Nanoscaled Zinc Pyrazolate Metal–Organic Frameworks as Drug-Delivery Systems

This work describes synthesis at the nanoscale of the isoreticular metal–organic framework (MOF) series ZnBDP_X, based on the assembly of Zn^II metal ions and the functionalized organic spacers 1,4-bis­(1<i>H</i>-pyrazol-4-yl)-2-X-benzene (H₂BDP_X; X = H, NO₂, NH₂, OH). The colloidal stability of these systems was evaluated under different relevant intravenous and oral-simulated physiological conditions, showing that ZnBDP_OH nanoparticles exhibit good structural and colloidal stability probably because of the formation of a protein corona on their surface that prevents their aggregation. Furthermore, two antitumor drugs (mitroxantrone and [Ru­(<i>p</i>-cymene)­Cl₂(pta)] (RAPTA-C) where pta = 1,3,5-triaza-7-phospaadamantane) were encapsulated within the pores of the ZnBDP_X series in order to investigate the effect of the framework functionalization on the incorporation/delivery of bioactive molecules. Thus, the loading capacity of both drugs within the ZnBDP_X series seems to directly depend on the surface area of the solids. Moreover, ligand functionalization significantly affects both the delivery kinetics and the total amount of released drug. In particular, ZnBDP_OH and ZnBDP_NH₂ matrixes show a slower rate of delivery and higher percentage of release than ZnBDP_NO₂ and ZnBDP_H systems. Additionally, RAPTA-C delivery from ZnBDP_OH is accompanied by a concomitant and progressive matrix degradation due to the higher polarity of the BPD_OH ligand, highlighting the impact of functionalization of the MOF cavities over the kinetics of delivery

Rationale of Drug Encapsulation and Release from Biocompatible Porous Metal–Organic Frameworks

A joint experimental and computational systematic exploration of the driving forces that govern (i) encapsulation of active ingredients (solvent, starting material dehydration, drug/material ratio, immersion time, and several consecutive impregnations) and (i) its kinetics of delivery (structure, polarity, ...) was performed using a series of porous biocompatible metal–organic frameworks (MOFs) that bear different topologies, connectivities, and chemical compositions. The liporeductor cosmetic caffeine was selected as the active molecule. Its encapsulation is a challenge for the cosmetic industry due to its high tendency to crystallize leading to poor loadings (<5 wt %) and uncontrolled releases with a subsequent low efficiency. It was evidenced that caffeine entrapping reaches exceptional payloads up to 50 wt %, while progressive release of this cosmetic agent upon immersion in the simulated physiological media (phosphate buffer solution pH = 7.4 or distilled water pH = 6.3, 37 °C) occurred mainly depending on the degree of MOF stability, caffeine mobility, and MOF–caffeine interactions. Thus, MIL-100 and UiO-66 appear as very promising carriers for topical administration of caffeine with both spectacular cosmetic payloads and progressive releases within 24 h

Comparison of Porous Iron Trimesates Basolite F300 and MIL-100(Fe) As Heterogeneous Catalysts for Lewis Acid and Oxidation Reactions: Roles of Structural Defects and Stability

Two porous iron trimesates, namely, commercial Basolite F300 (Fe­(BTC); BTC = 1,3,5-benzenetricarboxylate) with unknown structure and synthetic MIL-100­(Fe) (MIL stands for Material of Institut Lavoisier) of well-defined crystalline structure, have been compared as heterogeneous catalysts for four different reactions. It was found that while for catalytic processes requiring strong Lewis acid sites, Fe­(BTC) performs better, MIL-100­(Fe) is the preferred catalyst for oxidation reactions. These catalytic results have been rationalized by a combined in situ infrared and ⁵⁷Fe Mössbauer spectroscopic characterization. It is proposed that the presence of extra Brønsted acid sites on the Fe­(BTC) and the easier redox behavior of the MIL-100­(Fe) could explain these comparative catalytic performances. The results illustrate the importance of structural defects (presence of weak Brønsted acid sites) and structural stability (MIL-100­(Fe) is stable upon annealing at 280 °C despite Fe³⁺-to-Fe²⁺ reduction) on the catalytic activity of these two solids, depending on the reaction type

Structure and Dynamics of the Functionalized MOF Type UiO-66(Zr): NMR and Dielectric Relaxation Spectroscopies Coupled with DFT Calculations

Advanced one- and two-dimensional high-field and ultrafast MAS NMR measurements have been conducted in tandem with DFT calculations for the NMR parameters to deeply characterize the local environment and the long-range structure order of the porous metal–organic framework (MOF) type UiO-66­(Zr) (UiO for University of Oslo) functionalized by a series of polar −Br, −2OH, and −NH₂ groups. Such an innovative combining approach applied to the complex architecture of MOFs has been revealed successful not only to unambiguously assign all the NMR signals to the corresponding crystallographic sites but also to validate the crystal structures for each functionalized material that were only predicted so far. A further step consisted of probing the impact of the grafted functions on the ligand dynamics of these MOFs by means of dielectric relaxation spectroscopy measurements. It has been evidenced that the rotational motion of the organic linker requires overpassing an energy barrier that strongly depends on the functional groups, the −NH₂ functionalized version implying the highest activation energy. Such a finding was further explained by the relatively strong intraframework interactions which take place between the grafted function and the inorganic node as suggested by the analysis of the corresponding simulated crystal structure

In Situ Energy-Dispersive X‑ray Diffraction for the Synthesis Optimization and Scale-up of the Porous Zirconium Terephthalate UiO-66

The synthesis optimization and scale-up of the benchmarked microporous zirconium terephthalate UiO-66­(Zr) were investigated by evaluating the impact of several parameters (zirconium precursors, acidic conditions, addition of water, and temperature) over the kinetics of crystallization by time-resolved in situ energy-dispersive X-ray diffraction. Both the addition of hydrochloric acid and water were found to speed up the reaction. The use of the less acidic ZrOCl₂·8H₂O as the precursor seemed to be a suitable alternative to ZrCl₄·<i>x</i>H₂O, avoiding possible reproducibility issues as a consequence of the high hygroscopic character of ZrCl₄. ZrOCl₂·8H₂O allowed the formation of smaller good quality UiO-66­(Zr) submicronic particles, paving the way for their use within the nanotechnology domain, in addition to higher reaction yields, which makes this synthesis route suitable for the preparation of UiO-66­(Zr) at a larger scale. In a final step, UiO-66­(Zr) was prepared using conventional reflux conditions at the 0.5 kg scale, leading to a rather high space-time yield of 490 kg m^–3 day^–1, while keeping physicochemical properties similar to those obtained from smaller scale solvothermally prepared batches

Impact of the Flexible Character of MIL-88 Iron(III) Dicarboxylates on the Adsorption of <i>n</i>‑Alkanes

Adsorption of <i>n</i>-alkane vapors was performed to probe the unusual highly flexible character of a series of iron­(III) dicarboxylate materials of the MIL-88 structure type. In agreement with the presence of strong intraframework interactions within the dried closed pores form of MIL-88, it appears first that an increase of the size and aromaticity of the spacer makes it more difficult to adsorb alkanes at room temperature. Thus, this led to a high level of adsorption in the iron fumarate MIL-88A and poor levels in the terephthalate and naphthalenedicarboxylate based MIL-88­(B and C, respectively). Second, upon increase in the length of the alkane, diffusion limitations of the guest occur within the very narrow pores, also illustrated through kinetics of adsorption measurements, which result in an overall decrease in the adsorption capacity. Noteworthy, the swelling of the flexible non modified MIL-88 solids occurs only for the MIL-88A sample, because of the number and orientation of aromatic rings that are arranged in trimers within the MIL-88 structures and, therefore, making those more difficult to open than those where the rings are arranged in dimers such as the metal terephthalate MIL-53 structures. Interestingly, modification of the organic linkers by grafting several bulky functional groups (2CF₃, 4CH₃) makes the adsorption of <i>n-</i>alkanes easier because of a strong decrease in interactions within these trimers associated with a lower pore contraction upon drying, while the substitution of a hydrogen atom by a bromine one on the spacer proved to be not sufficient for an improvement of the adsorbed amounts

Caffeine Confinement into a Series of Functionalized Porous Zirconium MOFs: A Joint Experimental/Modeling Exploration

A multitechnique approach was conducted to investigate the confinement of caffeine in a series of UiO-66­(Zr)-type MOFs, functionalized with −H, −NH₂, −Br, and −2OH groups. DFT calculations were first undertaken to elucidate the preferential geometries of the drug within the pores and the resulting drug/host framework interactions. It was shown that the caffeine molecules are preferentially located in the smaller cages, giving rise to only weak interactions with the function groups grafted on the organic linker. These host/guest interactions were concomitantly probed by advanced 1D and 2D high-field/ultrafast MAS NMR and FTIR spectroscopies, which allowed us to not only validate the DFT predictions but also to bring complementary insight into the nature of the interacting sites of both the caffeine and the MOFs. Dielectric relaxation measurements further revealed significant modifications of the ligand dynamics upon the drug encapsulation for all UiO-66­(Zr) solids. It was demonstrated that the perturbation of the ligand flip strongly depends on the nature of the grafted function. While the dynamics of the ligand is slightly enhanced in the case of the −NH₂ form, it is significantly slower for the −Br analogue. Such specific behaviors were then interpreted in light of the conclusions drawn from the DFT calculations and NMR observations

Toward Understanding the Influence of Ethylbenzene in <i>p</i>-Xylene Selectivity of the Porous Titanium Amino Terephthalate MIL-125(Ti): Adsorption Equilibrium and Separation of Xylene Isomers

The potential of the porous crystalline titanium dicarboxylate MIL-125­(Ti) in powder form was studied for the separation in liquid phase of xylene isomers and ethylbenzene (MIL stands for Materials from Institut Lavoisier). We report here a detailed experimental study consisting of binary and multi-component adsorption equilibrium of xylene isomers in MIL-125­(Ti) powder at low (≤0.8 M) and bulk (≥0.8 M) concentrations. A series of multi-component breakthrough experiments was first performed using <i>n</i>-heptane as the eluent at 313 K, and the obtained selectivities were compared, followed by binary breakthrough experiments to determine the adsorption isotherms at 313 K, using <i>n</i>-heptane as the eluent. MIL-125­(Ti) is a <i>para</i>-selective material suitable at low concentrations to separate <i>p</i>-xylene from the other xylene isomers. Pulse experiments indicate a separation factor of 1.3 for <i>p</i>-xylene over <i>o</i>-xylene and <i>m</i>-xylene, while breakthrough experiments using a diluted ternary mixture lead to selectivity values of 1.5 and 1.6 for <i>p</i>-xylene over <i>m</i>-xylene and <i>o</i>-xylene, respectively. Introduction of ethylbenzene in the mixture results however in a decrease of the selectivity

Metal–Organic Frameworks as Efficient Oral Detoxifying Agents

Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal–organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time. Orally administered upon a salicylate overdose, this MOF is able to reduce the salicylate gastrointestinal absorption and toxicity more than 40-fold (avoiding histological damage) while exhibiting exceptional gastrointestinal stability (<9% degradation), poor intestinal permeation, and safety

How Interpenetration Ensures Rigidity and Permanent Porosity in a Highly Flexible Hybrid Solid

The synthesis and the crystal structure determination, using a synchrotron microdiffraction setup, of the interwoven analogue of the highly flexible iron­(III) dicarboxylate MIL-88D structure are reported. Unlike its flexible counterpart, MIL-126, or Fe^III₃O­(H₂O)₂(OH)­[(O₂C)-C₁₂H₈-(CO₂)]₃·<i>n</i>(solv), exhibits a rigid structure with an accessible three dimensional (3D) pore system resulting in a Brunauer–Emmett–Teller (BET) surface area over 1700 m²·g^–1. Moreover, a large amount of coordinatively unsaturated Fe sites of +2 and +3 oxidation states are accessible to NO and acetonitrile molecules as shown by infrared spectroscopy. MIL-126 might be thus used for the removal of aromatic N-heterocyclic compounds from fossil fuel streams, as shown here in the efficient capture of indole from model benzothiophene/indole mixtures in heptane/toluene