Insights into electron tunneling across hydrogen-bonded base-pairs in complete molecular circuits for single-stranded DNA sequencing

Abstract

We report a first-principles study of electron ballistic transport through a molecular junction containing deoxycytidine-monophosphate (dCMP) connected to metal electrodes. A guanidinium ion and guanine nucleobase are tethered to gold electrodes on opposite sides to form hydrogen bonds with the dCMP molecule providing an electric circuit. The circuit mimics a component of a potential device for sequencing unmodified single-stranded DNA. The molecular conductance is obtained from DFT Green's function scattering methods and is compared to estimates from the electron tunneling decay constant obtained from the complex band structure. The result is that a complete molecular dCMP circuit of 'linker((CH 2 ) 2 )-guanidinium-phosphate-deoxyribose-cytosineguanine' has a very low conductance (of the order of fS) while the hydrogen-bonded guaninecytosine base-pair has a moderate conductance (of the order of tens to hundreds of nS). Thus, while the transverse electron transfer through base-pairing is moderately conductive, electron transfer through a complete molecular dCMP circuit is not. The gold Fermi level is found to be aligned very close to the HOMO for both the guanine-cytosine base-pair and the complete molecular dCMP circuit. Results for two different plausible geometries of the hydrogen-bonded dCMP molecule reveal that the conductance varies from fS for an extended structure to pS for a slightly compressed structure.

Theoretical electrical conductivity of hydrogen-bonded benzamide-derived molecules and single DNA bases

“…10a), despite that the energy levels are hardly affected as we increase hydrogen bond length. This is consistent with the results obtained in [13]. The decay factor β H is 3.82Å −1 , much larger than the one obtained from the molecule system with only a covalent bond, which is less than 1Å −1 .…”

“…Ohshiro and Umezawa [12] has shown that hydrogen bonds can facilitate electron tunneling so that tunneling current decays more slowly when it is formed between a Watson-Crick complementary base pair compared to a non-complementary base pair. Also, the electron-tunneling property of different base pairs (G-C, A-T, G-T, and 2AA-T) has been investigated by Lee et al [13] with methods of complex band structure and Green's function scattering theory for I-V characteristics, showing that as more hydrogen bonds are formed between the DNA bases, higher conductance can be observed, and the decay factor for a unit cell of base pair will increase as the hydrogen bond distance increases with a linear relationship. Experiments on DNA sequence through hydrogenbonded electron tunneling have been performed [14][15][16][17][18].…”

Advances and applications in the FIREBALLab initio tight‐binding molecular‐dynamics formalism

“…The formulation in terms of local orbitals has an added value, as the transport properties can be easily calculated from the resulting first-principles tight-binding Hamiltonian using Green's function techniques. In particular, Sankey has developed a Green's function method based on the FIREBALL Hamiltonian and used it to describe molecular conductance in simple alkene chains, ply-alanine, DNA, and other molecular systems [104,[106][107][108][109][110]. More recently, a non-perturbative scattering theory framework for transport calculations was introduced inside the FIREBALL Hamiltonian to describe ballistic conductance in nanostructures using the Lippmann-Schwinger (LS) scattering theory [111,112]; the local-orbital DFT Hamiltonian can be readily used within a self-consistent NEGF formalism [113,114] to describe the inelastic tunneling spectroscopy (e.g., C 60 [115]) and electron-phonon interactions in quatro-alanine bridges [116].…”

DNA sequencing with titanium nitride electrodes

“…Using these requirements, there are very limited (almost unique) options to connect the reader molecules to DNA bases by forming hydrogen bonds between the readers and the base. As VASP is not good enough to optimize isolated systems such as molecules, we performed the calculations in quantum chemistry package NWChem 5.1 with 6‐311G basis set and used the perdew exchange‐correlation functional, which is most suitable for dealing with hydrogen‐bonds . The final optimized structures for the connected systems with two identical readers and the four normal DNA bases, which are A, C, G, T, as well as 5methylC bases, are shown in Figure .…”

“…, they calculated the transverse current through double‐stranded DNA nucleotide and showed that the current–voltage features provide signatures for DNA sequencing. Also electron‐tunneling properties of different base pairs (G‐C, A‐T, G‐T, and 2AA‐T) have been investigated by Lee and Sankey . They used methods of complex band structure and Green's function scattering theory for I – V characteristics, showing that as more hydrogen bonds are formed between the DNA bases higher conductance can be observed, and the decay factor for the base pair will increase as hydrogen‐bond distance increases with a linear relationship.…”