Preparation Of Layered Double Hydroxides (LDHs) And Applied Research Of Intercalated Amino Substances

In this paper, amino drugs (Threnoine, L-Alanyl-Glutamine and Glutathiose)were intercalated into layered double hydroxides (LDHs), in order to investigate theirchemical behavior. The intercalation mechanism and fixed characteristics between theLDHs’ layers were also studied, which could provide a theoretical basis for LDHmaterials as drug carrier. With computer molecular simulation technology, themicro-structure of the LDH compounds was elucidated, and the arrangement of theamino substances in the interlayer, as well as the interaction between the layers wasalso investigated. The configuration stabilization of the drug molecules afterintercalation and the release behavior were studied. The main contents were asfollows:1. Through ion exchange method, the Thr-LDHs compounds under differenttemperature were synthesized by intercalating threonine into Mg-Al-LDHs. Modernanalytical spectroscopic techniques such as Fourier transform infrared spectroscopy(FT-IR), Raman spectroscopy (Raman), X-ray powder diffraction (XRD), X-rayphotoelectron spectroscopy (XPS), thermogravimetry-differential thermal analysis(TG-DTA) and13C solid-state nuclear magnetic resonance (13C MAS NMR) wereused to evalute the drug-loading LDH compounds, so that a detailed structure ofLDHs could be expressed.2. The nanomaterial L-(Ala-Gln)-LDHs was synthesized by intercalatingL-Alanyl-Glutamine (L-(Ala-Gln)) into Mg-Al-LDHs. The material properties and thereaction mechanism of the LDH compounds were studied, in order to demonstrate theLDH interlayer’s restrictive feature as “molecular container”, which could giveconfiguration protection for the intercalated L-(Ala-Gln). The solid-state UV-visspectroscopy confirmed that the LDHs’ cationic layers had shielding effect on UVlight, so that the configuration stabilization in the LDH interlayer could be achieved.Density Functional theory (DFT) calculations was used to verify the experimentalresults, and showed that the reaction temperature could not support L-(Ala-Gln) togive an excite state, but it could be excited under the irradiation of UV light with a wavelength less than240nm and undergo conformational transition. Whenintercalated in the interlayer of LDHs, L-(Ala-Gln) was involved in strong guest-hostinteraction with the layers and thus inhibition of configuration conversion is effectivein LDH interlayer.3. Glutathione (GSH) was intercalated into the layered double hydroxides (LDHs)by ion exchange method and the tripetide/LDHs (GSH-LDHs) compounds wereprepared. Multiple characterization tools have been employed to investigate thestructure of this drug-LDH composite. And experimental measurements andtheoretical computation were combined to study the microstructure of LDHs and thereaction mechanism of intercalating GSH into LDHs. The GSH intercalated intoLDHs was explained by computer simulation and revealed that, GSH in water solvent,first suffered hydrogen transfer and proton migration, and then could be intercalatedinto LDH through ion exchange to occupy an interlayer site of NO3-.4. The precursor Mg-Al-NO3--LDHs with microcrystalline structure wasprepared by using ammonia coprecipitation method, then the nano-sizedL-(Ala-Gln)-LDHs compounds were synthesized. The superiority of nano drugmaterials was that it could effectively improve the targeting and sustained release. Thesustained-release experiment showed that the particle size of L-(Ala-Gln)-LDHs-nanowas smaller, the time for the release of half-life was shorter. The release process wasconsidered to be starting in the internal of the nano drug-particles, then throughdiffusion, the L-(Ala-Gln) anions in the LDHs’ interlayer were exchanged out by thesurrounded PBS buffer solution, and gradually reached the balanced diffusion.