Magnetic fields facilitate DNA-mediated charge transport

Exaggerate radical-induced DNA damage under magnetic fields is of great concerns to medical biosafety and to bio-molecular device based upon DNA electronic conductivity. In this report, the effect of applying an external magnetic field (MF) on DNA-mediated charge transport (CT) was investigated by studying guanine oxidation by a kinetics trap (8CPG) via photoirradiation of anthraquinone (AQ) in the presence of an external MF. Positive enhancement in CT efficiencies was observed in both the proximal and distal 8CPG after applying a static MF of 300 mT. MF assisted CT has shown sensitivities to magnetic field strength, duplex structures, and the integrity of base pair stacking. MF effects on spin evolution of charge injection upon AQ irradiation and alignment of base pairs to CT-active conformation during radical propagation were proposed to be the two major factors that MF attributed to facilitate DNA-mediated CT. Herein, our results suggested that the electronic conductivity of duplex DNA can be enhanced by applying an external MF. MF effects on DNA-mediated CT may offer a new avenue for designing DNA-based electronic device, and unraveled MF effects on redox and radical relevant biological processes

Back-electron transfer suppresses the periodic length dependence of DNA-mediated charge transport across adenine tracts

DNA-mediated charge transport (CT) is exquisitely sensitive to the integrity of the bridging π-stack and is characterized by a shallow distance dependence. These properties are obscured by poor coupling between the donor/acceptor pair and the DNA bridge, or by convolution with other processes. Previously, we found a surprising periodic length dependence for the rate of DNA-mediated CT across adenine tracts monitored by 2-aminopurine fluorescence. Here we report a similar periodicity by monitoring N2-cyclopropylguanosine decomposition by rhodium and anthraquinone photooxidants. Furthermore, we find that this periodicity is attenuated by consequent back-electron transfer (BET), as observed by direct comparison between sequences that allow and suppress BET. Thus, the periodicity can be controlled by engineering the extent of BET across the bridge. The periodic length dependence is not consistent with a periodicity predicted by molecular wire theory but is consistent with a model where multiples of four to five base pairs form an ideal CT-active length of a bridging adenine domain

Programmable DNA-mediated multitasking processor

Because of DNA appealing features as perfect material, including minuscule size, defined structural repeat and rigidity, programmable DNA-mediated processing is a promising computing paradigm, which employs DNAs as information storing and processing substrates to tackle the computational problems. The massive parallelism of DNA hybridization exhibits transcendent potential to improve multitasking capabilities and yield a tremendous speed-up over the conventional electronic processors with stepwise signal cascade. As an example of multitasking capability, we present an in vitro programmable DNA-mediated optimal route planning processor as a functional unit embedded in contemporary navigation systems. The novel programmable DNA-mediated processor has several advantages over the existing silicon-mediated methods, such as conducting massive data storage and simultaneous processing via much fewer materials than conventional silicon devices

Synthesis and Characterization of Iridium(III) Cyclometalated Complexes with Oligonucleotides: Insights into Redox Reactions with DNA

Heteroleptic cyclometalated complexes of Ir(III) containing the dipyridophenazine ligand are synthesized through the direct introduction of a functionalized dipyridophenazine ligand onto a bis(dichloro)-bridged Ir(III) precusor and characterized by ^1H NMR, mass spectrometry, as well as spectroscopic and electrochemical properties. The excited state of the Ir(III) complexes have sufficient driving force to oxidize purines and to reduce pyrimidine nucleobases. Luminescence and EPR measurements of the Ir(III) complex with an unmodified dppz bound to DNA show the formation of a guanine radical upon irradiation, resulting from an oxidative photoinduced electron-transfer process. Evidence is also obtained indirectly for reductive photoinduced electron transfer from the excited complex to the thymine base in DNA. We have also utilized cyclopropylamine-substituted nucleosides as ultrafast kinetic traps to report transient charge occupancy in oligonucleotides when DNA is irradiated in the presence of noncovalently bound complexes. These experiments establish that the derivatized Ir(III) complexes, with photoactivation, can trigger the oxidation of guanine and the reduction of cytosine

DNA-Mediated Hole and Electron Transport

Since the elucidation of the double helical structure of DNA, it has been proposed that the dynamic [pi]-stacking base pair array may mediate charge migration, hole transport (HT), and electron transport (ET). In this thesis work, both DNA-mediated HT and ET are investigated to explore their mechanisms by using kinetically fast electron/hole traps: cyclopropylamine-substituted bases, especially N4-cyclopropylcytosine (CPC), and N2-cyclopropylguanine (CPG). Both biochemical reaction with a variety of photooxidants and electrochemistry show that the modified bases, CPC and CPG, have similar redox properties as the natural DNA bases and are irreversible kinetic traps by ring opening on the picosecond time scale. In DNA assemblies containing either [Rh(phi)2(bpy')]3+ (Rh) or an anthraquinone derivative (AQ), two high energy photooxidants, appreciable oxidative damage at a distant CPC is observed, which shows that hole migration must involve also the higher energy pyrimidine bases. The damage yield is modulated by lower energy guanine sites on the same or complementary strand. Significantly, the efficiency in trapping at CPC is similar to that at flanking CPG. Thus, HT is not simply a function of the relative energies of the isolated bases, but instead may require orbital mixing among the bases. Hole migration through DNA involves occupation of all the DNA bases with radical delocalization. The oxidation of CPC via distant photooxidants has been found also to be sensitive to intervening structure and sequences. AQ-modified DNA assemblies of identical base composition but different base sequence have been probed. Single and double base substitutions within A-tracts modulate CPC decomposition. In fact, the entire sequence within the DNA assembly is seen to govern CPC oxidation, not simply the bases intervening between CPC and the tethered photooxidant. These data are reconciled in a mechanistic model of conformationally gated hole transport through delocalized DNA domains. Oxidation of CPG separated from a tethered photooxidant by A-tracts with a series of lengths over 50 A exhibits a nonmonotonically periodic distance dependence and shows that the domain sizes in the A-tract is 4-5 base pairs. Sequence-dependent DNA structure and dynamics are essential to the transient formation of the domains and hole propagation among the domains. This dynamic, delocalized model provides a basis to reconcile and exploit DNA HT chemistry. Just as long-range hole transport through DNA has now been established, DNA-mediated electron transport has not been as well characterized. Three iridium complexes have therefore been designed in order to initiate both photooxidative and photoreductive reaction of DNA and allow direct comparison between the two. Redox potentials of excited Ir complexes are determined by both triplet energy (E0-0) and ground state redox potentials. Two of the iridium complexes prepared have excited state potentials that are suffcient to oxidize purines, but not pyrimidines. The excited state oxidation potentials of three Ir complexes are around -1.0 V and would be able to reduce DNA pyrimidines. Both CPC and CPG in DNA can be decomposed by photoirradiation with the noncovalently bound iridium complexes. In particular, two of the complexes have the potential to probe oxidation of purines and reduction of pyrimidines in DNA. Studies were also conducted using one of the iridium complexes covalently tethered to DNA oligonucleotides. Hence the metal complex serves as both a photooxidant and photoreductant in the study of DNA-mediated hole and electron transport. In the Ir-tethered DNA assemblies, a metal complex stabilizes the DNA duplex through its intercalative, functionalized dppz ligand. Cyclopropylamine-substituted bases, CPC and CPG, are used as kinetic fast electron and hole traps to probe the resulting charge migration processes after direct photoirradiation of the assemblies. Reductive decomposition of CPC via ET as well as the oxidation of CPG via HT is observed. Thus, the iridium tethered DNA containing cyclopropylamine-substituted bases provides a unique model system to explore the two DNA-mediated charge transport processes through the same DNA bridges. For the first time, ET and HT can be initialized by the same photoredox probe employing the identical electronic interaction mode with DNA. A flash quench technique was also applied to Iridium-tethered DNA in order to generate the ground state photoreductant and initiate photoreduction using 5'-bromo-uridine (BrU) as the electron trap. Efficiencies of BrU reduction in Ir-DNA upon flash quench technique was found to be comparable to that of CPG oxidation upon direct photoirradiation of Ir-DNA. Furthermore, in Ir-tethered DNA assemblies containing CPG or BrU as either the hole or electron trap, the sequence dependence of HT versus ET through an A-tract was examed. When CPG and BrU are placed in either purine or pyrimidine strands in A-tract, decomposition of both modified bases are observed. Thus, transient electron occupancy during ET, as well as hole occupancy during HT, are distributed onto both purine and pymidine strands in A-tract. Additionally, BrU decomposes in a more efficient fashion when it is located on a thyime-containing strands, which indicates that DNA-mediated ET prefers to pyrimidine strands rather than purine strands.</p

Long-Range Electron and Hole Transport through DNA with Tethered Cyclometalated Iridium(III) Complexes

A cyclometalated complex of Ir(III) is covalently tethered to DNA oligonucleotides and serves as both a photooxidant and photoreductant in the study of DNA-mediated hole transport (HT) and electron transport (ET). Spectroscopic and melting temperature studies support intercalation of the tethered complex into the DNA duplex through the functionalized dppz ligand. Using these tethered assemblies, ET and HT is initiated in DNA by the same photoredox probe. Cyclopropylamine substituted bases, N_4-cyclopropylcytosine (^(CP)C) and N_2-cyclopropylguanine (^(CP)G) are used as kinetically fast electron and hole traps to probe the resulting electron migration processes after direct irradiation of the tethered Ir assembly. Oxidation of ^(CP)G and ^(CP)C is promoted efficiently by HT from photoexcited Ir(III) when the modified bases are positioned in the purine strands of the A-tract. In contrast, when CPC is embedded in a pyrimidine tract, ET to yield reductive decomposition is observed. Thus, the Ir(III)-tethered DNA assembly containing cyclopropyl-modified bases provides a unique model system to explore the two DNA-mediated electron migration processes using the same photoredox probe and the same DNA bridge

8-Cyclopropyl-2′-Deoxyguanosine: a hole trap for DNA-mediated charge transport

DNA duplexes containing 8-cyclopropyl-2′-deoxyguanosine (8CPG) were synthesized to investigate the effect of the C8-modified deoxyguanosine as a kinetic trap for transient hole occupancy on guanines during DNA-mediated hole transport (HT). Thermal denaturation and CD spectra show that DNA duplexes containing 8CPG are able to form stable B-form duplexes. Photoirradiation of terminal tethered anthraquinone can induce oxidative decomposition of 8CPG through DNA HT along adenine tracts with lengths of up to 4.8 nm. Shallow and periodic distance dependence was observed in a long adenine tract with intervening guanines. The efficient charge transport indicates that 8CPG can electronically couple well with a DNA bridge and form HT-active conformational domains to facilitate transient hole delocalization over an adenine tract

Hole Transport in A-form DNA/RNA Hybrid Duplexes

DNA/RNA hybrid duplexes are prevalent in many cellular functions and are an attractive target form for electrochemical biosensing and electric nanodevice. However the electronic conductivities of DNA/RNA hybrid duplex remain relatively unexplored and limited further technological applications. Here cyclopropyl-modified deoxyribose- and ribose-adenosines were developed to explore hole transport (HT) in both DNA duplex and DNA/RNA hybrids by probing the transient hole occupancies on adenine tracts. HT yields through both B-form and A-form double helixes displayed similar shallow distance dependence, although the HT yields of DNA/RNA hybrid duplexes were lower than those of DNA duplexes. The lack of oscillatory periods and direction dependence in HT through both helixes implied efficient hole propagation can be achieved via the hole delocalization and coherent HT over adenine tracts, regardless of the structural variations.MOE (Min. of Education, S’pore)Published versio

Charge Migration along the DNA Duplex: Hole versus Electron Transport

Cyclometalated Ir(III) complexes tethered to 18-mer oligonucleotides through a functionalized dipyridophenazine ligand have been used to study the distance dependence profile of hole and electron transport along DNA. These DNA assemblies allow a direct comparison of hole and electron transport with a single donor coupled into the base stack. Interestingly, both processes, monitored with modified bases as hole or electron kinetic traps incorporated in the strands, appear to have similarly shallow dependences in their reactions with distance. As with hole transport, perturbations to the base stack also attenuate electron transport

Sequence Dependence of Charge Transport through DNA Domains

Here we examine the photooxidation of two kinetically fast electron hole traps, N_4-cyclopropylcytosine (^(CP)C) and N_2-cyclopropylamine-guanosine (CPG), incorporated in DNA duplexes of various sequence using different photooxidants. DNA oxidation studies are carried out either with noncovalently bound [Ru(phen)(dppz)(bpy‘)]^(3+) (dppz = dipyridophenazine) and [Rh(phi)_2(bpy)]^(3+) (phi = phenanthrenequinone diimine) or with anthraquinone tethered to DNA. Because the cyclopropylamine-substituted bases decompose rapidly upon oxidation, their efficiency of decomposition provides a measure of relative hole localization. Consistent with a higher oxidation potential for ^(CP)C versus ^(CP)G in DNA, ^(CP)C decomposes with photooxidation by [Rh(phi)_2(bpy)]^(3+), while CPG undergoes ring-opening both with photoexcited [Rh(phi)_2(bpy)]^(3+) and with [Ru(phen)(dppz)(bpy‘)]^(3+). Anthraquinone-modified DNA assemblies of identical base composition but different base sequence are also probed. Single and double base substitutions within adenine tracts modulate ^(CP)C decomposition. In fact, the entire sequence within the DNA assembly is seen to govern ^(CP)C oxidation, not simply the bases intervening between ^(CP)C and the tethered photooxidant. These data are reconciled in the context of a mechanistic model of conformationally gated charge transport through delocalized DNA domains. Photooxidations of anthraquinone-modified DNA assemblies containing both ^(CP)C and ^(CP)G, but with varied distances separating the modified bases, point to a domain size of at least three bases. Our model for DNA charge transport is distinguished from polaron models. In our model, delocalized domains within the base pair stack form transiently based upon sequence-dependent DNA structure and dynamics. Given these results, DNA charge transport is indeed remarkably sensitive to DNA sequence and structure