Electronic analysis of hydrogen-bonded molecular complexes: the case of DNA sensed in a functionalized nanogap.

DNA nucleotides can be interrogated by nanomaterials in order to be detected. With the aid of quantum-mechanical simulations, we unravel the intrinsic details of the electronic transport across nanoelectrodes functionalized with tiny modified diamond-like molecules. These electrodes generate a gap in which DNA nucleotides are placed and can be identified. The identification is strongly affected by the hydrogen bonding characteristics of the diamond-like particle and the nucleotides. The results point to the connection of the electronic transmission across the functionalized nanogap and the electronic and bonding characteristics of the molecular complexes within the nanogap. Specifically, our discussion focuses on the influence of the DNA dynamics on the electronic signals across the nanogap. We identify the molecular complex's details that hinder or promote the electronic transport through an analysis that moves from the bonding within the molecular complex up to the electronic current that this can accommodate. Accordingly, our work discusses pathways for analyzing hydrogen-bonded molecular complexes or molecules hydrogen-bonded to a material part having the optimization of the design of biosensing nanogaps and read-out nanopores in mind. The presented approach, though, is applicable to a wide range of applications utilizing exactly the bio/nano interface.

Functionalized Nanogap for DNA Read-Out: Nucleotide Rotation and Current-Voltage Curves.

Functionalized nanogaps embedded in nanopores show a strong potential for enhancing the detection of biomolecules, their length, type, and sequence. This detection is strongly dependent on the features of the target biomolecules, as well as the characteristics of the sensing device. In this work, through quantum-mechanical calculations, we elaborate on representative such aspects for the specific case of DNA detection and read-out. These aspects include the influence of single DNA nucleotide rotation within the nanogap and the current-voltage (I-V) characteristics of the nanogap. The results unveil a distinct variation in the electronic current across the functionalized device for the four natural DNA nucleotides with the applied voltage. These also underline the asymmetric response of the rotating nucleotides on this applied voltage and the respective variation in the rectification ratio of the device. The electronic tunneling current across the nanogap can be further enhanced through the proper choice of an applied bias voltage. We were able to correlate the enhancement of this current to the nucleotide rotation dynamics and a shift of the electronic transmission peaks towards the Fermi level. This nucleotide specific shift further reveals the sensitivity of the device in reading-out the identity of the DNA nucleotides for all different configurations in the nanogap. We underline the important information that can be obtained from both the I-V curves and the rectification characteristics of the nanogap device in view of accurately reading-out the DNA information. We show that tuning the applied bias can enhance this detection and discuss the implications in view of novel functionalized nanopore sequencers.

The influence of a solvent on the electronic transport across diamondoid-functionalized biosensing electrodes.

Electrodes embedded in nanopores have the potential to detect the identity of biomolecules, such as DNA. This identification is typically being done through electronic current measurements across the electrodes in a solvent. In this work, using quantum-mechanical calculations, we qualitatively present the influence of this solvent on the current signals. For this, we model electrodes functionalized with a small diamond-like molecule known as diamondoid and place a DNA nucleotide within the electrode gap. The influence of an aqueous solvent is taken explicitly into account through Quantum-Mechanics/Molecular Mechanics (QM/MM) simulations. From these, we could clearly reveal that at the (111) surface of the Au electrode, water molecules form an adlayer-like structure through hydrogen bond networks. From the temporal evolution of the hydrogen bond between a nucleotide and the functionalizing diamondoid, we could extract information on the conductance across the device. In order to evaluate the influence of the solvent, we compare these results with ground-state electronic structure calculations in combination with the non-equilibrium Green's function (NEGF) approach. These allow access to the electronic transport across the electrodes and show a difference in the detection signals with and without the aqueous solution. We analyze the results with respect to the density of states in the device. In the end, we demonstrate that the presence of water does not hinder the detection of a mutation over a healthy DNA nucleotide. We discuss these results in view of sequencing DNA with nanopores.

The role of a diamondoid as a hydrogen donor or acceptor in probing DNA nucleobases.

It has been shown that diamondoids can interact with DNA by forming relatively strong hydrogen bonds to DNA units, such as nucleobases. For this interaction to occur the diamondoids must be chemically modified in order to provide donor/acceptor groups for the hydrogen bond. We show here that the exact arrangement of an amine-modified adamantane with respect to a neighboring nucleobase has a significant influence on the strength of the hydrogen bond. Whether the diamondoid acts as a hydrogen donor or acceptor in the hydrogen binding to the nucleobase affects the electronic structure and thereby the electronic band-gaps of the diamondoid-nucleobase complex. In a donor arrangement of the diamondoid close to a nucleobase, the interaction energies are weak, but the electronic band-gaps differ significantly. Exactly the opposite trend is observed in an acceptor arrangement of the diamondoid. In each of these cases the frontier orbitals of the diamondoid and the nucleobase play a different role in the binding. The results are discussed in view of a diamondoid-based biosensing device.

Type-dependent identification of DNA nucleobases by using diamondoids.

The possibility of distinguishing between DNA nucleobases of different sizes is manifested here through quantum-mechanical simulations. By using derivatives of small, modified diamond clusters, known as diamondoids, it is possible to separate the pyrimidines (cytosine and thymine) from the larger purines (adenine and guanine), according to the collective electronic and binding properties of these DNA nucleobases and the diamondoid. The latter acts as a probe with which these properties can be examined in detail. Short single-stranded DNA is built up from single nucleobases to reveal the effect of each DNA unit on the sensing abilities of the diamondoid probe. Several ways of orienting the nucleobases, nucleosides, nucleotides, and short single-stranded DNA are investigated; these lead to quite different electronic properties and may or may not enhance the possibility of separating the DNA nucleobases. For the optimum orientation, that is, one that promotes stronger hydrogen bonding of the diamondoid to the short DNA strand, it is found that the electronic band gaps of a purine strand lie in a completely different range to the band gaps of a pyrimidine strand. This difference can be over 1 eV, which is measurable and shows the potential of using diamondoids and their derivatives in biosensing devices.