Conformational, calorimetric and NMR spectroscopic studies on inclusion complexes of cyclodextrins with substituted phenyl and adamantane derivatives

Abstract

Inclusion modes in complexes with a-and byclodextrins in water have been investigated by NMR spectroscopy at 400 or 500 MHz, and compared with structures obtained by computer-aided molecular modelling and with calorimetric data. The NOEs observed on 0-and m-aryl protons upon irradiation of either H3 or H5 inside the CD cavity indicate for all phenols an inclusion mode with the hydroxy group at the wide cavity end, and an increasingly deep immersion for phenol or phenolate with iodine compared with this nitro group, aspara-substituent. This is found to be in line with the complexationinduced NMR shifts. Adamantane-l-carboxylate is indicated by distinct NOEs to be fully immersed into the PCD cavity; the corresponding complex with a-CD shows contact only at the wider rim and a tilted conformation which allows formation of a hydrogen bond between the guest COO-and the 2-OH group of the CD. The same conformation is found by CHARMm calculations, including simulations in a water box. The results, together with some A@ values derived from N M R titrations, are in line with data from calorimetric studies. These show for complexes with tight fit (in a-CD) large enthalpies of up to 43 W mol-l as the predominating driving force against sizeable entropy disadvantages (TAS" < -24 kJ mol-'), particularly for guest molecules of higher electron density and/or polarizibility. These observations point to predominating dispersive interactions. In contrast, inclusion in the wider fLCD cavity suffers less from entropy disadvantage (TAS" < -11 W mol-*); the binding, however, is still dominated by AH", pointing to predominant cohesive and not entropic hydrophobic forces.

Controllable Nanocage Structure Derived from Cyclodextrin-Intercalated Layered Double Hydroxides and Its Inclusion Properties for Dodecylbenzene

“…An alternative explanation is that both DDB environments involve insertion into the CD host, as it was previously shown that insertion of substituted phenyl compounds into CDs might give a mixture of two or more alternative forms. 42,43 Based on our experiments and previous studies, the observed kinetics for DDB in DDB/CMCD-LDH can be explained by a dynamic equilibrium between DDB molecules that are tightly bound to CMCD (with a relatively long fluorescence decay time) and those that are located near the exit of the hydrophobic cavity (with a relatively short fluorescence decay time).…”

Study on the Supramolecular Interaction of β‐Cyclodextrin with Gemfibrozil by Spectrofluorimetry and Its Analytical Application

“…Thus the variation of the shape, shift and intensity of the absorption peaks of the guest or host could provide enough information for the occurrence of the inclusion. 20 By comparison of IR spectra of gemfibrozil, β-CD, the physical mixture (gemfibrozil∶β-CD, 1∶1) of gemfibrozil and β-CD and the inclusion complex (Figure 6), it could be seen that the spectrum of c was essentially the combination of a and b, which indicated that physical mixture (gemfibrozil∶β-CD, 1∶1) could not lead to inclusion. There were apparent differences between the spectra of c and d and some characteristic IR absorption peaks of gemfibrozil and β-CD were changed obviously in inclusion complex: the benzene ring -C＝C-bond stretching vibration absorption peak at 1600 cm -1 of gemfibrozil red-shifted to 1590 cm -1 ; the 1270 cm -1 absorption assigned to Ar-O red-shifted to 1230 cm -1 .…”

“…According to the partial 1 H NMR spectra of gemfibrozil, β-CD and the inclusion complex, apparent changes in chemical shifts of different protons could be observed ( Figure 7): compared with the dramatic upfield shifts of β-CD interior H-3, H-5 and H-6 protons, which resulted from the shielding effect exerted by the inclusion of gemfibrozil's benzene ring into β-CD cavity, the shifts of β-CD outside H-2 and H-4 protons could be neglected; the apparent shift changes of β-CD H-3 indicated that the guest molecule entered β-CD cavity along with its wide rim which possessed secondary hydrogens; 20 H-1, H-2 and H-3 of gemfibrozil benzene ring protons had dramatic chemical shift changes, otherwise other protons of gemfibrozil changed little. All of the changes showed that gemfibrozil benzene ring was included into the β-CD cavity and this was in good agreement with the results obtained from IR spectrum.…”

Self‐Assembled Nanostructures of Tailored Multi‐Metal Complexes and Morphology Control by Counter‐Anion Exchange

“…[19] The upfield shift of the inner H3 and H5 protons of b-CD and downfield shift of the outer H2 and H4 protons from the free b-CD were observed as seen in the reported complexes between b-CD and the adamantane derivatives. [20,21] The formation of an inclusion complex was directly proved by the ROE correlation peaks between the inner protons of the b-CD and those of adamantane. As shown in many complexes between the b-CD and adamantane derivatives, [21] H3 showed stronger ROE cross-peaks with the proton of adamantane than H5 (Figure 4).…”

“…[20,21] The formation of an inclusion complex was directly proved by the ROE correlation peaks between the inner protons of the b-CD and those of adamantane. As shown in many complexes between the b-CD and adamantane derivatives, [21] H3 showed stronger ROE cross-peaks with the proton of adamantane than H5 (Figure 4). Isothermal titration calorimetry (ITC) was used to confirm the affinity of the adamantane···b-CD interaction.…”