Molecular electronics is an interdisciplinary subject that aims to assemble electronic components in a bottom-up approach using conducting molecules as building blocks. It represents an alternative to the lithography-based top-down preparation of silicon-based electronic circuits. A large variety of organic molecules with potentially useful electronic properties are available [1, 2]; however, one of the major obstacles for taking advantages of the unique properties of these molecules is the challenge associated with connecting the molecular components in a controllable manner.

Conjugated oligomers and polymers have been used extensively in bulk organic electronics such as light-emitting diodes, field-effect transistors, and polymeric solar cells [3, 4]. The study of the single molecule properties of conjugated polymers is more limited; however, studies have been performed using, e.g., scanning tunnel microscopy [5] and single molecule spectroscopy [6, 7]. The major problem in the production of single molecular-based electronics is the inability to arrange the components to form circuits.

In a seminal theoretical paper from 1987, Robinson and Seeman proposed a design for an electronic molecular memory chip formed by DNA guided self-assembly of conjugated polymer as wires and metal complexes as memory components [8]. Throughout the past 18 years a major focus of our laboratory has been to implement, at least in part, Robinson and Seeman’s vision to use DNA-directed self-assembly to generate and/or position molecular conjugated wires [9]. DNA nanotechnology provides a useful tool for controlling and connecting individual conjugated oligomer and polymer molecules at the nanoscale [10]. In order to exploit DNA nanotechnology for controlling organic molecules, the molecules have to be functionalized with single stranded DNA (ssDNA) sequences, which in turn direct the assembly of the molecules. In this paper, we will provide an overview of our work in this area, and we have summarized the contributions from others to the area at the end of the paper.

1 Modular Self-Assembly of Molecular Components

Our entry into this area was inspired by the intense interest in molecular electronics and the emergence of DNA-templated synthesis in beginning of the new millennium [11, 12]. We envisioned that DNA-templated synthesis may serve as a tool to both assemble and couple individual components to a fully conjugated oligomer as shown in Fig. 1.

Fig. 1
Three structures illustrate the concept of D N A-directed assembly and coupling individual components. 8 colored wavy lines at the top assemble and joins together. Then, it ends with the shape of a tripodal rod.

Concept of DNA-directed assembly and coupling of organic rod monomers into conjugated organic oligomers (linear and tripodal black rods: molecular monomers; colored wavy lines: DNA)

Full size image

Bunz and coworkers had shown that it was possible to assemble molecular rod oligomers using rod monomers displaying DNA at each terminus; however, the resulting oligomers were unconjugated as their rods were separated by DNA helices [13]. In 2001, Czlapinski and Sheppard reported on the DNA-directed coupling of salicylaldehydes into metal-salen complexes [14]. The metal-salen coupling was ideal for assembly of conjugated oligomers since the linkages are linear between the headgroups to form a conjugated oligomer. Furthermore, the electronic properties of the complexes should be interchangeable by changing the metal ion.

In our first approach to solve this problem, reported in 2004, we described the development of a DNA-directed bottom-up method for programmed assembly that utilized covalent couplings between multiple organic modules [15, 16]. The basic building blocks are rigid conjugated modules with an oligo(phenylene ethylene) backbone and have salicylaldehyde-derived termini. Additionally, each terminus contains a hydroxyl linker that is functionalized with either a 4,4’-dimethoxytrityl (DMT) protecting group or a phosphoramidite moiety. This allowed for incorporation of the module into the 3’-end of a DNA strand followed by removal of the DMT protecting group and synthesis of the second DNA strand. The modules were synthesized both as a linear oligonucleotide-functionalized module (LOM) and a tripoidal oligonucleotide-functionalized module (TOM) (Fig. 2a). By using complementary strands on the modules, it was possible to direct the assembly without the need for additional DNA templates. The modules were covalently coupled with metal-salen formation between the salicylaldehydes at the termini of the modules by reaction with ethylenediamine (EDA) and a manganese salt. The salicylaldehyde groups of two modules are brought in close proximity when their complementary DNA strands are annealed together allowing a pseudo-intramolecular reaction to occur (Fig. 2b).

Fig. 2
Four chemical structures. a. A two-part chemical structure of L O M 1, while b is the T O M 1. A schematic illustration represents the D N A-templated coupling which is distant on the left and closed to the right. c and d represent the illustration of linear oligomer and tripoidal constructs.

a Chemical structure of LOM and TOM. LOM-1 contains two 15-mer sequences: a and b’. TOM-1 contains three 15-mer sequences: one c’ and two b. b schematic illustration of the DNA-templated coupling. First step is an annealing of the two complementary strands, bringing the two reactive groups into close proximity. The next step is the formation of a covalent Mn-salen link between the two terminal salicylaldehydes by reaction with EDA and Mn(OAc)2. c Illustration of the linear oligomer and gel electrophoresis in 8 M urea shows that Mn-salen products are covalently linked. d Analogous illustration of the tripoidal constructs. Adapted with permission from [15]. Copyright (2004) American Chemical Society

Full size image

The DNA sequences on the modules can be altered, which makes it possible to combine the LOMs and TOMs to form a variety of linear and branched predefined structures. Self-assembly and coupling of up to four differently encoded linear modules was successfully obtained (Fig. 2c). More complex structures were built by combining LOMs and TOMs (Fig. 2d). Up to three LOMs was successfully coupled to a single TOM. This method provides a unique degree of control of the architecture of the molecular wire; however, a major challenge of the approach was that there seemed to be a limit of assembling four modules. Despite many attempts, we never managed to make penta- or higher-order structures in reasonable yields.

The research in this direction was continued to improve the system. In 2005, Nielsen et al. [17] investigated the DNA-directed double reductive amination of salicylaldehydes in the presence of EDA to form tetrahydrosalen. This amine-linked structure was found to be much more stable toward acid, heat, methylamine, and ethylenediamine tetraacetic acid (EDTA).

Additionally, the selective cleavage of DNA strands from the conjugated backbone was enabled by installing disulfide bridges between the DNA sequence and the LOM, called LOMS (Fig. 3a). The disulfide modified strands were successfully cleaved from the backbone by treatment with tris(2-carboxyethyl)phosphine (TCEP) [17, 18].

Fig. 3
An illustration of the D N A-directed coupling on the left, and a chemical structure of an elongated linear oligonucleotide-functionalized module (E L O M).

a Illustration of DNA-directed coupling of LOSM by metal-salen formation, followed by cleavage of DNA strands by reaction with TCEP. Adapted from [18] with permission from the Royal Society of Chemistry. b Chemical structure of the elongated linear oligonucleotide-functionalized module (ELOM)

Full size image

The attempts to improve the system did not make it possible to assemble more than four modules with a satisfactory yield. We speculated that this may be caused by steric and charge repulsion between the large oligonucleotide duplexes, as the diameter of a duplex is around 2 nm which is the same as the length of a LOM. Therefore, it is expected that the duplexes will induce steric strain as the structures grow. One possible solution to this problem is to extend the length of the linear module. In 2006, Blakskjær et al. [19] reported the synthesis of an elongated linear oligonucleotide-functionalized module (ELOM) (Fig. 3b). The DNA-directed coupling between an ELOM and LOM was successful; however, attempts to couple two or three ELOMs were unsuccessful. It is proposed that this is due to the amphiphilic nature of the ELOMs.

In 2008, a new strategy for DNA-programmed coupling of molecular rods was reported by Andersen et al. [20]. The aim of the new method was to make a simpler setup that only requires one conjugate to form dimers or higher-order structures. Two 10-mer oligonucleotide-functionalized rod-type modules were synthesized and arranged on a DNA template strand. This design places the rod modules approximately on the same side of the double helix, one helical turn apart. Inspired by the previous studies, the modules were functionalized with salicylaldehydes in each terminus. The rod was also functionalized with an activated ester in the middle of the structure, in order to couple to an amino-modified oligonucleotide. The templated coupling was tested by mixing a 20-mer template strand with two equivalents of reactive strand. The strands were annealed followed by reaction with ethylene diamine and a metal salt to form the pseudo-intramolecular coupling between the two reactive strands (Fig. 4a). Denaturation of the double helix allows for purification of the single stranded coupled product. It was possible to isolate the desired Mn-salen dimer in 10% yield, whereas the Ni-salen dimer was isolated in 25% yield. Additionally, it was also possible to form heterodimers by using two different DNA sequences. The preparation of a trimer was also attempted; however, it was not possible to identify the product by mass spectrometry. The starting materials were consumed in all reactions, which suggests that the low yield could be due to side reactions or loss of material due to aggregation. A more hydrophilic molecule could potentially solve the aggregation problems and allow for the formation of higher-order structures. An advantage of this method compared to the previous published method using LOM and TOM modules is that this method yields a coupled module with extending single strands. These strands could be hybridized to other DNA nanostructures, allowing a precise positioning of the nanowire. While the synthesis was simpler than LOM/TOM approach, it was limited by low yields and inability to form structures more complex than a dimer.

Fig. 4
Two chemical structures. a. Two reactive strands with D N A template combine together like a D N A structure. Then, denaturation removes the template strand and purifies. b. An illustration of a 4-helix bundle shaped like a waveform.

Copyright 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. b Illustration of 4-helix bundle with four modules

a DNA-templated dimerization of two molecular rods by metal-salen formation. Two reactive strands are annealed with a template strand to bring the molecular rods in close proximity. The rods are coupled by reaction with EDA and a metal salt. By denaturation, the template strand is removed, and the coupled product is purified by RP-HPLC. Adopted from [20] with permission from John Wiley and Sons.

Full size image

In the continuous search for DNA structures that can serve as templates for DNA-directed couplings of conjugated organic molecules, interhelical couplings in a DNA 4-helix bundle (4-HB) have been investigated [21]. A conjugated linear molecule containing terminal salicylaldehyde groups and a central activated ester was synthesized. The module was coupled to amino-modified DNA strands and incorporated into specific locations in a well-defined 4-HB, to allow for selective interhelical couplings (Fig. 4b). The coupling of the modules was tested with both a metal-salen and dihydrazone formation; the coupled products were then analyzed by denaturing PAGE analysis. The couplings were found to be very distance dependent, and no non-templated couplings were observed. With the metal-salen coupling, it was possible to obtain dimers in moderate yields; however, higher-order structures were not obtained. For the dihydrazone couplings, trimer formation was achieved.

The coupling of salicylaldehydes to form metal-salen linkages has been successful in other contexts. In a very recent study, the single molecule electronic properties of Mn(III), Co(III), and Fe(III)-salen complexes in a break junction were studied. The study showed that the metal-salen bridge is a relatively poor conductor but that the conductivity is dependent on the nature of the metal [22]. Unfortunately, the metal-salen formation is reversible, and the complex is labile in aqueous media. Therefore, alternative coupling strategies have been investigated in order to form irreversible, hydrolysis-resistant, and conjugated linkages between molecular modules. A method for DNA-directed formation of 1,3-diyne linkages between conjugated molecular building blocks has been reported by Ravnsbæk et al. [23]. The 1,3-diynes can be obtained by a Glaser-Eglinton reaction between terminal alkynes. An oligo(phenylene ethylene) molecular rod containing two terminal acetylene groups was synthesized to enable the formation of a conjugated linear oligomer. Additionally, each monomer was functionalized with DMT and phosphoramidite functionalities for incorporation into a DNA strand by automated oligonucleotide synthesis (Fig. 5a + b). A series of four 30-mer oligonucleotides were prepared by automated oligonucleotide synthesis, during which the phosphoramidite rod monomer was incorporated in the middle of the strand. This resulted in four oligonucleotide-functionalized diacetylene modules (ODM) consisting of organic module with two 15-mer sequences in each terminal region (Fig. 5c). The DNA-directed Glaser-Eglinton reactions were performed between the different ODM strands. Denaturing PAGE analysis of the crude products shows the formation of dimer and trimer in a high yield (Fig. 5d, lanes 2–4), while the tetramer shows a lower yield (Fig. 5d, lane 5). The lower yield is believed to be caused by the increasing electrostatic repulsion and steric hindrance between the increasing number of DNA strands. The electrostatic repulsion could be removed by changing the DNA strands to PNA strands; however, this would also result in a much less soluble molecule. The formed oligomers have a size of around 4–8 nm and could have an application as conducting nanowire. The oligomer contains single stranded DNA in each terminus, which could be used as handles for a specific positioning of the nanowire on a DNA origami structure.

Fig. 5
A chemical structure and three illustrations. a. A chemical structure with two terminal acetylene groups. b. An illustration of the coupling process of the two modified D N A strands that ends with four O D M in illustration c. In d, a denaturing P A G E analysis of D N A-directed Glaser Eglinton is present.

Copyright 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

a Chemical structure of the oligo(phenylene ethylene) phosphoramidite monomer. b illustration of annealing and subsequent Glaser-Eglinton coupling between two modified DNA strands. c oligomerization of ODM monomers by multiple Glaser-Eglinton reactions. d denaturing PAGE analysis of DNA-directed Glaser-Eglinton oligomerization of ODM sequences. Reproduced from [23] with permission from John Wiley and Sons.

Full size image

Despite the advances in DNA-directed synthesis, it was not possible to obtain structures longer than tetramers. Significantly longer sequence specific oligomers have been prepared by DNA-directed synthesis by others; however, these oligomers were not conjugated, and only one DNA strand is linked to the products [24,25,26].

2 Conjugated Polymers on DNA Origami

During the cause of our work on the modular DNA-directed assembly, the DNA origami method was published by Rothemund in 2006 [27]. This method enabled the self-assembly of, from a DNA point of view, very large structures with unique addressability, such as the rectangular mono-layer origami with dimensions of 100 × 70 nm2. Such a structure appeared to be an almost perfect breadboard for assembly and coupling of the molecular modules described above. However, upon closer consideration, it would require extremely efficient immobilization and chemical cross-linking to form a continuous wire of 100 nm across the origami structures. The modules are only 2 nm long, and it would require immobilization of approximately 50 modules and 49 coupling reactions that should all be successful to create a continuous wire. Especially in light of the poor yields obtained when attempting to template the assembly in a 4-helix sheet as described above [23], we chose to abandon the modular assembly strategy for creating larger wires on DNA origami.

Instead, we turned our attention to conjugated polymers that offers a continuous single molecular conjugated system that may be more than 100 nm long [28]. The drawback is the lack of full control over the length of the polymer; however as long as it is possible to remove shorter polymers, this may be acceptable. In order to control the assembly of such a polymer on DNA origami, it was a requirement to conjugate DNA sequences along the polymer to create a graft-type polymer. Based on our previous experience with hydrophobic wires and DNA, we assumed that a high density of DNA along the polymer (one DNA strand per monomer) would be required to avoid aggregation and precipitation. The DNA strands could be attached to the polymer by three different methods: (1) premade DNA strands are coupled to the monomers which are then polymerized, (2) premade DNA strands with a chemical handle are coupled to a complementary functional group on a premade polymer, and (3) the polymer is immobilized on a solid support, and the DNA strands are synthesized on the polymer by automated synthesis. We decided to pursue the latter approach since we believed this would enable the synthesis of long polymers with a high density of DNA.

As described by Knudsen et al. [29], poly(phenylene vinylene) containing a triethylene glycol (TEG) linker appending from each repeat unit was synthesized (Fig. 6). The TEG linkers were terminated with a tert-butyldiphenylsilyl (TBDPS) protecting group, and after deprotection, the terminal alcohol served as starting point for the DNA synthesis. Before DNA synthesis, the polymers were characterized by scanning tunneling microscopy (STM) (Fig. 7a) [30]. In addition to providing information about the molecular structure and composition of the polymer, this also showed that a fraction of the polymers was very long (>200 nm).

Fig. 6
A chemical structure illustrates the polymer synthesis at the top and solid phase D N A synthesis at the bottom, respectively. a. The process includes T B D P S deprotection that gives 4 b, while at the bottom, poly is deprotected and cleaved.

Synthesis of poly(APPV-DNA). The PPV polymer (4a) is synthesized by a dithiocarbamate route. Partial TBDPS deprotection to give 4b allows immobilization on a phosphoramidite-functionalized CPG support. After removal of the remaining protecting groups, ssDNA sequences are synthesized on the polymer by automated DNA synthesis. As the last step, poly(APPV-DNA) is deprotected and cleaved from the solid support. Reused with permission from MacMillan Publishers Ltd: [Nature Nanotechnology] [29] copyright (2015)

Full size image
Fig. 7
A S T M image illustrates the P P V T B D P S on the left and a schematic map of different polymer strands on the right. The lines representing the different lengths move in different directions. In b, an A F M topography illustrates the dispersal of poly on the mica surface, and a graph of height versus position fluctuates.

a left: STM image of PPV-TBDPS (4a) on Au(111), right: schematic map showing the different polymer strands and their respective lengths. Polymer strands are only measured as far as the edges of the STM image field. Reproduced from [30] with permission from The Royal Society of Chemistry. b left: AFM topography image showing poly(APPV-DNA) dispersed onto a mica surface, right: height measurements of poly(APPV-DNA) on the mica surface. Scale bar = 100 nm. Reused with permission from MacMillan Publishers Ltd: [Nature Nanotechnology] [29] copyright (2015)

Full size image

By partially deprotecting the side chains and exposing approximately 20–40% of the hydroxyl groups, it was possible to immobilize the polymer onto a solid support through phosphoramidite chemistry. This was followed by deprotection of the remaining side chains and synthesis of ssDNA directly onto the side chains of the polymer through automated solid phase oligonucleotide synthesis. Upon cleavage, deprotection, and purification, a water-soluble material was obtained (poly(APPV-DNA)).

By this method, we obtained very long DNA grafted polymers of around 200 nm that disperse well on a mica surface as shown in the AFM image in Fig. 7b. It was later discovered that the polymers had a tendency to aggregate in the presence of divalent cations, which significantly lowered the intensity of the emission [31]. The polymers were purified by size exclusion chromatography, and the fractions containing the longer polymers were selected for further experiments.

In order to control the immobilization of the polymer along a specific track on DNA origami, we used Rothemund’s rectangular DNA origami structure containing a line of single stranded DNA appending for every 5 nm on the origami surface. The density of DNA on the polymer is much higher as approximately 2/3 of each repeat unit of the polymer has a 9-mer sequence. The thermal stability of the attachment was greater than the 9-mer’s melting temperature because of the polyvalent binding of these oligos to the origami.

As shown in Fig. 8a, the polymer was efficiently immobilized along designed linear, bent, and U-shaped tracks on the DNA origami [29]. The polymer was also routed on a 3D barrel shaped DNA origami structure designed by Wickham et al. [32]. The 3D shape of the polymer was characterized by PAINT super-resolution imaging as shown in Fig. 8b.

Fig. 8
A three-part illustration of the poly on a flat rectangular surface and an A F M topography of those structures is at the top. At the bottom, is a 3-D D N A paint of polymers on the left, the next four graphical representations illustrate the measurements in nano millimeters, and on the right is the 3-D D N A paint of the polymer.

a Top: Illustrations of the of poly(APPV-DNA) immobilized in designed patterns on flat rectangular origa.bottom Bottom: AFM topography images of these structures. b left: 3D DNA PAINT of guide staple strands on the DNA structure, right: 3D DNA PAINT of the polymer attached to the DNA structure. Scale bar = 50 nm. Reused with permission from MacMillan Publishers Ltd: [Nature Nanotechnology] [29] copyright (2015)

Full size image

In further studies, a method for controlling the dynamics of single polymers on DNA origami was developed by Krissanaprasit et al. [33]. It was possible to switch the conformation of single polymer molecules by toehold-mediated strand displacement reactions. The polymer could be directed to one of two tracks on a DNA origami by addition of linker strands. The linker strands could be removed by toehold-mediated strand displacement with remover stands allowing switching to the other track (Fig. 9).

Fig. 9
An illustration at the top describes the switch of the confirmation of a single polymer. A flat rectangular surface and a concave curve combine and result in polymer on D N A origami. At the bottom, a graph illustrates the F R E T measurements in a fluctuating trend.

Top Illustration of the conformational switching of single polymer molecules on DNA origami by toehold-mediated strand displacement reactions. Bottom FRET measurements of the switching showing six successful events. Reprinted with permission from [33]. Copyright (2016) American Chemical Society

Full size image

Immobilizing conjugated polymers onto a DNA origami platform allows the discovery of new properties of these polymers. One of the goals motivating the development of DNA grafted conjugated polymers is to enable characterization of intra- and intermolecular energy transfer for single polymer molecules. For this purpose, a fluorene-based DNA grafted polymer (poly(F-DNA)) was synthesized using the same approach as for the poly(APPV-DNA) [34]. By positioning both the poly(F-DNA) and poly(APPV-DNA) on the same origami structure, the energy transfer between poly(F-DNA) and poly(APPV-DNA) could be investigated (Fig. 10a). When polymers were immobilized on opposite sites of the DNA origami, no energy transfer was detected. This is believed to be due to lacking physical contact between the polymers. Therefore, the energy transfer was tested in solution by using complementary DNA strands on the polymers. Energy transfer from poly(F-DNA) to poly(APPV-DNA) was observed with a relative efficiency of 37%. It is assumed that the complementary DNA grafted polymers form a multi-polymer particle, which means that the energy transfer most likely is not taking place between individual polymers (Fig. 10b).

Fig. 10
An illustration and A F M topography in a describes the orthogonal alignment of the same flat origami structure of F D N A, and A P P V D N A. b. Two illustrations of complementary D N A sequence and non-complementary D N A sequence. c. A graphical representation of the quantification of energy transfer.

Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

a Illustration and AFM topography image of poly(F-DNA) and poly(APPV-DNA) immobilized in an orthogonal alignment on opposite surfaces of the same flat rectangular origami structure. Scale bar = 300 nm. b Energy transfer between poly(F-DNA) and poly(APPV-DNA). Left: Illustration showing that sequence complementarity results in multiple-strand complexes between the DNA grafted polymers, whereas non-complementary strands result in separate DNA grafted polymers. Right: Quantification of energy transfer from poly(F-DNA) to poly(APPV-DNA). Reproduced from [34] with permission from John Wiley and Sons.

Full size image

In order to investigate the intermolecular energy transfer between individual polymers, immobilization onto the same side of an origami structure is necessary to both obtain physical contact between the polymers and control over the stoichiometry. Ideally, this setup can be improved in future to arrange multiple different conjugated polymers on one origami platform and transfer energy to a final acceptor. This will allow harvesting light energy at a broad range of wavelength to exploit the white light of the sun.

The nanoscale transport of light in photosynthesis is a fundamental process where light energy is converted to chemical energy and is a prototypical “green” source of energy. Thus, the ability to harvest light at the nanoscale has been investigated intensely [35, 36]; however, most research has focused on energy transfer cascades using small molecule dyes. In a recent report by Madsen et al. [37], a single molecule polymer poly(APPV-DNA) was investigated for its properties as a photonic wire. The DNA grafted polymer was immobilized onto a single DNA origami by hybridization to a track of single stranded staple strands extending from the origami structure. On the same, origami structure donor and acceptor fluorophores were placed at specific positions along the polymer, allowing for energy transfer from the donor fluorophores to the polymer, through the polymer, and from the polymer to an acceptor fluorophore (Fig. 11a). The energy transfer was studied by both ensemble fluorescence spectroscopy and single molecule spectroscopy. The distance dependence of energy transfer through poly(APPV-DNA) was tested by investigating six different donor–acceptor distances on a DNA origami platform. Distances ranging from 10.5 nm to 24 nm were investigated, and it was found that the energy transfer efficiency decreased with increased distance (Fig. 11b). Interestingly, energy transfer was still observed at 24 nm distance between donor and acceptor. As the energy transfer efficiency did not approach zero at the longest distance, it is expected that energy transfer at longer distances should be feasible. This efficient intramolecular energy transfer makes poly(APPV-DNA) an efficient antenna molecule for use in light harvesting nanodevices.

Fig. 11
An illustration of A P P V D N A on a D N A origami platform on the left, and a graphical representation of distance dependence energy transfer. It plots a decreasing trend.

a Schematic illustration of poly(APPV-DNA) hybridized to a DNA origami platform containing donor and acceptor fluorophores. Upon excitation of donor fluorophores energy is transferred to the polymer and finally to acceptor fluorophore in the middle of the origami. b Data showing the distance dependence energy transfer through poly(APPV-DNA). Reprinted with permission from [37]. Copyright (2021) Americal Chemical Society

Full size image

3 Work from Other Groups

Other groups have also contributed to the work within this field. Sleiman’s group has shown that nucleobase templated polymerization can be used to control the length and polydispersity of a conjugated polymer [38]. A templated polymer with controlled molecular weight and narrow polydisperisity was synthesized by a living polymerization method. A thymine displaying template polymer was synthesized by ring-opening metathesis polymerization. Adenine-modified conjugated monomers were aligned on the template polymer by hydrogen-bonding interactions. Subsequent Sonogashira polymerization leads to the synthesis of a conjugated polymer (Fig. 12). The daughter polymer was found to have a narrow molecular weight distribution and a chain length of around 25 monomeric units, close to the length of the template polymer. This is in contrast to non-templated polymerization, or polymerization with an incorrect template, which gave rise to short polymers with high polydispersities. This method is a very useful tool in the synthesis of conjugated polymers of a defined length, and it could potentially enable the synthesis of sequence specific polymers by exploiting all four nucleobases. However, the method will be limited by the number of different monomers that can be incorporated. Additionally, this method does not allow for incorporation of a conjugated polymer into other DNA nanostructures due to the lack of ssDNA sequences on the polymer.

Fig. 12
A chemical structure of sonogashira polymerization leads to the thymine-containing template polymer. The chemical process has hydrogen bonding.

Templated Sonogashira polymerization of adenine-containing monomers by hydrogen bonding to a thymine containing template polymer. Adapted with permission from [38]. Copyright (2009) Americal Chemical Society

Full size image

More recently, other groups have studied conjugated polymers and oligomers using DNA origami platforms. Mertig’s group has synthesized end-functionalized polythiophenes [39]. A single DNA strand was attached to the end of each individual polymer, and these end-functionalized polymers were then immobilized onto a DNA origami in different patterns. They were able to demonstrate that the optical properties of densely immobilized conjugated polymers can be fine-tuned by controlling the π-π stacking interactions between the polymers. Addition of surfactant molecules was able to break up the stacked polythiophene backbones and thus enhanced the fluorescent emission of the polymers (Fig. 13a, b).

Fig. 13
An illustration of a stacked polythiophene backbone on the D N A origami platform is on the left, while on the right is the graph of intensity versus the wavelength. The graph plots a bell-shaped curve at different concentrations.

a Scheme of surfactant-induced breakup of stacked polythiophene backbones on a DNA origami platform. DDAO = N,N-dimethyldodecylamine N-oxide. b fluorescence emission spectra of polythiophene at different DDAO concentrations (0.0, 0.003, 0.03, 0.3 wt%). Fluorescence increases with increasing DDAO concentration. Reprinted with permission from [39]. Copyright (2017) Americal Chemical Society

Full size image

The Seeman and Canary groups have presented the synthesis of aniline octamers, which were functionalized with ssDNA sequences in each end [40]. The DNA oligoaniline conjugates were successfully incorporated into 3D DNA crystals. It was possible to switch between different oxidation states of the oligoaniline by chemical treatment, and the oxidation state could be determined by the visual appearance of the DNA crystal (Fig. 14a). This reversible switching opens up the opportunity of controlling the conductivity of DNA-based systems. However, the electronic properties of the DNA structure were not been tested experimentally.

Fig. 14
An illustration of the change of the charge and oxidation state is at the top. It includes emeraldine salt, emeraldine base, per nigraniline, and luecoemeraldine. At the bottom, is an illustration of the D N A origami-based molecular electrooptical modulator which exhibits an X shape.

Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. b Illustration of DNA origami-based molecular electro-optical modulator. The DNA grafted oligomers hybridize to extended stable strands and form an “X” shape. Redox reactions makes it possible to tune the fluorescence intensity of the modulator. Reprinted with permission from [41]. Copyright (2018) American Chemical Society

a Image of DNA crystals with incorporated oligoaniline. Changing the charge and oxidation state of oligoaniline leads to color changes directly correlated to the oligoaniline form present. Reproduced from [40] with permission from John Wiley and Sons.

Full size image

More recently, the same groups reported the preparation of a DNA origami-based molecular electro-optical modulator [41]. Two different types of conjugated oligomers were synthesized and functionalized with DNA sequences at each end. The DNA functionalized oligomers were incorporated into a flat DNA origami structure with a central cavity and formed an “X”-shape. They showed that it was possible to reversibly alter the fluorescence signal output by redox reactions (Fig. 14b).

4 Conclusion

The combined work in this field has developed unique tools to handle conjugated oligomers and polymers at the single molecule level within the field of DNA nanotechnology. The original vision was to develop methods to realize the assembly and coupling of wires and components for molecular electronics, but we are still far away from this, since we have not yet been able to characterize the conductivity of the oligomers or polymers. First of all, it is extremely difficult to make two contacts to a single molecule organic oligomer/polymer to measure conductivity. This kind of measurement has been realized by STM in ultra-high vacuum [6], and it has also been shown for carbon nanotubes on DNA origami [42]. However, in spite of several attempts, we have not been able to reliably measure the conductivity through any of the oligomers/polymers described above. Secondly, the polymers are semiconductors, and therefore, it is doubtful that the single molecule polymers would show efficient conductivity in the absence of dopants. On the other hand, we believe that the structural control of the conjugated polymers has great potential for making single molecule optical circuits. As we have recently shown, it is possible to transfer excitation from one dye to another through the polymers [37]. For future studies, we believe that the key utility will be to build systems for light harvesting. With the spatial and chemical control that this approach offers, it may become possible to build systems that mimic photosynthesis.