Charge Transfer Mechanism in Guanine-Based Self-Assembled Monolayers on a Gold Surface.

In this work, we have theoretically determined the one-electron oxidation potentials and charge transfer mechanisms in complex systems based on a self-assembled monolayer of guanine molecules adsorbed on a gold surface through different organic linkers. Classical molecular dynamics simulations were carried out to sample the conformational space of both the neutral and the cationic species. Thus, the redox potentials were determined for the ensembles of geometries through multiscale quantum-mechanics/molecular-mechanics/continuum solvation model calculations in the framework of the Marcus theory and in combination with an additive scheme previously developed. In this context, conformational sampling, description of the environment, and effects caused by the linker have been considered. Applying this methodology, we unravel the phenomena of electric current transport by evaluating the different stages in which charge transfer could occur. The results revealed how the positive charge migrates from the organic layer to the gold surface. Specifically, the transport mechanism seems to take place mainly along a single ligand and driven with the help of the electrostatic interactions of the surrounding molecules. Aside, several self-assembled monolayers with different linkers have been analyzed to understand how the nature of that moiety can tune the redox properties and the efficiency of the transport. We have found that the conjugation between the guanine and the linker, at the same time conjugated to the gold surface, gives rise to a more efficient transport. In conclusion, the established computational protocol sheds light on the mechanism behind charge transport in electrochemical DNA-based biosensor nanodevices.

Modeling One-Electron Oxidation Potentials and Hole Delocalization in Double-Stranded DNA by Multilayer and Dynamic Approaches.

The number of innovative applications for DNA nowadays is growing quickly. Its use as a nanowire or electrochemical biosensor leads to the need for a deep understanding of the charge-transfer process along the strand, as well as its redox properties. These features are computationally simulated and analyzed in detail throughout this work by combining molecular dynamics, multilayer schemes, and the Marcus theory. One-electron oxidation potential and hole delocalization have been analyzed for six DNA double strands that cover all possible binary combinations of nucleotides. The results have revealed that the one-electron oxidation potential decreases with respect to the single-stranded DNA, giving evidence that the greater rigidity of a double helix induces an increase in the capacity of storing the positive charge generated upon oxidation. In addition, the hole is mainly stored in nucleobases with large reducer character, i.e., purines, especially when those are arranged in a stacked configuration in the same strand. From the computational point of view, the sampling needed to describe biological systems implies a significant computational cost. Here, we show that a small number of representative conformations generated by clustering analysis provides accurate results when compared with those obtained from sampling, reducing considerably the computational cost.

One-Electron Oxidation Potentials and Hole Delocalization in Heterogeneous Single-Stranded DNA.

The study of DNA processes is essential to understand not only its intrinsic biological functions but also its role in many innovative applications. The use of DNA as a nanowire or electrochemical biosensor leads to the need for a deep investigation of the charge transfer process along the strand as well as of the redox properties. In this contribution, the one-electron oxidation potential and the charge delocalization of the hole formed after oxidation are computationally investigated for different heterogeneous single-stranded DNA strands. We have established a two-step protocol: (i) molecular dynamics simulations in the frame of quantum mechanics/molecular mechanics (QM/MM) were performed to sample the conformational space; (ii) energetic properties were then obtained within a QM1/QM2/continuum approach in combination with the Marcus theory over an ensemble of selected geometries. The results reveal that the one-electron oxidation potential in the heterogeneous strands can be seen as a linear combination of that property within the homogeneous strands. In addition, the hole delocalization between different nucleobases is, in general, small, supporting the conclusion of a hopping mechanism for charge transport along the strands. However, charge delocalization becomes more important, and so does the tunneling mechanism contribution, when the reducing power of the nucleobases forming the strand is similar. Moreover, charge delocalization is slightly enhanced when there is a correlation between pairs of some of the interbase coordinates of the strand: twist/shift, twist/slide, shift/slide, and rise/tilt. However, the internal structure of the strand is not the predominant factor for hole delocalization but the specific sequence of nucleotides that compose the strand.

Intramolecular and intermolecular hole delocalization rules the reducer character of isolated nucleobases and homogeneous single-stranded DNA.

The use of DNA strands as nanowires or electrochemical biosensors requires a deep understanding of charge transfer processes along the strand, as well as of the redox properties. These properties are computationally assessed in detail throughout this study. By applying molecular dynamics and hybrid QM/continuum and QM/QM/continuum schemes, the vertical ionization energies, adiabatic ionization energies, vertical attachment energies, one-electron oxidation potentials, and delocalization of the hole generated upon oxidation have been determined for nucleobases in their free form and as part of a pure single-stranded DNA. We show that the reducer ability of the isolated nucleobases is explained by the intramolecular delocalization of the positively charged hole, while the enhancement of the reducer character when going from aqueous solution to the strand correlates very well with the intermolecular hole delocalization. Our simulations suggest that the redox properties of DNA strands can be tuned by playing with the balance between intramolecular and intermolecular charge delocalization.

An Efficient Multilayer Approach to Model DNA-Based Nanobiosensors.

In this work, we present a full computational protocol to successfully obtain the one-electron reduction potential of nanobiosensors based on a self-assembled monolayer of DNA nucleobases linked to a gold substrate. The model is able to account for conformational sampling and environmental effects at a quantum mechanical (QM) level efficiently, by combining molecular mechanics (MM) molecular dynamics and multilayer QM/MM/continuum calculations within the framework of Marcus theory. The theoretical model shows that a guanine-based biosensor is more prone to be oxidized than the isolated nucleobase in water due to the electrostatic interactions between the assembled guanine molecules. In addition, the redox properties of the biosensor can be tuned by modifying the nature of the linker that anchor the nucleobases to the metal support.

MoBioTools: A toolkit to setup quantum mechanics/molecular mechanics calculations.

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The package is currently compatible with trajectory and topology files in Amber, CHARMM, GROMACS and NAMD formats, and has the possibility to generate QM/MM input files for Gaussian (09 and 16), Orca (≥4.0), NWChem and (Open)Molcas. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.

Computation of Oxidation Potentials of Solvated Nucleobases by Static and Dynamic Multilayer Approaches.

The determination of the redox properties of nucleobases is of paramount importance to get insight into the charge-transfer processes in which they are involved, such as those occurring in DNA-inspired biosensors. Although many theoretical and experimental studies have been conducted, the value of the one-electron oxidation potentials of nucleobases is not well-defined. Moreover, the most appropriate theoretical protocol to model the redox properties has not been established yet. In this work, we have implemented and evaluated different static and dynamic approaches to compute the one-electron oxidation potentials of solvated nucleobases. In the static framework, two thermodynamic cycles have been tested to assess their accuracy against the direct determination of oxidation potentials from the adiabatic ionization energies. Then, the introduction of vibrational sampling, the effect of implicit and explicit solvation models, and the application of the Marcus theory have been analyzed through dynamic methods. The results revealed that the static direct determination provides more accurate results than thermodynamic cycles. Moreover, the effect of sampling has not shown to be relevant, and the results are improved within the dynamic framework when the Marcus theory is applied, especially in explicit solvent, with respect to the direct approach. Finally, the presence of different tautomers in water does not affect significantly the one-electron oxidation potentials.