Local molecular organizations of ibuprofen, flurbiprofen and ketoprofen in the liquid phase: Insights from molecular dynamics simulations

In this paper, the local molecular organization of ibuprofen, flurbiprofen and ketoprofen in the liquid state have been investigated using molecular dynamics simulations. The different hydrogen bonding associating structures have been characterized. Dipolar correlations between molecules have been probed by calculating the Kirkwood factor. For the three liquids, the present investigation performed at relatively high temperatures from 500 to 380 K revealed the presence of a specific local molecular organization composed of small hydrogen bonding aggregates corresponding to cyclic dimers possessing anti-parallel dipolar organization. This organization becomes more and more probable upon decreasing temperature and it is suggested that this trend would continue to lower temperatures for which cyclic dimers would become the dominant organization i.e. precursor of the crystalline structures. At all investigated temperatures, the probability of forming the cyclic dimers association is significantly lower in ketoprofen than in ibuprofen or flurbiprofen. This difference would suggest why a peculiar low frequency Debye process is detected in ibuprofen and flurbiprofen and not in ketoprofen.