Complexation of mefenamic acid by low-generation PAMAM dendrimers: Insight from NMR spectroscopy studies and molecular dynamics simulations

Pabla A. Barra, Luis Barraza, Verõnica A. Jiménez, José A. Gavín, Joel B. Alderete

Resultado de la investigación: Article

11 Citas (Scopus)

Resumen

The complexation of mefenamic acid (MA) with poly(amido amine) dendrimers of the second and third generation (PAMAM-G2 and PAMAM-G3) at pH 7.0 is studied by aqueous solubility experiments, DOSY and 2D-NOESY spectroscopy, and fully atomistic molecular dynamics (MD) simulations. Solubility profiles account for the formation of MA:PAMAM complexes of the type 10:1 and 15:1, for PAMAM-G2 and PAMAM-G3, respectively, with a maximum solubilization enhancement of 14.6 mol of MA per mol dendrimer. Diffusion ordered sepectroscopy (DOSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments suggest that MA association occurs through both external electrostatic interactions with the PAMAM surface and internal encapsulation into the deep dendrimer cavities. MD simulations are consistent with these experimental findings and show that the internal drug encapsulation is enhanced as the dendrimer generation increases. The involvement of internal and external interactions in the complexation of MA with low-generation PAMAM dendrimers differs from the general behavior expected for acidic anionic guests, for which external electrostatic contacts with the positively charged PAMAM surface have been postulated as the most relevant factor for drug association.

Idioma originalEnglish
Páginas (desde-hasta)372-383
Número de páginas12
PublicaciónMacromolecular Chemistry and Physics
Volumen215
N.º4
DOI
EstadoPublished - 2014

Huella dactilar

Mefenamic Acid
Dendrimers
dendrimers
Complexation
Nuclear magnetic resonance spectroscopy
Molecular dynamics
molecular dynamics
nuclear magnetic resonance
acids
Acids
Computer simulation
Overhauser effect
spectroscopy
Spectroscopy
Encapsulation
simulation
drugs
solubility
Solubility
Association reactions

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Physical and Theoretical Chemistry
  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

Citar esto

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abstract = "The complexation of mefenamic acid (MA) with poly(amido amine) dendrimers of the second and third generation (PAMAM-G2 and PAMAM-G3) at pH 7.0 is studied by aqueous solubility experiments, DOSY and 2D-NOESY spectroscopy, and fully atomistic molecular dynamics (MD) simulations. Solubility profiles account for the formation of MA:PAMAM complexes of the type 10:1 and 15:1, for PAMAM-G2 and PAMAM-G3, respectively, with a maximum solubilization enhancement of 14.6 mol of MA per mol dendrimer. Diffusion ordered sepectroscopy (DOSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments suggest that MA association occurs through both external electrostatic interactions with the PAMAM surface and internal encapsulation into the deep dendrimer cavities. MD simulations are consistent with these experimental findings and show that the internal drug encapsulation is enhanced as the dendrimer generation increases. The involvement of internal and external interactions in the complexation of MA with low-generation PAMAM dendrimers differs from the general behavior expected for acidic anionic guests, for which external electrostatic contacts with the positively charged PAMAM surface have been postulated as the most relevant factor for drug association.",
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Complexation of mefenamic acid by low-generation PAMAM dendrimers : Insight from NMR spectroscopy studies and molecular dynamics simulations. / Barra, Pabla A.; Barraza, Luis; Jiménez, Verõnica A.; Gavín, José A.; Alderete, Joel B.

En: Macromolecular Chemistry and Physics, Vol. 215, N.º 4, 2014, p. 372-383.

Resultado de la investigación: Article

TY - JOUR

T1 - Complexation of mefenamic acid by low-generation PAMAM dendrimers

T2 - Insight from NMR spectroscopy studies and molecular dynamics simulations

AU - Barra, Pabla A.

AU - Barraza, Luis

AU - Jiménez, Verõnica A.

AU - Gavín, José A.

AU - Alderete, Joel B.

PY - 2014

Y1 - 2014

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AB - The complexation of mefenamic acid (MA) with poly(amido amine) dendrimers of the second and third generation (PAMAM-G2 and PAMAM-G3) at pH 7.0 is studied by aqueous solubility experiments, DOSY and 2D-NOESY spectroscopy, and fully atomistic molecular dynamics (MD) simulations. Solubility profiles account for the formation of MA:PAMAM complexes of the type 10:1 and 15:1, for PAMAM-G2 and PAMAM-G3, respectively, with a maximum solubilization enhancement of 14.6 mol of MA per mol dendrimer. Diffusion ordered sepectroscopy (DOSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments suggest that MA association occurs through both external electrostatic interactions with the PAMAM surface and internal encapsulation into the deep dendrimer cavities. MD simulations are consistent with these experimental findings and show that the internal drug encapsulation is enhanced as the dendrimer generation increases. The involvement of internal and external interactions in the complexation of MA with low-generation PAMAM dendrimers differs from the general behavior expected for acidic anionic guests, for which external electrostatic contacts with the positively charged PAMAM surface have been postulated as the most relevant factor for drug association.

KW - dendrimers

KW - diffusion

KW - host-guest systems

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