DOI: 10.1021/cg1011023
New Efficient Intercalation of Bioactive Molecules into Layered Double Hydroxide Materials by Solid-State Exchange: An in Situ XRPD Study
2010, Vol. 10 4710–4712
Marco Milanesio,† Eleonora Conterosito,† Davide Viterbo,† Luana Perioli,‡ and Gianluca Croce*,† †
Dipartimento di Scienze e Tecnologie Avanzate and Nano-SiSTeMI Interdisciplinary Centre, Universit a del Piemonte Orientale “A. Avogadro”, V.le T. Michel 11, I-15121 Alessandria, Italy, and ‡ Dipartimento di Chimica e Tecnologia del Farmaco, Universit a di Perugia Via del Liceo 1, 06123 Perugia, Italy Received August 23, 2010; Revised Manuscript Received September 16, 2010
ABSTRACT: A new soft and fast solid state reaction is exploited for the preparation of exchanged layered double hydroxide materials and, in particular, for intercalating bioactive molecules. The characterization of the nanocomposite, carried out by crystallographic and thermogravimetric techniques, revealed that this synthesis yield is comparable to that of standard methods but with time, solvent, and energy saving advantages. Moreover, the in situ diffraction experiments also allowed us to shed some light on the kinetics of the intercalation process. Hydrotalcites (anionic clays) are inorganic natural or synthetic layered double hydroxides (LDH) of divalent and trivalent metals. The inorganic layers are positively loaded, because of the presence of the trivalent cation, and the interlayer region usually contains inorganic anions (chloride, nitrate, or carbonate are the most common) able to balance this positive charge. These anions can be substituted by other anions, in particular organic ones, via anionic exchange to obtain hybrid LDH nanocomposites. Many authors proposed the use of LDH for intercalating bioactive molecules, largely employed in the pharmaceutical and cosmetic fields, with the purpose of protecting them by degradation and/or to obtain modified release properties.1-3 In the case of sunscreens, the intercalation into LDH prevents the contact between the organic moiety and the skin and can improve the sunscreen photostability.4-6 One of the key processes in hybrid LDH nanocomposite preparation is the intercalation of the organic molecule into LDH layers. This is usually obtained by a two step method, with the first step being the LDH preparation with the inorganic anion, followed by the exchange in solution or suspension with a large excess of solvent.1 Recently, a one-pot approach was proposed, in which the organic molecule is directly inserted during the hydrothermal synthesis.7 To go further toward efficient, fast, and green preparation methods, we demonstrate in this paper that inside LDH the exchange of the inorganic anion (chloride or nitrate) with an organic molecule is possible in an almost solventfree environment, by exploiting and adapting the methods widely applied in molecular complex chemistry, such as kneading and solvent-assisted grinding. This mechanochemical approach, based on the cogrinding of powdered reactants in the presence of a small amount of solvent, has been described as a sort of “solvent catalysis” of the solid-state process, in which a small amount of solvent acts as a lubricant for molecular diffusion.8 Based on our positive experience in the study of organicinorganic layered solids, such as the model system stearatehydrotalcite,9 the ancient nanocomposite Maya Blu (formed by intercalating indigo into palygorskite),10 the solid-state preparation of the fluorene-TCNQ molecular complex,11 and zeolite Y dealumination,12 the in situ X-ray powder diffraction (XRPD) approach has been exploited to demonstrate the intercalation of bioactive molecules into LDH, demonstrating that the intercalation of the organic anion into LDH occurs in the solid-state. The *To whom correspondence should be addressed. E-mail: gianluca.croce@ mfn.unipmn.it. pubs.acs.org/crystal
Published on Web 10/07/2010
intercalation of organic molecules into LDH by in situ XRPD was studied in the pioneering works by O’Hare’s group,13 who elegantly carried out, within the in situ XRPD experimental setup, the standard1 intercalation method of organic molecules into LDH, i.e. in excess of solvent. Furthermore, it was recently demonstrated that Mg-Al-NO3-LDH can be prepared by manual grinding, in a mortar,14 or electromechanically in a ball mill.15,16 Combining these approaches, in this work we obtained for the first time, by kneading and solvent assisted grinding techniques, the exchange of a [Zn0.7Al0.3(OH)2](NO3)0.3 3 0.4H2O nitrate LDH (LDH-NO3 hereinafter) with the anionic form of a commercial sunscreen product (Eusolex, chemical name 2-phenylbenzimidazol-5-sulfonic acid, named EUS hereinafter). The characterization of the obtained (LDH-EUS) nanocomposite has been carried out by crystallographic and thermogravimetric techniques. The in situ XRPD experiments also allowed us to shed some light on the kinetics of the intercalation process, unraveled by using the AvramiErofe’ev approach.
Initially, 100 mg of LDH-NO3 was mechanically mixed with 73 mg of EUS in order to obtain a (1:1) molar ratio between EUS anion and exchange sites. The XRPD analysis of the mechanical mixture, measured after grinding followed by 24 h and 1 month of aging, clearly revealed the presence of two distinct reactant phases (LDH-NO3 and EUS) and no evidence of intercalation product, indicating that the dried solid mixture is not reactive at room temperature. From this mixture, two samples of LDH-EUS, named 1 and 2, were prepared and then characterized. Sample 1 was prepared by solvent-assisted grinding: 0.5 mL of 0.5 M NaOH was added to the above-described solid mixture of EUS and LDH-NO3, manually ground in an agate mortar for 1 min at room temperature, and dried for 24 h at room temperature. Sample 2 was obtained from dried sample 1 after washing three times with outgassed water and three times with ethanol and finally drying again at room temperature for another 24 h. The composition and crystallinity of the prepared samples, in comparison with LDH-EUS prepared in the standard way, were investigated r 2010 American Chemical Society
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Figure 1. TGA and normalized DTG profiles of samples 1 and 2.
Figure 3. (a) XRPD data collected in the first 3 h of the in situ solid state reaction of LDH-EUS. (b) Avrami-Erofe’ev and reaction extent R (inset) plots used to deduce the kinetics of the LDH-EUS formation. Figure 2. XRPD patterns of sample 2 with unreacted LDH-NO3 indicated by /. In the inset is the comparison of the normalized (00l) peak intensities of 1 (thin line) and 2 (solid line).
by thermogravimetric (Figure 1) and XRPD (Figure 2) analyses of 1 and 2. The exchange reaction is shown by the growth of the (001), (002), and (003) reflections centered at 2θ 4.20°, 8.32°, and 12.38°, respectively, typical of LDH-EUS. Lattice parameters were obtained by Pawley fit, as implemented into Topas Academic,17 and resulted in full agreement with those of a standard3 LDHEUS sample obtained from high resolution synchrotron data.18 The TGA profiles of samples 1 and 2 revealed a total weight loss of about 40%, and it was possible to recognize: (i) the loss of physically and chemically adsorbed water in the 50-150 °C range, (ii) the loss due to layer deoxydrilation at around 290 °C, and (iii) the loss due to degradation of the intercalated EUS after 400 °C. The main differences between 1 and 2 were observed in the 350650 °C range. The presence in 1 of a DTG broad peak, starting at 390 °C and centered at 450 °C, was consistent with the melting and decomposition of NaNO3, detected by XRPD (see Supporting Information). At the same time, the broadening in 1 of the DTG peak centered at 500 °C, ascribed to the removal of the intercalated EUS, indicated a noncomplete and/or a nonperfect exchange with the formation of defects and with a nonuniform distribution of EUS into the LDH layers. These features disappeared in the DTG profile of 2, indicating that washing was able to remove the NaNO3 coproduct and improve the crystallinity of LDH-EUS. The improved crystallinity was also confirmed by the comparison of the (00l) peaks in the two samples, indicating the much larger scattering power of 2. We can conclude that the final compound 2 is identical to LDH-EUS obtained with standard solution methods.3 Therefore, a very little amount of solvent and much less time (2 instead of 7 days3) were enough to induce the exchange by
solvent-assisted grinding and obtain LDH-EUS. (As suggested by one of the reviewers, we tried to synthesize LDH-EUS by directly grinding the LDH precursors and EUS in the presence of a small amount of NaOH solution. The intercalated composite was obtained, but in low yield and very poor crystalline form. Experimental details are reported in the Supporting Information.) To further explore the kinetic features of the exchange reaction in the solid state, an in situ XRPD experiment was carried out on a sample obtained by solvent assisted grinding. The data collection was started less than 30 s after grinding, thus monitoring the EUS intercalation into LDH in the first 7 h of reaction, and the obtained data are reported in Figure 3a. In situ XRPD data indicated that LDH-EUS is formed as indicated by the growth of the (00l) peaks (2θ = 4.20°, 8.32°, and 12.38°). In fact, we already recorded the presence of intercalated EUS in the first minute of the experiment and the typical (00l) peaks increased in sharpness and intensity, reaching a plateau after 120 min. In the first 60 min, we also observed a fast disappearance of the EUS peaks and the slower decrease of the LDH-NO3 peaks, which continued during the full reaction time. After this period, only a small and constant amount of unreacted and crystalline LDH-NO3 phase is detected. It is worth noting that a relevant degree of exchange is observed in the first pattern, indicating that the exchange already occurred during the grinding procedure and in the very first minutes of drying. Peak positions undergo a small shift toward low angles (as can be seen in Figure 3a), indicating that the final parting of the LDH layers is reached only after full exchange of nitrate with EUS, but the largest widening is observed at the very beginning of the reaction, when little EUS is intercalated, supporting the mechanism proposed by O’Hare’s group.13 This peak shift is affected by an increase of the zero error, due to the sample volume reduction induced by drying. This problem cannot be avoided in the used Bragg-Brentano flat sample geometry. (To overcome the above-mentioned zero error increase during the XRPD experiment
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and to improve time resolution, in order to explore the early stages of the intercalation, we are planning an in situ synchrotron radiation experiment where the reaction will be carried out in a capillary with a Debye-Scherrer geometry, insensitive to volume reduction from the viewpoint of peak position.) The peak sharpness undergoes a moderate increase during the sample drying, indicating an increase of crystallinity. Finally, only a small amount of unreacted LDH-NO3 phase was observed, while no evidence of unreacted EUS in its neutral or salt crystalline form was found. The area increase of the (001) peak (Figure 3a) was used to estimate the reaction extent R for the LDH-EUS formation. These data were used to derive more information on the kinetics and the mechanism involved in the intercalation process (Figure 3b). The kinetic analysis was carried out using the Avrami-Erofe’ev expression, and the obtained reaction order (n) was about 1.7. As proposed by Thomas et al.,19 such a reaction order suggests that, as expected for layered materials, the intercalation proceeds with an approximately 2D behavior. The estimated value of n = 1.7, barely significantly smaller than n = 2 (ideal 2D reaction), may suggest a slower EUS diffusion into LDH-NO3. The presented results show that the ionic exchange starts instantly after solvent addition. Moreover, exchange occurs mainly in the solid state, since no dissolution of LDH-NO3 is observed. The absence or the presence of very limited amounts of liquids and/or amorphous LDH-EUS is confirmed by the small background observed in the XRPD patterns. The very little amount of solvent has only the function of creating an active LDH-NO3|EUS interface. A small amount of EUS is able to strongly interact with LDH-NO3, as demonstrated by the disappearance of EUS and the strong reduction of LDH-NO3 peaks in the initial steps of the reaction (from t = 0 to 11 min), without the appearance of the equivalent amount of LDH-EUS. Then defective and not completely exchanged LDH-EUS is formed (t = 60 min). Finally, LDH-EUS crystallization proceeds in the first 3 h of reaction and remains stable. Washing can further improve the crystallinity, to obtain a sample identical to the standard one.3 On one hand, the presented results show that new soft and fast methods, such as solvent-assisted grinding or kneading at room temperature (borrowed from the molecular complex world),8 can be exploited also for the preparation of exchanged LDH. The crystallinity and yield in LDH-EUS by solvent-assisted grinding are comparable to those of standard methods (in solution at 60 °C for several days hours),3 but with several advantages: (i) much shorter time needed, (ii) solvent saving, and (iii) on the large scale syntheses, also energy saving because of the milder (room temperature instead of 60°) conditions. On the other hand, important information on the exchange process of nitrate with EUS anions was supplied by the kinetic analysis. The reaction clearly occurs in the solid state, since only 0.5 mL of solvent was used with more than 100 mg of solid mixture. The small amount of solvent needed indicates that EUS is first deprotonated and then interacts with LDH-NO3 to form LDH-EUS.
Milanesio et al. Acknowledgment. MIUR (PRIN-2007 project: “Sviluppo di nanocompositi ibridi “host-guest” per il rilascio modificato di farmaci mediante approcci innovativi di caratterizzazione sperimentale a livello molecolare”) funds are gratefully acknowledged. The authors are grateful to Dr. L. Palin (Universit a del Piemonte Orientale) and Prof. J. Breu (Bayreuth University) for useful discussions. Supporting Information Available: Experimental details and full data of the in situ experiment are available. This material is available free of charge via the Internet at http://pubs.acs.org.
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