A three-step kinetic model for electrochemical charge transfer in the hopping regime.

Single-step nonadiabatic electron tunneling models are widely used to analyze electrochemical rates through self-assembled monolayer films (SAMs). For some systems, such as nucleic acids, long-range charge transfer can occur in a "hopping" regime that involves multiple charge transfer events and intermediate states. This report describes a three-step kinetic scheme to model charge transfer in this regime. Some of the features of the three-step model are probed experimentally by changing the chemical composition of the SAM. This work uses the three-step model and a temperature dependence of the charge transfer rate to extract the charge injection barrier for a SAM composed of a 10-mer peptide nucleic acid that operates in the hopping regime.

Identification and optimization of short helical peptides with novel reactive functionality as catalysts for acyl transfer by reactive tagging.

Herein we describe the screening and subsequent optimization of peptide catalysts for ester activation. A combinatorial methodology using dye-tagged substrate analogs is described for determining which components of a His-containing helical library display acyl transfer activity. We found that helical peptides display high activity, and amino acids that reinforce this propensity are advantaged. Through this approach two new structural motifs have been discovered that are capable of activating esters in organic solvents. Unlike most acyl transfer catalysts functioning in organic solvents, these catalysts are histidine- rather than N-alkyl histidine-based. Longer peptides with localization of reactive groups on the C-terminal end of the peptide were found to further enhance catalytic activity up to ∼2800-fold over background.

The single-molecule conductance and electrochemical electron-transfer rate are related by a power law.

This study examines quantitative correlations between molecular conductances and standard electrochemical rate constants for alkanes and peptide nucleic acid (PNA) oligomers as a function of the length, structure, and charge transport mechanism. The experimental data show a power-law relationship between conductances and charge transfer rates within a given class of molecules with the same bridge chemistry, and a lack of correlation when a more diverse group of molecules is compared, in contrast with some theoretical predictions. Surprisingly, the PNA duplexes exhibit the lowest charge-transfer rates and the highest molecular conductances. The nonlinear rate-conductance relationships for structures with the same bridging chemistries are attributed to differences in the charge-mediation characteristics of the molecular bridge, energy barrier shifts and electronic dephasing, in the two different experimental settings.

Charge transfer through modified peptide nucleic acids.

We studied the charge transfer properties of bipyridine-modified peptide nucleic acid (PNA) in the absence and presence of Zn(II). Characterization of the PNA in solution showed that Zn(II) interacts with the bipyridine ligands, but the stability of the duplexes was not affected significantly by the binding of Zn(II). The charge transfer properties of these molecules were examined by electrochemistry for self-assembled monolayers of ferrocene-terminated PNAs and by conductive probe atomic force microscopy for cysteine-terminated PNAs. Both electrochemical and single molecular studies showed that the bipyridine modification and Zn(II) binding do not affect significantly the charge transfer of the PNA duplexes.

Coordination-driven inversion of handedness in ligand-modified PNA.

Peptide nucleic acid (PNA) is a synthetic analogue of DNA, which has the same nucleobases as DNA but typically has a backbone based on aminoethyl glycine (Aeg). PNA forms duplexes by Watson Crick hybridization. The Aeg-based PNA duplexes adopt a chiral helical structure but do not have a preferred handedness because they do not contain a chiral center. An L-lysine situated at the C-end of one or both strands of a PNA duplex causes the duplex to preferably adopt a left-handed structure. We have introduced into the PNA duplexes both a C-terminal L-lysine and one or two PNA monomers that have a γ-(S)-methyl-aminoethyl glycine backbone, which is known to induce a preference for a right-handed structure. Indeed, we found that in these duplexes the γ-methyl monomer exerts the dominant chiral induction effect causing the duplexes to adopt a right-handed structure. The chiral PNA monomer had a 2,2':6',2''-terpyridine (Tpy) ligand instead of a nucleobase and PNA duplexes that contained one or two Tpys formed [Cu(Tpy)(2)](2+) complexes in the presence of Cu(2+). The CD spectroscopy studies showed that these metal-coordinated duplexes were right-handed due to the chiral induction effect exerted by the S-Tpy PNA monomer(s) except for the cases when the [Cu(Tpy)(2)](2+) complex was formed with Tpy ligands from two different PNA duplexes. In the latter case, the metal complex bridged the two PNA duplexes and the duplexes were left-handed. The results of this study show that the preferred handedness of a ligand-modified PNA can be switched as a consequence of metal coordination to the ligand. This finding could be used as a tool in the design of functional nucleic-acid based nanostructures.

Evidence for a near-resonant charge transfer mechanism for double-stranded peptide nucleic acid.

We present evidence for a near-resonant mechanism of charge transfer in short peptide nucleic acid (PNA) duplexes obtained through electrochemical, STM break junction (STM-BJ), and computational studies. A seven base pair (7-bp) PNA duplex with the sequence (TA)(3)-(XY)-(TA)(3) was studied, in which XY is a complementary nucleobase pair. The experiments showed that the heterogeneous charge transfer rate constant (k(0)) and the single-molecule conductance (σ) correlate with the oxidation potential of the purine base in the XY base pair. The electrochemical measurements showed that the enhancement of k(0) is independent, within experimental error, of which of the two PNA strands contains the purine base of the XY base pair. 7-bp PNA duplexes with one or two GC base pairs had similar measured k(0) and conductance values. While a simple superexchange model, previously used to rationalize charge transfer in single stranded PNA (Paul et al. J. Am. Chem. Soc. 2009, 131, 6498-6507), describes some of the experimental observations, the model does not explain the absence of an enhancement in the experimental k(0) and σ upon increasing the G content in the duplexes from one to two. Moreover, the superexchange model is not consistent with other studies (Paul et al. J. Phys. Chem. B 2010, 114, 14140), that showed a hopping charge transport mechanism is likely important for PNA duplexes longer than seven base pairs. A quantitative computational analysis shows that a near-resonant charge transfer regime, wherein a mix of superexchange and hopping mechanisms are expected to coexist, can rationalize all of the experimental results.

Role of nucleobase energetics and nucleobase interactions in single-stranded peptide nucleic acid charge transfer.

Self-assembled monolayers of single-stranded (ss) peptide nucleic acids (PNAs) containing seven nucleotides (TTTXTTT), a C-terminus cysteine, and an N-terminus ferrocene redox group were formed on gold electrodes. The PNA monomer group (X) was selected to be either cytosine (C), thymine (T), adenine (A), guanine (G), or a methyl group (Bk). The charge transfer rate through the oligonucleotides was found to correlate with the oxidation potential of X. Kinetic measurements and computational studies of the ss-PNA fragments show that a nucleobase mediated charge transport mechanism in the deep tunneling superexchange regime can explain the observed dependence of the kinetics of charge transfer on the PNA sequence. Theoretical analysis suggests that the charge transport is dominantly hole-mediated and takes place through the filled bridge orbitals. The strongest contribution to conductance comes from the highest filled orbitals (HOMO, HOMO-1, and HOMO-2) of individual bases, with a rapid drop off in contributions from lower lying filled orbitals. Our studies further suggest that the linear correlation observed between the experimental charge transfer rates and the oxidation potential of base X arises from weak average interbase couplings and similar stacking geometries for the four TTTXTTT systems.