Studying molecular dynamics of the slow, structural, and secondary relaxation processes in series of substituted ibuprofens

Abstract

In this paper, the molecular dynamics of a series of ester derivatives of ibuprofen (IBU), in which the hydrogen atom from the hydroxyl group was substituted by the methyl, isopropyl, hexyl, and benzyl moieties, has been investigated using Broadband dielectric (BD), Nuclear magnetic resonance (NMR), and Raman spectroscopies. We found that except for benzyl IBU (Ben-IBU), an additional process (slow mode, SM) appears in dielectric spectra in all examined compounds. It is worth noting that this relaxation process was observed for the first time in non-modified IBU (a Debye relaxation). According to suggestions by Affouard and Correia [J. Phys. Chem. B. 114, 11397 (2010)] as well as further studies by Adrjanowicz et al. [J. Chem. Phys. 139, 111103 (2013)] on Met-IBU, it was attributed to synperiplanar-antiperiplanar conformational changes within the molecule. Herein, we have shown that with an increasing molecular weight of the substituent, the relaxation times of the SM become longer and its activation energy significantly increases. Moreover, this new relaxation mode was found to be broader than a simple Debye relaxation in Iso-IBU and Hex-IBU. Additional complementary NMR studies indicated that either there is a significant slowdown of the rotation around the O=C-O-R moiety or this kind of movement is completely suppressed in the case of Ben-IBU. Therefore, the SM is not observed in the dielectric loss spectra of this compound. Finally, we carried out isothermal experiments on the samples which have a different thermal history. Interestingly, it turned out that the relaxation times of the structural processes are slightly shorter with respect to those obtained from temperature dependent measurements. This effect was the most prominent in the case of Hex-IBU, while for Ben-IBU, it was not observed at all. Additional time-dependent measurements revealed the ongoing equilibration manifested by the continuous shift of the structural process, until it finally reached its equilibrium position. Further Raman investigations showed that this effect may be related to the rotational/conformational equilibration of the long hexyl chains. Our results are the first ones demonstrating that the structural process is sensitive to the conformational equilibration occurring in the specific highly viscous systems.

Impact of Intermolecular Interactions, Dimeric Structures on the Glass Forming Ability of Naproxen, and a Series of Its Derivatives

“…As can be observed, the lowest and the highest steepness indexes were determined for Met-NAP and Ben-NAP ( m = 75 and m = 93, respectively). Interestingly in contrast to esters of IBU, isobaric fragility generally increases with the molecular weight of the compound in the studied NAP derivatives. One can only suppose that the highest m estimated for Ben-NAP might be caused by the enhanced interactions between aromatic rings (the so-called pi stacking) in this compound.…”

“…It may be caused by the plasticizing effect generated by the flexible substituents, as was discussed by Carpenter et al and Jedrzejowska et al The exception to this rule is Ben-NAP. However, in this case, by the analogy to the studies on IBU esters, the higher T g might be related to the reduced mobility of the benzyl moiety, which is substituted in place of the hydrogen atom in the carboxylic group of NAP. Alternatively, the higher T g in this ester can be due to the enhancement of interactions between aromatic rings (possibly pi stacking) with respect to the other investigated herein esters of NAP …”

Influence of Annealing in the Close Vicinity of Tg on the Reorganization within Dimers and Its Impact on the Crystallization Kinetics of Gemfibrozil

“…In turn, the ΔC p for metGEM (van der Waals system) is somewhat higher than that of GEM and dGEM. Interestingly, the higher value of this thermodynamic parameter in comparison to the neat API was also determined for the methyl, isopropyl hexyl, and benzyl derivative of IBU (thermograms presented in our recent paper): 37 ΔC p IBU = 0.362 J/g K, while ΔC p IBUesters varies within the range 0.487− 0.526 J/g K. Based on the above, one can suppose that the change in the intermolecular interactions (from H-bonded to van der Waals) results in the increase in the value of heat capacity jump at T g for the systems characterized by the very similar backbone.…”

Correlation between Locally Ordered (Hydrogen-Bonded) Nanodomains and Puzzling Dynamics of Polymethysiloxane Derivative

“…Briefly, one can to stress that generally for strongly associating systems, apart from the α-process responsible for the vitrification phenomenon, an additional slower mode of still unknown origin (generally of exponential shape) is observed. 59 However, it is not the strict rule since there are many exceptions such as metatoluidine, water, the phenyl derivative of ibuprofen, and so on. 60,61 In our case, this local ordering might indicate the formation of a hydrogen-bonded (ladder-like) structure of the length scale higher than segments.…”