TY - JOUR
T1 - Propionic acid derivatives confined in mesoporous silica
T2 - monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations
AU - Delle Piane, Massimo
AU - Corno, Marta
AU - Ugliengo, Piero
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - AIMD
KW - DFT
KW - Drug delivery
KW - Ibuprofen
KW - Mesoporous silica
KW - Propionic acid derivatives
UR - http://www.scopus.com/inward/record.url?scp=84958239508&partnerID=8YFLogxK
U2 - 10.1007/s00214-016-1817-9
DO - 10.1007/s00214-016-1817-9
M3 - Article
SN - 1432-881X
VL - 135
SP - 1
EP - 10
JO - Theoretical Chemistry Accounts
JF - Theoretical Chemistry Accounts
IS - 3
M1 - 53
ER -