Spectral Study and Molecular Modeling of the Inclusion Complexes of β-Cyclodextrin with Some Phenoxathiin Derivatives

Abstract

The inclusion complexes of 3-formyl-(1), 3-acetyl-(2), and 3-carboxyphenoxathiin (3) were investigated by steady-state fluorescence spectroscopy. In the presence of β-cyclodextrin (β-CD), the fluorescence spectra of 1 and 2 point out an enhancement of the emission and a hypsochromic shift of the maxima. In the case of the carboxy derivative the measurements were conducted in buffer solutions, pH ) 2.11 and pH ) 9.18, to ensure the presence of either the neutral (3a) or dissociated carboxylate (3b) form, as a single predominant species. A different behavior was observed for these two species: en enhancement of the emission for the neutral form and a quenching for 3b. For all the compounds the best fit to the experimental data was obtained for 1:1 stoichiometry and points out association constants in the range 5000-7000 M -1 , for 1, 2, and 3b and 1770 M -1 for 3a. Molecular modeling of the complexes was performed by both molecular mechanics and quantum semiempirical methods. The ligands were introduced in the host cavity, either with the unsubstituted phenyl ring (model A) or with the substituted moiety (model B). For the neutral compounds, about 70% of the binding energy, was due to the van der Waals contribution whereas for 3b the electrostatic interaction was the dominant term. The distance between the center of the cavity and the mass center of the four carbon atoms in the median heteroring of the ligand, points out a deep penetration of the ligands. The flexibility of the sulfur-containing ring could be a positive factor for a better fit of the ligand into the cavity accounting for the large values of the association constants. The calculated heat of formation of the complexes are in the range usually found for the inclusion complexes excepting 3b, for which unexpected large values were predicted. The calculations did not allow us to distinguish between the two possible ways the ligands approach the cavity, the results for model A and model B being similar.

Binding Mechanisms in Supramolecular Complexes

“…[595,596,603,606] Van der Waals and polar interactions are often assumed to be significant factors, based also on the results of recent simulations. [607] It must be taken into account in the interpretation of thermodynamic values that cyclodextrins have a tendency to form nontrivial 1:1 complexes, [608] and that, as already mentioned in Section 3.2, [91] contrary to expectation, the substrate often binds outside the cavity. [609] With predominantly hydrophobic forces it is also found by "offering" guest molecules that bear groups of varying size, that the groups that bind inside the cavity are specifically those that do not fill it, [610] but instead leave room for water molecules (see also Section 10).…”

Interaction of naproxen with β-cyclodextrin and its derivatives/polymer: experimental and molecular modeling studies

“…Many experimental methods such as UV-Visible (UV-Vis), Fourier Transform Infrared (FTIR), fluorescence, circular dichroism, calorimetry, and Nuclear Magnetic resonance (NMR) have been developed to study the complexation behaviours of native and functionalized CDs [17,18]. In order to get a better understanding of the binding events, a lot of theoretical methods [19] including molecular mechanics (MM) [20,21], molecular dynamics [22] and quantum mechanics (QM) [23] methods, have also been used to study the CD complexes.…”

Insights into the Binding of 3-(1-Phenylsulfonyl-2-methylindol-3-ylcarbonyl) Propanoic Acid to Bovine Serum Albumin: Spectroscopy and Molecular Modelling Studies

“…At larger ligand concentration, a new fluorescence emission was initially observed at 382 nm as a shoulder peak and a red shifted towards 388 nm as a band was noticed continuously for the the maximum position of the free ligand. This may be due to the hydrophobic environment around the included species provided by the cyclodextrin [23] cavity which explains this hypsochromic shift. The mechanism and binding constant could be obtained according to the stern volmer plot shown Fig.…”