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. 2024 Apr 18;16(17):21427–21437. doi: 10.1021/acsami.3c18400

Detecting Hachimoji DNA: An Eight-Building-Block Genetic System with MoS2 and Janus MoSSe Monolayers

Vasudeo Babar †, Sitansh Sharma ‡,*, Abdul Rajjak Shaikh ‡, Romina Oliva §, Mohit Chawla †, Luigi Cavallo †,*
PMCID: PMC11071042  PMID: 38634539

Abstract

graphic file with name am3c18400_0012.jpg

In the pursuit of personalized medicine, the development of efficient, cost-effective, and reliable DNA sequencing technology is crucial. Nanotechnology, particularly the exploration of two-dimensional materials, has opened different avenues for DNA nucleobase detection, owing to their impressive surface-to-volume ratio. This study employs density functional theory with van der Waals corrections to methodically scrutinize the adsorption behavior and electronic band structure properties of a DNA system composed of eight hachimoji nucleotide letters adsorbed on both MoS2 and MoSSe monolayers. Through a comprehensive conformational search, we pinpoint the most favorable adsorption sites, quantifying their adsorption energies and charge transfer properties. The analysis of electronic band structure unveils the emergence of flat bands in close proximity to the Fermi level post-adsorption, a departure from the pristine MoS2 and MoSSe monolayers. Furthermore, leveraging the nonequilibrium Green’s function approach, we compute the current–voltage characteristics, providing valuable insights into the electronic transport properties of the system. All hachimoji bases exhibit physisorption with a horizontal orientation on both monolayers. Notably, base G demonstrates high sensitivity on both substrates. The obtained current–voltage (I–V) characteristics, both without and with base adsorption on MoS2 and the Se side of MoSSe, affirm excellent sensing performance. This research significantly advances our understanding of potential DNA sensing platforms and their electronic characteristics, thereby propelling the endeavor for personalized medicine through enhanced DNA sequencing technologies.

Keywords: 2D-materials, DNA sensing, density functional theory, MoS2, MoSSe

1. Introduction

Biomolecular detection holds significant importance in disease diagnostics and biomolecular analysis, driving the pursuit of rapid, sensitive, and selective detection methods for deoxyribonucleic acid (DNA) and other small biomolecules.1,2 In addition to the four natural bases—adenine (A), thymine (T), guanine (G), and cytosine (C), DNA may contain modified bases in small quantities.3 DNA base modification serves as a critical epigenetic mechanism regulating gene expression in both plants and animals.

In recent years, the field of synthetic biology has made significant progress in expanding the genetic code of DNA through the development of novel modified nucleotides. These specialized nucleotides have been extensively investigated for various applications, including precise site-specific labeling,4−6 targeted detection probing,7,8 and structural analysis of nucleic acids.9−17 In this scenario, Hoshika et al.18 integrated modified nucleotides (B, S, P, and Z) with the natural bases (A, T, G, and C) into oligonucleotides. Specifically, B represents 6-amino-9-(1′-β-d-2′-deoxyribofuranosyl)-4-hydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1H-purin-2-one, S is 3-methyl-6-amino-5-(1′-β-d-2′-deoxyribofuranosyl)-pyrimidin-2-one, P is 2-amino-8-(1′-β-d-2′-deoxyribofuranosyl)-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one, and Z is 6-amino- 3-(1′-β-d-2′-deoxyribofuranosyl)-5-nitro-1H-pyridin-2-one. A, T, G, and C represent adenine, thymine, guanine, and cytosine, respectively. This ground breaking development resulted in the creation of DNA containing an expanded eight-base genetic alphabet (A, T, G, C, B, S, P, and Z, as illustrated in Figure 1). This innovative DNA structure exhibits significantly enhanced information-storage capacity compared to the conventional four-base natural alphabet, as well as previously reported six-base systems, which relied on combinations of canonical pairs with either Romesberg’s hydrophobic pairs19 or Benner’s P:Z pair.20 This newly engineered class of nucleic acids has been named “hachimoji” (eight-letter) DNA.

Figure 1.

Figure 1

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Molecular structures of hachimoji natural and modified DNA bases. In the representation, C, N, O, and H atoms are denoted by brown, gray, red, and pink balls, respectively.

One potential application of an expanded genetic code is diagnostic in medicine. Optical and electrical detection methods using fluorescent or electrochemical labels are commonly employed but involve complex and costly procedures compared to label-free detection. Researchers have explored various two-dimensional materials such as graphene,21−24 silicene,25,26 phosphorene,27 h-BN,28,29 Ti2CO2 MXene,30 Ti3C2 MXene,31 germanene,32 monolayer C2N,33,34 and monolayer GaS35 as a sensing platforms for DNA nucleobase detection. Recently, two-dimensional transition metal dichalcogenides (TMDs) have garnered increasing attention due to their large surface-to-volume ratio and exceptional optical and electrical properties. Researchers have investigated the sensing performance of monolayer MoS2 for DNA detection, both experimentally and theoretically. Farimani et al.36 employed atomistic and quantum simulations and found that single-layer MoS2 (nanopore and nanochannel) exhibits extraordinary characteristics for DNA sequencing. The MoS2 nanopore demonstrates distinct current signals for the detection of individual nucleobases with low noise. Furthermore, single-layer MoS2 exhibits characteristic response in density of states and band structure when nucleobases are placed on pristine MoS2 and armchair MoS2 nanoribbons.36 Jin et al.37 reported a novel Au-modified monolayer MoS2 sensor that enables rapid, sensitive, and selective detection of DNA molecules. The interaction between Au and SH groups enhances DNA adsorption on MoS2 by approximately 1 order of magnitude.37 Graf et al.38 demonstrated the technical feasibility of fabricating freestanding MoS2 nanoribbons with nanopore. DNA molecules are sensed through correlated signals from the ionic current passing through the nanopore and the transverse current passing through the nanoribbon.38 Since nanopore sequencing technology is widely used for DNA detection; however, it suffers from many limitations. Therefore, in the present study, we tend to probe a more robust technique and material that could be cheaper and able to commercialize for this sensing activity. For this, we are trying to study on top sensor mechanism instead of nanogap and nanopore mechanism.39,40

The Janus monolayer MoSSe is synthesized by replacing the top layer sulfur (S) in MoS2 with selenium (Se) atoms.41,43 Transitioning from monolayer MoS2 to monolayer MoSSe, which breaks the out-of-plane mirror symmetry, results in a substantial vertical dipole moment. As the sensing process on two-dimensional materials primarily occurs at the surface, the presence of a dipole moment in experimentally synthesized Janus monolayer MoSSe is expected to influence the sensing performance compared with monolayer MoS2 in detecting DNA nucleobases. Consequently, this study aims to investigate the potential application of two-dimensional materials, primarily MoS2 and MoSSe monolayers,42−44 for the detection of hachimoji DNA bases proposed for the expansion of genetic information system45 using density functional theory aided with van der Waals dispersion correction.

This investigation aims to identify the optimal adsorption sites and distances for DNA nucleobases. Commonly employed theoretical parameters, including the adsorption energy and charge transfer, have been leveraged to assess the sensing capabilities. The intermolecular interactions between the MoS2/MoSSe layer and DNA base pairs will be scrutinized through NCI plot analysis. Before and after nucleobase adsorption, the current–voltage (I–V) characteristics will be computed using the nonequilibrium Green’s function formalism. The outcomes of this research offer valuable insights into the influence of dipole moments on the monolayer surface in the context of DNA sensing. This understanding is poised to facilitate the identification of promising candidates for DNA sensing applications.

2. Computational Details

First-principles calculations are conducted using density functional theory as implemented in the Vienna Ab initio Simulation Package.46−48 The exchange-correlation potential is treated in the generalized gradient approximation of Perdew–Burke–Ernzerhof (PBE). Projector-augmented wave potentials are utilized, considering the valence state as follows: 1s1 for H, 2s22p2 for C, 2s22p3 for N, 2s22p4 for O, 3s23p4 for S, 4s24p4 for Se, and 4p64d55s1 for Mo.49 The van der Waals interaction is accounted for using the DFT-D3 method.50 The electronic wave functions are expanded in a plane-wave basis set with a cutoff energy of 500 eV. Brillouin zone integrations are performed on 3 × 3 × 1 Monkhorst–Pack k-meshes.51 All structures are relaxed, using the conjugate gradient algorithm, until the total energy and atomic forces converge to below 10–6 eV and 5 × 10–3 eV/Å, respectively.

To construct the 2D material (slab model), a vacuum layer with a thickness of 16 Å is added in the out-of-plane direction. For adsorption studies, the supercell of size 5 × 5 × 1 is employed. The adsorption strength of a base molecule on monolayer (MoS2/MoSSe) is evaluated in terms of the adsorption energy (Ead) of eq 1,

2. 1

where Emonolayer+base, Emonolayer, and Ebase are the total energies of the combined system, monolayer (MoS2/MoSSe), and base molecule, respectively. The adsorption energy Ead provides information about the stability of the adsorption between a monolayer and a base molecule. A negative Ead value indicates an exothermic adsorption process, resulting in a favorable base/monolayer structure. For the calculations of the current, we utilize the nonequilibrium Green’s function method as implemented in the TranSIESTA method.52 This method employs the Landauer–Büttiker formula to calculate current, as in eq 2

2. 2

where fL(E) and fR(E) are the Fermi distribution functions of the left and right leads, respectively, and T(E,V) is the transmission coefficient at energy E and bias voltage V. The electronic wave functions are expanded in a polarized double-ζ basis with a cutoff energy of 700 Ry (see Figure S1). The Brillouin zone is sampled on 1 × 5 × 51 and 1 × 5 × 1 Monkhorst-Pack k-meshes for the lead and transport calculations, respectively. Charge transfers are obtained by Bader charge analysis.53 The charge density difference plot of eq 3

2. 3

is derived from the charge density distributions of the combined system (ρmonolayer+base), monolayer (ρmonolayer), and molecule (ρbase). To calculate the charge density distributions of the monolayer and molecule, we extracted the structures from the combined system.

3. Results and Discussion

3.1. Adsorption of Hachimoji DNA Bases on MoS2 and MoSSe Monolayers

The unit cells of the MoS2 and MoSSe monolayers consist of three atoms each, with Mo sandwiched between two layers of S or S and Se, as depicted in Figure 2. For the MoS2 monolayer, we achieved an optimized lattice constant of a = b = 3.16 Å, with average Mo–S bond lengths of 2.40 Å. The thickness of MoS2 is measured as 3.13 Å, and the S–Mo–S angle is determined to be 82.25◦. The electronic band structure exhibits characteristics of a semiconductor with a direct band gap of 1.75 eV, consistent with previous findings.54 For the MoSSe monolayer, the optimized lattice constants are a = b = 3.22 Å, and the Mo–S and Mo–Se bond lengths are 2.41 and 2.53 Å, respectively. The thickness of MoSSe is calculated as 3.24 Å and the dipole moment is 0.24 D in good agreement with previous reports.55 The electronic band structure reveals a semiconducting behavior with a direct band gap of 1.63 eV. The more diffuse orbitals of Se as compared to S atom lead to weaker overlap with the Mo orbitals, which can result in a reduction in the band gap.

Figure 2.

Figure 2

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Atomic structure with electronic band structure of the hexagonal unit cell in MoS2 and MoSSe monolayers. The Mo, S, and Se atoms are represented by purple, yellow, and green balls, respectively.

In order to examine the interaction between natural DNA bases (A–C) and their modified counterparts (B–Z) on MoS2 and MoSSe monolayers, our initial step involves optimizing the molecular structures of the bases. The centers of mass of these molecules are kept at various possible adsorption sites on MoS2 and MoSSe monolayers with different orientations, and the lowest-energy configurations are obtained. All possible adsorption sites (HC: hexagonal center, B: bridge, TMo: top of Mo atom, TX: top of S or Se atom) are shown in Figure 2.

The lowest-energy configurations of the natural and modified base molecules on the MoS2 monolayer are shown in Figure 3. All bases prefer a horizontal orientation with a binding distance of ≈3.0 Å from the monolayer surface. Additionally, we included the adsorption energy values for the various binding sites in Table S1.

Figure 3.

Figure 3

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Lowest-energy configurations of natural (A, T, G, C) and modified (B, S, P, Z) base molecules on the MoS2 monolayer, with both top and side views. Mo, S, C, N, O, and H atoms are represented by purple, yellow, brown, gray, red, and pink balls, respectively.

In the MoS2 monolayer, A, T, and G bases prefer HC, B, and HC sites, respectively, with adsorption energies of −0.789 eV, −0.748 eV, and −0.953 eV. The C base favors the TMo site with an adsorption energy of −0.756 eV, while the modified B base prefers the HC site with an adsorption energy of −0.930 eV. Base S adsorbs on the top of the S atom site (TS) with an adsorption energy of −0.851 eV. The modified base P molecule achieves its lowest energy at the TMo site with an adsorption energy of −0.912 eV, and the base Z molecule at the B site with an adsorption energy of −0.876 eV. Notably, bond lengths in MoS2 and base molecules show no modification except for the N–H bond length in G and B bases, indicating physisorption.

The adsorption energy results, summarized in Table 1, indicate that all of the bases primarily exhibit physisorption. Notably, among the natural and modified bases studied, base G and base T exhibit the highest and lowest affinities for adsorption, respectively, with the following trend: G > B > P > Z > S > A > C > T. It is worth highlighting that the modified bases considered in this investigation display strong adsorption on all monolayers, as illustrated in Table 1. The adsorption energy trend for natural bases (G > A > C > T) aligns closely with findings from prior studies.56 This phenomenon can be attributed to the relatively larger size of purine bases in comparison to pyrimidines, leading to an increased surface area for interaction with the monolayer and consequently resulting in higher adsorption energies, with the exception of base A. Furthermore, the observed trends in adsorption energies exhibit a direct correlation with the number of heteroatoms within the base molecules.

Table 1. Preferred Adsorption Site, Binding Distance (Dh) (Shortest Atom-to-Atom Distance Between Monolayer and Base Molecule), Adsorption Energy (Ead), and Charge Transfer (ΔQ: ∓ Sign Indicates Charge Depletion from or Charge Accumulation on Base Molecule) of the Hachimoji Bases Adsorbed on the MoS2/MoSSe Monolayer.

  MoS2
 MoSSe_S
 MoSSe_Se
base site Dh (Å) Ead (eV) ΔQ (e) site Dh (Å) Ead (eV) ΔQ (e) site Dh (Å) Ead (eV) ΔQ(e)
A HC 3.00 –0.789 –0.011 HC 2.99 –0.780 –0.003 HC 3.13 –0.804 0.006
T B 2.88 –0.748 0.012 B 2.88 –0.742 0.017 B 2.97 –0.771 0.030
G HC 2.88 –0.953 –0.007 HC 2.83 –0.951 0.003 HC 3.04 –0.974 0.016
C TMo 2.89 –0.756 –0.012 TMo 3.01 –0.744 –0.004 TMo 3.02 –0.779 0.004
B HC 3.10 –0.930 –0.004 HC 2.89 –0.904 0.006 HC 3.09 –0.944 0.019
S TS 2.78 –0.851 –0.007 B 2.94 –0.825 –0.001 TSe 2.98 –0.861 0.013
P TMo 2.94 –0.912 –0.011 TMo 3.20 –0.896 –0.006 TMo 3.35 –0.928 0.006
Z B 3.01 –0.876 0.016 B 3.02 –0.869 0.023 B 3.20 –0.894 0.037
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In the context of monolayer MoSSe, we examined the adsorption behavior of natural and modified bases on both sides, denoted as S (MoSSe_S) and Se (MoSSe_Se). As illustrated in Figure S2, adsorption attributes were analyzed for all DNA bases on the S side of the MoSSe monolayer. These investigations unveiled trends and behaviors that closely mirrored those observed in the context of the monolayer MoS2, and thus, we do not discuss them further. Differently, unique behavior was discerned by analyzing adsorption on the Se side (see Figure 4). As illustrated in Table 1, akin to the S side of both MoS2 and MoSSe, the Se side of the MoSSe monolayer displayed a noticeably higher attraction for the DNA base G. All of the hachimoji bases exhibit robust interactions with the Se side of the MoSSe monolayer. Noteworthy, the adsorption energy on the Se side of MoSSe is approximately 3% higher (or lower for the S side) in comparison to the MoS2 monolayer. Crucially, the same consistent adsorption energy trends (G > B > P > Z > S > A > C > T) are observed for both MoS2 and MoSSe monolayers, irrespective of the side considered (S or Se).

Figure 4.

Figure 4

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Top and side perspectives of the lowest-energy conformations of natural (A, T, G, and C) and modified (B, S, P, and Z) base molecules on the selenium (Se) side of the MoSSe monolayer. Mo, S, Se, C, N, O, and H atoms are depicted by purple, yellow, green, brown, gray, red, and pink balls, respectively.

To differentiate between distinct modes of interaction between nucleobases and surfaces, we employ non-covalent interaction (NCI) plots, as originally introduced by Contreras-García et al.57 and computational details is given in the Supporting Information. These plots are presented in Figure 5 for molecules exhibiting varying degrees of adsorption. The NCI plot for the remaining base pairs is displayed in Figure S3. The NCI plot clearly illustrates the presence of weak van der Waals interactions between the base pairs and surfaces with no chemical bonds observed between them.

Figure 5.

Figure 5

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Visualization of 3D-NCI plots depicting interaction profiles for (a) G base, (b) T base, (c) B base, and (d) S base on the MoS2 surface. Additionally, (e) G base and (f) T base, along with (g) B base and (h) S base on MoSSe_Se surface. The accompanying neighboring graph showcases 2D-NCI plots representing the reduced density gradient (s) against the sign of the Laplacian of electron density (l2*r) in atomic units.

3.2. Charge Redistribution in Hachimoji DNA Base Adsorption on MoS2 and MoSse Monolayers

To gain a deeper understanding of the interaction’s nature, we have depicted charge density difference plots in Figures 6 and 7, resulting from the adsorption of the bases on both monolayer MoS2 and MoSSe (Se side). These visual representations effectively illustrate how the adsorption of the bases induces a redistribution of charge density, leading to a substantial overlap of electron clouds between the base molecule and the monolayers. Notably, this charge density accumulation aligns closely with the adsorption energy trends for both monolayers, with the exception of base C. The extent of charge transfer between the bases and the MoS2/MoSSe monolayer is quantified using Bader charge analysis, and the corresponding values are summarized in Table 1. This variation in charge redistributions, observed for different base molecules after adsorption on MoS2 (Figure 6) and MoSSe_Se (Figure 7) monolayers, is anticipated to exert a significant influence on the current–voltage characteristics. These insights hold promise for facilitating the identification of specific bases for practical applications.

Figure 6.

Figure 6

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Top and side views of the charge density difference induced by adsorption base molecules on the MoS2 monolayer. Magenta and cyan isosurfaces represent charge accumulation and depletion, respectively (isosurface value: 5.0 × 10–4 electrons/Å3).

Figure 7.

Figure 7

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Top and side views of the charge density difference induced by adsorption base molecules on the MoSSe_Se monolayer. Magenta and cyan isosurfaces represent charge accumulation and depletion, respectively (isosurface value: 5.0 × 10–4 electrons/Å3).

Figure 8 illustrates the modification in the electronic band structure of monolayer MoS2 after bases adsorption. We note that after adsorption molecular states are being introduced in between the band gap of pristine MoS2, which further lowers the band gap and hence will influence the electronic transport behavior. Due to similar adsorption behavior of the bases on the S side of MoSSe monolayer, similar electronic band structure features are observed (see Figure S4). Interestingly, in the case of monolayer MoSSe, no molecular states are introduced in between the band gap, except for base B (see Figure 9). These electronic band structure features show that the electronic transport behavior for monolayer MoS2 should be similar to S side of MoSSe, while for Se side of monolayer MoSSe, we expect to observe different behavior. Therefore, for further electronic transport studies, we only considered monolayer MoS2 and the Se side of monolayer MoSSe.

Figure 8.

Figure 8

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Electronic band structure of the natural (A, T, G, C) and modified (B, S, P, Z) base molecules on the MoS2 monolayer. Molecular contributions are highlighted in red color.

Figure 9.

Figure 9

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Electronic band structure of the natural (A, T, G, C) and modified (B, S, P, Z) base molecules on the MoSSe_Se monolayer. Molecular contributions are highlighted in red color.

3.3. Sensing Potential of MoS2/MoSSe Monolayers for Hachimoji DNA Bases

Quantitative assessment of the sensing potential of biosensor made up of MoS2/MoSSe monolayer for base molecule detection can be achieved by analyzing the changes in current–voltage characteristics (resistivity change) before and after the adsorption of base molecules. In our study, we consider the flow of current in both the armchair and zigzag directions using a setup comprising semi-infinite left and right leads connected to a central scattering region (Figure 10). For monolayer MoS2, the dimensions of the leads are 15.82 Å × 10.96 Å (armchair) and 16.44 Å × 9.49 Å (zigzag), and the scattering region have sizes of 15.82 Å × 16.44 Å (armchair) and 16.44 Å × 15.82 Å (zigzag), respectively. In case of monolayer MoSSe (Se side), the dimensions of the leads are 16.14 Å × 11.18 Å (16.78 Å × 9.70 Å) and the scattering region have a size of 16.14 Å Å × 16.78 Å (16.78 Å × 16.14 Å) for armchair (zigzag) direction. For both the monolayers, the current behavior is obtained at bias ranging from 0.0 to 2.4 V, with a step size of 0.3 V bias. The transport setup and resulting current–voltage characteristics, without and with adsorbed base molecules for both armchair and zigzag directions, are shown in Figure 10.

Figure 10.

Figure 10

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Transport setup and current–voltage characteristics of MoS2 and MoSSe_Se monolayers in armchair and zigzag directions, with and without adsorbed base molecules. The insets display the current value for base molecules on both monolayers at an applied voltage of 2.4 V. The horizontal line represents the current value for pure monolayers.

Both monolayers exhibit anisotropic electronic transport behavior, with higher current observed along the zigzag direction in contrast to the armchair direction. This intriguing phenomenon can be attributed to the substantial transmission coefficient favoring the zigzag direction, which, in turn, provides a more conductive channel for electron transport compared to the armchair direction. Furthermore, the pronounced dispersion in the electronic band along the zigzag direction suggests a lower effective mass, thus resulting in a higher current in comparison to the armchair direction (as illustrated in Figure S5). The transmission coefficient plots at applied zero bias voltage, following the adsorption of bases on both monolayers, are depicted in Figure S6. These plots reveal that within the selected energy range for the studied monolayers, different bases exhibit distinctive transmission profiles, indicative of varying currents (as defined in eq 2). This divergence underscores their potential for selective base detection.

In the context of electronic transport, the band gap plays a critical role in determining the current flow in monolayer MoSSe (Se side) in comparison to the MoS2 monolayer, as depicted in Figure 10. It is important to note that current flow cannot occur when the applied bias voltage is within the range of the band gap. Up to an applied bias of 1.5 V, no significant current is observed in both monolayers. At 1.8 V, the MoS2 monolayer exhibits negligible current flow, while in the case of the MoSSe_Se monolayer, a current on the order of 0.001 μA is detected, consistent with their respective band gap values. The narrower band gap of monolayer MoSSe results in an earlier onset of current compared to MoS2. With further increases in bias voltage, both monolayers exhibit a significant increase in current, with MoSSe monolayer demonstrating higher current levels.

At an applied voltage of 2.4 V along the armchair direction in the MoS2 monolayer, the maximum (minimum) current is observed for the P (G) base, while along the zigzag direction, the maximum (minimum) current corresponds to the B (P) base. The order of currents for the studied bases along the armchair direction increases as follows: P > T > B > A > Z > S > C > G. Along the zigzag direction, the order is B > G > S > C > T > A > Z > P. Conversely, in the case of the MoSSe_Se monolayer at 2.4 V, the maximum current along the armchair (zigzag) direction is obtained for the P (S) base, while the minimum current corresponds to the G (P) base. Along the armchair direction, the order of current is P > Z > T > C > B > S > A > G. Along the zigzag direction, the trend is S > C > T > A > Z > B > G > P.

The strong adsorption of the G base to both monolayers results in increased resistance to electron flow, consequently reducing the current following adsorption on the sensing platform compared with the pristine monolayers. At 2.4 V, the adsorption of base G on MoS2 (Se side of MoSSe) decreases the current along the armchair direction by 20% (21.50%) and increases (reduces) it along the zigzag direction by 5% (9%), respectively. The adsorption of base T on MoS2 (Se side of MoSSe) results in a 3% reduction (4% increase) in current along the armchair direction and a 0.5% reduction (1.5% reduction) in current along the zigzag direction, respectively. These variations highlight the impact of base adsorption on the electronic transport characteristics, demonstrating the potential for the selective base detection.

To create an effective DNA base sensor, the primary requirement is the ability to detect a specific base. The sensitivity of a given monolayer to a particular base molecule is quantified by assessing the change in current relative to the baseline current (corresponding to the pristine monolayer). This assessment is achieved through the relationship of eq 4:

3.3. 4

where Imonolayer+base represents the current flow in the monolayer upon adsorption of a particular base and Imonolayer represents the current flow in the pristine monolayer. The resulting response values for base molecules, subsequent to adsorption onto the biosensors composed of both MoS2 and MoSSe (Se side) as the sensing platform at an applied voltage of 2.4 V.

Intriguingly, while the current values are higher along the zigzag direction for both MoS2 and MoSSe monolayers, the armchair direction exhibits a more pronounced response in terms of selectivity. Specifically, at an applied voltage of 2.4 V, the G base demonstrates the highest response on both monolayers, whereas the T base exhibits the lowest response post adsorption. Figure 11 illustrates that along the armchair direction, the MoSSe monolayer (Se side) effectively discriminates between natural bases with maximum and minimum current responses for bases G and T, respectively. Moreover, it distinguishes hachimoji bases (B, P, S, Z) from natural bases (A, T, G, C), though only base P is selectively identified, while bases B, S, and Z are indistinguishable. Conversely, along the zigzag direction, the MoSSe monolayer identifies only base G, with A, T, and C being indistinguishable. Among hachimoji bases, bases B and P are distinguishable, while bases S and Z are indistinguishable. For the MoS2 monolayer, along the armchair direction, natural bases can be separated from each other and are distinguishable from hachimoji bases except for base P, whose response falls below 1%. However, along the zigzag direction of the MoS2 monolayer, only bases G, B, and P are distinguishable, while bases S and Z are indistinguishable. Notably, the low response percentage (<1%) makes it challenging to detect bases A, T, and C.

Figure 11.

Figure 11

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Sensitivity plots for base molecules on monolayers of MoS2 and MoSSe (Se side) at an applied voltage of 2.4 V.

Comparing response plots between MoS2 and MoSSe (Se side) based biosensors, it is evident that, in both directions, the MoSSe monolayer outperforms the MoS2 monolayer, except in cases involving base C along the armchair direction and base B along the zigzag direction.

For the comparative analysis, we compared our results with a recent study on the detection of Hachimoji nucleobases using a hybrid graphene/h-BN nanopore device.58 The previous study reported transconductance sensitivity values, whereas we calculated the current sensitivity values in our study. We presented the transconductance sensitivity value for our materials using a gate voltage of +1.38 V (+1.20 V) for MoS2 (MoSSe_Se). Hybrid graphene/h-BN exhibited superior sensitivity compared to both MoS2 and MoSSe_Se, with B nucleobase demonstrating the highest sensitivity, followed by S, P, and Z nucleobases.58 However, when comparing the adsorption energy values, we observed weak interactions of Hachimoji bases with the graphene/h-BN nanopore, with a positive binding energy of +0.05 eV detected for base P. Base Z and ribose S (rS) exhibited binding energies of −0.02 eV, which are lower than the thermal energy at room temperature. These findings suggest that some bases, such as P, Z, and rS, may be challenging to detect using the hybrid graphene/h-BN nanopore, while B and S can be selectively detected. Conversely, these bases showed moderate interaction with the MoS2 (MoSSe_Se) materials presented in this work.

4. Conclusions

In this study, we have employed density functional theory and nonequilibrium Green’s function to explore the potential for natural and modified DNA nucleobase sensing on monolayers of MoS2 and MoSSe. Our analysis reveals that both MoS2 and MoSSe monolayers exhibit moderate adsorption energies for a range of nucleobases, positioning them as promising candidates for DNA sequencing applications. Of particular note is the strong adsorption affinity of base G on both monolayers. These findings collectively indicate that MoSSe (Se side) monolayers hold promise as a superior platform for the selective detection of DNA bases. The strong adsorption of certain bases impacts the electron flow, and the observed variations in current can be harnessed for practical applications.

In summary, our research contributes to the development of efficient hachimoji base sensors, providing a foundation for the design of novel biosensing devices with improved selectivity and sensitivity. The insights gained from this study can be instrumental in advancing the field of personalized medicine, where precise DNA analysis is essential for tailoring medical treatments and therapies.

Acknowledgments

The research reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST). Computational resources were provided by the Supercomputing Laboratory of KAUST.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.3c18400.

  • Computational details for NCI plots, adsorption energy values for different binding sites, top and side views of the lowest-energy conformations of natural (A, T, G, C) and modified (B, S, P, Z) base molecules on the S side of the MoSSe monolayer, NCI surface and NCI plot illustrating the base monolayer interactions, electronic band structure of the natural (A, T, G, C) and modified (B, S, P, Z) base molecules on S side of MoSSe monolayer, atomic structure with electronic band structure of rectangular unit cell of MoS2 and MoSSe monolayers, and transmission coefficient plots at applied zero bias voltage for MoS2 and MoSSe (Se side) along armchair and zigzag directions without and with base molecules (PDF)

The authors declare the following competing financial interest(s): S.S. and A.R.S. were employed by the company STEMskills Research and Education Lab Private Limited, Faridabad, Haryana, India.

Supplementary Material

am3c18400_si_001.pdf (1.2MB, pdf)

References

  1. Li F.; Huang Y.; Yang Q.; Zhong Z.; Li D.; Wang L.; Song S.; Fan C. A Graphene-Enhanced Molecular Beacon for Homogeneous DNA Detection. Nanoscale 2010, 2 (6), 1021–1026. 10.1039/b9nr00401g. [DOI] [PubMed] [Google Scholar]
  2. He S.; Song B.; Li D.; Zhu C.; Qi W.; Wen Y.; Wang L.; Song S.; Fang H.; Fan C. A Graphene Nanoprobe for Rapid, Sensitive, and Multicolor Fluorescent DNA Analysis. Adv. Funct. Mater. 2010, 20 (3), 453–459. 10.1002/adfm.200901639. [DOI] [Google Scholar]
  3. Kumar S. Epigenomics of Plant Responses to Environmental Stress. Epigenomes 2018, 2 (1), 6. 10.3390/epigenomes2010006. [DOI] [Google Scholar]
  4. Hikida Y.; Kimoto M.; Yokoyama S.; Hirao I. Site-Specific Fluorescent Probing of RNA Molecules by Unnatural Base-Pair Transcription for Local Structural Conformation Analysis. Nat. Protoc. 2010, 5, 1312–1323. 10.1038/nprot.2010.77. [DOI] [PubMed] [Google Scholar]
  5. Kimoto M.; Mitsui T.; Yamashige R.; Sato A.; Yokoyama S.; Hirao I. A New Unnatural Base Pair System Between Fluorophore and Quencher Base Analogues for Nucleic Acid-Based Imaging Technology. J. Am. Chem. Soc. 2010, 132, 15418–15426. 10.1021/ja1072383. [DOI] [PubMed] [Google Scholar]
  6. Kimoto M.; Mitsui T.; Yokoyama S.; Hirao I. A Unique Fluorescent Base Analogue for the Expansion of the Genetic Alphabet. J. Am. Chem. Soc. 2010, 132, 4988–4989. 10.1021/ja100806c. [DOI] [PubMed] [Google Scholar]
  7. Hoshika S.; Chen F.; Leal N. A.; Benner S. A. Artificial Genetic Systems: Self-Avoiding DNA in PCR and Multiplexed PCR. Angew. Chem., Int. Ed. 2010, 49, 5554–5557. 10.1002/anie.201001977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Sherrill C. B.; Marshall D. J.; Moser M. J.; Larsen C. A.; Daude-Snow L.; Prudent J. R. Nucleic Acid Analysis using an Expanded Genetic Alphabet to Quench Fluorescence. J. Am. Chem. Soc. 2004, 126, 4550–4556. 10.1021/ja0315558. [DOI] [PubMed] [Google Scholar]
  9. Kimoto M.; Endo M.; Mitsui T.; Okuni T.; Hirao I.; Yokoyama S. Site-Specific Incorporation of a Photo-Crosslinking Component into RNA by T7 Transcription Mediated by Unnatural Base Pairs. Chem. Biol. 2004, 11, 47–55. 10.1016/j.chembiol.2003.12.016. [DOI] [PubMed] [Google Scholar]
  10. Kimoto M.; Kawai R.; Mitsui T.; Yokoyama S.; Hirao I. An Unnatural Base Pair System for Efficient PCR Amplification and Functionalization of DNA Molecules. Nucleic Acids Res. 2009, 37, e14 10.1093/nar/gkn956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimoto M.; Mitsui T.; Harada Y.; Sato A.; Yokoyama S.; Hirao I. Fluorescent Probing for RNA Molecules by an Unnatural Base-Pair System. Nucleic Acids Res. 2007, 35, 5360–5369. 10.1093/nar/gkm508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Flamme M.; Röthlisberger P.; Levi-Acobas F.; Chawla M.; Oliva R.; Cavallo L.; Gasser G.; Marlière P.; Herdewijn P.; Hollenstein M. Enzymatic Formation of an Artificial Base Pair Using a Modified Purine Nucleoside Triphosphate. ACS Chem. Biol. 2020, 15 (11), 2872–2884. 10.1021/acschembio.0c00396. [DOI] [PubMed] [Google Scholar]
  13. Chawla M.; Poater A.; Besalú-Sala P.; Kalra K.; Oliva R.; Cavallo L. Theoretical Characterization of Sulfur-to-Selenium Substitution in an Emissive RNA Alphabet. Phys. Chem. Chem. Phys. 2018, 20, 7676–7685. 10.1039/C7CP07656H. [DOI] [PubMed] [Google Scholar]
  14. Chawla M.; Poater A.; Oliva R.; Cavallo L. Structural and Energetic Characterization of the Emissive RNA Alphabet Based on the Isothiazolo[4,3-d]Pyrimidine Heterocycle Core. Phys. Chem. Chem. Phys. 2016, 18, 18045–18053. 10.1039/C6CP03268K. [DOI] [PubMed] [Google Scholar]
  15. Chawla M.; Credendino R.; Oliva R.; Cavallo L. Structural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and Its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Molecules. J. Phys. Chem. B 2015, 119 (41), 12982–12989. 10.1021/acs.jpcb.5b06861. [DOI] [PubMed] [Google Scholar]
  16. Chawla M.; Gorle S.; Shaikh A. R.; Oliva R.; Cavallo L. Replacing Thymine with a Strongly Pairing Fifth Base: A Combined Quantum Mechanics and Molecular Dynamics Study. Comput. Struct. Biotechnol. J. 2021, 19, 1312–1324. 10.1016/j.csbj.2021.02.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Chawla M.; Minenkov Y.; Vu K. B.; Oliva R.; Cavallo L. Structural and Energetic Impact of Non-natural 7-Deaza-8-azaguanine, 7-Deaza-8-azaisoguanine, and Their 7-Substituted Derivatives on Hydrogen-Bond Pairing with Cytosine and Isocytosine. ChemBiochem 2019, 20 (17), 2262–2270. 10.1002/cbic.201900245. [DOI] [PubMed] [Google Scholar]
  18. Hoshika S.; Leal N. A.; Kim M.-J.; Kim M.-S.; Karalkar N. B.; Kim H.-J.; Bates A. M.; Watkins N. E. Jr; SantaLucia H. A.; Meyer A. J.; DasGupta S.; Piccirilli J. A.; Ellington A. D.; SantaLucia J. Jr; Georgiadis M. M.; Benner S. A. Hachimoji DNA and RNA: A Genetic System with Eight Building Blocks. Science 2019, 363 (6429), 884–887. 10.1126/science.aat0971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dhami K.; Malyshev D. A.; Ordoukhanian P.; Kubelka T.; Hocek M.; Romesberg F. E. Systematic Exploration of a Class of Hydrophobic Unnatural Base Pairs Yields Multiple New Candidates for the Expansion of the Genetic Alphabet. Nucleic Acids Res. 2014, 42 (16), 10235–10244. 10.1093/nar/gku715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yang Z.; Chen F.; Alvarado J. B.; Benner S. A. Amplification, Mutation, and Sequencing of a Six-Letter Synthetic Genetic System. J. Am. Chem. Soc. 2011, 133 (38), 15105–15112. 10.1021/ja204910n. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dontschuk N.; Stacey A.; Tadich A.; Rietwyk K. J.; Schenk A.; Edmonds M. T.; Shimoni O.; Pakes C. I.; Prawer S.; Cervenka J. A graphene Field-Effect Transistor as a Molecule-Specific Probe of DNA Nucleobases. Nat. Commun. 2015, 6, 6563. 10.1038/ncomms7563. [DOI] [PubMed] [Google Scholar]
  22. Heerema S. J.; Dekker C. Graphene Nanodevices for DNA Sequencing. Nat. Nanotechnol. 2016, 11, 127–136. 10.1038/nnano.2015.307. [DOI] [PubMed] [Google Scholar]
  23. Lee J.-H.; Choi Y.-K.; Kim H.-J.; Scheicher R. H.; Cho J.-H. Physisorption of DNA Nucleobases on h-BN and Graphene: vdW-Corrected DFT Calculations. J. Phys. Chem. C 2013, 117, 13435–13441. 10.1021/jp402403f. [DOI] [Google Scholar]
  24. Vovusha H.; Sanyal B. Adsorption of Nucleobases on 2D Transition-Metal Dichalcogenidesand Graphene Sheet: A First Principles Density Functional Theory Study. RSC Adv. 2015, 5, 67427. 10.1039/C5RA14664J. [DOI] [Google Scholar]
  25. Amorim R. G.; Scheicher R. H. Silicene as a New Potential DNA Sequencing Device. Nanotechnology 2015, 26, 154002. 10.1088/0957-4484/26/15/154002. [DOI] [PubMed] [Google Scholar]
  26. Li Q.; Liu H.; Tian Y.; Guo J.; Chen G.; Lee J. Y. Methylation Detection and DNA Sequencing Based on Adsorption of Nucleobases on Silicene Nanoribbon. J. Phys. Chem. C 2020, 124, 10823–10831. 10.1021/acs.jpcc.0c01734. [DOI] [Google Scholar]
  27. Cortés-Arriagada D. Phosphorene as a Template Material for Physisorption of DNA/RNA Nucleobases and Resembling of Base Pairs: A Cluster DFT Study and Comparisons with Graphene. J. Phys. Chem. C 2018, 122, 4870–4880. 10.1021/acs.jpcc.7b11268. [DOI] [Google Scholar]
  28. Bhai S.; Ganguly B. Exploiting the Optical Sensing of Fluorophore-Tagged DNA Nucleobases on Hexagonal BN and Al-doped BN Sheets: A Computational Study. Phys. Chem. Chem. Phys. 2022, 24, 829. 10.1039/D1CP04009J. [DOI] [PubMed] [Google Scholar]
  29. Tyagi A.; Chu K.; Hossain M. D.; Abidi I. H.; Lin W.; Yan Y.; Zhang K.; Luo Z. Revealing the Mechanism of DNA Passing Through Graphene and Boron Nitride Nanopores. Nanoscale 2019, 11, 23438. 10.1039/C9NR07651D. [DOI] [PubMed] [Google Scholar]
  30. Gouveia J. D.; Novell-Leruth G.; Viñes F.; Illas F.; Gomes J. R. B. The Ti2CO2MXene as a Nucleobase 2D Sensor: A First-Principles Study. Appl. Surf. Sci. 2021, 544, 148946. 10.1016/j.apsusc.2021.148946. [DOI] [Google Scholar]
  31. Yadav P.; Cao Z.; Farimani A. B. DNA Detection with Single-Layer Ti3C2Mxene Nanopore. ACS Nano 2021, 15, 4861–4869. 10.1021/acsnano.0c09595. [DOI] [PubMed] [Google Scholar]
  32. Rezapour M. R.; Biel B. DNA/RNA Sequencing using Germanene Nanoribbons via Two Dimensional Molecular Electronic Spectroscopy: an Ab Initio Study. Nanoscale 2022, 14, 5147–5153. 10.1039/D1NR07336B. [DOI] [PubMed] [Google Scholar]
  33. Gu Z.; Zhao L.; Liu S.; Duan G.; Perez-Aguilar J. M.; Luo J.; Li W.; Zhou R. Orientational Binding of DNA Guided by the C2N Template. ACS Nano 2017, 11, 3198–3206. 10.1021/acsnano.7b00236. [DOI] [PubMed] [Google Scholar]
  34. Mukhopadhyay T. K.; Bhattacharyya K.; Datta A. Gauging the Nanotoxicity of h2D-C2N Toward Single-Stranded DNA: an in Silico Molecular Simulation Approach. ACS Appl. Mater. Interfaces 2018, 10, 13805–13818. 10.1021/acsami.8b00494. [DOI] [PubMed] [Google Scholar]
  35. Singh D.; Panda P. K.; Mishra Y. K.; Ahuja R. Van der Waals Induced Molecular Recognition of Canonical DNA Nucleobases on a 2D GaS Monolayer. Phys. Chem. Chem. Phys. 2020, 22, 6706. 10.1039/C9CP06418D. [DOI] [PubMed] [Google Scholar]
  36. Farimani A. B.; Min K.; Aluru N. R. DNA Base Detection using a Single-Layer MoS2. ACS Nano 2014, 8, 7914–7922. 10.1021/nn5029295. [DOI] [PubMed] [Google Scholar]
  37. Jin K.; Xie L.; Tian Y.; Liu D. Au-Modified Monolayer MoS2 Sensor for DNA Detection. J. Phys. Chem. C 2016, 120, 11204–11209. 10.1021/acs.jpcc.6b01193. [DOI] [Google Scholar]
  38. Graf M.; Lihter M.; Altus D.; Marion S.; Radenovic A. Transverse Detection of DNA Using a MoS2 Nanopore. Nano Lett. 2019, 19, 9075–9083. 10.1021/acs.nanolett.9b04180. [DOI] [PubMed] [Google Scholar]
  39. Xue L.; Yamazaki H.; Ren R.; Wanunu M.; Ivanov A. P.; Edel J. B. Solid-state nanopore sensors. Nat. Rev. Mater. 2020, 5 (12), 931–951. 10.1038/s41578-020-0229-6. [DOI] [Google Scholar]
  40. Qiu H.; Sarathy A.; Schulten K.; Leburton J.-P. Detection and mapping of DNA methylation with 2D material nanopores. npj 2D Mater. Appl. 2017, 1 (1), 3. 10.1038/s41699-017-0005-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wan X.; Chen E.; Yao J.; Gao M.; Miao X.; Wang S.; Gu Y.; Xiao S.; Zhan R.; Chen K.; et al. Synthesis and Characterization of Metallic Janus MoSH Monolayer. ACS Nano 2021, 15, 20319–20331. 10.1021/acsnano.1c08531. [DOI] [PubMed] [Google Scholar]
  42. Lee Y.-H.; Zhang X.-Q.; Zhang W.; Chang M.-T.; Lin C.-T.; Chang K.-D.; Yu Y.-C.; Wang J. T.-W.; Chang C.-S.; Li L.-J.; et al. Synthesis of Large-Area MoS2 Atomic Layers with Chemical Vapor Deposition. Adv. Mater. 2012, 24 (17), 2320–2325. 10.1002/adma.201104798. [DOI] [PubMed] [Google Scholar]
  43. Lu A.-Y.; Zhu H.; Xiao J.; Chuu C.-P.; Han Y.; Chiu M.-H.; Cheng C.-C.; Yang C.-W.; Wei K.-H.; Yang Y.; et al. Janus Monolayers of Transition Metal Dichalcogenides. Nat. Nanotechnol. 2017, 12, 744–749. 10.1038/nnano.2017.100. [DOI] [PubMed] [Google Scholar]
  44. Zhang J.; Jia S.; Kholmanov I.; Dong L.; Er D.; Chen W.; Guo H.; Jin Z.; Shenoy V. B.; Shi L.; et al. Janus Monolayer Transition-Metal Dichalcogenides. ACS Nano 2017, 11, 8192–8198. 10.1021/acsnano.7b03186. [DOI] [PubMed] [Google Scholar]
  45. Chawla M.; Credendino R.; Chermak E.; Oliva R.; Cavallo L. Theoretical Characterization of the H-Bonding and Stacking Potential of Two Nonstandard Nucleobases Expanding the Genetic Alphabet. J. Phys. Chem. B 2016, 120 (9), 2216–2224. 10.1021/acs.jpcb.6b00125. [DOI] [PubMed] [Google Scholar]
  46. Kresse G.; Hafner J. Ab Initio Molecular Dynamics for Liquid Metals. Phys. Rev. B 1993, 47, 558–561. 10.1103/PhysRevB.47.558. [DOI] [PubMed] [Google Scholar]
  47. Kresse G.; Furthmüller J. Efficient Iterative Schemes for Ab Initio Total-Energy Calculations using a Plane-Wave Basis Set. Phys. Rev. B 1996, 54, 11169–11186. 10.1103/PhysRevB.54.11169. [DOI] [PubMed] [Google Scholar]
  48. Kresse G.; Joubert D. From Ultrasoft Pseudopotentials to the Projector Augmented-Wave Method. Phys. Rev. B 1999, 59, 1758–1775. 10.1103/PhysRevB.59.1758. [DOI] [Google Scholar]
  49. Blöchl P. E. Projector Augmented Wave Method. Phys. Rev. B 1994, 50, 17953–17979. 10.1103/PhysRevB.50.17953. [DOI] [PubMed] [Google Scholar]
  50. Grimme S.; Antony J.; Ehrlich S.; Krieg H. A Consistent and Accurate Ab Initio Parametrization of Density Functional Dispersion Correction (DFT-D) for the 94 Elements H-Pu. J. Chem. Phys. 2010, 132, 154104. 10.1063/1.3382344. [DOI] [PubMed] [Google Scholar]
  51. Monkhorst H. J.; Pack J. D. Special Points for Brillouin-Zone Integrations. Phys. Rev. B 1976, 13, 5188–5192. 10.1103/PhysRevB.13.5188. [DOI] [Google Scholar]
  52. Brandbyge M.; Mozos J.-L.; Ordejón P.; Taylor J.; Stokbro K. Density-Functional Method for Nonequilibrium Electron Transport. Phys. Rev. B 2002, 65, 165401. 10.1103/PhysRevB.65.165401. [DOI] [Google Scholar]
  53. Henkelman G.; Arnaldsson A.; Jónsson H. A Fast and Robust Algorithm for Bader Decomposition of Charge Density. Comput. Mater. Sci. 2006, 36, 354–360. 10.1016/j.commatsci.2005.04.010. [DOI] [Google Scholar]
  54. Le O. K.; Chihaia V.; Pham-Ho M.-P.; Son D. N. Electronic and Optical Properties of Monolayer MoS2 under the Influence of Polyethyleneimine Adsorption and Pressure. RSC Adv. 2020, 10, 4201–4210. 10.1039/C9RA09042H. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Zhao N.; Schwingenschlögl U. Dipole-Induced Ohmic Contacts between Monolayer Janus MoSSe and Bulk Metals. Npj 2D Mater. Appl. 2021, 5, 72. 10.1038/s41699-021-00253-w. [DOI] [Google Scholar]
  56. Sadeghi M.; Jahanshahi M.; Ghorbanzadeh M.; Najafpour G. Adsorption of DNA/RNA Nucleobases onto Single-Layer MoS2 and Li-Doped MoS2: A Dispersion-Corrected DFT Study. Appl. Surf. Sci. 2018, 434, 176–187. 10.1016/j.apsusc.2017.10.162. [DOI] [Google Scholar]
  57. Contreras-García J.; Johnson E. R.; Keinan S.; Chaudret R.; Piquemal J.-P.; Beratan D. N.; Yang W. NCIPLOT: A Computational Tool for Visualizing Noncovalent Interaction Regions. J. Chem. Theory Comput. 2011, 7, 625–632. 10.1021/ct100641a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. De Souza F. A. L.; Sivaraman G.; Scheicher R. H.; Scopel W. L.; Fyta M.; Amorim R. G. Electrically Sensing Hachimoji DNA Nucleotides through a Hybrid Graphene/h-BN Nanopore. Nanoscale 2020, 12, 18289–18295. 10.1039/D0NR04363J. [DOI] [PubMed] [Google Scholar]

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