Charge Transport in Sequence-Defined Conjugated Oligomers

Article abstract of DOI:10.1021/jacs.0c00043

A major challenge in synthetic polymers lies in understanding how primary monomer sequence affects materials properties. In this work, we show that charge transport in single molecule junctions of conjugated oligomers critically depends on the primary seq

Full text of DOI:10.1021/jacs.0c00043

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Article
Charge Transport in Sequence-Defined Conjugated Oligomers
Hao Yu, Songsong Li, Kenneth E. Schwieter, Yun Liu, Boran Sun, Jeffrey S. Moore, and Charles M. Schroeder
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c00043 • Publication Date (Web): 18 Feb 2020
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Charge Transport in Sequence-Defined
Conjugated Oligomers
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Hao Yu 1†, Songsong Li2,4†, Kenneth E. Schwieter3, Yun Liu3,4, Boran Sun1, Jeffrey S. Moore2,3,4
and Charles M. Schroeder1,2,3,4*
,
1Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-
Champaign, Urbana, Illinois 61801, United States
2Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign,
Urbana, Illinois 61801, United States
3Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801,
United States
4Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-
Champaign, Urbana, Illinois 61801, United States
†Contributed equally to this work.
*To whom correspondence should be addressed.
Email: cms@illinois.edu
Keywords: sequence-defined oligomers, single molecule charge transport, scanning tunneling
microscope break-junction (STM-BJ)
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ABSTRACT
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A major challenge in synthetic polymers lies in understanding how primary monomer sequence
affects materials properties. In this work, we show that charge transport in single molecule
junctions of conjugated oligomers critically depends on the primary sequence of monomers. A
series of sequence-defined oligomers ranging from two to seven units was synthesized by an
iterative approach based on the van Leusen reaction, providing conjugated oligomers with
backbones consisting of para-linked phenylenes connected to oxazole, imidazole, or nitro-
substituted pyrrole. The charge transport properties of these materials were characterized using
a scanning tunneling microscope-break junction (STM-BJ) technique, thereby enabling direct
measurement of molecular conductance for sequence-defined dimers, trimers, pentamers, and
a heptamer. Our results show that oligomers with specific monomer sequences exhibit
unexpected and distinct charge transport pathways that enhance molecular conductance more
than 10-fold. A systematic analysis using monomer substitution patterns established that sequence-
defined pentamers containing imidazole or pyrrole groups in specific locations provide
molecular attachment points on the backbone to the gold electrodes, thereby giving rise to
multiple conductance pathways. These findings reveal the subtle but important role of
molecular structure including steric hinderance and directionality of heterocycles in
determining charge transport in these molecular junctions. This work brings new understanding
for designing molecular electronic components.
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INTRODUCTION
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Sequence-defined oligomers (SDOs) and sequence-defined polymers (SDPs) are chain
molecules with a precise order of monomer units; each molecule has a monomeric sequence that
is identical to every other molecule1,2. Sequence definition in nucleic acids and proteins is essential
to the molecular blueprint of cellular functions. In synthetic materials, SDOs and SDPs offer a new
dimension to manipulate self-assembly3,4, catalysis5, nanoelectronics6, molecular recognition7,
molecular encoding of information8, and phase behavior in polyelectrolytes9. Despite many recent
advances, relating primary monomer sequence to the physical, chemical, and electronic properties
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of organic materials remains an unsolved problem10,11
.
The synthetic availability of precision SDOs has hindered progress in realizing structure-
function relations1. Major challenges lie in the efficient and scalable production of non-
biological oligomers and polymers with discrete chain lengths and sequences. Indeed, the efficient
synthesis of non-biological SDOs and SDPs has been called a “Holy Grail” of polymer science12.
Various synthetic methods have been pursued, including iterative synthesis13,14, template-based
synthesis15, and controlled step- or chain-growth statistical polymerization6,16–19. Recently,
advanced synthesis methods and molecular designs including automated synthesis techniques20,21
and artificial catalytic molecular machines22 have been introduced into this burgeoning field and
continue to open new avenues for the precise synthesis of sequence-defined materials. However,
developing synthetic schemes that afford conjugated backbones remains a key challenge. The most
useful synthetic methods would be able to draw from a variety of building blocks such as aromatic
carbocyclics and heterocyclics. Such methods make possible the establishment of sequence-
property correlations beginning from a discrete reference sequence followed by the addition or
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replacement of monomers at specific locations and subsequently determining the change in
properties.
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To date, there have been limited studies correlating sequence and properties in a ‘monomer by
monomer’ fashion. Nevertheless, pioneering works from Hawker23, Li24, Lutz25, McNeil26,
Meyer27, Noonan28, Segalman29 and Zuckermann30 have highlighted sequence-regulation as a
promising and powerful method to control the properties of SDOs and SDPs. In SDOs and SDPs,
each monomer contributes to the backbone’s electronic structure and functional group
placement by altering chain conformation and molecular geometry. Intrinsic monomeric
contributions to bulk materials properties are difficult to disentangle due to the contributions
from intermolecular and intramolecular factors. To this end, single molecule techniques offer
the ability to directly probe properties at the molecular scale, thereby enabling elucidation of
quantitative structure-property relationships (QSPR) for sequence-defined materials31,32. Single
molecule junctions have been used to study charge transport as a function of molecular length33,
aromaticity34, anchor groups35, chemical substituents36, bias voltage37, molecular conformation38
and orbital alignment between molecular bridges and metallic electrodes39. The direct
measurement of single molecule conductance provides the opportunity to probe the intrinsic
relationship between sequence and electronic properties.
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In this work, the synthesis of precisely defined conjugated SDOs is described together with
single molecule conductance measurements and molecular simulations. We first establish an
iterative strategy for synthesizing sequence-defined conjugated oligomers using the van Leusen
heterocycle synthesis. This approach was applied to the synthesis of a series of SDOs consisting
of alternating p-phenylene and heterocyclic units. Unlike traditional iterative synthetic schemes
that require chemically distinct monomers, our approach provides sequence definition by
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altering reaction conditions in each synthetic cycle using a universal monomer. Following
synthesis, we directly characterize the molecular conductance and charge transport properties
of the SDO library using a scanning tunneling microscope-break junction (STM-BJ) method.
Our results show that molecular junctions with specific monomer sequences exhibit multiple
distinct charge transport pathways, some of which enhance conductance more than 10-fold. In
tandem, we characterize the distinct conductance pathways using a series of structural
analogues in concert with molecular modeling. Our results show that the high conductance
pathways emerge from gold-molecule linkages through imidazole and nitro-substituted pyrrole
located within the oligomer backbone. In this way, geometrical effects including sequence-
controlled directionality and steric hinderance of side chains determine intramolecular charge
transport in conjugated oligomers. The role of primary monomer sequence and its role on charge
transport in molecular junctions is elucidated, which will inform the design of molecular
electronic devices.
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RESULTS AND DISCUSSION
Synthetic Strategy, Preparation, and Characterization
An iterative approach was developed for synthesizing discrete, conjugated oligomers with
wide ranging compositions and sequence variations. Since 1972, tosylmethyl isocyanide
(TosMIC) and its aryl-substituted homologues have been widely used as a C-N=C synthon in
the synthesis of multiple heterocycles including oxazoles, imidazoles, and pyrroles, which are
collectively known as van Leusen multicomponent reactions (van Leusen MCRs)40. Here, we
design a monomer (M) containing the requisite tosylmethyl isocyanide group for heterocycle
synthesis and a latent functionality (nitrile) for subsequent additions by reductive conversion to
a terminal aldehyde. The iterative method consists of two steps (Fig. 1a): (1) a coupling reaction,
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a
universal
monomer (M)
universal
monomer (M)
universal
monomer (M)
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octyl
N
NO2
O
S
N
H
O
S
O
S
O
CN
MeNO2
NH4OAc
AcOH, 80℃
O
O
CN
CN
Me
MeOH, rt
K2CO3
MeOH/DME (3:1)
60℃
N
C
N
C
NH2
6
C
K2CO3
MeOH/DME (3:1)
60℃
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n-BuLi, LiBr
THF, -40℃
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O
O
octyl
O2N
O
N
N
O
N
NH
H
H
H
CN
CN
CN
Me
Me
Me
DCM, -78℃
Me
Me
Al
H
Al
H
Me
Me
Me
Me
Me
Me
Al
H
DCM, -78℃
DCM, -78℃
Me
b
universal monomer (M)
N
N
O
N
O
N
SMe
O
S
O
… …
S
O
O
Me
CN
SMe
Me
Al
O
MeS
MeS
N
C
N
C
R
R
O
H
NH
H
Me
O2N
Me
H
octyl
octyl
N
N
SMe
MeS
… …
… …
oxazole synthesis
imidazole synthesis
pyrrole synthesis
oxazole synthesis
imidazole synthesis
pyrrole synthesis
DIBAL-H reduction
O
O
MeS
MeS
H
H
N
N
O
O
R = H, 1,2 dimethoxyethane
O2
N
O2
N
NH
NH
SMe
MeS
MeS
Figure 1. Iterative Synthesis of Sequence-Defined Oligomers.
(a) Iterative approach consisting of a coupling reaction and a subsequent reduction for the
synthesis of alternating para-substituted phenyls linked to oxazole, imidazole, or nitro-
substituted pyrrole.
(b)
Schematic of sequence-controlled synthesis for pentamers. Three different heterocycles
(oxazole, imidazole, or nitro-substituted pyrrole) are generated by varying the reaction
conditions in each cycle to achieve sequence-defined oligomers. Oligomers are terminated with
methyl sulfide to facilitate single molecule conductance measurements.
which is used to generate a heterocycle (oxazole, imidazole, or nitro-substituted pyrrole) from
an aldehyde by proceeding through one of three homologous van Leusen MCRs, and (2) a
reduction, which returns an aldehyde from the terminal nitrile using diisobutylaluminium
hydride (DIBAL-H), thereby enabling additional coupling reactions in subsequent steps.
Oligomers prepared by this approach have an orthro connectivity to the heterocycle, which
leads to a twisting between the phenylene and heterocycle in the molecular backbone.
Additional diversity was achieved by including chemical substitutions such as 1,2-
dimethoxyethane on the phenylene group. Broadly speaking, this strategy allows for preparation
of compositionally rich sequences of defined length with a limited set of building blocks.
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O
O
octyl
O2N
N
N
O
N
NH
a
sequence definition
O
O
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R
O
I
P
G
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trimer
N
N
N
NH
O
octyl
O2N
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SMe
SMe
SMe
MeS
MeS
MeS
PO
PI
PR
POP
PIP
PRP
pentamer
oligomer with side chain
O
N
O
O
O
MeS
O
GO
GOP
POPOP
POPIP
POPRP
GOPOG
GOPOP
PIPOP
PIPIP
PIPRP
heptamer
O
N
MeS
SMe
O
N
O
N
PRPOP
PRPIP
PRPRP
attempts failed
POPOPOP
b
SMe
SMe
N
O
NH
O2
N
=
=
N
NH
O
O2N
MeS
MeS
POPRP
PRPOP
Figure 2. Sequence-Defined Conjugated Oligomers with Alternating Phenyl Heterocycle
Backbones.
Building blocks for sequence definition, O (oxazole), I (imidazole), R (pyrrole), P
(phenyl), and G (substituted phenyl). Molecular library of sequence-defined dimers, trimers,
pentamers, and heptamer.
(a)
(b)
Crystal structures of POPRP and PRPOP formed by slow evaporation from a mixed
solvent (chloroform/n-hexane). Hydrogen atoms are removed for clarity, and a CHCl3
molecule is located within the unit cell of PRPOP.
Using the iterative approach described above, 19 SDOs were prepared ranging in length from
dimer to heptamer (Fig. 2a). In particular, we synthesized nearly all possible dimeric, trimeric,
and pentametric sequences with unsubstituted phenylene units. Attempts to synthesize the
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Figure 3. Single Molecule Conductance of Sequence-Defined Oligomers.
(a)
(b)
Schematic illustration of single molecule break junction.
Characteristic single molecule conductance traces of sequence-defined pentamers
showing a single conductance peak (applied bias 0.25 V).
(c) Characteristic single molecule conductance traces of sequence-defined pentamers
exhibiting multiple conductance peaks (applied bias 0.25 V). For these oligomers, two well-
spaced conductance peaks are observed (high conductance 10-3.5 G0, low conductance 10-4-10-
5 G0).
(d)
Series of 1D conductance histograms for 10 sequence-defined pentamers (applied bias
0.25 V). Some sequences exhibit multiple conductance peaks associated with multiple
molecular conductance pathways. Dotted line shows the result of Lorentzian fitting.
pentamer containing two pyrrole units failed, presumably because of side reactions between the
pyrrole-containing precursor and the reagent n-butyllithium in the second iterative cycle.
Broadly speaking, this methodology is generalizable to synthesize oligomers beyond the
heptameric length and the sequence variations described here.
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1
13
The structure of each SDO was confirmed by H and C NMR spectroscopy and mass
spectrometry (Supporting Information, Sections 1-3 and Figs. S1-S80). Sequence-defined
oligomers are referred to using a naming convention based on the substituent building blocks
(Fig. 2). Pentamers containing the same composition but with different sequences are
structurally distinct. For example, PIPOP and POPIP are constitutional isomers with different
heterocycle directionalities that may impact charge transport, as discussed below. A pair of
isomeric pentamers, POPRP and PRPOP, crystallized as slender prisms under ambient
conditions. Single-crystal X-ray diffraction analysis reveal that both oligomers have similar
twisted U-shaped conformations in the solid state (Fig. 2b). Interestingly, primary sequence
also plays an important role in solid state structures such that POPRP and PRPOP have
different packing patterns (Supporting Information, Figs. S81-S84). By using different
solutions as mixed solvents (chloroform/n-hexane or ethyl acetate/n-hexane), we also observed
two polymorphs of POPRP (Supporting Information, Tables S1-S2 and Figs. S81-S82) and
one solvatomorph of PRPOP (Supporting Information, Tables S3-S4 and Figs. S83-S84).
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Single Molecule Conductance of Sequence-Defined Oligomers
We employed a single molecule measurement - electronic conductance - to directly measure
the charge transport properties of each SDO. In particular, molecular conductance is determined
using a scanning tunneling microscope-break junction (STM-BJ) technique as previously
described (Fig. 3a and Supporting Information, Sections 5 and Figs. S85-S105)29, 41. In all cases,
experiments are repeated on at least 103-104 individual molecules using the STM-BJ technique to
enable robust statistical analysis. The SDOs contain dual terminal methyl sulfide (-SMe) groups
that serve as anchors for making robust connections to gold electrodes33,41,43. Individual
molecular conductance traces (Figs. 3b, 3c) are compiled into one-dimensional (1D) histograms
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without data selection (Fig. 3d). In this way, 1D conductance histograms enable determination of
the average molecular conductance by fitting the histogrammed data to a Lorentzian function44.
For the alternating phenylene-heterocycle oligomers in this work, we generally observe an average
molecular conductance in the range between ~10-3-10-5 G0 (Tables S5-S7), where G0 = 77.5 µS is
the quantum unit of conductance. The ortho connectivity around heterocycles leads to a twisting
between the heterocycle and phenylene, which slightly lowers the molecular conductance
compared to fully planar structures, such as oligothiophene.33
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Molecular conductance in the pentamer series shows a remarkable sequence-dependent
behavior. For example, conductance histograms of two compositionally identical pentamers
POPIP and PIPOP are markedly different (Figs. S86, S89, and S93), such that POPIP shows a
predominent single peak at low conductance whereas PIPOP exhibits two well-spaced peaks in
molecular conductance (Fig. 3d). We observed two dominant and well-spaced conductance peaks
(high G and low G) in pentamers with sequences - PIPRP, PIPOP, POPRP, and PIPIP (Figs. 3c,
3d, and S86). Specifically, the conductance of the high G state (10-3.5 G0) is more than one order
magnitude larger than the corresponding low G state (10-4-10-5 G0) for this set of pentamers. On
the other hand, a different set of pentamers (PRPIP, POPRP, GOPOG, PRPOP, GOPOP, and
POPOP) exhibits a primary conductance peak around 10-4-10-5 G0 and a possible obscured or
weak shoulder at a higher molecular conductance around 10-3.5 G0. To quantitatively characterize
this behavior, we used a Lorentzian fitting method to determine the relative dominance or ratio of
the primary conductance peak to possible shoulders or obscured peaks (Supporting Information,
Sections 5.4, Fig. S106-S111). Our results show that the pentamers PRPIP, POPIP, GOPOG,
PRPOP, GOPOP, and POPOP are well described by a primary conductance peak, which
suggests that charge transport primarily occurs through a single dominant molecular conductance
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ꢁ
N
multiple charge
octyl
ꢃ
N
SMe transport pathways
➜
➜
➜
➜
➜
➜
ꢀ
ꢀ
ꢀ
ꢁ
ꢁ
ꢂ
ꢁ
ꢂ
ꢃ
ꢂ
ꢃ
ꢃ
7
8
9
MeS
O
N
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ꢀ
ꢂ
PIPOP
octyl
octyl
N
N
N
N
SMe
➜
➜
➜
➜
➜
➜
ꢀ
ꢀ
ꢁ
ꢁ
ꢂ
ꢂ
ꢁ
ꢁ
ꢂ
ꢂ
ꢃ
ꢃ
MeS
N
O
N
O
S-PIPOP-H
H-PIPOP-S
octyl
N
N
SMe
octyl
N
N
➜
➜
➜
ꢂ ꢃ
ꢀ
ꢁ
ꢁ
ꢂ
O
N
MeS
N
O
H-OP-S
S-PIP-H
H-PIPOP-H
Figure 4. Structural Deconstruction to Determine Conductance Pathways. The pentamer
PIPOP has six possible charge transport pathways corresponding to conductance from the
terminal anchors and/or intramolecular heterocycles. Here, we synthesized five control
compounds with lower structural complexity providing suitable models to understand the
conductance pathway of the pentamer. In this way, the compounds H-PIPOP-H, S-PIP-H, and
H-OP-S only contain a single well-defined conductive pathway.
state. Together, these results imply that the charge transport pathway in the pentamer series is
dependent on primary sequence. Finally, molecular conductance results for trimers (POP, PIP,
PRP, and GOP) and a heptamer (POPOPOP) with heterocycles located in the backbone generally
show 1D conductance histograms with a single statistical conductance value (Figs. S85, S86, and
S99).
Identifying Sequence-Controlled Conductance Pathways
Compositional variations among the 19 SDOs introduce multiple conductance pathways owing
to the possibility that internal heterocycles provide anchor points between the conducting molecule
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and the gold electrodes. In particular, the nitro group in pyrrole R is known to serve as a dative
anchor for making robust linkages to gold electrodes45,46. Recent work has shown that oxazole O
serves as an efficient chemical anchor to gold electrodes for single molecule electronics47, and the
imidazole I has a free lone electron pair on the nitrogen atom that can potentially serve as an
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in-backbone anchoring site to gold electrodes48,49
.
A systematic structural deconstruction method was used to identify the charge transport
pathways of distinct conductance in the pentameric SDOs. We began by focusing on the
pentamer PIPOP and systematically examined a series of related fragments including H-OP-S
(dimer), S-PIP-H (trimer lacking thiomethyl anchor on one terminus), S-PIPOP-H (pentamer
lacking thiomethyl anchor on one terminus), H-PIPOP-S (pentamer lacking thiomethyl anchor on
one terminus), and H-PIPOP-H (pentamer lacking thiomethyl anchor on both termini) (Fig. 4).
These lower structural complexity analogs of PIPOP generally consist of sub-segments of the
pentamer or molecules lacking terminal thiomethyl anchors. In this way, the charge transport
pathways in these short molecular analogs are well-defined, which provides a logical and
systematic approach to experimentally deconstruct conductance pathways in pentamers of varying
sequence.
The molecular conductance of the parent pentamer and its simpler analogs were further
analyzed using two-dimensional (2D) histograms of conductance versus displacement. Prior STM-
BJ measurements have shown that the maximum displacement between the tip and substrate at
which finite conductance is measured is strongly correlated with the contour length of the
molecular junction50,51. As shown in Fig. 5a, the 2D conductance histograms for the pentamer
PIPOP show that the high G conductance state is associated with a small tip-to-substrate
displacement of ca. 0.4 nm, whereas the low G conductance state occurs with larger molecular
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a
b
c
101
100
101
100
101
100
SMe
O
N
octyl
N
N
N
SMe
N
octyl
10-1
10-2
10-3
10-4
10-5
10-1
10-2
10-3
10-4
10-5
10-1
10-2
10-3
10-4
10-5
MeS
N
O
MeS
O
N
MeS
POPOP
S-PIP-H
PIPOP
high G
low G
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0.0
0.2
0.4
0.6
0.8
0.0
0.2
0.4
0.6
0.8
0.0
0.2
0.4
0.6
0.8
Displacement (nm)
Displacement (nm)
Displacement (nm)
0.25 V
0.50 V
0.75 V
0.25 V
0.50 V
0.75 V
0.25 V
0.50 V
0.75 V
-6
-5
-4
-3
-2
-1
0
-5
-4
-3
-2
-1
0
-6
-5
-4
-3
-2
-1
0
Conductance (log(G/G0))
Conductance (log(G/G0))
Conductance (log(G/G0))
d
e
f
SMe
N
N
octyl
high G
low G
N
O
MeS
SMe
N
N
octyl
N
O
MeS
Figure 5. Molecular Conductance Pathways in Sequence-Defined Pentamers.
2D (top) conductance histograms at 0.75 V applied bias and 1D (bottom) conductance
histograms (at 0.25 V, 0.50 V and 0.75 V) of (a) PIPOP; (b) S-PIP-H; and (c), POPOP.
Mechanism for high conductance (high G) and low conductance (low G) pathways for
PIPOP.
Molecular conformations for single molecule junctions in NEGF-DFT simulations for
determining transmission spectra for two distinct conductance pathways for PIPOP.
(d)
(e)
(f)
Transmission probabilities of two distinct conductance pathways of PIPOP from
NEGF-DFT simulations.
extensions of ca. 0.6 nm. This observation suggests that the high G state is associated with charge
transport through shorter segments of the pentamer compared to the low G state.
To understand the high G charge transport pathway of the pentamer PIPOP, we began by
characterizing the molecular conductance of S-PIP-H (Figs. 5b and S101), which has a defined
charge transport pathway through the terminal thiomethyl anchor and the internal imidazole. Our
results show that S-PIP-H exhibits a molecular conductance that is consistent with the high G state
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of PIPOP (Fig. 5a) both in displacement and magnitude, across a wide range of applied bias (0.25
V, 0.50 V and 0.75 V) (Figs. S89, 101). These results are consistent with conductance in the dimer
PI (Fig. S87c) and likely arise by attaching the backbone to the gold electrode with terminal
thiomethyl anchor on one end and the central imidazole on the other. Moreover, the structural
analog S-PIPOP-H (Fig. S100) exhibits a similar high G conductance state as S-PIP-H (Fig.
S101), which is again attributed to charge transport through in-backbone imidazole linkages.
Interestingly, none of the other simpler analogs of PIPOP show a high G conductance state
observed in the parent pentamer PIPOP (Figs. S102 and S103). Taken together, these results
strongly suggest that the high G conductance pathway of PIPOP arises from charge transport
through the terminal thiomethyl anchor and the internal imidazole.
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Next, we analyzed the monothiolated control compounds S-PIP-H, S-PIPOP-H, and H-
PIPOP-S to reveal the nature of the low G charge transport pathway. We found that these
compounds generally exhibit conductance over a maximum displacement of ca. 0.4-0.5 nm (Figs.
S100-S102), whereas the low G state of PIPOP exhibits a molecular extension above 0.6 nm (Fig.
5a). Moreover, control compounds S-PIP-H and S-PIPOP-H only exhibit the high G state
consistent with PIPOP. On the other hand, the molecular conductance and displacement of the
low G state of PIPOP is consistent with pentamers that show a single conductance pathway such
as POPOP (Figs. 5c, S93-S98). Together, these results suggest that the low G conductance state
is associated with a charge transport pathway through the two terminal methyl sulfide anchors.
These results are in agreement with prior work by Gonzalez49 and Lu52, where the end-to-end
molecular charge transport pathway was generally found to exhibit a lower conductance compared
to in-backbone charge transport. Our findings are summarized in a schematic in Fig. 5d that shows
the observed charge transport pathways for the pentamer PIPOP.
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Molecular Origin of Sequence-Controlled Conductance Pathways
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Molecular modeling using nonequilibrium Green’s function-density functional theory (NEGF-
DFT) is a useful way to understand charge transport pathways in sequence-defined oligomers. In
all cases, molecular geometries are optimized using DFT calculations performed on Spartan’16
Parallel Suite using the B3LYP functional with a 6-31G (d,p) basis set, followed by determination
of transmission functions for relaxed molecules via the Atomistix Toolkit package (Fig. 5e).
NEGF-DFT simulations show that molecular conductance through in-backbone imidazole
linkages is >10x larger than conductance through the entire end-to-end molecular contour (Fig.
5f). These results are consistent with the experimental results based on simpler control compounds
derived from the reference pentamer.
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We excluded the possibility that the high G conductance state arises from multipodal linkages
between the oligomers and the gold tip and substrate. For example, it has been observed that 1,2-
disilaacenaphthenes51 exhibit a relatively high conductance state arising due to multipodal linkages
between the molecule and electrode surface. However, in our control experiments, the high G
conductance state is observed in S-PIP-H, which only has two anchors including the central
imidazole and terminal methyl sulfide. These results strongly suggest that the multipodal linkage
mechanism is likely not observed in the phenylene heterocycle oligomers in this work.
Prior work has also shown that transient molecular conformations leads to a switching of
conductance states in oligosilanes53 and oligogermanes54; however, this potential mechanism is
not observed in our molecular library. DFT calculations show that the majority of pentamers have
two conformations in solution: (1) a Z-shaped conformation, where the molecular backbone has a
zig-zag geometry, and (2) a U-shaped conformation, where the oligomer backbone has a hairpin
shape (Fig. S112-S121). In particular, we found that the 1,2-dimethoxyethane side chain has a
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octyl
a
b
c
d
N
N
SMe
SMe
octyl
N
N
SMe
MeS
MeS
NH
O2
N
PIPXP
PXPRP
NH
MeS
O2
N
X = O
X = O
X = I
⋯⋯PRP
( in-backbone linkage via pyrrole)
PIP⋯⋯
(in-backbone linkage via imidazole)
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X = I
O2
N
SMe
NH
X = R
N
N
MeS
octyl
SMe
octyl
⋯⋯PIP
N
N
PRP⋯⋯
NH
(no in-backbone linkage via imidazole)
O2
N
(no in-backbone linkage via pyrrole)
H-PRP-S
MeS
S-PIP-H
-5.5 -5.0 -4.5 -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0
Conductance (Log(G/G0))
-5.5 -5.0 -4.5 -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0
Conductance (Log(G/G0))
Figure 6. The Effect of Sequence on Charge Transport in Molecular Junctions.
(a) Comparison of control compound S-PIP-H with pentamers containing the general
sequence PIPXP (where X represents an arbitrary heterocycle such as oxazole, imidazole, or
nitro-substituted pyrrole) at 0.25 V.
(b)
sequence PXPRP sequence at 0.25 V.
(c) Geometrical evaluation of imidazole at different positions from NEGF-DFT
simulations.
Comparison of control compound H-PRP-S with pentamers containing the general
(d)
Geometrical evaluation of pyrrole at different positions from NEGF-DFT simulations.
The directionality of PIPXP and PXPRP facilitates in-backbone linkages through imidazole or
nitro-substituted pyrrole, thereby leading to a high G state. However, in-backbone linkages
(high G) for PXPIP and PRPXP are inhibited due to unfavorable geometries and steric
hinderance effects.
strong influence on the ratio of the Z-shaped conformation versus U-shaped conformation. For
example, the Z/U conformational ratio of POPOP, GOPOP, and GOPOG gradually decreases
from 2:1 to 0:1, such that GOPOG exclusively adopts the U-shaped geometry. Overall, our results
show that these different molecular conformations generally exhibit similar conductance states.
We next considered the high G conductance states of the pentamer subset consisting of
molecules PIPOP, PIPIP, PIPRP, and POPRP. The high G conductance states of PIPOP, PIPIP,
and PIPRP are consistent with control compound S-PIP-H both in displacement and magnitude
under different applied biases (0.25 V, 0.50 V and 0.75 V) (Figs. 6a, S89-91). This result
demonstrates that the high G conductance state of pentamers with a PIPXP sequence (where X
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represents an arbitrary heterocycle such as oxazole, imidazole, or nitro-substituted pyrrole) all
derive from an identical imidazole in-backbone linkage. In order to understand the nature of high
G conductance of pentamers with a PXPRP sequence (POPRP and PIPRP), we further
considered the oligomeric fragment H-PRP-S which is a trimeric structure lacking a thiomethyl
anchor on one terminus (Fig. 6b). Comparing POPRP and PIPRP with H-PRP-S, we attribute
the high G conductance state to an in-backbone linkage through the nitro-substituted pyrrole and
terminal methyl sulfide (Figs. 6b, S90 and S92). The slight difference in conductance magnitudes
between POPRP, PIPRP, and control compound H-PRP-S is likely due to differences in
conjugation in each molecular structure. The results are consistent across a wide range of bias
voltages (0.25 V, 0.50 V and 0.75 V) (Figs. S104 and S105). Nevertheless, we note that PIPRP
contains both imidazole and nitro-substituted pyrrole that may form in-backbone linkages, such
that conductance in PIPRP could arise due to a combination of two different in-backbone linkages.
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To more deeply understand the molecular origins of monomer sequence on conductance,
we considered the effects of electrode-molecule alignment due to backbone geometry and
conformation, monomer orientation, and steric interactions. Interestingly, we observe dual
conductance peaks for PIPOP, PIPRP, and POPRP, but only a single conductance peak for
their regioisomers POPIP, PRPIP, and PRPOP, despite both sets of molecules having the
identical composition in terms of in-backbone anchor groups (PIPOP versus POPIP, PIPRP
versus PRPIP, and POPRP versus PRPOP). Imidazole and nitro-substituted pyrrole groups
link to gold electrodes by a noncovalent coordination interaction, and the donor-acceptor linkage
is expected to be highly orientated as reported prior literature43,48. We therefore posit that the
alignment between in-backbone anchor sites and adjacent terminal anchoring groups is critically
important for forming robust in-backbone linkages. To test this hypothesis, we carried out DFT
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simulations for geometrical analysis of the metal-molecule junction. Indeed, DFT results show that
favorable in-backbone linkages are formed in structures beginning with a PIP sequence (e.g.
PIPXX), which is greatly facilitated by a linear alignment between the imidazole anchor and the
terminal methyl sulfide in a two-electrode STM-BJ configuration (Fig. 6c). However, for
structures ending with a PIP sequence (e.g. XXPIP), a robust in-backbone linkage is not formed
largely because the relative angle between the terminal methyl sulfide and the second anchor site
is much smaller than 90 degrees. Moreover, octyl side chains on the substituted imidazole group
also introduce strong steric hinderance in molecular junctions, which further inhibit in-backbone
linkages.
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Similar results are observed in cases where the in-backboned linkage is formed by a nitro-
substituted pyrrole. In particular, we observe that robust in-backbone linkages are only formed in
structures ending with a PRP sequence (e.g. XXPRP), wherein alignment between the in-
backbone anchor (nitro-substituted pyrrole) and the terminal anchor (methyl sulfide) is nearly
linear (Fig. 6d). This result is consistent with our experimental observation that only pentamers
with these two sequence characteristics (PIPXX or XXPRP sequence) exhibit two well-spaced
conductance peaks (Figs. 6a and 6b). In general, we find that the alignment between the in-
backbone anchor and the terminal anchor is critically important in the formation of in-backbone
linkages.
We further note that in-backbone oxazole heterocycles generally do not form robust linkages
to gold electrodes in our sequence-defined oligomers. Prior work has shown that the electron-
donating ability of a lone electron pair is a key dominant factor for determining coupling strength48.
Due to the strong electronegative character of oxygen, we posit that the nitrogen atom in oxazole
heterocycle has a relatively weak electron-donating ability compared to the nitrogen atom in
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imidazole. Such concepts are also familiar from coordination chemistry; for example, the reported
basicity of oxazole (pKa = 0.8 for the conjugate acid) and imidazole (pKa = 6.9 for the conjugate
acid) are consistent with our conjecture55. Overall, our results on sequence-controlled conductive
pathways are best explained in the context of geometrical directionality and local steric hinderance.
Together, these results may prove generalizable beyond the chemical structures described here and
could provide a design framework to understand sequence-effects in molecular electronics.
CONCLUSION
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In summary, we have demonstrated that the charge transport pathway in conjugated SDOs
is precisely controlled by primary sequence, which mainly results from sequence-controlled
electrode-molecule alignment. Using an iterative synthetic approach, the position and
directionality of three distinct heterocycles (oxazole, imidazole, and nitro-substituted pyrrole)
are precisely controlled along p-conjugated backbones for oligomers ranging in size from
dimers, trimers, pentamers, and a heptamer. Among 19 SDOs and dozens of control compounds,
single molecule conductance measurements show that four pentamers with specific sequences
exhibit two distinct conductance pathways consisting of a high conductance state (ca. 10-3.5 G0)
and a low conductance state (ca. 10-4-10-5 G0). By extensively studying a series of structural
analogues coupled with molecular modeling and simulations, we find that the high conductance
state arises from charge transport through an in-backbone linkage of imidazole or nitro-
substituted pyrrole, whereas the low G conductance state arises from charge transport through
terminal methyl sulfide anchor groups. The insights provided from NEGF-DFT simulations
suggest that a linear metal-molecule alignment geometry and minimal steric hinderance between
the metallic electrode and side chain facilitate the in-backbone linkage through heterocycles.
Broadly speaking, the synthesis scheme developed in this work will enhance the capabilities of
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preparing sequence-defined materials with controlled charge transport pathways. In addition, the
realization of underlying factors such as molecular geometry and steric interactions that are
regulated by primary sequence will enable new strategic molecular design strategies to build
materials with sequence-dependent properties.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
XXX. Description of chemical synthesis, chemical and physical characterization of oxazole-
terminated molecules, experimental details on STM-BJ, simulation methods, supporting text,
supporting figures.
Corresponding Author
cms@illinois.edu
Author Contributions
H.Y. and S.L. contributed equally to this work.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGEMENTS
We thank Latha Venkataraman and Yaping Zang for generously providing advice in building the
STM-BJ instrument. We also thank Prapti Kafle and Ying Diao for useful discussions and Toby
Woods for X-ray diffraction analysis. This work was supported by the U.S. Department of Defense
by a MURI (Multi-University Research Initiative) through the Army Research Office (ARO)
through Award W911NF-16-1-037 to C.M.S. and J.S.M.
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REFERENCES
6
7
8
9
(1)
(2)
(3)
Badi, N.; Lutz, J.-F. Sequence Control in Polymer Synthesis. Chem. Soc. Rev. 2009, 38
(12), 3383–3390.
Lutz, J.-F.; Ouchi, M.; Liu, D. R.; Sawamoto, M. Sequence-Controlled Polymers. Science
(80-. ). 2013, 341 (6146).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Davidson, E. C.; M. Rosales, A.; L. Patterson, A.; Russ, B.; Yu, B.; N. Zuckermann, R.;
A. Segalman, R. Impact of Helical Chain Shape in Sequence-Defined Polymers on
Polypeptoid Block Copolymer Self-Assembly. Macromolecules 2018, 51 (5), 2089–2098.
Epps Thomas H., I. I. I.; O’Reilly, R. K. Block Copolymers: Controlling Nanostructure to
Generate Functional Materials – Synthesis, Characterization, and Engineering. Chem. Sci.
2016, 7 (3), 1674–1689.
Le, D. N.; Hansen, E.; Khan, H. A.; Kim, B.; Wiest, O.; Dong, V. M. Hydrogenation
Catalyst Generates Cyclic Peptide Stereocentres in Sequence. Nat. Chem. 2018, 10, 968.
Gutekunst, W. R.; Hawker, C. J. A General Approach to Sequence-Controlled Polymers
Using Macrocyclic Ring Opening Metathesis Polymerization. J. Am. Chem. Soc. 2015,
137 (25), 8038–8041.
Hirao, T.; Kudo, H.; Amimoto, T.; Haino, T. Sequence-Controlled Supramolecular
Terpolymerization Directed by Specific Molecular Recognitions. Nat. Commun. 2017, 8
(1), 634.
Lutz, J.-F. Coding Macromolecules: Inputting Information in Polymers Using Monomer-
Based Alphabets. Macromolecules 2015, 48 (14), 4759–4767.
Lytle, T. K.; Chang, L.-W.; Markiewicz, N.; L. Perry, S.; E. Sing, C. Designing
Electrostatic Interactions via Polyelectrolyte Monomer Sequence. ACS Cent. Sci. 2019, 5
(4), 709–718.
(4)
(5)
(6)
(7)
(8)
(9)
(10) Lutz, J.-F. Defining the Field of Sequence-Controlled Polymers. Macromol. Rapid
Commun. 2017, 38 (24), 1700582.
(11) Lutz, J.-F.; Ouchi, M.; Sawamoto, M.; Meyer, T. Y. Sequence-Controlled Polymers:
Synthesis, Self-Assembly, and Properties. ACS Symposium Series. American Chemical
Society January 1, 2014, p 0.
(12) Lutz, J.-F. Sequence-Controlled Polymerizations: The next Holy Grail in Polymer
Science? Polym. Chem. 2010, 1 (1), 55–62.
(13) Barnes, J. C.; Ehrlich, D. J. C.; Gao, A. X.; Leibfarth, F. A.; Jiang, Y.; Zhou, E.; Jamison,
T. F.; Johnson, J. A. Iterative Exponential Growth of Stereo- and Sequence-Controlled
Polymers. Nat. Chem. 2015, 7, 810.
(14) Yang, C.; Flynn, J. P.; Niu, J. Facile Synthesis of Sequence-Regulated Synthetic Polymers
Using Orthogonal SuFEx and CuAAC Click Reactions. Angew. Chemie Int. Ed. 2018, 57
(49), 16194–16199.
(15) Niu, J.; Hili, R.; Liu, D. R. Enzyme-Free Translation of DNA into Sequence-Defined
Synthetic Polymers Structurally Unrelated to Nucleic Acids. Nat. Chem. 2013, 5, 282.
(16) Pfeifer, S.; Lutz, J.-F. A Facile Procedure for Controlling Monomer Sequence Distribution
in Radical Chain Polymerizations. J. Am. Chem. Soc. 2007, 129 (31), 9542–9543.
(17) Nowalk, J. A.; Fang, C.; L. Short, A.; M. Weiss, R.; H. Swisher, J.; Liu, P.; Y. Meyer, T.
Sequence-Controlled Polymers Through Entropy-Driven Ring-Opening Metathesis
Polymerization: Theory, Molecular Weight Control, and Monomer Design. J. Am. Chem.
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1
2
3
4
5
6
Soc. 2019, 141 (14), 5741–5752.
(18) Kobayashi, S.; M. Pitet, L.; A. Hillmyer, M. Regio- and Stereoselective Ring-Opening
Metathesis Polymerization of 3-Substituted Cyclooctenes. J. Am. Chem. Soc. 2011, 133
(15), 5794–5797.
7
(19) Satoh, K.; Ozawa, S.; Mizutani, M.; Nagai, K.; Kamigaito, M. Sequence-Regulated Vinyl
Copolymers by Metal-Catalysed Step-Growth Radical Polymerization. Nat. Commun.
2010, 1, 6.
(20) Li, T.; Liu, L.; Wei, N.; Yang, J.-Y.; Chapla, D. G.; Moremen, K. W.; Boons, G.-J. An
Automated Platform for the Enzyme-Mediated Assembly of Complex Oligosaccharides.
Nat. Chem. 2019, 11 (3), 229–236.
(21) Li, J.; Ballmer, S. G.; Gillis, E. P.; Fujii, S.; Schmidt, M. J.; Palazzolo, A. M. E.;
Lehmann, J. W.; Morehouse, G. F.; Burke, M. D. Synthesis of Many Different Types of
Organic Small Molecules Using One Automated Process. Science (80-. ). 2015, 347
(6227), 1221 LP – 1226.
(22) Lewandowski, B.; De Bo, G.; Ward, J. W.; Papmeyer, M.; Kuschel, S.; Aldegunde, M. J.;
Gramlich, P. M. E.; Heckmann, D.; Goldup, S. M.; D’Souza, D. M.; Fernandes, A. E.;
Leigh, D. A. Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule
Machine. Science (80-. ). 2013, 339 (6116), 189 LP – 193.
(23) Lawrence, J.; Goto, E.; M. Ren, J.; McDearmon, B.; Sub Kim, D.; Ochiai, Y.; G. Clark,
P.; Laitar, D.; Higashihara, T.; J. Hawker, C. A Versatile and Efficient Strategy to
Discrete Conjugated Oligomers. J. Am. Chem. Soc. 2017, 139 (39), 13735–13739.
(24) Liang, L.; Wang, J.-T.; Xiang, X.; Ling, J.; Zhao, F.-G.; Li, W.-S. Influence of Moiety
Sequence on the Performance of Small Molecular Photovoltaic Materials. J. Mater. Chem.
A 2014, 2 (37), 15396–15405.
(25) Roy, R. K.; Lutz, J.-F. Compartmentalization of Single Polymer Chains by Stepwise
Intramolecular Cross-Linking of Sequence-Controlled Macromolecules. J. Am. Chem.
Soc. 2014, 136 (37), 12888–12891.
(26) F. Palermo, E.; J. McNeil, A. Impact of Copolymer Sequence on Solid-State Properties for
Random, Gradient and Block Copolymers Containing Thiophene and Selenophene.
Macromolecules 2012, 45 (15), 5948–5955.
(27) Zhang, S.; E. Bauer, N.; Y. Kanal, I.; You, W.; R. Hutchison, G.; Y. Meyer, T. Sequence
Effects in Donor–Acceptor Oligomeric Semiconductors Comprising Benzothiadiazole and
Phenylenevinylene Monomers. Macromolecules 2016, 50 (1), 151–161.
(28) Fortney, A.; Tsai, C.-H.; Banerjee, M.; Yaron, D.; Kowalewski, T.; J. T. Noonan, K.
Impact of Precise Control over Microstructure in Thiophene–Selenophene Copolymers.
Macromolecules 2018, 51 (23), 9494–9501.
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48
49
50
51
52
53
54
55
56
57
58
59
60
(29) Patterson, A. L.; P. O. Danielsen, S.; Yu, B.; C. Davidson, E.; H. Fredrickson, G.; A.
Segalman, R. Sequence Effects on Block Copolymer Self-Assembly through Tuning
Chain Conformation and Segregation Strength Utilizing Sequence-Defined Polypeptoids.
Macromolecules 2019, 52 (3), 1277–1286.
(30) Sun, J.; Liao, X.; M. Minor, A.; P. Balsara, N.; N. Zuckermann, R. Morphology-
Conductivity Relationship in Crystalline and Amorphous Sequence-Defined Peptoid
Block Copolymer Electrolytes. J. Am. Chem. Soc. 2014, 136 (42), 14990–14997.
(31) Xin, N.; Guan, J.; Zhou, C.; Chen, X.; Gu, C.; Li, Y.; Ratner, M. A.; Nitzan, A.; Stoddart,
J. F.; Guo, X. Concepts in the Design and Engineering of Single-Molecule Electronic
Devices. Nat. Rev. Phys. 2019, 1 (3), 211–230.
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1
2
3
4
5
6
7
8
9
(32) Meier, M. A. R.; Barner-Kowollik, C. A New Class of Materials: Sequence-Defined
Macromolecules and Their Emerging Applications. Adv. Mater. 2019, 31 (26), 1806027.
(33) Capozzi, B.; Dell, E. J.; Berkelbach, T. C.; Reichman, D. R.; Venkataraman, L.; Campos,
L. M. Length-Dependent Conductance of Oligothiophenes. J. Am. Chem. Soc. 2014, 136
(29), 10486–10492.
(34) Yin, X.; Zang, Y.; Zhu, L.; Low, J. Z.; Liu, Z.-F.; Cui, J.; Neaton, J. B.; Venkataraman,
L.; Campos, L. M. A Reversible Single-Molecule Switch Based on Activated
Antiaromaticity. Sci. Adv. 2017, 3 (10), eaao2615.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(35) Moreno-García, P.; Gulcur, M.; Zsolt Manrique, D.; Pope, T.; Hong, W.; Kaliginedi, V.;
Huang, C.; S. Batsanov, A.; R. Bryce, M.; Lambert, C.; Wandlowski, T. Single-Molecule
Conductance of Functionalized Oligoynes: Length Dependence and Junction Evolution. J.
Am. Chem. Soc. 2013, 135 (33), 12228–12240.
(36) Zhang, N.; Lo, W.-Y.; Cai, Z.; Li, L.; Yu, L. Molecular Rectification Tuned by Through-
Space Gating Effect. Nano Lett. 2016, 17 (1), 308–312.
(37) Bai, J.; Daaoub, A.; Sangtarash, S.; Li, X.; Tang, Y.; Zou, Q.; Sadeghi, H.; Liu, S.; Huang,
X.; Tan, Z.; Liu, J.; Yang, Y.; Shi, J.; Mészáros, G.; Chen, W.; Lambert, C.; Hong, W.
Anti-Resonance Features of Destructive Quantum Interference in Single-Molecule
Thiophene Junctions Achieved by Electrochemical Gating. Nat. Mater. 2019, 18 (4), 364–
369.
(38) Aragonès, A. C.; Darwish, N.; Im, J.; Lim, B.; Choi, J.; Koo, S.; Díez-Pérez, I. Fine-
Tuning of Single-Molecule Conductance by Tweaking Both Electronic Structure and
Conformation of Side Substituents. Chem. – A Eur. J. 2015, 21 (21), 7716–7720.
(39) Chen, F.; J. Tao, N. Electron Transport in Single Molecules: From Benzene to Graphene.
Acc. Chem. Res. 2009, 42 (3), 429–438.
(40) van Leusen, A. M.; Siderius, H.; Hoogenboom, B. E.; van Leusen, D. A New and Simple
Synthesis of the Pyrrole Ring System from Michael Acceptors and
Tosylmethylisocyanides. Tetrahedron Lett. 1972, 13 (52), 5337–5340.
(41) Li, B.; Yu, H.; Montoto, E. C.; Liu, Y.; Li, S.; Schwieter, K.; Rodríguez-López, J.; Moore,
J. S.; Schroeder, C. M. Intrachain Charge Transport through Conjugated Donor–Acceptor
Oligomers. ACS Appl. Electron. Mater. 2019, 1 (1), 7–12.
(42) Aradhya, S. V; Venkataraman, L. Single-Molecule Junctions beyond Electronic Transport.
Nat. Nanotechnol. 2013, 8, 399.
(43) Su, T. A.; Neupane, M.; Steigerwald, M. L.; Venkataraman, L.; Nuckolls, C. Chemical
Principles of Single-Molecule Electronics. Nat. Rev. Mater. 2016, 1, 16002.
(44) Venkataraman, L.; Klare, J. E.; Nuckolls, C.; Hybertsen, M. S.; Steigerwald, M. L.
Dependence of Single-Molecule Junction Conductance on Molecular Conformation.
Nature 2006, 442 (7105), 904–907.
(45) Zotti, L. A.; Kirchner, T.; Cuevas, J.-C.; Pauly, F.; Huhn, T.; Scheer, E.; Erbe, A.
Revealing the Role of Anchoring Groups in the Electrical Conduction Through Single-
Molecule Junctions. Small 2010, 6 (14), 1529–1535.
(46) Kaliginedi, V.; V. Rudnev, A.; Moreno-García, P.; Baghernejad, M.; Huang, C.; Hong,
W.; Wandlowski, T. Promising Anchoring Groups for Single-Molecule Conductance
Measurements. Phys. Chem. Chem. Phys. 2014, 16 (43), 23529–23539.
(47) Li, S.; Yu, H.; Schwieter, K.; Chen, K.; Li, B.; Liu, Y.; S. Moore, J.; M. Schroeder, C.
Charge Transport and Quantum Interference Effects in Oxazole-Terminated Conjugated
Oligomers. J. Am. Chem. Soc. 2019, 141 (40), 16079–16084.
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1
2
3
4
5
6
(48) Leary, E.; La Rosa, A.; González, M. T.; Rubio-Bollinger, G.; Agraït, N.; Martín, N.
Incorporating Single Molecules into Electrical Circuits. The Role of the Chemical
Anchoring Group. Chem. Soc. Rev. 2015, 44 (4), 920–942.
(49) Miguel, D.; Álvarez de Cienfuegos, L.; Martín-Lasanta, A.; P. Morcillo, S.; A. Zotti, L.;
Leary, E.; Bürkle, M.; Asai, Y.; Jurado, R.; J. Cárdenas, D.; Rubio-Bollinger, G.; Agraït,
H.; Cuerva, J. M.; González, M. T.Toward Multiple Conductance Pathways with
Heterocycle-Based Oligo(Phenyleneethynylene) Derivatives. J. Am. Chem. Soc. 2015, 137
(43), 13818–13826.
(50) Kamenetska, M.; Koentopp, M.; Whalley, A. C.; Park, Y. S.; Steigerwald, M. L.;
Nuckolls, C.; Hybertsen, M. S.; Venkataraman, L. Formation and Evolution of Single-
Molecule Junctions. Phys. Rev. Lett. 2009, 102 (12), 126803.
(51) T. Kim, N.; Li, H.; Venkataraman, L.; L. Leighton, J. High-Conductance Pathways in
Ring-Strained Disilanes by Way of Direct σ-Si–Si to Au Coordination. J. Am. Chem. Soc.
2016, 138 (36), 11505–11508.
(52) Cai, Z.; Zhang, N.; Awais, M. A.; Filatov, A. S.; Yu, L. Synthesis of Alternating Donor–
Acceptor Ladder-Type Molecules and Investigation of Their Multiple Charge-Transfer
Pathways. Angew. Chemie Int. Ed. 2018, 57 (22), 6442–6448.
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59
60
(53) Su, T. A.; Li, H.; Steigerwald, M. L.; Venkataraman, L.; Nuckolls, C. Stereoelectronic
Switching in Single-Molecule Junctions. Nat. Chem. 2015, 7, 215.
(54) A. Su, T.; Li, H.; Zhang, V.; Neupane, M.; Batra, A.; S. Klausen, R.; Kumar, B.; L.
Steigerwald, M.; Venkataraman, L.; Nuckolls, C. Single-Molecule Conductance in
Atomically Precise Germanium Wires. J. Am. Chem. Soc. 2015, 137 (38), 12400–12405.
(55) Catalán, J.; Elguero, J. Basicity of Azoles. IV. Empirical Relationships between Basicity
and Ionization Potential for Aromatic Five Membered Rings Containing Nitrogen or
Oxygen. J. Heterocycl. Chem. 1984, 21 (1), 269–270.
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Page 26 of 32
universal
monomer (M)
universal
monomer (M)
universal
monomer (M)
octyl
H
1
2
3
4
5
6
7
8
NO2
N
O
S
O
S
O
S
O
CN
MeNO2
NH4OAc
AcOH, 80℃
O
O
CN
N
C
CN
Me
MeOH, rt
K2CO3
MeOH/DME (3:1)
60℃
N
C
NH2
N
C
6
K2CO3
MeOH/DME (3:1)
60℃
n-BuLi, LiBr
THF, -40℃
O
O
9
octyl
O2N
O
N
O
N
N
NH
10
11
12
13
14
15
16
17
H
H
H
CN
CN
CN
Me
Me
Me
DCM, -78℃
Me
Me
Me
Al
H
Al
H
Me
Me
Me
Me
Me
Al
H
DCM, -78℃
DCM, -78℃
Me
18
b
19
universal monomer (M)
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
N
N
O
N
O
N
SMe
O
S
O
… …
S
O
O
Me
CN
SMe
Me
Al
O
MeS
MeS
N
C
N
C
R
R
O
H
NH
H
Me
O2N
Me
H
octyl
octyl
N
N
SMe
MeS
… …
… …
oxazole synthesis
imidazole synthesis
pyrrole synthesis
oxazole synthesis
imidazole synthesis
pyrrole synthesis
DIBAL-H reduction
O
O
MeS
MeS
H
H
N
N
O
O
R = H, 1,2 dimethoxyethane
O2N
O2N
NH
NH
SMe
ACS Paragon Plus Environment
MeS
MeS

O
octyl
Journal of the American Chemical Society
O N
O
Page 27 of 32
2
N
N
O
N
NH
a
sequence definition
O
O
1
2
3
4
5
R
O
I
P
G
6
7
8
9
dimer
trimer
N
N
N
NH
O
octyl
O2N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
SMe
SMe
SMe
MeS
MeS
MeS
PO
PI
PR
POP
PIP
PRP
pentamer
oligomer with side chain
O
N
O
O
O
MeS
O
GO
GOP
POPOP
POPIP
POPRP
GOPOG
GOPOP
PIPOP
PIPIP
PIPRP
heptamer
O
N
MeS
SMe
O
N
O
N
PRPOP
PRPIP
PRPRP
attempts failed
POPOPOP
58
59
60
b
SMe
SMe
N
O
NH
O2N
=
=
N
NH
O
O2N
MeS
MeS
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PRPOP

Journal of the American Chemical Society
Page 28 of 32
a
1
2
3
4
5
6
d
PRPIP
POPIP
GOPOG
PRPOP
GOPOP
POPOP
PIPRP
PIPOP
POPRP
PIPIP
7
b
PRPIP
POPIP
GOPOG
PRPOP
GOPOP
POPOP
8
100
10-1
10-2
10-3
10-4
10-5
10-6
9
10
11
12
13
14
15
16
17
18
19
20
21
1 nm
Displacement (nm)
22
c
PIPRP
PIPOP
POPRP
PIPIP
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
100
10-1
10-2
10-3
10-4
10-5
10-6
1 nm
-5
-4
-3
-2
-1
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Displacement (nm)

Page 29 of 32
Journal of the American Chemical Society
Ⅱ
multiple charge
octyl
Ⅳ
N
N
1
2
3
4
5
6
7
8
SMe transport pathways
➜
➜
➜
➜
➜
➜
Ⅰ
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅲ
Ⅱ
Ⅲ
Ⅳ
Ⅲ
Ⅳ
Ⅳ
MeS
O
N
Ⅰ
9
10
11
12
13
14
15
16
17
Ⅲ
PIPOP
18
octyl
octyl
N
N
N
N
19
20
21
22
23
SMe
➜
➜
➜
➜
➜
➜
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅲ
Ⅲ
Ⅱ
Ⅱ
Ⅲ
Ⅲ
Ⅳ
Ⅳ
24
MeS
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
N
O
N
O
S-PIPOP-H
H-PIPOP-S
octyl
N
N
SMe
octyl
N
N
➜
➜
➜
Ⅲ Ⅳ
Ⅰ
Ⅱ
Ⅱ
Ⅲ
O
N
MeS
N
O
ACS Paragon Plus Environment
H-OP-S
S-PIP-H
H-PIPOP-H