Structural Chemistry

, Volume 30, Issue 1, pp 369–384 | Cite as

Molecular dynamics assessment of doxorubicin–carbon nanotubes molecular interactions for the design of drug delivery systems

  • M. Leonor ContrerasEmail author
  • Camila Torres
  • Ignacio Villarroel
  • Roberto Rozas
Original Research


Carbon nanotubes (CNTs) constitute an interesting material for nanomedicine applications because of their unique properties, especially their ability to penetrate membranes, to transport drugs specifically and to be easily functionalized. In this work, the energies of the intermolecular interactions of single-walled CNTs and the anticancer drug doxorubicin (DOX) were determined using the AMBER 12 molecular dynamics MM/PBSA and MM/GBSA methods with the aim of better understanding how the structural parameters of the nanotube can improve the interactions with the drug and to determine which structural parameters are more important for increasing the stability of the complexes formed between the CNTs and DOX. The armchair, zigzag, and chiral nanotubes were finite hydrogen-terminated open tubes, and the DOX was encapsulated inside the tube or adsorbed on the nanotube surface. Pentagon/heptagon bumpy defects and polyethylene glycol (PEG) nanotube functionalization were also studied. The best interaction occurred when the drug was located inside the cavity of the nanotube. Armchair and zigzag nanotubes doped with nitrogen, favored interaction with the drug, whereas chiral nanotubes exhibited better drug interactions when having bumpy defects. The π-π stacking and N-H…π electrostatic interactions were important components of the attractive drug-nanotube forces, enabling significant flattening of the nanotube to favor a dual strong interaction with the encapsulated drug, with DOX–CNT equilibrium distances of 3.1–3.9 Å. These results can contribute to the modeling of new drug-nanotube delivery systems.


Bumpy nanotubes Nitrogen-doped carbon nanotubes Doxorubicin encapsulation Drug delivery system Interaction energies Noncovalent interactions π-π stacking 



This work was partially supported by the Direction of Scientific and Technological Research DICYT-USACH Project Nr. 061641CF and by the Sociedad de Desarrollo Tecnológico SDT-USACH Project Nr. CIA 2981. We are also grateful for the allocation of computer time at the Chemistry and Biology Faculty cluster. We also thank Mr. Rodrigo Yañez for computer facilities.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11224_2018_1210_Fig10_ESM.png (531 kb)
Fig. S1

The Poisson-Boltzmann (PB) and the Generalized Bond (GB) binding-energies for DOX–CNT complexes obtained by means of the MM/PBSA and MM/GBSA methods in explicit solvent using the TIP3P and the TIP4P water models (PNG 531 kb)

11224_2018_1210_MOESM1_ESM.tif (75 kb)
High Resolution Image (TIF 74 kb)
11224_2018_1210_Fig11_ESM.png (551 kb)
Fig. S2

Graphical comparison of DOX Mulliken charges with DOX RESP charges (PNG 551 kb)

11224_2018_1210_MOESM2_ESM.tif (51 kb)
High Resolution Image (TIF 51 kb)
11224_2018_1210_MOESM3_ESM.docx (21 kb)
Table S1 (DOCX 21 kb)
11224_2018_1210_MOESM4_ESM.docx (15 kb)
Table S2 (DOCX 15 kb)
11224_2018_1210_MOESM5_ESM.docx (17 kb)
Table S3 (DOCX 16 kb)


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Authors and Affiliations

  1. 1.Laboratorio de Química Computacional y Propiedad Intelectual, Departamento de Ciencias del Ambiente, Facultad de Química y BiologíaUniversidad de Santiago de Chile, USACHSantiagoChile
  2. 2.Departamento de Computación e Informática, Facultad de IngenieríaUniversidad de Santiago de Chile, USACHSantiagoChile

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