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Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations

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Abstract

Confinement in mesoporous silica can greatly increase the solubility of pharmaceutical compounds. Propionic acid derivatives (a very popular class of drugs that include ibuprofen and ketoprofen) would greatly benefit from such technology, given their common apolar character. However, it is still debated whether, after confinement, these drugs are adsorbed on the pore walls as individual molecules or they keep the H-bonded dimeric structure that exists in their crystalline form. Their physical state inside the mesopores could have important consequences on the final performances of the drug delivery system. We employed accurate periodic density functional theory simulations, both static and dynamic, to investigate the issue. We simulated ibuprofen, as a model for all propionic acid derivatives, adsorbed both as a monomer and as a dimer inside a realistic model for the MCM-41 mesoporous silica. We found that adsorption is energetically favored in both cases, driven by both vdW and H-bond interactions. However, through ab initio molecular dynamics, we observed a continuous forming, breaking and reforming of these interactions. In the end, by comparing computed energetics, vibrational spectra and mobility, we were able to provide some important clues on the physical state of this class of drugs inside mesoporous silica, helping to define which drug family (monomer or dimer) is more probable after confinement.

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Acknowledgments

Models have been visualized and manipulated by MOLDRAW [48] and VMD [49]. Figures have been rendered with the Tachyon ray tracer, built into VMD. The vast majority of the calculations have been carried out thanks to the PRACE (PaRtnership for Advanced Computing in Europe) project pra50810 “Mesoporous silica for drug delivery: a quantum mechanical simulation” (20 million CPU hours on SuperMUC, LRZ, Munich, Germany). CRYSTAL developers are acknowledged for providing up to date development versions of the code and fruitful advice.

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Authors and Affiliations

  1. Department of Chemistry, NIS Centre, University of Torino, Via Pietro Giuria 7, 10125, Turin, Italy

    Massimo Delle Piane, Marta Corno & Piero Ugliengo

Authors
  1. Massimo Delle Piane
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  2. Marta Corno
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  3. Piero Ugliengo
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Correspondence to Piero Ugliengo.

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Published as part of the special collection of articles “CHITEL 2015 - Torino - Italy”.

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Delle Piane, M., Corno, M. & Ugliengo, P. Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations. Theor Chem Acc 135, 53 (2016). https://doi.org/10.1007/s00214-016-1817-9

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