الملخص الإنجليزي
This work explored the interaction of two different drugs, cetirizine (CTZ) and
tetrahydrozoline (THZ) with two different cucurbit[n]urils CB[n], cucurbit[6]uril (CB[6])
and cucuribit[7]uril (CB[7]). Two binary inclusion complexes were investigated in
solution and in the solid-state, by lyophilization and by the formation of physical
mixtures. In most of the cases 1:1 complex was obtained, for both studied drug. 1HNMR
and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass
spectrometry were used to study the complexes prepared in solution. The lyophilized
solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR),
powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and
differential scanning calorimetry (DSC). MALDI-TOF, FT-IR and PXRD experimental
results established in this work reveal the presence of the non-covalent interaction
between the selected drugs and the two hosts. The TGA and DSC confirmed the
enhancement of the thermal stability of each drug and the production of a thermally stable
solid complex. The 1HNMR has shown that the guests’ protons faced shifting in ppm and
broadening of peaks upon the formation of inclusion complexes with the selected CB[n]s.
Among all prepared complexes, CTZ@CB[6] is the only complex where most of its
aliphatic protons remain unchanged in the presence of CB[6] which suggest the formation
of a weak complex or an external complex. The diffusion coefficients (D), obtained from
the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the
complexation of the selected drugs with CB[6] and CB[7], were decreased in presence of
hosts compared to the free guests indicating formation of guest-host adduct. The density
functional theory (DFT) calculations confirmed the formation of a weak complex
between CTZ and CB[6] while favorable complexes of CTZ@CB[7] and THZ@CB[6,7].
The results presented in this thesis show that CTZ form a stable inclusion complex CB[7]
and THZ form stable complex with the two hosts through non-covalent interactions such
as van der Walls interactions, hydrogen bonding, and ion-dipole interactions resulting in
enhanced chemical stability of these pharmaceutical compounds. This study generates
initial data for potential drug delivery systems for these selected pharmaceutical
compounds by CB[n].
