Role of Order in the Mechanism of Charge Transport across Single-Stranded and Double-Stranded DNA Monolayers in Tunnel Junctions.

Deoxyribonucleic acid (DNA) has been hypothesized to act as a molecular wire due to the presence of an extended π-stack between base pairs, but the factors that are detrimental in the mechanism of charge transport (CT) across tunnel junctions with DNA are still unclear. Here we systematically investigate CT across dense DNA monolayers in large-area biomolecular tunnel junctions to determine when intrachain or interchain CT dominates and under which conditions the mechanism of CT becomes thermally activated. In our junctions, double-stranded DNA (dsDNA) is 30-fold more conductive than single-stranded DNA (ssDNA). The main reason for this large change in conductivity is that dsDNA forms ordered monolayers where intrachain tunneling dominates, resulting in high CT rates. By varying the temperature T and the length of the DNA fragments in the junctions, which determines the tunneling distance, we reveal a complex interplay between T, the length of DNA, and structural order on the mechanism of charge transport. Both the increase in the tunneling distance and the decrease in structural order result in a change in the mechanism of CT from coherent tunneling to incoherent tunneling (hopping). Our results highlight the importance of the interplay between structural order, tunneling distance, and temperature on the CT mechanism across DNA in molecular junctions.

Duplex Healing of Selectively Thiolated Guanosine Mismatches through a Cd2+ Chemical Stimulus.

The on-column selective conversion of guanosine to thioguanosine (tG) yields modified oligomers that exhibit destabilisation over the fully complementary duplex. Restoration to a stabilised duplex is induced through thio-directed Cd2+ coordination; a route for healing DNA damage. Short oligomers are G-specifically thiolated through a modified on-column protocol without the need for costly thioguanosine phosphoramidites. Addition of Cd2+ ions to a duplex containing a highly disrupted tG central mismatch sequence, 3'-A6 tG4 T6 -5', suggests a (tG)8 Cd2 central coordination regime, resulting in increased base stacking and duplex stability. Equilibrium molecular dynamic calculations support the hypothesis of metal-induced healing of the thiolated duplex. The 2 nm displacement of the central tG mismatched region is dramatically reduced after the addition of a chemical stimuli, Cd2+ ions, returning to a minimized fluctuational state comparable to the unmodified fully complementary oligomer.

Self-Priming Enzymatic Fabrication of Multiply Modified DNA.

The self-priming synthesis of multiply modified DNA by the extension of repeating unit duplex "oligoseeds" provides a source of versatile DNA. Sterically-demanding nucleotides 5-Br-dUTP, 7-deaza-7-I-dATP, 6-S-dGTP, 5-I-dCTP as well as 5-(octadiynyl)-dCTP were incorporated into two extending oligoseeds; [GATC]5 /[GATC]5 and [A4 G]4 /[CT4 ]4 . The products contained modifications on one or both strands of DNA, demonstrating their recognition by the polymerase as both template (reading) and substrate (writing). Nucleobase modifications that lie in the major groove were reliably read and written by the polymerase during the extension reaction, even when bulky or in contiguous sequences. Repeat sequence DNA over 500 bp long, bearing four different modified units was produced by this method. The number, position and type of modification, as well as the overall length of the DNA can be controlled to yield designer DNA that offers sequence-determined sites for further chemical adaptations, targeted small molecule binding studies, or sensing and sequencing applications.

Nanoscale silicon substrate patterns from self-assembly of cylinder forming poly(styrene)-block-poly(dimethylsiloxane) block copolymer on silane functionalized surfaces.

Poly(styrene)-block-poly(dimethylsiloxane) (PS-b-PDMS) is an excellent block copolymer (BCP) system for self-assembly and inorganic template fabrication because of its high Flory-Huggins parameter (χ âˆ¼ 0.26) at room temperature in comparison to other BCPs, and high selective etch contrast between PS and PDMS block for nanopatterning. In this work, self-assembly in PS-b-PDMS BCP is achieved by combining hydroxyl-terminated poly(dimethylsiloxane) (PDMS-OH) brush surfaces with solvent vapor annealing. As an alternative to standard brush chemistry, we report a simple method based on the use of surfaces functionalized with silane-based self-assembled monolayers (SAMs). A solution-based approach to SAM formation was adopted in this investigation. The influence of the SAM-modified surfaces upon BCP films was compared with polymer brush-based surfaces. The cylinder forming PS-b-PDMS BCP and PDMS-OH polymer brush were synthesized by sequential living anionic polymerization. It was observed that silane SAMs provided the appropriate surface chemistry which, when combined with solvent annealing, led to microphase segregation in the BCP. It was also demonstrated that orientation of the PDMS cylinders may be controlled by judicious choice of the appropriate silane. The PDMS patterns were successfully used as an on-chip etch mask to transfer the BCP pattern to underlying silicon substrate with sub-25 nm silicon nanoscale features. This alternative SAM/BCP approach to nanopattern formation shows promising results, pertinent in the field of nanotechnology, and with much potential for application, such as in the fabrication of nanoimprint lithography stamps, nanofluidic devices or in narrow and multilevel interconnected lines.

Click modification of diazido acridine intercalators: a versatile route towards decorated DNA nanostructures.

Diazido derivatives of 3,6-diamino acridine (proflavine) intercalate into DNA and undergo functionalization through click chemistry to form 1D nanostructures with redox active, conductive nanowire, and fluorescent properties. This two-step approach, intercalation followed by click modification allows for the controlled decoration of DNA nanostructures.

Enzymatic Method for the Synthesis of Long DNA Sequences with Multiple Repeat Units.

A polymerase chain reaction (PCR) derived method for preparing long DNA, consisting of multiple repeat units of one to ten base pairs, is described. Two seeding oligodeoxynucleotides, so-called oligoseeds, which encode the repeat unit and produce a duplex with 5'-overhangs, are extended using a thermostable archaeal DNA polymerase. Multiple rounds of heat-cool extension cycles, akin to PCR, rapidly elongate the oligoseed. Twenty cycles produced long DNA with uniformly repeating sequences to over 20 kilobases (kb) in length. The polynucleotides prepared include [A]n /[T]n , [AG]n /[TC]n , [A2 G]n /[T2 C]n , [A3 G]n /[T3 C]n , [A4 G]n /[T4 C]n , [A9 G]n /[T9 C]n , [GATC]n /[CTAG]n , and [ACTGATCAGC]n /[TGACTAGTCG]n , indicating that the method is extremely flexible with regard to the repeat length and base sequence of the initial oligoseeds. DNA of this length (20 kb≈7 µm) with strictly defined base reiterations should find use in nanomaterial applications.

Coordination chemistry of 6-thioguanine derivatives with cobalt: toward formation of electrical conductive one-dimensional coordination polymers.

In this work we have synthetized and characterized by X-ray diffraction five cobalt complexes with 6-thioguanine (6-ThioGH), 6-thioguanosine (6-ThioGuoH), or 2'-deoxy-6-thioguanosine (2'-d-6-ThioGuoH) ligands. In all cases, these ligands coordinate to cobalt via N7 and S6 forming a chelate ring. However, independently of reagents ratio, 6-ThioGH provided monodimensional cobalt(II) coordination polymers, in which the 6-ThioG(-) acts as bridging ligand. However, for 2'-d-6-ThioGuoH and 6-ThioGuoH, the structure directing effect of the sugar residue gives rise to mononuclear cobalt complexes which form extensive H-bond interactions to generate 3D supramolecular networks. Furthermore, with 2'-d-6-ThioGuoH the cobalt ion remains in the divalent state, whereas with 6-ThioGuoH oxidation occurs and Co(III) is found. The electrical and magnetic properties of the coordination polymers isolated have been studied and the results discussed with the aid of DFT calculations, in the context of molecular wires.

Temperature-Dependent Coherent Tunneling across Graphene-Ferritin Biomolecular Junctions.

Understanding the mechanisms of charge transport (CT) across biomolecules in solid-state devices is imperative to realize biomolecular electronic devices in a predictive manner. Although it is well-accepted that biomolecule-electrode interactions play an essential role, it is often overlooked. This paper reveals the prominent role of graphene interfaces with Fe-storing proteins in the net CT across their tunnel junctions. Here, ferritin (AfFtn-AA) is adsorbed on the graphene by noncovalent amine-graphene interactions confirmed with Raman spectroscopy. In contrast to junctions with metal electrodes, graphene has a vanishing density of states toward its intrinsic Fermi level ("Dirac point"), which increases away from the Fermi level. Therefore, the amount of charge carriers is highly sensitive to temperature and electrostatic charging (induced doping), as deduced from a detailed analysis of CT as a function of temperature and iron loading. Remarkably, the temperature dependence can be fully explained within the coherent tunneling regime due to excitation of hot carriers. Graphene is not only demonstrated as an alternative platform to study CT across biomolecular tunnel junctions, but it also opens rich possibilities in employing interface electrostatics in tuning CT behavior.

Pyrrolyl-, 2-(2-thienyl)pyrrolyl- and 2,5-bis(2-thienyl)pyrrolyl-nucleosides: synthesis, molecular and electronic structure, and redox behaviour of C5-thymidine derivatives.

A series of modified nucleosides based on thymidine have been prepared by Pd-catalysed cross-coupling between N-alkyl-alkynyl functionalised pyrrolyl- (py), 2-(2-thienyl)pyrrolyl- (tp) or 2,5-bis(2-thienyl)pyrrolyl (tpt) groups with 5-iodo-2'-deoxyuridine. The length of the alkyl chain linking the nucleoside and pyrrolyl-containing unit, N(CH(2))(n)C[triple bond, length as m-dash]C-nucleoside (where n = 1-3) was also varied. The compounds have been characterised by (1)H NMR, ES-MS, UV-vis, cyclic voltammetry (CV) and, in some cases, single-crystal X-ray diffraction. Cyclic voltammetry studies demonstrated that all the py-, tp- and tpt-alkynyl derivatives 1-7 can be electrochemically polymerised to form conductive materials. It was found that increasing the N-alkyl chain length in these cases resulted in only minor changes in the oxidation potential. The same behaviour was observed for the tp- and tpt-modified nucleosides 9-12; however, the py-derivative, 8, produced a poorly conducting material. DFT calculations on the one-electron oxidised cation of the modified nucleosides bearing tp or tpt showed that spin density is located on the pyrrolyl and thienyl units in all cases and that the coplanarity of adjacent rings increases upon oxidation. In contrast, in the corresponding pyrrolyl cases the spin density is distributed over the whole molecule, suggesting that polymerisation does not occur solely at the pyrrolyl-Cα position and the conjugation is interrupted.

DNA-based routes to semiconducting nanomaterials.

The controlled preparation and assembly of opto-electronic nanoscale materials is being tackled by top-down and bottom-up approaches. The latter draws inspiration from biology, where complex hierarchical systems are assembled from simpler building blocks. One of these, DNA, is proving especially useful: its size, stability, topology; the assorted chemical functional groups; plus its capacity for self-assembly provide a powerful nanoscale toolbox for materials preparation. Here we review recent research that shows the roles DNA can play in the preparation and organisation of semiconductor nanomaterials. Studies show that both hard inorganic and soft polymer materials can be directed to grow at nanoscale lengths using DNA and its constituents. In some cases the resulting materials have been used as components in simple electrical devices and the methodology has been extended to analytical tools. Intriguingly, these DNA-semiconductor hybrid materials have been found to self-assemble themselves, forming highly regular rope-like assemblies and conducting network structures.

The Synthesis of Designer DNA.

The synthesis of designer DNA requires an approach where the user can determine both the sequence and the number of nucleobases. The protocol outlined here describes an enzymatic method for the synthesis of long repeat-sequence DNA. The method utilizes a PCR-based approach; starting with short oligo-seeds, c.a. 20 bp, bearing a minimum of two repeating units of >8 bp sequences. During each heat-cool cycle, the oligo-seeds reanneal imperfectly leaving an overhang, which is then extended by the polymerase. The final length of the DNA is determined by the number of heat-cool cycles performed, reaching up to 20,000 bp after 20 cycles.

DNA-templated nanowires: morphology and electrical conductivity.

DNA-templating has been used to create nanowires from metals, compound semiconductors and conductive polymers. The mechanism of growth involves nucleation at binding sites on the DNA followed by growth of spherical particles and then, under favourable conditions, a slow transformation to a smooth nanowire. The final transformation is favoured by restricting the amount of templated material per unit length of template and occurs most readily for materials of low surface tension. Electrical measurements on DNA-templated nanowires can be facilitated using three techniques: (i) standard current-voltage measurements with contact electrodes embedded in a dielectric so that there is a minimal step height at the dielectric/electrode boundary across which nanowires may be aligned by molecular combing, (ii) the use of a dried droplet technique and conductive AFM to determine contact resistance by moving the tip along the length of an individual nanowire and (iii) non-contact assessment of conductivity by scanned conductance microscopy on Si/SiO2 substrates.

DNA-modified single crystal and nanoporous silicon.

The functionalization of silicon as elemental crystalline wafer, nanoporous layers, or nanocrystalline particles with DNA oligonucleotides using automated solid phase synthesis is described. The procedures provide semiconductor surfaces covalently modified with oligomers suitable for capturing complementary oligonucleotide strands.

Electrochemical scanning tunnelling spectroscopy of a ferrocene-modified n-Si(111)-surface: electrolyte gating and ambipolar FET behaviour.

As revealed for the first time by in situ scanning tunnelling spectroscopy (STS), ferrocene-modified Si(111) substrates show ambipolar field effect transistor (FET) behaviour upon electrolyte gating.

Modification of DNA-templated conductive polymer nanowires via click chemistry.

DNA templated nanowires of a pentynyl-modified poly2-(2-thienyl)-pyrrole undergo functionalisation via"click chemistry" and retain their 1D-nanostructure and conductive properties.

Ferrocenyl-modified DNA: synthesis, characterization and integration with semiconductor electrodes.

The ferrocenyl-nucleoside, 5-ethynylferrocenyl-2'-deoxycytidine (1) has been prepared by Pd-catalyzed cross-coupling between ethynylferrocene and 5-iodo-2'-deoxycytidine and incorporated into oligonucleotides by using automated solid-phase synthesis at both silica supports (CPG) and modified single-crystal silicon electrodes. Analysis of DNA oligonucleotides prepared and cleaved from conventional solid supports confirms that the ferrocenyl-nucleoside remains intact during synthesis and deprotection and that the resulting strands may be oxidised and reduced in a chemically reversible manner. Melting curve data show that the ferrocenyl-modified oligonucleotides form duplex structures with native complementary strands. The redox potential of fully solvated ferrocenyl 12-mers, 350 mV versus SCE, was shifted by +40 mV to a more positive potential upon treatment with the complement contrary to the anticipated negative shift based on a simple electrostatic basis. Automated solid-phase methods were also used to synthesise 12-mer ferrocenyl-containing oligonucleotides directly at chemically modified silicon <111> electrodes. Hybridisation to the surface-bound ferrocenyl-DNA caused a shift in the reduction potential of +34 mV to more positive values, indicating that, even when a ferrocenyl nucleoside is contained in a film, the increased density of anions from the phosphate backbone of the complement is still dominated by other factors, for example, the hydrophobic environment of the ferrocene moiety in the duplex or changes in the ferrocene-phosphate distances. The reduction potential is shifted >100 mV after hybridisation when the aqueous electrolyte is replaced by THF/LiClO(4), a solvent of much lower dielectric constant; this is consistent with an explanation based on conformation-induced changes in ferrocene-phosphate distances.

Metallocene-DNA: synthesis, molecular and electronic structure and DNA incorporation of C5-ferrocenylthymidine derivatives.

Ferrocenylthymidine derivatives have been prepared by Pd-catalysed cross-coupling between ethynylferrocene or vinylferrocene and 5-iodo-2'-deoxyuridine. In the latter case a mixture of trans (2a) and gem (2b) isomers was obtained. The cis-vinylferrocenyl (2c), and ethylferrocenyl (3) derivatives were obtained by catalytic hydrogenation of ethynylferrocenyl-dT (1a), and 2c respectively. Single-crystal X-ray data for 1a, the ferrocenyl-2'furano-pyrimidone 1b, and 2a show that the nucleobase is essentially co-planar with the substituted Cp ring of the metallocene. The selective reduction of the linkage between the ferrocenyl and thymidine moieties, from -C identical to C- to -CH2CH2-, causes a shift in the reduction potential of -124 mV. DFT calculations for the one-electron oxidised species indicate that the diminished conjugation reduces the spin transfer onto the bridging C2 group, but has less effect on the extent transferred to the nucleobase from the ferrocenyl group. Compound 1a was incorporated site-specifically into DNA oligonucleotides by using automated solid-phase methods. However, some interconversion of 1a-->1b occurs, even under rapid mild conditions of deprotection.