β-Cyclodextrin-Naproxen Inclusion Complex And Its NMR Characterization

In the recent years,theβ-cyclodextrin(CD) has been the hotpot in the field of supermolecular chemistry, which is one of the best hosts. The study on molecular recognition and molecular assemble with order of CD plays an extremely vital role in the development of the supermolecular chemistry. Naproxen is one kind of antipyretic analgesics and nonsteroidal anti-inflammatoryagents, with low toxicity and small side effects. Due to the limited water solubility of naproxen, its application receives certain limit. Based on theβ-CD's structure, the inclusion (β-CD - Nap) can be prepared by Nap withβ-CD, which may improve solubility of Nap in water, and has very good clinical practice value.The interaction and the equilibrium constants of interaction between naproxen and cyclodextrins were studied by two-dimensional diffusion ordered NMR spectroscopy (2D-DOSY) in this paper. The self-diffusion coefficient of the main object was measured in different temperature, volume of water, pH and anionic strength, and then the mechanism of inclusion reaction was further discussed. The results show that: inclusion reaction of naproxen with cyclodextrin was a spontaneous endothermic entropy-driven process. With the temperature increasing, the diffusion coefficient and equilibrium constant of naproxen were also increasing; The inclusion cooperation is very weak in DMSO solution; With the volume of water in solution increaseing, the reaction equilibrium constant increased, and the package Hop reacts easily; The solubility of naproxen and the equilibrium constant are gradually increasing with the pH incresed. The increase of ionic strength is beneficial to the package reaction.In addition, 2D DOSY NMR showed that naproxen has entered the cavity ofβ-cyclodextrin inclusion complex. 2D ROESY NMR spectrum proved deeply embedded object naproxen withβ-cyclodextrin cavity, and naproxen in the carboxy-terminalβ-cyclodextrin in the port side of the large cavity, methoxy terminalβ-rings in dextrin narrow mouth end, and to determine the spatial and host-guest binding mode of binding sites. Naproxen and its inclusion compound by ¹³C-NMR spectra showed that the methoxy carbon by the end of the shielding effect of a larger, may have entered into theβ-cyclodextrin cavity. Which proposed the formation of inclusion complexes of naproxen when the methoxy-side only from the wide mouth ofβ-cyclodextrin side (Chung-carbon hydroxyl band) into theβ-cyclodextrin cavity, and then paste from the β-ring narrow-mouth side out fine, and naproxen are located in the carboxyl terminal ofβ-cyclodextrin cavity side of big mouth.Finally, changes in T1 relaxation time of inclusion made possible kinetic mechanism of the process and get theβ-cyclodextrin and naproxen hydrogen bonds formed between the exchange rate. This work expanded applications of NMR spectroscopy in the weak interactions between molecules.