Scanning tunneling microscope break junction measurements are used to examine how the molecular conductance of nucleic acids depends on the composition of their backbone and the linker group to the electrodes. Molecular conductances of 10 base pair long homoduplexes of DNA, aeg-PNA, γ-PNA, and a heteroduplex of DNA/aeg-PNA with identical nucleobase sequence were measured. The molecular conductance was found to vary by 12 to 13 times with the change in backbone. Computational studies show that the molecular conductance differences between nucleic acids of different backbones correlate with differences in backbone structural flexibility. The molecular conductance was also measured for duplexes connected to the electrode through two different linkers, one directly to the backbone and one directly to the nucleobase stack. While the linker causes an order-of-magnitude increase in the overall conductance for a particular duplex, the differences in the electrical conductance with backbone composition are preserved. The highest molecular conductance value, 0.06G, was measured for aeg-PNA duplexes with a base stack linker. These findings reveal an important new strategy for creating longer and more complex electroactive, nucleic acid assemblies.

Three cobalt-containing macrocyclic compounds previously shown to antagonize cyanide toxicity have been comparatively evaluated for the amelioration of sublethal azide toxicity in juvenile (7−8 weeks) Swiss-Webster mice. The lowest effective doses were determined for hydroxocobalamin, a cobalt porphyrin, and a cobalt-Schiff base macrocycle by giving the antidotes 5 min prior to the toxicant, 27 mg (415 μmol) /kg sodium azide. Both male and female mice were evaluated for their response to the toxicant as well as the antidotes, and no significant differences were noted once weight differences were taken into account. Two of the three compounds significantly decreased the recovery time of azide-intoxicated mice at 10 min after the administration of sodium azide, as determined by a behavioral test (pole climbing). Additionally, azide was determined to cause a several degree drop (∼3 °C) in measured tail temperature, and warming the mice led to a more rapid recovery. The mice were also shown to recover more rapidly when given sodium nitrite, 24 mg (350 μmol)/kg, 5 min after the toxicant; this treatment also suppressed the azide-induced tail temperature decrease. Electron paramagnetic resonance (EPR) measurements of mouse blood treated with sodium azide demonstrated the presence of nitrosylhemoglobin at levels of 10−20 μM which persisted for ∼300 min. The presence of the methemoglobin azide adduct was also detected by EPR at a maximum level of ∼300 μM, but these signals disappeared around 200 min after the administration of azide. The treatment of mice with 15 N sodium azide proved that the nitrosylhemoglobin was a product of the administered azide by the appearance of a two-line hyperfine (due to the 15 N) in the EPR spectrum of mouse blood.■ EXPERIMENTAL SECTION Chemicals. Gases were purchased from Matheson, and all nongaseous reagents (ACS grade or better), including Na 15 N 3 (98%

This work investigates how the conductance of a nucleic acid duplex with a “nick” in its backbone compares with that of a duplex with a fully covalent backbone. Statistical analyses of the single-molecule conductance properties reveal that molecular junctions with a nicked duplex have an average conductance close to that found for non-nicked structures but exhibit greater variability in the molecular conductance. This effect is shown for both DNA homoduplexes and DNA/PNA heteroduplexes, with the heteroduplexes showing a greater average molecular conductance and a smaller degree of variability. The average molecular conductance of the heteroduplexes is also shown to be affected by their PNA content; the conductance of duplexes increases as the ratio of PNA to DNA increases. These observations suggest that the charge-transfer properties of nucleic acid-based assemblies can support complex functions.

There is presently no antidote available to treat azide poisoning. Here, the Schiff-base compound Co(II)-2, 12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaenyl dibromide (Co(II)N 4 [11.3.1]) is investigated to determine if it has the capability to antagonize azide toxicity through a decorporation mechanism. The stopped-flow kinetics of azide binding to Co(II)N 4 [11.3.1] in the absence of oxygen exhibited three experimentally observable phases: I (fast); II (intermediate); and III (slow). The intermediate phase II accounted for ∼70% of the overall absorbance changes, representing the major process observed, with second-order rate constants of 29 (±4) M −1 s −1 at 25 °C and 70 (±10) M −1 s −1 at 37 °C. The data demonstrated pH independence of the reaction around neutrality, suggesting the unprotonated azide anion to be the attacking species. The binding of azide to Co(II)N 4 [11.3.1] appears to have a complicated mechanism leading to less than ideal antidotal capability; nonetheless, this cobalt complex does protect against azide intoxication. Administration of Co(II)N 4 [11.3.1] at 5 min post sodium azide injection (ip) to mice resulted in a substantial decrease of righting-recovery times, 12 (±4) min, compared to controls, 40 (±8) min. In addition, only two out of seven mice "knocked down" when the antidote was administered compared to the controls given toxicant only (100% knockdown).

The flow of charge through molecules is central to the function of supramolecular machines, and charge transport in nucleic acids is implicated in molecular signaling and DNA repair. We examine the transport of electrons through nucleic acids to understand the interplay of resonant and nonresonant charge carrier transport mechanisms. This study reports STM break junction measurements of peptide nucleic acids (PNAs) with a G-block structure and contrasts the findings with previous results for DNA duplexes. The conductance of G-block PNA duplexes is much higher than that of the corresponding DNA duplexes of the same sequence; however, they do not display the strong even–odd dependence conductance oscillations found in G-block DNA. Theoretical analysis finds that the conductance oscillation magnitude in PNA is suppressed because of the increased level of electronic coupling interaction between G-blocks in PNA and the stronger PNA–electrode interaction compared to that in DNA duplexes. The strong interactions in the G-block PNA duplexes produce molecular conductances as high as 3% G 0, where G 0 is the quantum of conductance, for 5 nm duplexes.