Coarse-Grained Model for Sequence-Dependent Adsorption ofssDNA on Carbon NanotubesOlga Kucher, Irena Yungerman, and Simcha Srebnik*

Department of Chemical Engineering, Technion − Israel Institute of Technology, Haifa 32000, Israel

ABSTRACT: Single-walled carbon nanotubes (SWCNTs) have extraordinaryproperties due to their symmetry, high aspect ratio, and thermal conductivity, allof which make them attractive toward many applications in medicine,nanotechnology, electronics, optics, and other fields. ssDNA is known toform stable dispersions of SWCNTs, and depending on its sequence canremarkably enable separation of SWCNTs of a particular chirality. In this work,we use a minimalist coarse-grained simulation model to explore general aspectsof the sequence-dependent interaction of ssDNA with SWCNTs. Oligomericchains of guanine and thymine nucleobases were investigated, revealing asignificant difference in the thermodynamic behavior of three investigatedsequences. G12 was found to adsorb most readily owing to the strong and stablestacking interactions between its bases and the nanotube surface. On the otherhand, the smaller thymine bases allow the T12 chains to form stackinginteractions between neighboring bases as well as with the nanotube simultaneously. (GT)6 interacts most weakly with theSWCNT and reveals a greater sensitivity toward nanotubes with different radii, in contrast to the homo-oligomers. Theuniqueness of each sequence is attributed to geometric as well as energetic differences between neighboring bases.

■ INTRODUCTIONDNA and carbon nanotubes, although not encounteredtogether in nature, have complementary structural featuresthat make it possible to assemble them into stable hybridstructures. Their complexation has become a subject of intenseinterest, due to unique opportunities for the development oftechnological applications in nanoelectronics, medicine, envi-ronmental safety, and microbiology through exploitation of theremarkable properties of carbon nanotubes.1 Their phenomenalstiffness and tensile strength combined with low density andelastic deformability make them preferred candidates forcomposite materials with improved mechanical properties.2

Electronic properties of nanotubes can vary widely, fromsemiconducting to metallic; thus, their use opens the windowfor novel electronic devices.3 Carbon nanotubes have also beenconsidered in biomedical applications.4,5

However, separation of carbon nanotubes is complicated dueto the polydisperse mixtures that result from standard synthesisand their poor solubility in aqueous and organic solvents.6

Standard methods to achieve stable dispersions includesurfactants, covalent functionalization, chemical oxidation, andpolymer wrapping.7,8 Remarkably, dispersions using single-stranded DNA (ssDNA) were used to selectively separateSWCNTs according to their chiral indices.9,10 The mechanismof ssDNA selective adsorption on SWCNTs is still not clear,but many experimental works have shown very good solubilityof SWCNTs and their bundles in aqueous DNA solutions.The understanding of sequence-dependent interaction is at

its infancy, and its advancement is hindered by seeminglycontradictory reports. Generally, ssDNA is expected to interactmore favorably with tubes of larger diameters, since the less

curved surface of the large diameter SWCNT allows for bettercontact with the nucleic acid bases and therefore increases thebinding energy.11 Increase in temperature dramatically speedsup desorption of the DNA,12 resulting in a decrease of stackinginteractions between the ssDNA and SWCNT.13 According tothermal dissociation measurements, the hybrid stability ofSWCNT−homopolymer was found to be poly(G) > poly(C) >poly(A) ∼ poly(T),14 though others suggest an essentiallyopposite trend.15 Simulations of these sequences suggest theorder may strongly depend on SWCNT chirality and/ordiameter.16 Furthermore, computational studies on single baseinteractions17−19 as well as oligonucleotides17,20 with SWCNTsreveal binding energies with the trend G > A > T ∼ C, againwith variations that are apparently dependent on SWCNTtype.21 Notably, there is general agreement that purine Gstrands adsorb more strongly than pyrimidine chains,13,22

though simulation studies on more complex sequences showstrong energetic dependence on nanotube chirality.12,23

Experiments on homo-oligonucleotides also report differentand opposing observations presumably due to the largedifference in experimental measurements, solution conditions,SWCNT type and purity, and ssDNA chain length. Forexample, Albertorio et al.14 observed that G12 > C12 > A12 > T12,while Khamis et al.20 reported that G21 > A21 > C21 > T21.Hughes et al.24 found that C30 > T30 ∼ A30 > G30 yet that T15 >C15 > G15 > A15 in a later study by the group.

15 On graphite, thebinding strength per base of T > A > G > C for 50−100-base-

Received: April 30, 2014Revised: July 17, 2014Published: July 17, 2014

Article

pubs.acs.org/JPCC

© 2014 American Chemical Society 17677 dx.doi.org/10.1021/jp504230w | J. Phys. Chem. C 2014, 118, 17677−17685

long chains was reported.25,26 It is hence difficult to formdefinite conclusions about which homo-oligomer chain formsthe most stable complexation, if any, and why. Other issues,such as self-organization of some chains in solution, and theform of dispersion (single nanotubes versus bundles) may alsoinfluence the predicted rankings.Hetero-oligomeric chains consisting of alternating guanine

and thymine have been intensively studied12,27 due to theirunique specificity and strong binding affinity. However, therelative binding affinity of GT chains compared with ACsequences seems to depend on chain length,28 with shorterstrands favoring GT but longer strands favoring AC. However,Haggenmueller et al.29 report a similar efficiency between theseand other sequences. Again, the differences arise from the largevariation in experimental setup.π-Stacking of the nucleotides with the surface of the

nanotube is generally believed to be the driving mechanismfor ssDNA adsorption and dispersion of SWCNTs. Recentstudies have revealed that it is energetically unlikely for thebases to desorb and form base pair interactions.30 Keeping thisin mind, some argue that the greater contribution of the π-stacking energy of purines leads to better binding of chainsenriched with purines relative to pyrimidines.17 However,others found that poly(T) wraps more successfully with certainSWCNTs than poly(G),31 suggesting that self-stacking betweenpurine bases in solution lowers their interaction with theSWCNT.13 Oligo(GT) chains have been the subject of manyexperimental and computational studies, since they were shownto be very good dispersants early on. The peculiarity of the(GT)n sequence was suggested to be due to its tendency toundergo hydrogen bonding between two antiparallel strands,providing a supramolecular rigid structure which will packtightly on the SWCNT surface.10 However, MD simulations ofwrapping of (GT)20 sequences onto SWCNT surfaces haveshown instability of such complexes.17

There are many more examples of inconsistencies regardingssDNA sequence-dependent behavior in SWCNT complex-ation. The cause for the various predictions and highly diverseresults derives on the one hand from the complex nature ofssDNA and SWCNT chirality-dependent electronic propertiesand on the other hand from differences in experimentalconditions, differences in type and geometry of the chosennanotube, the force field used in the simulations, or theaccuracy and the quality of experimental or computationalwork. In this work, we use a minimalist coarse-grained MonteCarlo simulation to focus on differences in adsorbed behaviorarising from the different sizes of the bases, which translates todifferences in the van der Waals (vdW) interaction potential.We study the preferred base orientation with respect to theSWCNT surface for various sequences, focusing on competi-tion between base−base stacking interactions and base−SWCNT stacking interactions. The effect of nanotube radiusand ssDNA sequence in this context is also studied.

■ SIMULATION MODELWe model the ssDNA/SWCNT system using a coarse-grainedMonte Carlo simulation in the canonical ensemble (NVT).Each nucleic acid base is represented by a three-site model,schematically shown in Figure 1, composed of a negativelycharged spherical phosphate, neutral spherical sugar group, andneutral ellipsoidal base. Electroneutrality is conserved by addingmonovalent positively charged spherical counterions. 12-merchains are considered, where the bases are differentiated

according to their size. The nanotube is modeled as a smoothand neutral infinite cylindrical surface. The chains weregenerally initiated in random configurations, though low energyinitial conformations (base−base stacked or base−SWCNTstacked) were also tested to ensure equilibration at lowtemperatures, revealing similar behavior. Simulation runs wereequilibrated for at least 106 trial steps, and averages werecalculated over an additional 106 simulation cycles, sampledevery 102 trial moves. Trial moves consisted of rotation andtranslation, with steps adjusted to achieve 50% acceptance.The interaction potential for our model system is given by

the summation of five interactions

θ φ θ= + + + +

+

V V r V r V r V r V

V r

( , , ) ( ) ( ) ( ) ( )

( )

tot RE LJ C H B

Cyl (1)

The Lennard-Jones (LJ) potential, VLJ, determines theinteraction between nonbonded isotropic molecules, and isgiven by

ϵσ σ

= − −⎛

⎝⎜⎜⎛⎝⎜⎜

⎞⎠⎟⎟

⎛⎝⎜⎜

⎞⎠⎟⎟

⎞

⎠⎟⎟V r

r rV r( ) 4 ( )ij ij

ij

ij

ij

ijLJ

12 6

shift c

(2)

where rij is the distance between interacting spherical particles iand j and σij and ϵij are the LJ parameters for these particles,obtained with the standard Lorentz−Berthelot mixing rules.The shifted form of VLJ is used for continuity at the cutoffradius of the potential. Spatial integration of the LJ potential incylindrical coordinates over the axial coordinates of thecylinderical shell is used to describe the nanotube surfacepotential, leading to an expression that is dependent on theperpendicular distance, D, of the interacting particle and thetube surface only32

∫π ϵ θ= −π ⎛

⎝⎜⎞⎠⎟V D R

r D r D( ) 8 d

63512 ( )

316 ( )icyl cyl c

0

2

11/12 5/2

(3)

where Rcyl is the radius of the cylindrical shell, ϵci is the LJinteraction parameter for particle i with the cylinder, and r2 =Rcyl

2 + (Rcyl + D)2 − 2Rcyl(Rcyl + D) cos θ. Vcyl is integratednumerically once at the start of the simulation to obtain anarray of θ for a given Rcyl. Only vdW interactions between thebases and with the SWCNT were considered, as they have beenshown to contribute most significantly to the interactionenergy.33,34 The shape and relative orientation of theanisotropic ellipsoids is accounted for using the RE-squaredpotential, VRE.

35,36 The Hamaker constant of the VRE potential

Figure 1. Schematic representation of the ssDNA-CNT model.Negatively charged phosphate, sugar, and counterions are representedby spheres, and the bases, by disc-like ellipsoids of different size todistinguish between purine and pyrimidine base types.

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was parametrized against the LJ potential in eq 2 for a sphere ofunit radius and εLJ = 1. Parameterization of the bases used inour model is based on the coarse-grained DNA model ofPlotkin and co-workers,37 and is summarized in Table 1. Underthis parametrization, the potential well depth (kcal/mol) in thestacked configuration of G−G and T−T base interactions is 5.2and 3.7, respectively.

Phosphate groups on the DNA chain carry a negative partialcharge close to unity in solution, and are counteracted bymonovalent positively charged ions in our model. Electrostaticinteractions are modeled using the Coulomb (VC) potential inan aqueous solvent modeled as a dielectric medium

=V r kq q

r( )ij

i j

ijC C

(4)

where qi is the effective charge of particle i. kC = 1/(4πεrε0),where εr ≅ 80 is the dielectric constant of water and ε0 is thepermittivity of free space. The ratio of kC to the LJ interactionparameter of a sphere of unit radius was taken to be unity.The ssDNA chain is modeled as a bead−spring chain, where

the bond stiffness between neighboring beads is determined bythe harmonic bond potential, VH

= −V k r r( )H H H2

(5)

where kH and rH are the harmonic constant and equilibriumbond length, respectively. The bond length is taken as the sumof the radii of two neighboring beads, and kH was set to equal50/εLJσLJ

2. A bending interaction potential determines theoverall flexibility of the chain, and is given by

θ θ= −V k (cos cos )B B B2

(6)

where kB and θB are the bending interaction constant andequilibrium bending angle between vectors that connect

consecutive bonded beads, respectively. θB was set to 180°between neighboring spheres and 90° between spheres andbases. kB/εLJ was set to 50/εLJ to provide sufficient stiffness tothe chain. This form of the potential as opposed to the standardharmonic form is used for computational efficiency. The lengthparameters in eqs 2−6 were set in reference to the van derWaals diameter of sp2 carbon, approximately equal to 4 Å. Thereference energy unit was chosen as 1.4 kcal/mol, according tothe work of ref 37.The nucleobases are believed to interact with the nanotube

surface via π-stacking interactions,24,38 where each of the fournucleobases (adenine, guanine, cytosine, and thymine) orient indistinct ways with respect to the nanotube’s long axis.24 Suchinteractions cannot be modeled with coarse-grained or standardatomistic force fields,39 but their significance for molecules with10 carbons or less (the case for all nucleobases) isquestionable.40 Still, we find that the small difference in vdWinteractions that arises from the different geometry of thebodies under consideration lead to different “stacked”configurations in our model. That is, the relatively large surfacearea of the flat ellipsoidal bases may lead to base−nanotubestacking as well as base−base stacking.

■ RESULTS AND DISCUSSION

Our minimalist model serves to concentrate on the effect of sizeand hence vdW interaction on the adsorbed configuration ofoligonucleotides. We concentrate on three DNA sequen-ces(GG)n, (GT)n, and (TT)nthat have attracted consid-erable interest in this field. Twelve-base-long oligomers (n = 6)were chosen as a representative size of sequences that havebeen shown to effectively disperse SWCNTs.14,41 Thesequence-dependent adsorption of ssDNA has mostly beenattributed to local differences in the interactions of the bases,and particularly in the stacking interactions of the bases withthe SWCNT surface. Figure 2 presents the average contributionof base−base and base−cylinder interactions for the threesequences, respectively. The average base−base contribution tothe interaction energy follows the average size of thenucleobase in the sequence, in the order purine−purine >purine−pyrimidine > pyrimidine−pyrimidine, as might beexpected in solution.42 The larger surface area of the purinescorresponds to stronger short-range attraction; hence, thisbehavior is anticipated. The base−cylinder interactions for thehomo-oligomers also show this anticipated order. However, T12has an energetically more favorable interaction with thecylinder on average than the hetero-oligomer (GT)6, forreasons further discussed below. The contribution of base−

Table 1. Dimensionless Parameters for the Particles Used inthe Modela

σx, σy, σz εx, εy, εz charge

guanine 3.0, 3.0, 1.0 1.0, 1.0, 1.0 0thymine 2.0, 2.0, 1.0 1.0, 1.0, 1.0 0sugar 2.0, 2.0, 2.0 1.0, 1.0, 1.0 0phoshphate 1.0, 1.0, 1.0 1.0, 1.0, 1.0 −1ion 1.0, 1.0, 1.0 1.0, 1.0, 1.0 +1

aThe parameters are given in LJ units. The cylinder radius was takento be 2.0σLJ unless otherwise stated.

Figure 2. Average contribution to the interaction energy of (a) base−base neighbors and (b) base−cylinder as a function of temperature (solidcurves serve to guide the eye).

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SWCNT stacking to the binding energy of the adsorbed ssDNAchains is of the order of 1.4, 0.2, and 0.6 kcal/mol per base forthe bound T12, (GT)6, and G12 chains, respectively. Thesevalues are somewhat lower but correspond in order ofmagnitude to atomistic simulations.13,16,17

The average fraction of bases near the surface of the cylinder,shown in Figure 3 as a function of temperature, confirms thepreference of homo-oligomer interaction with the SWCNTover the hetero-oligomer. Among the homo-oligomers, we findthat G12 is somewhat more thermally stable than T12, incontrast to the findings of a previous MD simulation,13 but inagreement with experimental findings, according to whicholigomers of thymine form less stable hybrids with nanotubesthan those of guanine.14 That guanine chains are more stronglybound to the SWCNT surface than thymine can be explainedby the difference in the interaction potential well of the basewith the SWCNT surface compared with the base−basepotential well (Δ = 0.27 for thymine and 0.33 for guanine).However, the lower stability of (GT)6 is surprising, since themain stabilization of ssDNA−SWCNT complexation isexpected to be vdW attraction of the nucleobases with thenanotube surface, based on base−SWCNT19 and base−base42studies. The specific heat, Cv, shows a relatively sharp peak inthe range T = 0.3−0.4 for the selected sequences, whichcorresponds to the adsorption transition of the ssDNA. Thereis an indication of a second peak at lower temperatures aroundT = 0.15 corresponding to reorganization and alignment of thebases in the vicinity of the SWCNT surface to form eitherbase−SWCNT stacked or base−base stacked configurations. Inmost of our work below, we concentrate on this lowertemperature range leading up to the desorption transition.To refine our understanding of the structure of the complex

in the investigated systems, we plot the fraction of bases as afunction of distance from the nanotube surface in Figure 4.Guanine and thymine homo-ologomers show two cleardominant peaks, implying two favorable localizations of thecenter of mass of the bases for these sequences. Moreover,these two peaks are of similar magnitude for T12 but not forG12. These peaks correspond to cylinder-stacked and base-stacked configurations, respectively, and suggest the presence oftwo dominant and competitive intermolecular (base−base) andintramolecular (base−SWCNT) interactions for the adsorbedconformations of homo-oligomeric ssDNA sequences. On theother hand, (GT)6 shows only one relatively wide peak,suggesting that the adsorption process for the given sequence ismore disordered, with a small preference toward SWCNT-stacked orientations but also the presence of base−base stacked

and disordered structures. Atomistic simulations clearly suggestthe competition between these two stacking interactions aswell, and particularly for sequences comprised of purines.23

The preference toward stacking interactions betweenneighboring bases or between base and cylinder was furtheranalyzed through relative orientations of the two bodies, asdepicted in Figure 5. For this purpose, we defined the base to

be in a stacked configuration if the distance between the centerof mass of two adjacent bodies (two neighboring bases or baseand nanotube surface) is less than or equal to 3.5 Å.43 Theorientation between the two investigated bodies was charac-terized through the angle formed by the two relevant planes.For the base, the plane is through the largest circumference,

Figure 3. (a) Average fraction of bases near the SWCNT surface as a function of temperature. The density of bases was determined by summingover the number of bases in the boundary layer of the nanotube surface, defined as 6 Å plus the maximal radius of the given base, in order to includeboth possible configurations of base−SWCNT stacked and base−base stacked configurations (see schematics in Figure 4). (b) Specific heat as afunction of temperature for the studied sequences.

Figure 4. Density distribution of bases near the nanotube surface at atemperature of 0.15. Schematics serve to illustrate ssDNA/SWCNTconfigurations for base−SWCNT stacked in a staggered conformation(left) and base−base stacked (right).

Figure 5. Schematic representation of limiting angles between baseand cylinder (left) and between bases (right).

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and for the SWCNT, it is the axial cross section that isperpendicular to the radial vector in the direction of the centerof mass of the interacting base. Two bodies were assumed to bein parallel orientation if the angle between planes was ≤ |30°|.Figure 6 presents the change in stacking interactions between

bases and the cylinder and among neighboring bases as afunction of temperature. As anticipated and suggested in Figure4, the guanine chain tends to form more stacking interactionswith the nanotube surface than the other sequences. At lowtemperatures, it appears that (GT)6 creates slightly morestacking interactions with the SWCNT surface than T12, duemainly to the larger surface area of guanine that stabilizes itsinteractions with the nanotube. Comparison with stackingbetween neighboring bases reveals that G12 and T12 create morebase-stacked configurations than (GT)6. Moreover, T12 formssignificantly more such interactions than the guanine chain.That is, when adsorbed, the smaller thymine bases can adoptorientations that allow for both kinds of stacking interactions tobe maximized, while the large size of the guanines prevents theexistence of both types of interactions simultaneously due tosteric considerations. Due to the large surface area of thenanotube, the effective LJ potential between the bases and thecylinder is stronger than that between the bases, and thiscompetition between stacking interactions between neighborbases and bases with the nanotube surface for G12 in addition tothe steric limitations of the larger bases gives way to nanotube-stacked orientation. Nonetheless, non-negligible base−basestacking is still observed.Figure 2 shows an initial increase in adsorbed fraction of

bases with temperature. At low temperatures, the chain seeksthe lowest energy conformations, leading to greater competi-tion between intramolecular interactions and interactions withthe SWCNT. The entropic contribution increases withtemperature, allowing for greater conformational flexibility ofthe chain on the one hand but also rearrangement to the moredominating chain−SWCNT interactions on the other, resultingin a greater fraction of the bases adsorbed. Comparison withFigure 6 shows that the increased adsorption corresponds to amonotonic decrease in stacking ineractions for T12 and (GT)6but a slight increase in base−SWCNT stacking interactions forthe guanine chain. The large size of the bases of the latter leadsto strong competition between the two types of stackinginteractions that is relieved with increasing temperatures.For a large number of rotation moves, a random probability

of all the possible orientations would be expected in theabsence of orientational order. Such a random probabilitydistribution is described by

θ φ θ θ φ=P( , ) sin d d (7)

Integration over the azimuthal angle φ in the xy-plane gives thedistribution in terms of the polar angle only, or P(θ) ∝ sin θ.Orientational ordering will result in deviation from thesinusoidal distribution, where the extreme possibilities areschematically shown in Figure 5. To stress the orientationaldeviation from a random distribution, we plot in the figuresbelow the difference in the obtained distributions and therandom distribution, and present only the positive deviations.Figures 7−9 present base−cylinder and base−base angle

histograms for G12, T12, and (GT)6, respectively. For G12, we

observe two prominent peaks near 0 and 180°, suggestingsignificant stacking interactions between guanine bases and thenanotube surface. Furthermore, there is a clear preference tocreate angles near 90° between neighboring bases. Visualsnapshots (Figure 7b) suggest that the chain wraps around theSWCNT with its bases staggered with respect to the backbone,as was previously shown for dinucleotides,23 in such a way thatthe nucleobases form strong and stable stacking interactionswith the nanotube surface and are concurrently perpendicularto each other (Figure 7c). A second contribution to the 90°angle observed is the small fraction of nucleobases that stackamong themselves (Figure 6b) and in turn form nearlyperpendicular orientations with the cylinder-stacked bases(Figure 7b). These results reinforce the existence of the twocompeting types of interactionsnanotube-stacked and base-stacked for G12.As opposed to the guanine chain, the smaller thymine bases

of T12 have little steric restrictions between them. As can beseen from the snapshot in Figure 8 and from the anglehistograms, the smaller size of the bases enables the chain toadsorb on the same side of the SWCNT, and hence form

Figure 6. Average fraction of stacking contacts (A) between bases and the nanotube surface and (B) between neighboring bases as a function oftemperature.

Figure 7. (A) Angle probability distribution for G12, (B) snapshot ofthe G12−CNT hybrid, and (C) schematic top view of the ssDNA−CNT wrapped conformation. Results shown for T* = 0.15.

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stacking interactions to a similar extent between bases andbetween the bases and the nanotube. We note, however, thatatomistic simulations predict adsorption on alternating sideswith respect to the chain backbone for poly-T chains, as withsequences containing guanine, due to hydrogen-bondinginteractions between multiple adsorbed chains.44

For (GT)6, the angles between neighboring bases are seen tobe essentially randomly distributed (Figure 9), suggesting that

the constraint of chain connectivity and the difference betweenthe sizes of the neighboring bases prevents them from finding apreferable orientation with respect to each other. There doesappear to be a small preference to form stacking interactionswith the nanotube, though significantly less than for the homo-oligomer chains. Angle histograms of the separate contributionsof guanine and thymine within the same chain (GT)6 (Figure10) reveals, as might be expected, that stacking betweenguanine and the SWCNT is considerably greater than that ofthymine. Additionally, the contribution to the interactionenergy of the base−SWCNT (Figure 11) shows that forguanine it is somewhat stronger than for thymine, in generalagreement with experiments and simulations on base andoligonucleotide−SWCNT complexation, and as might beexpected since stacking interactions generally increase withincreasing surface area of the interacting bodies.40 It appearsthat the difference in size of the nucleobases within the samechain reduces the overall stability of the complex. These resultsare consistent with the difference in free energy betweendesorbed and adsorbed states of (GT)7 for the separatecontributions of its bases, investigated by Johnson et al.22 Theauthors found that thymine has a lower preference foradsorption on the SWCNT than guanine. The competition

between the larger guanine bases with stronger interactions andthe smaller thymine bases with weaker interactions renders the(GT)7−SWCNT complex less stable. An important conclusionis that the binding tendency of the ssDNA onto the nanotubesurface is sequence specific and cannot be evaluated accordingto the sum of individual base−SWCNT energies.Adsorption for these sequences was also investigated for

SWCNTs with diameters corresponding to 1.6 and 3.2 nm. Thesmaller size corresponds to typical SWCNT diameters, whilethe larger diameter was chosen to represent the often presentbundles and multiwalled carbon nanotube impurities. Figures12−14 compare the LJ energy, the density of bases near thenanotube surface, and the number of base−SWCNT stackinginteractions as the function of temperature, for these two radiiand for the different ssDNA sequences, respectively. It isgenerally seen that adsorption is more favorable on the largertubes. This is expected, since the lower curvature of the largertube leads to effectively stronger vdW attraction, and agreeswith observations of a thicker ssDNA layer on nanotubebundles.45 Quantum mechanical studies of nucleobase inter-actions with graphene and nanotubes confirm these observa-tions.11 Particularly striking is the significant difference in thebehavior of (GT)6 relative to T12 and G12 at temperaturesaround the adsorption transition. The latter two show similar

Figure 8. (A) Angle probability distribution for T12 and (B) snapshotof the T12−CNT hybrid. Results shown for T* = 0.15.

Figure 9. (A) Angle probability distribution for (GT)6 and (B)snapshot of the (GT)6−CNT hybrid. Results shown for T* = 0.15.

Figure 10. Angle probability distributions of the (GT)6−SWCNThybrid. Orange peaks represent the distribution of angles between theentire (GT)6 chain with the nanotube surface, while green and bluepeaks show the separate contributions of guanine and thymine,respectively. Results shown for T* = 0.15.

Figure 11. Average base−CNT contribution to the energy for theguanine nucleobase and the thymine nucleobase of the (GT)6sequence. Results shown for T* = 0.15.

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results for both SWCNT diameters, which is repeated in all ofthe investigated variables, while the hetero-oligomer showssignificant differences in its behavior for the two diameters.That is, (GT)6 is more sensitive to differences in the SWCNTdiameters than the homo-oligomers.The homo-oligomer chains already adsorb in relatively

ordered low entropy conformations on the smaller tubes;hence, the effect of curvature, or in other words the effect ofincreased local potential, is smaller. The stronger local surfacepotential, however, leads to loss of entropy and lower energyconformations for the relatively disordered (GT)6 chain. Theunique sensitivity of (GT)6 and presumably other hetero-oligonucleotide sequences might explain its more specificadsorption on nanotubes and hence their separation from thebundles to individual SWCNTs.10 That is, the sequence ofssDNA determines its adsorption capacity, but moreimportantly, there is a significant difference in the behavior ofhomo-oligomers and hetero-oligomers in their sensitivity todifferent SWCNTs.

■ CONCLUDING REMARKS

Using a simple coarse-grained model, we show that complex-ation of ssDNA with SWCNTs is strongly dependent on chainsequence. We found that physical properties, i.e., the size andsequence of the nucleobases, play a prominent role in exploringthe sequence dependent sorting mechanism of SWCNTs, bydefining the orientation of the bases in the adsorbedconformation. G12 was shown to form stable complexes withits bases stacked and staggered around the nanotube surface.The small size of the model pyrimidine groups of T12 allows itto form stacking interactions between neighboring bases and

with the nanotube surface, simultaneously. The adsorbedconformations of G12 and T12 suggest the presence of twodominant and competitive intermolecular (base−base) andintramolecular (base−SWCNT) interactions. The hetero-oligomer (GT)6, on the other hand, exhibits structuralheterogeneity due to the presence of bases of different size. Itappears to have no favorable orientations of the bases relativeto the nanotube surface nor among the neighboring bases,though its guanine nucleobases are more strongly adsorbed andstacked on the SWCNT surface than the thymine bases. Whilelarge cylinder radii lead to relative ease of adsorption of ssDNAdue to stronger attractive interactions, weaker topologicalconstraints, and greater contact area, T12 and G12 show similarbehavior on both SWCNT diameters studied. (GT)6 againdisplays different behavior than the homo-oligomers, andreveals sensitivity in its adsorption behavior for SWCNT withdifferent diameters. These striking differences in adsorptionbehavior, that are driven by physical differences arising from thesequence of bases in the ssDNA chains, are likely to be furthermodulated by chemical differences of the ssDNA as well asdifferent SWCNTs. Future work in our lab will focus onexperimentation and further comparison between hetero-oligomer sequences to reveal the source of the uniquesensitivity observed for (GT)6.

■ AUTHOR INFORMATION

NotesThe authors declare no competing financial interest.

Figure 12. Average base−SWCNT interaction energy as a function of temperature for G12, (GT)6, and T12.

Figure 13. Average fraction of bases near the SWCNT surface as a function of temperature for G12, (GT)6, and T12.

Figure 14. Average fraction of SWCNT-stacked bases as a function of temperature for G12, (GT)6, and T12.

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■ ACKNOWLEDGMENTS

This research was supported in part by the Russell BerrieNanotechnology Institute (RBNI) Nevet research fund, E. andM. Mendelson research fund, and E. and J. Bishop researchfund.

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