252709 Encapsulation Mechanism of DNA Nucleobases Onto Carbon Nanotubes: Free Energy Landscapes

Wednesday, October 31, 2012: 5:21 PM
404 (Convention Center )
Fernando J.A.L. Cruz1,2, JosÚ P. B. Mota1 and Juan J. de Pablo3, (1)Requimte/CQFB, Dept. Chemistry, Universidade Nova de Lisboa, Caparica, Portugal, (2)Dept. Chem. Bio. Eng., University of Wisconsin-Madison, Madison, WI, (3)Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI

<>I. Introduction

     Ever since the unravelling of the double helix structure of DNA, the molecule has been considered as the building block of biological organisms. Because DNA is the agent that carries genetic information from one generation to the next, the knowledge of its physical and chemical properties is of paramount importance. Much of that information has to do with the way the nucleobases (NBs)—DNA's own building blocks—interact with their surrounding environment. Owing to their nanoscale dimensions, carbon nanotubes are able to selectively interact with DNA almost at the atomic level: homo- and heteropolymer ssDNA will readily adsorb onto the external walls of small diameter SWCNTs,1 according to a p–stacking mechanism of the NBs on the walls. We have already characterized the SWCNTs energetic landscape regarding exo- and endoadsorption, using small probe molecules.2,3 While exoadsorption on small diameter nanotubes (< 1 nm) is reasonably understood, confinement driven adsorption/binding is a phenomenon that remains quite unexplored. Okada4 determined the encapsulation energy of (in vacuum) ssDNA as a function of nanotube diameter, and suggested an intricate relationship between both, particularly in the range 1.25 < D (nm) < 1.8. As far as we are aware, there are no previous studies of intratubularly confined aqueous nucleobases. We shall address this issue using the well-tempered metadynamics scheme proposed by Parrinello,5 estimating the free-energy landscapes associated with the encapsulation process of Adenine (purine) and Thymine (pyrimidine) onto two different diameter (zig-zag) nanotubes, (16,0) with D = 1.25 nm and (23,0) with D = 1.8 nm. These two topologies correspond to the narrowest and largest nanopores obtained by electric-arc discharge.3 Because nanotubes can be electrically charged,6 the effect of charge density will be addressed considering purely hydrophobic solids and nanotubes with electric charges of q = + 0.05 e/C. Physiological conditions (T=310K) are mimicked by explicitly including H2O molecules and Cl ions in the calculations.

II. Results and Discussion

     The encapsulation mechanism of both purine- and pyrimidine-types onto hydrophobic SWCNTs is energetically favorable and irreversible during the time windows spanned in the simulations (0.1 Ás); the resulting NB/SWCNT hybrids exhibit lower free energies compared to the unconfined systems (Fig.1). The highly symmetrical free-energy landscapes obtained are essentially one dimensionally isotropic regarding the x1 order parameter, in direct relationship to the nanotubes quasi 1-D symmetry. Once confined inside the nanotube, a nucleobase can explore a region whose boundaries are comprised between the entrances, 0.15 < x1 (nm) < Lz (where Lz is the SWCNT length), and the inner surface of the wall, never returning to the bulk. It is very interesting to observe that confinement effects are remarkably stronger at the nanopore center, where free energy differences are largest,  [ x1, x2](16,0) = (1.1, 0.08) nm and [x1, x2](23,0) = (1.7, 0.08) nm. Independent umbrella sampling calculations identified a unique probability distribution maximum corresponding to a domain comprised between the solid walls and the nanopore center (Fig.2). Once confined, molecules are in direct contact with the walls at a minimum distance of closest approach of 0.26–0.28 nm. No layer of solvent could be observed between hydrophobic slabs. This is due to a robust  pi-stacking mechanism of the NB onto the graphitic mesh, leading to strong dispersive energies of interaction with both the (16,0) and (23,0) topologies (Table I). These results have been compared with DFT and experimental data for graphene. Contrary to exoadsorption, intratubular binding affinity increases with nanotube curvature, as a result of enhanced interaction with the wall immediately opposite to the adsorptive one. We have estimated a diameter of D = 2.05 nm above which the SWCNT curvature mimics a flat graphene sheet and confinement effects tend to be negligible. Adenine and thymine evidence similar interaction energies with the hydrophobic nanopores, however, adenine confinement results in slightly favored energetics of ca. 0.9 – 1.4 kJ/mol (Table I). This previously unobserved finding indicate a binding affinity order: purines > pyrimidines.

     Electrically charged nanotubes evidence a completely different behavior. The narrowest nanopore employed here, (16,0), inhibits encapsulation of either the purine or pyrimidine moiety. Instead, that nanotube favors adsorption at a region very close to the pore entrance as indicated by the probability distribution maxima at  W = 0.97 nm and  W = 1.04 nm (Fig.2). When the nucleobases are put in contact with the (23,0) solids, several encapsulation/exit events can occur (Fig.3); moreover, the confined systems exhibit lower free energies. The probability distribution curves indicate two maxima: i) close to the pore center, overlapping the one obtained for the corresponding hydrophobic solid, and ii) at the pore entrance. This second region of confinement is energetically less stable than the pore center (Table I), particularly in the case of adenine where deltaE=40 kJ/mol. Because the pyrimidine molecule has a larger dipole moment, its exposure to the bulk solution carries smaller electrostatic penalties, and therefore its location at the pore center is stabilized by only ca. 12 kJ/mol compared to the entrance.

Hydrophobic SWCNTs

Charged SWCNTs

FIGURE 1. Free energy landscapes, F(x1, x2), of the nucleobases in contact with (16,0) and (23,0) nanotubes. The two collective variables, x1 and x2, correspond to the distance between the nucleobase center of mass and the nanotube entrance or geometrical center, respectively, projected along the z-axis. For the hydrophobic solids, the absolute free energy minima at [ x1, x2](16,0) = (1.1, 0.08) nm and [x1, x2](23,0) = (1.7, 0.08) nm coincide almost exactly with the SWCNT center. When the SWCNTs are charged, two free energy minima can be observed: at the nanotube center [ x1, x2](16,0) = (1.09, 0.08) nm and [x1, x2](23,0) = (1.72, 0.08) nm, and at the entrance, [ x1, x2](16,0) = (0.08, 1.08) nm and [x1, x2](23,0) = (0.08–0.33, 1.41–1.70) nm. Note that the nanopore entrances are symmetrical about the SWCNTs center of mass and thus the sets of collective variables are equivalent: [x1, x2](16,0) = (0, 1.1)  = [ x1, x2](16,0) = (2.2, 1.1) and  [ x1, x2](23,0) = (0, 1.7)  = [ x1, x2](23,0) = (3.4, 1.7).

FIGURE 2. Potential of mean­­ force (PMF) and probability distribu­tion profiles: black) hydrophobic and red) electrically charged nanotubes. The order parameter, W, corresponds to the absolute distance between the center of mass of the nucleobase and that of the solid. Notice the parallel alignment of the nucleobases with the hydrophobic solid walls and the existence of two maxima in the probability curves for the electrically charged (23,0) nanotubes.

FIGURE 3. Distance between a nucleobase and electrically charged SWCNT center: black) adenine, blue) thymine. The distance plateaus at ca. 1nm (16,0) and 1.35nm (23,0) essentially correspond to the nanopore entrances.

Table I. Interaction energies between the nucleobases and the carbon nanotubes, Eint= Evdw+ ECoul,

where Evdw is the dispersive energy and ECoul corresponds to the electrostatic contribution.

Evdw (kJ/mol)

ECoul (kJ/mol)

Eint (kJ/mol)









-83.1 ▒ 0.1

-82.2 ▒ 0.1






-68.6 ▒ 0.1

-67.2 ▒ 0.1







-35.2 ▒ 0.2

-31.8 ▒ 0.3

-19.8 ▒ 0.3

-20.6 ▒ 0.3




-65.3 ▒ 0.1

-51.4 ▒ 0.3

-38.8 ▒ 0.2

-37.6 ▒ 0.3




-40.6 ▒ 0.2

-45.8 ▒ 0.3

-24.2 ▒ 0.2

-31.4 ▒ 0.3



aresults for the (16,0) electrically charged nanotubes correspond to exoadsorbed nucleobases.

bconfinement close to the nanopore center and cat the pore entrance


 ADDIN EN.REFLIST (1) Johnson, R. R.; Johnson, A. T. C.; Klein, M. L. Nano Letters 2008, 8, 69.

(2) Cruz, F. J. A. L.; Mota, J. P. B. Phys. Rev. B 2009, 79, 165426.

(3) Cruz, F. J. A. L.; Esteves, I. A. A. C.; Agnihotri, S.; Mota, J. P. B. J. Phys. Chem. C 2011, 115, 2622.

(4) Kamiya, K.; Okada, S. Phys. Rev. B 2011, 83, 155444.

(5) Barducci, A.; Bussi, G.; Parrinello, M. Phys. Rev. Let. 2008, 100, 020603.

(6) Zhao, X.; Johnson, J. K. J. Am. Chem. Soc. 2007, 129, 10438.

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