Hexa-
p
-
tert
-butylcalix[6]arene
(1)
is believed
to adopt a winged conformation in a solution,
featured by four phenyl rings perpendicular to the calix basis and
two others at 1,4-positions lying down. However, there is some controversy
on the occurrence of this conformation because it has never been found
in the solid state of calix[6]arenes, regardless of the substitution
pattern at lower and upper rims. Here, we have observed the winged-cone
conformation for the first time in a solvate form of
1
with dimethyl sulfoxide (DMSO), dimethylformamide, and pyridine.
The DMSO molecule is strongly encapsulated into
1
through
two OH···O hydrogen bonds with both flattened phenolic
moieties, one lp
(S)
···π and four CH···π
interactions with the four perpendicular phenyl rings. This host–guest
complex has energy lower by 23.4 kcal mol
–1
than
the isolated species. In addition, another DMSO solvate form with
1,2,3-alternate conformation was also obtained in this study, and
its structure is compared with that of the precedent one. A detailed
density functional theory study has also been carried out to understand
the energetic relationships among cone conformers, intramolecular
hydrogen-bonding patterns, and DMSO encapsulation.
In this study, the interaction between benzothiazole (BTA, concentration of a drug required for 50% inhibition in vitro (IC50) = 0.77 mM) and benzimidazole (BIA, IC50 = 2.14 mM) with urease was quantitatively assessed, using UV-Vis, molecular fluorescence, and circular dichroism. The results showed that both compounds interact with urease by a static fluorescence quenching mechanism with a non-fluorescent complex formation. The main forces responsible for stabilizing the supramolecular complex between BTA and urease were hydrophobic while, for BIA, van der Waals interactions and hydrogen bonds were the main ones. Urease conformation changes due to the interaction process were analyzed by circular dichroism and synchronous fluorescence. Besides, a competitive assay with substrate and inhibitors was used to evaluate the preferential urease site of interaction with BTA and BIA. Our experimental and theoretical studies supported that both, BTA and BIA, are mixed-inhibitors of ureases with a slight preference to the active site of such enzymes. Finally, both BTA and BIA showed to possess anti-H. pylori (one reference strain and six clinical isolates) activity, presenting minimal inhibitory concentration (MIC) values ranging from 38-150 and 20-164 μM, respectively. The urease inhibitors omeprazole and hydroxyurea showed MIC values in the range of 46-185 μM and 1683-> 3366 μM, respectively.
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