Patricia Horcajada

Metal–Organic Frameworks in Biomedicine

Metal Organic Frameworks in Biomedicine Patricia Horcajada,* Ruxandra Gref, Tarek Baati, Phoebe K. Allan, Guillaume Maurin, Patrick Couvreur, G erard F erey, Russell E. Morris, and Christian Serre* Institut Lavoisier, UMR CNRS 8180, Universit e de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France Facult e de Pharmacie, UMR CNRS 8612, Universit e Paris-Sud, 92296 Châtenay-Malabry Cedex, France Institut Charles Gerhardt Montpellier, UMR CNRS 5253, Universit e Montpellier 2, 34095 Montpellier cedex 05, France EaStChem School of Chemistry, University of St. Andrews Purdie Building, St Andrews, KY16 9ST U.K.

Flexible Porous Metal-Organic Frameworks for a Controlled Drug Delivery

Flexible nanoporous chromium or iron terephtalates (BDC) MIL-53(Cr, Fe) or M(OH)[BDC] have been used as matrices for the adsorption and in vitro drug delivery of Ibuprofen (or alpha- p-isobutylphenylpropionic acid). Both MIL-53(Cr) and MIL-53(Fe) solids adsorb around 20 wt % of Ibuprofen (Ibuprofen/dehydrated MIL-53 molar ratio = 0.22(1)), indicating that the amount of inserted drug does not depend on the metal (Cr, Fe) constitutive of the hybrid framework. Structural and spectroscopic characterizations are provided for the solid filled with Ibuprofen. In each case, the very slow and complete delivery of Ibuprofen was achieved under physiological conditions after 3 weeks with a predictable zero-order kinetics, which highlights the unique properties of flexible hybrid solids for adapting their pore opening to optimize the drug-matrix interactions.

BioMOFs: Metal–Organic Frameworks for Biological and Medical Applications

The class of highly porous materials called metal-organic frameworks offer many opportunities for applications across biology and medicine. Their wide range of chemical composition makes toxicologically acceptable formulation possible, and their high level of functionality enables possible applications as imaging agents and as delivery vehicles for therapeutic agents. The challenges in the area encompass not only the development of new solids but also improvements in the formulation and processing of the materials, including tailoring the morphology and surface chemistry of the frameworks to fit the proposed applications.

Synthesis and catalytic properties of MIL-100(Fe), an iron(III) carboxylate with large pores

The large-pore iron(III) carboxylate MIL-100(Fe) with a zeotype architecture has been isolated under hydrothermal conditions, its structure solved from synchrotron X-ray powder diffraction data, while Friedel-Crafts benzylation catalytic tests indicate a high activity and selectivity for MIL-100(Fe).

Functionalization in Flexible Porous Solids: Effects on the Pore Opening and the Host−Guest Interactions

The synthesis on the gram scale and characterization of a series of flexible functionalized iron terephthalate MIL-53(Fe) type solids are reported. Chemical groups of various polarities, hydrophilicities, and acidities (-Cl, -Br, -CF(3), -CH(3), -NH(2), -OH, -CO(2)H) were introduced through the aromatic linker, to systematically modify the pore surface. X-ray powder diffraction (XRPD), molecular simulations, thermogravimetric analyses, and in situ IR and (57)Fe Mössbauer spectrometries indicate some similarities with the pristine MIL-53(Fe) solid, with the adoption of the narrow pore form for all solids in both the hydrated and dry forms. Combined XRPD and computational structure determinations allow concluding that the geometry of the pore opening is predominantly correlated with the intraframework interactions rather than the steric hindrance of the substituent. Only (MIL-53(Fe)-(CF(3))(2)) exhibits a nitrogen accessible porosity (S(BET) approximately 100 m(2) g(-1)). The adsorption of some liquids leads to pore openings showing some very specific behaviors depending on the guest-MIL-53(Fe) framework interactions, which can be related to the energy difference between the narrow and large pore forms evaluated by molecular simulation.

High-Throughput Assisted Rationalization of the Formation of Metal Organic Frameworks in the Iron(III) Aminoterephthalate Solvothermal System

Through the use of high-throughput methods, solvothermal reactions of FeCl 3 and 2-aminoterephthalic acid in protic as well as aprotic reaction media were systematically studied. Thus, the fields of formation of the isoreticular structures of MIL-53, MIL-88, and MIL-101 based on Fe(III) and aminoterephthalate could be identified for the first time. The resulting 3D framework materials with amino-functionalized pores have been characterized using X-ray diffraction; IR spectroscopy; and thermogravimetric, elemental, and energy dispersive X-ray analysis. Due to the applied high-throughput method, a high density of information was obtained in a short period of time, which allows the extraction of important reaction trends and contributes to a better understanding of the role of compositional as well as process parameters in the synthesis of inorganic-organic hybrid materials. We have found that the nature of the reaction medium has the most profound impact on structure formation. Furthermore, the concentration of the starting mixture (i.e., the solvent content) and the temperature have also been identified as key parameters for the formation of the different hybrid phases.

Complex Adsorption of Short Linear Alkanes in the Flexible Metal-Organic-Framework MIL-53(Fe)

This investigation is based on a combination of experimental tools completed by a computational approach to deeply characterize the unusual adsorption behavior of the flexible MIL-53(Fe) in the presence of short linear alkanes. In contrast to the aluminum or chromium analogues we previously reported, the iron MIL-53 solid, which initially exhibits a closed structure in the dry state, shows more complex adsorption isotherms with multisteps occurring at pressures that depend on the nature of the alkane. This behavior has been attributed to the existence of four discrete pore openings during the whole adsorption process. Molecular simulations coupled with in situ X-ray powder diffraction were able to uncover these various structural states.

Biodegradable therapeutic MOFs for the delivery of bioactive molecules

A new metal organic framework (MOF) built up from non-toxic iron and the therapeutically active linker nicotinic acid, with pellagra-curative, vasodilating, and antilipemic properties, has been isolated and characterised via single crystal methods. The release of the therapeutic agent, which is a constituent of the framework, is achieved through the degradation of the hybrid phase, under simulated physiological conditions, allowing for the delivery of the bioactive molecule.

Stable polyoxometalate insertion within the mesoporous metal organic framework MIL-100(Fe)

Successful encapsulation of polyoxometalate (POM) within the framework of a mesoporous iron trimesate MIL-100(Fe) sample has been achieved by direct hydrothermal synthesis in the absence of fluorine. XRPD, 31P MAS NMR, IR, EELS, TEM and 57Fe Mossbauer spectrometry corroborate the insertion of POM within the cavities of the MOF. The experimental Mo/Fe ratio is 0.95, in agreement with the maximum theoretical amount of POM loaded within the pores of MIL-100(Fe), based on steric hindrance considerations. The POM-MIL-100(Fe) sample exhibits a pore volume of 0.373 cm3 g−1 and a BET surface area close to 1000 m2 g−1, indicating that small gas molecules can easily diffuse inside the cavities despite the presence of heavy phosphomolybdates. These latter contribute to the decrease in the overall surface area, due to the increase in molar weight, by 65%. Moreover, the resulting Keggin containing MIL-100(Fe) solid is stable in aqueous solution with no POM leaching even after more than 2 months. In addition, no exchange of the Keggin anions by tetrabutylammonium perchlorate in organic media has been observed.

Selective Removal of N‐Heterocyclic Aromatic Contaminants from Fuels by Lewis Acidic Metal–Organic Frameworks

Fossil fuels, such as diesel or gasoline, are blends of aromatic and aliphatic compounds that contain significant levels of heterocyclic aromatic contaminants. These contaminants have to be removed for environmental reasons. One of the most important issues is the presence of sulfur compounds, such as thiophene (TPH), benzothiophene (BT), and dibenzothiophene (DBT) in fuel feeds, which lead to the formation of SOx exhaust gases and eventually to acid rain. As environmental legislation becomes more stringent on SOx exhaust levels, it is imperative to keep lowering the sulfur concentrations to currently 10 ppmw S (parts per million by weight of sulfur) or less. The main industrial process is hydrodesulfurization (HDS) in which sulfur compounds are hydrogenated to hydrocarbons and H2S over typically a CoMo catalyst. However, nitrogen compounds, such as (substituted) indoles and carbazoles, which are also present in fossil fuels, compete for the active sites on these HDS catalysts, preventing a deep HDS. In the absence of nitrogen compounds, deep HDS can easily produce fuels with sulfur levels well below 10 ppmw, for instance by using the newest generations of materials based on Mo-W-Ni, which can lower sulfur levels to 5 ppmw. As the eventual aim is to have sulfur-free fuel, even these low concentrations will have to be removed. A promising way to selectively remove nitrogen contaminants would be adsorption on a microporous material. Efficient purification can be performed by adsorption as long as the interaction between the adsorbate and the adsorbent is relatively strong. A CuY zeolite has been described as a potential adsorbent for the removal of nitrogen compounds by p complexation, but the maximal capacity at saturation only amounted to 3 mg N per gram of adsorbent, and moreover sulfur compounds are adsorbed as well. An ideal adsorbent for such application should be easy to synthesize, stable in the given feed compositions, possess pores that are large enough to accommodate bulky organic molecules, such as carbazoles, have a sufficient capacity, and be highly selective for nitrogen over sulfur compounds. Metal–organic frameworks (MOFs) are an emerging class of highly porous materials, formed of inorganic subunits and organic linkers that bear multiple complexing functions (for example, carboxylates, phosphonates, and others), which enables a unique variety of potential interactions inside the pores. To date, they have been successfully used as adsorbents for the capture of greenhouse gases, such as CO2 and CH4, and in liquid-phase separations such as those of alkylaromatics and styrene, olefins and paraffins, and for fuel and water purification by adsorption of organic pollutants. Herein, we propose the use of mesoporous metal carboxylates with different topologies and compositions for the selective adsorption of nitrogen contaminants. These heterocyclic contaminants are found in fuel feeds that are typically aliphatic with a minor aromatic fraction. This system is simulated herein by using a solvent composed of heptane/toluene in a volumetric ratio of 80:20 (labeled hereafter as H/T). Specifically, the adsorptive removal of indole (IND), 2-methylindole (2MI), 1,2-dimethylindole (1,2DMI), carbazole (CBZ), and N-methylcarbazole (NMC) as well as of TPH, BT, and DBT has been studied. These molecules are the most important heterocyclic contaminants in fuel feeds. To study the influence of the toluenecontaining solvent on the adsorption and on the interaction strength between the host and the adsorbate, the adsorption of the contaminants has also been studied using a toluene/ [*] M. Maes, S. Schouteden, F. Vermoortele, Dr. L. Alaerts, Prof. Dr. D. E. De Vos Centre for Surface Chemistry and Catalysis Katholieke Universiteit Leuven Kasteelpark Arenberg 23, 3001 Leuven (Belgium) Fax: (+ 32)16-321-998 E-mail: dirk.devos@biw.kuleuven.be