not arise from intermolecular interactions or in-backbone linkages between the molecule and gold electrodes. To investigate the potential for solution-based aggregation, we performed an 1 H NMR dilution experiment at experimentally relevant concentrations for R6 (Supplementary Information, Section S.4; Supplementary Fig. 13). Overall, these experiments showed no significant spectral changes for concentrations between 0.1 mM and 10 mM, which further suggests that solutionbased molecular aggregation is not responsible for the high G state.</p><p>We further performed flicker noise analysis experiments for R6 at a solution concentration of 1 mM. Flicker noise analysis has been used in prior work to understand the nature of electronic coupling at metal-molecule interfaces. 26,28,29 In this way, through-bond transport is distinguished from through-space transport based on the power-law exponent of 'noise power' (determined from power spectral density analysis of conductance fluctuations) versus average conductance. 13 Intermolecular charge transport typically results in larger fluctuations in conductance, which corresponds to through-space distributions of flicker noise. 26 Our results show that the noise power scales as G 1.01 for the high G and G 1.36 for the low G state, corresponding to through-bond coupling in molecular junctions (Supplementary Fig. 10). Taken together, the combination of flicker noise analysis and control experiments indicates that the high G state arises from molecule-electrode linkages between SMe anchors at both termini.</p><p>Based on these results, we hypothesized that long alkyl side chains (n ≥ 3) promote adsorption of the terphenyl backbone onto gold surfaces through van der Waals interactions, thereby inducing backbone conformational changes leading to increasingly planar backbone geometries (Fig. 3f).</p><p>To test this hypothesis, we developed an analytical model based on Langmuir adsorption with a weakly bound conformation (low G state) that converts to a strongly bound state (high G state) (Supplementary Information, Section S.5). Here, the low G state corresponds to an upright molecular conformation with a junction anchored at both termini to metal electrodes, whereas the high G state corresponds to a molecular conformation in which a molecule is 'laying down' on the electrode surface via side chain-mediated van der Waals interactions. The concentration-dependent conductance behavior of the high G state suggests that molecular junctions transition from a 'standing up' to a 'laying down' conformation facilitated by intermolecular interactions between free molecules in solution and molecules linked to the surface electrode via a terminal anchor, 30 thereby planarizing the terphenyl backbone and reducing steric hindrance for the adsorbed molecule to lay down on the surface. The sequential two-state adsorption results in a threshold-level dependence of solution concentration for the 'laying down' conformation (Supplementary Fig. 14). As solution concentration is increased, the 'laying down' conformation becomes increasingly dominant, and the molecular sub-population exhibiting the high G state conductance increases. Overall, the results from the analytical model qualitatively agree with the concentrationdependent conductance behavior observed in experiments.</p><!><p>To further understand the role of terminal anchor groups on the conductance behavior of terphenyl derivatives, we synthesized two amine-terminated terphenyls with different alkyl side chain lengths (R4-N and R6-N) using our automated synthesis method (Fig. 4a). It is known that SMe and NH2 serve as dative coordination anchors for Au electrodes, yet exhibit different contact resistance, binding behavior, and adsorption free energies in single-molecule experiments. [31][32][33] Interestingly, our results show that amine-terminated terphenyls exhibit different concentrationdependent conductance behavior compared to their SMe-terminated counterparts. R4-N does not show a high G state even at relatively high concentrations (10 mM), suggesting a lack of side chain-mediated molecular adsorption for R4-N on electrode surfaces (Fig. 4b) despite containing identical alkyl chains as R4. We posit that this phenomenon arises from the low adsorption free energy and different binding behavior of NH2 compared to SMe anchors, which in turn inhibits backbone adsorption of R4-N at concentrations up to 10 mM. On the other hand, R6-N shows the emergence of an ultra-high conductance state (10 -2 G0) at 1 mM concentration (Fig. 4b-c), which contrasts with the behavior of R6 and R4-N. The ultra-high conductance state of R6-N occurs over small molecular displacements and likely arises due to perpendicular transport via Au-pi-orbital interactions (Fig. 4d), as reported in prior work. 34,35 If two terminal amine anchors are involved in surface binding, the probability of junction formation is likely reduced due to an inability of the tip to disrupt molecule-surface binding interactions. Terminal amine anchors only contain a single lone electron pair instead of two lone pairs for SMe anchors, which speculate may decrease the availability for dative interactions between a lone electron pair and the free orbital on the gold tip. This mechanism of transport is consistent with the conductance pattern of R6-H (containing a single terminal SMe anchor) at 1 mM concentration (Supplementary Fig. 9), which exhibits a similar ultra-high conductance state (10 -2 G0) as R6-N.</p><!><p>Oligo(ethylene glycol) (OEG) and alkoxy chains contain oxygen atoms that increase hydrophilicity, polarity, and chain flexibility compared to hydrophobic alkyl side chains. 36 Conjugated materials bearing OEG or alkoxy side chains exhibit different morphologies and electronic properties compared to their alkyl side chains counterparts. [36][37][38][39] To investigate the role of side chain chemistry and composition on molecular charge transport, we synthesized a series of derivatives with OEG and alkoxy side chains using automated synthesis (Fig. 5a). In general, molecules with OEG/alkoxy chains show higher conductance and reduced molecular adsorption behavior compared to their alkyl side chain counterparts (Fig. 5b, Supplementary Figs. 11-12). 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 14 (Supplementary Table 1). Second, molecules with oxygen-containing side chains generally show more planar backbone conformations, which enhances charge transport (Supplementary Table 1). 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. 36 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. 40,41 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. 5b). 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. 5b and Supplementary Fig. 12). These results are consistent with increased oxygenation of side chains increasing chain flexibility and suppressing side chain-mediated adsorption (Fig. 5c). Moreover, it is possible that aliphatic chains form stronger van der Waals interactions with the electrode surface than their oxygenated counterparts. 42 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.</p><!><p>The Supporting Information is available free of charge on the website at DOI: XXX. Description of chemical synthesis, experimental details on STM-BJ, supporting text, and supporting figures.</p><!><p>The authors declare no competing financial interests.</p>