Luminescent Ln3+-based silsesquioxanes with a ß-diketonate antenna ligand: toward the design of efficient temperature sensors.

We report the synthesis and single-crystal X-ray diffraction, magnetic, and luminescence measurements of a novel family of luminescent cage-like tetranuclear silsesquioxanes (PhSiO1.5)8(LnO1.5)4(O)(C5H8O2)6(EtOH)2(CH3CN)2⋅2CH3CN (where Ln = Tb, 1; Tb/Eu, 2; and Gd, 3), featuring seven-coordinated lanthanide ions arranged in a one-capped trigonal prism geometry. Compounds 1 and 2 exhibit characteristic Tb3+ and Tb3+/Eu3+-related emissions, respectively, sensitized by the chelating antenna acetylacetonate (acac) ligands upon excitation in the UV and visible spectral regions. Compound 3 is used to assess the energies of the triplet states of the acac ligand. For compound 1, theoretical calculations on the intramolecular energy transfer and multiphonon rates indicate a thermal balance between the 5D4 Stark components, while the mixed Tb3+/Eu3+ analog 2, with a Tb:Eu ratio of 3:1, showcases intra-cluster Tb3+-to-Eu3+ energy transfer, calculated theoretically as a function of temperature. By utilizing the intensity ratio between the 5D4→7F5 (Tb3+) and 5D0→7F2 (Eu3+) transitions in the range 11-373 K, we demonstrate the realization of a ratiometric luminescent thermometer with compound 2, operating in the range 11-373 K with a maximum relative sensitivity of 2.0% K-1 at 373 K. These findings highlight the potential of cage-like silsesquioxanes as versatile materials for optical sensing-enabled applications.

Luminescent Er3+ based single molecule magnets with fluorinated alkoxide or aryloxide ligands.

We report the synthesis, structures, and magnetic and luminescence properties of a series of new mono- and dinuclear Er3+ complexes derived from sterically demanding aryloxide and fluorinated alkoxide ligands: [4-tBu-2,6-(Ph2CH)2C6H2O]3Er(THF) (1), [(C6F5)3CO]3Er(Me3SiOH) (2), [(C6F5)3CO]3Er[(Me3Si)2NH] (3), [(C6F5)3CO]3Er(C6H5CH3) (4), [(C6F5)3CO]3Er(o-Me2NC6H4CH3) (5) and {[Ph(CF3)2CO]2Er(µ2-OC(CF3)2Ph)}2 (6). In compounds 1, 2, and 4, the Er3+ ion is four-coordinated and adopts a distorted trigonal pyramidal geometry, while in 3, 5, and 6, the coordination geometry of Er3+ is impacted by the presence of several relatively short Er⋯F distances, making them rather 6-coordinated. All compounds behave as field-induced Single Molecule Magnets (SMMs) and exhibit an Er3+ characteristic near infrared (NIR) emission associated with the 4I13/2 → 4I15/2 transition with a remarkably long lifetime going up to 73 µs, which makes them multifunctional luminescent SMMs. The deconvolution of the NIR emission spectra allowed us to provide a direct probe of the crystal field splitting in these compounds, which was correlated with magnetic data.

Tetranuclear lanthanide-based silsesquioxanes: towards a combination of a slow relaxation of the magnetization and a luminescent thermometry.

Lanthanide-based silsesquioxanes constitute an emerging family of cage-like metallasilsesquioxanes with exciting optical and magnetic properties. We report here the synthesis, structures and luminescence properties of a series of tetranuclear lanthanide-silsesquioxane compounds of general formula [NEt4]2[(Ph4Si4O8)2(Ln/Ln')4(NO3)6(EtOH)2(MeCN)2]·4(MeCN) with different lanthanide ions (where Ln/Ln' = Dy3+/Eu3+ (1), Dy3+/Tb3+ (2) and Eu3+/Tb3+/Y3+ (3)) and investigate the impact of the lanthanide ions combination on magnetic and photo-luminescent properties. Compound 1 behaves as a field-induced Single Molecule Magnet (SMM) and presents temperature-dependent luminescence characteristics of Eu3+ making it an emissive thermometer working in the temperature range 293-373 K with the maximum relative sensitivity of 1.15% K-1 achieved at 293 K. Compounds 2 and 3 are paramagnets, which demonstrate a characteristic photoluminescence with Dy3+ to Tb3+ and Tb3+ to Eu3+ energy transfers, respectively.

Hybrid multifunctionalized mesostructured stellate silica nanoparticles loaded with ß-diketonate Tb3+/Eu3+ complexes as efficient ratiometric emissive thermometers working in water.

Despite the great effort made in recent years on lanthanide-based ratiometric luminescent nanothermometers able to provide temperature measurements in water, their design remains challenging. We report on the synthesis and properties of efficient ratiometric nanothermometers that are based on mesoporous stellate nanoparticles (MSN) of ca. 90 nm functionalized with an acetylacetonate (acac) derivative inside the pores and loaded with ß-diketonate-Tb3+/Eu3+ complexes able to work in water, in PBS or in cells. Encapsulating a [(Tb/Eu)9(acac)16(µ3-OH)8(µ4-O)(µ4-OH)] complex (Tb/Eu ratio = 19/1 and 9/1) led to hybrid multifunctionalized nanoparticles exhibiting a Tb3+ and Eu3+ characteristic temperature-dependent luminescence with a high rate Tb3+-to-Eu3+ energy transfer. According to theoretical calculations, the modifications of photoluminescence properties and the increase in the pairwise Tb3+-to-Eu3+ energy transfer rate by about 10 times can be rationalized as a change of the coordination number of the Ln3+ sites of the complex from 7 to 8 accompanied by a symmetry evolution from Cs to C4v and a slight shortening of intramolecular Ln3+-Ln3+ distances upon the effect of encapsulation. These nanothermometers operate in the 20-70 °C range with excellent photothermal stability, cyclability and repeatability (>95%), displaying a maximum relative thermal sensitivity of 1.4% °C-1 (at 42.7 °C) in water. Furthermore, they can operate in cells with a thermal sensitivity of 8.6% °C-1 (at 40 °C), keeping in mind that adjusting the calibration for each system is necessary to ensure accurate measurements.

Hierarchical superparamagnetic metal-organic framework nanovectors as anti-inflammatory nanomedicines.

Among a plethora of drug nanocarriers, biocompatible nanoscale metal-organic frameworks (nanoMOFs) with a large surface area and an amphiphilic internal microenvironment have emerged as promising drug delivery platforms, mainly for cancer therapy. However, their application in biomedicine still suffers from shortcomings such as a limited chemical and/or colloidal stability and/or toxicity. Here, we report the design of a hierarchically porous nano-object (denoted as USPIO@MIL) combining a benchmark nanoMOF (that is, MIL-100(Fe)) and ultra-small superparamagnetic iron oxide (USPIO) nanoparticles (that is, maghemite) that is synthesized through a one-pot, cost-effective and environmentally friendly protocol. The synergistic coupling of the physico-chemical and functional properties of both nanoparticles confers to these nano-objects valuable features such as high colloidal stability, high biodegradability, low toxicity, high drug loading capacity as well as stimuli-responsive drug release and superparamagnetic properties. This bimodal MIL-100(Fe)/maghemite nanocarrier once loaded with anti-tumoral and anti-inflammatory drugs (doxorubicin and methotrexate) shows high anti-inflammatory and anti-tumoral activities. In addition, the USPIO@MIL nano-object exhibits excellent relaxometric properties and its applicability as an efficient contrast agent for magnetic resonance imaging is herein demonstrated. This highlights the high potential of the maghemite@MOF composite integrating the functions of imaging and therapy as a theranostic anti-inflammatory formulation.

Cascade strategy for triggered radical release by magnetic nanoparticles grafted with thermosensitive alkoxyamine.

The design of smart nanoplatforms presenting well-definite structures able to achieve controlled cascade action remotely triggered by external stimuli presents a great challenge. We report here a new nanosystem consisting of magnetic iron oxide nanoparticles covalently grafted with a thermosensitive radical initiator alkoxyamine, able to provide controlled and localized release of free radicals triggered by an alternating current (ac) magnetic field. These nanoparticles exhibit a high intrinsic loss power of 4.73 nHm2 kg-1 providing rapid heating of their surface under the action of an ac field, inducing the homolysis of alkoxyamine C-ON bond and then the oxygen-independent formation of radicals. This latter was demonstrated by electronic paramagnetic resonance spectroscopy, and the kinetics of homolysis has been investigated allowing a comparison of the temperature of alkoxyamine's homolysis with the one measured during the magnetothermia process.

Magneto-Induced Hyperthermia and Temperature Detection in Single Iron Oxide Core-Silica/Tb3+/Eu3+(Acac) Shell Nano-Objects.

Multifunctional nano-objects containing a magnetic heater and a temperature emissive sensor in the same nanoparticle have recently emerged as promising tools towards personalized nanomedicine permitting hyperthermia-assisted treatment under local temperature control. However, a fine control of nano-systems' morphology permitting the synthesis of a single magnetic core with controlled position of the sensor presents a main challenge. We report here the design of new iron oxide core-silica shell nano-objects containing luminescent Tb3+/Eu3+-(acetylacetonate) moieties covalently anchored to the silica surface, which act as a promising heater/thermometer system. They present a single magnetic core and a controlled thickness of the silica shell, permitting a uniform spatial distribution of the emissive nanothermometer relative to the heat source. These nanoparticles exhibit the Tb3+ and Eu3+ characteristic emissions and suitable magnetic properties that make them efficient as a nanoheater with a Ln3+-based emissive self-referencing temperature sensor covalently coupled to it. Heating capacity under an alternating current magnetic field was demonstrated by thermal imaging. This system offers a new strategy permitting a rapid heating of a solution under an applied magnetic field and a local self-referencing temperature sensing with excellent thermal sensitivity (1.64%·K-1 (at 40 °C)) in the range 25-70 °C, good photostability, and reproducibility after several heating cycles.

Multifunctionalized Mesostructured Silica Nanoparticles Containing Mn2 Complex for Improved Catalase-Mimicking Activity in Water.

We report the synthesis of a hybrid nanocatalyst obtained through the immobilization of bio-inspired [{Mn(bpy)(H2O)}(µ-2-MeC6H4COO)2(µ-O){Mn(bpy)(NO3)}]NO3 compound into functionalized, monodispersed, mesoporous silica nanoparticles. The in situ dual functionalization sol-gel strategy adopted here leads to the synthesis of raspberry-shaped silica nanoparticles of ca. 72 nm with a large open porosity with preferential localization of 1,4-pyridine within the pores and sulfobetaine zwitterion on the nanoparticles' periphery. These nano-objects exhibit improved catalase-mimicking activity in water thanks to the encapsulation/immobilization of the catalytic active complex and high colloidal stability in water, as demonstrated through the dismutation reaction of hydrogen peroxide.

A rational study of the influence of Mn2+-insertion in Prussian blue nanoparticles on their photothermal properties.

We investigated a series of Mn2+-Prussian blue (PB) nanoparticles NazMnxFe1-x[Fe(CN)6]1-y□y·nH2O of similar size, surface state and cubic morphology with various amounts of Mn2+ synthesized through a one step self-assembly reaction. We demonstrated by a combined experimental-theoretical approach that during the synthesis, Mn2+ substituted Fe3+ up to a Mn/Na-Mn-Fe ratio of 32 at% in the PB structure, while for higher amounts, the Mn2[Fe(CN)6] analogue is obtained. For comparison, the post-synthetic insertion of Mn2+ in PB nanoparticles was also investigated and completed with Monte-Carlo simulations to probe the plausible adsorption sites. The photothermal conversion efficiency (η) of selected samples was determined and showed a clear dependence on the Mn2+amount with a maximum efficiency for a Mn/Na-Mn-Fe ratio of 10 at% associated with a dependence on the nanoparticle concentration. Evaluation of the in vitro photothermal properties of these nanoparticles performed on triple negative human breast adenocarcinoma (MDA-MB-231) cells by using continuous and pulsed laser irradiation confirm their excellent PTT efficiency permitting low dose use.

Long-term in vivo performances of polylactide/iron oxide nanoparticles core-shell fibrous nanocomposites as MRI-visible magneto-scaffolds.

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and superparamagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPION suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPION nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPION nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Temperature sensing in Tb3+/Eu3+-based tetranuclear silsesquioxane cages with tunable emission.

New luminescent cage-like tetranuclear silsesquioxanes [NEt4][(Ph4Si4O8)2(Tb3Eu)(NO3)4(OH)(EtOH)3(H2O)]·4(EtOH) (1) and [NEt4]2[(Ph4Si4O8)2(Tb2Eu2)(NO3)6(EtOH)2(MeCN)2]·4(MeCN) (2) present a tunable thermosensitive Tb3+-to-Eu3+ energy transfer driven by Tb3+ and Eu3+ emission and may be used as temperature sensors operating in the range 41-100 °C with excellent linearity (R 2 = 0.9990) and repeatability (>95%). The thermometer performance was evidenced by the maximum relative sensitivity of 0.63% °C-1 achieved at 68 °C.

Unveiling the Structure and Reactivity of Fatty-Acid Based (Nano)materials Thanks to Efficient and Scalable 17O and 18O-Isotopic Labeling Schemes.

Fatty acids are ubiquitous in biological systems and widely used in materials science, including for the formulation of drugs and the surface-functionalization of nanoparticles. However, important questions regarding the structure and reactivity of these molecules are still to be elucidated, including their mode of binding to certain metal cations or materials surfaces. In this context, we have developed novel, efficient, user-friendly, and cost-effective synthetic protocols based on ball-milling, for the 17O and 18O isotopic labeling of two key fatty acids which are widely used in (nano)materials science, namely stearic and oleic acid. Labeled molecules were analyzed by 1H and 13C solution NMR, IR spectroscopy, and mass spectrometry (ESI-TOF and LC-MS), as well as 17O solid state NMR (for the 17O labeled species). In both cases, the labeling procedures were scaled-up to produce up to gram quantities of 17O- or 18O-enriched molecules in just half-a-day, with very good synthetic yields (all ≥84%) and enrichment levels (up to an average of 46% per carboxylic oxygen). The 17O-labeled oleic acid was then used for the synthesis of a metal soap (Zn-oleate) and the surface-functionalization of ZnO nanoparticles (NPs), which were characterized for the first time by high-resolution 17O NMR (at 14.1 and 35.2 T). This allowed very detailed insight into (i) the coordination mode of the oleate ligand in Zn-oleate to be achieved (including information on Zn···O distances) and (ii) the mode of attachment of oleic-acid at the surface of ZnO (including novel information on its photoreactivity upon UV-irradiation). Overall, this work demonstrates the high interest of these fatty acid-enrichment protocols for understanding the structure and reactivity of a variety of functional (nano)materials systems using high resolution analyses like 17O NMR.

Formation of a Single-Crystal Aluminum-Based MOF Nanowire with Graphene Oxide Nanoscrolls as Structure-Directing Agents.

An innovative strategy is proposed to synthesize single-crystal nanowires (NWs) of the Al3+ dicarboxylate MIL-69(Al) MOF by using graphene oxide nanoscrolls as structure-directing agents. MIL-69(Al) NWs with an average diameter of 70±20 nm and lengths up to 2 µm were found to preferentially grow along the [001] crystallographic direction. Advanced characterization methods (electron diffraction, TEM, STEM-HAADF, SEM, XPS) and molecular modeling revealed the mechanism of formation of MIL-69(Al) NWs involving size-confinement and templating effects. The formation of MIL-69(Al) seeds and the self-scroll of GO sheets followed by the anisotropic growth of MIL-69(Al) crystals are mediated by specific GO sheets/MOF interactions. This study delivers an unprecedented approach to control the design of 1D MOF nanostructures and superstructures.

Synergic effect of doxorubicin release and two-photon irradiation of Mn2+-doped Prussian blue nanoparticles on cancer therapy.

We demonstrate here that Mn2+-doped Prussian blue nanoparticles of ca. 55 nm loaded with doxorubicin may be used as efficient therapeutic agents for combined photothermal and chemo-therapy of cancer cells with a synergic effect under two photon irradiation.

Cellular Uptake, Intracellular Trafficking, and Stability of Biocompatible Metal-Organic Framework (MOF) Particles in Kupffer Cells.

Rapid intracellular degradation of current drug-delivery nanocarriers presents a challenge for achieving ideal controlled drug-release kinetics. Recent in vivo studies have shown that porous hybrid metal-organic frameworks (MOFs), belonging to the Materials of Institute Lavoisier (MIL) family, display prolonged biodegradation behavior. In this study, we investigated stability of these materials in Kupffer cells, a relevant target for the treatment of several life-threatening immune-mediated liver diseases. For this aim, we selected fluorescently labeled microporous MOF particles of MIL88A and MIL88B-NH2, built from trimers of Fe(III) octahedra, as an inorganic component, and fumarate (MIL88A) or 2-amino terephthalate (MIL88B-NH2), as an organic linker. Cell uptake inhibition analysis of MOF particles by a Kupffer cell line (KUP5) has shown that phagocytosis is the major endocytic pathway involved in MIL88B-NH2 internalization. Investigation of MOF interaction with KUP5 cells by real-time microscopy indicated that the structure of MIL88B-NH2 MOFs stays intact up to 15 min after uptake, followed by MOF accumulation in acidic cell compartments and slow degradation, reaching a minimum of 10-15% decomposition over 24 h. MIL88A particles demonstrated similar degradation kinetics. Analysis of the mechanisms of MOF degradation has shown that inhibition of phagosome acidification as well as protease activity does not prevent decomposition of MIL88B-NH2 particles. Thus, our study demonstrates the relative stability of the MOF structure in the phagolysosomal environment of Kupffer cells, revealing potential use of these materials for controlled drug delivery in a case of immune-mediated liver diseases.

Metal Organic Framework (MOF) Particles as Potential Bacteria-Mimicking Delivery Systems for Infectious Diseases: Characterization and Cellular Internalization in Alveolar Macrophages.

PURPOSE: Intramacrophagic bacteria pose a great challenge for the treatment of infectious diseases despite many macrophage targeted drug delivery approaches explored. The use of biomimetic approaches for treating infectious diseases is promising, but not studied extensively. The study purpose is to evaluate iron-based metal-organic frameworks (MOF) as a potential bacteria-mimicking delivery system for infectious diseases. METHODS: Two types of carboxylated MOFs, MIL-88A(Fe) and MIL-100(Fe) were developed as "pathogen-like" particles by surface coating with mannose. MOF morphology, cellular uptake kinetics, and endocytic mechanisms in 3D4/21 alveolar macrophages were characterized. RESULTS: MIL-88A(Fe) is rod-shape (aspect ratio 1:5) with a long-axis size of 3628 ± 573 nm and MIL-100(Fe) is spherical with diameter of 103.9 ± 7.2 nm. Cellular uptake kinetics of MOFs showed that MIL-100(Fe) nanoparticles were internalized at a faster rate and higher extent compared to MIL-88A(Fe) microparticles. Mannosylation did not improve the uptake of MIL-100(Fe) particles, whereas it highly increased MIL-88A(Fe) cellular uptake and number of cells involved in internalization. Cell uptake inhibition studies indicated that macropinocytosis/phagocytosis was the main endocytic pathway for internalization of MOFs. Accumulation of MOF particles in acidic compartments was clearly observed. CONCLUSIONS: The successfully synthesized "pathogen-like" particles provide a novel application of MOF-based particles as biomimetic delivery system for intramacrophagic-based infections.

Design of Laccase-Metal Organic Framework-Based Bioelectrodes for Biocatalytic Oxygen Reduction Reaction.

Laccase in combination with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a mediator is a well-known bioelectrocatalyst for the 4-electron oxygen reduction reactions (ORR). The present work deals with the first exploitation of mesoporous iron(III) trimesate-based metal organic frameworks (MOF) MIL-100(Fe) (MIL stands for materials from Institut Lavoisier) as a new and efficient immobilization matrix of laccase for the building up of biocathodes for ORR. First, the immobilization of ABTS in the pores of the MOF was studied by combining micro-Raman spectroscopy, X-ray powder diffraction (XRPD), and N2 porosimetry. The ABTS-MIL-100(Fe)-based modified electrode presents excellent properties in terms of charge transfer kinetics and ionic conductivity as well as a very stable and reproducible electrochemical response, showing that MIL-100(Fe) provides a suitable and stabilizing microenvironment for electroactive ABTS molecules. In a second step, laccase was further immobilized on the MIL-100(Fe)-ABTS matrix. The Lac-ABTS-MIL-100(Fe)-CIE bioelectrode presents a high electrocatalytic current density of oxygen reduction and a reproducible electrochemical response characterized by a high stability over a long period of time (3 weeks). These results constitute a significant advance in the field of laccase-based bioelectrocatalysts for ORR. According to our work, it appears that the high catalytic efficiency of Lac-ABTS-MIL-100(Fe) for ORR may result from a synergy of chemical and catalytic properties of MIL-100(Fe) and laccase.

Adsorption of benzoxaboroles on hydroxyapatite phases.

UNLABELLED: Benzoxaboroles are a family of molecules that are finding an increasing number of applications in the biomedical field, particularly as a "privileged scaffold" for the design of new drugs. Here, for the first time, we determine the interaction of these molecules with hydroxyapatites, in view of establishing (i) how benzoxaborole drugs may adsorb onto biological apatites, as this could impact on their bioavailability, and (ii) how apatite-based materials can be used for their formulation. Studies on the adsorption of the benzoxaborole motif (C7H7BO2, referred to as BBzx) on two different apatite phases were thus performed, using a ceramic hydroxyapatite (HAceram) and a nanocrystalline hydroxyapatite (HAnano), the latter having a structure and composition more similar to the one found in bone mineral. In both cases, the grafting kinetics and mechanism were studied, and demonstration of the surface attachment of the benzoxaborole under the form of a tetrahedral benzoxaborolate anion was established using (11)B solid state NMR (including (11)B-(31)P correlation experiments). Irrespective of the apatite used, the grafting density of the benzoxaborolates was found to be low, and more generally, these anions demonstrated a poor affinity for apatite surfaces, notably in comparison with other anions commonly found in biological media, such as carboxylates and (organo)phosphates. The study was then extended to the adsorption of a molecule with antimicrobial and antifungal properties (3-piperazine-bis(benzoxaborole)), showing, on a more general perspective, how hydroxyapatites can be used for the development of novel formulations of benzoxaborole drugs. STATEMENT OF SIGNIFICANCE: Benzoxaboroles are an emerging family of molecules which have attracted much attention in the biomedical field, notably for the design of new drugs. However, the way in which these molecules, once introduced in the body, may interact with bone mineral is still unknown, and the possibility of associating benzoxaboroles to calcium phosphates for drug-formulation purposes has not been looked into. Here, we describe the first study of the adsorption of benzoxaboroles on hydroxyapatite, which is the main mineral phase present in bone. We describe the mode of grafting of benzoxaboroles on this material, and show that they only weakly bind to its surface, especially in comparison to other ionic species commonly found in physiological media, such as phosphates and carboxylates. This demonstrates that administered benzoxaborole drugs are unlikely to remain adsorbed on hydroxyapatite surfaces for long periods of time, which means that their biodistribution will not be affected by such phenomena. Moreover, this work shows that the formulation of benzoxaborole drugs by association to calcium phosphates like hydroxyapatite will lead to a rapid release of the molecules.

Formulation of benzoxaborole drugs in PLLA: from materials preparation to in vitro release kinetics and cellular assays.

Benzoxaboroles are a family of organoboron molecules, which have been finding over the past few years an increasing number of biological applications, notably for the design of new drugs. Given that these molecules are still relatively new in the biomedical context, very few investigations regarding their formulation have been reported to date. Here, a complete study on the formulation of benzoxaboroles in a biopolymer, poly-l-lactic acid (PLLA), is reported. The incorporation of two small benzoxaboroles, namely the simplest benzoxaborole molecule (BBzx) and the antifungal drug tavaborole (AN2690), inside PLLA films was investigated. Different variations in the film composition and texture were looked into, by performing a heat-treatment on the PLLA films, or by preparing PLLA-PEO (polyethylene oxide) blends or PLLA-LDH (layered double hydroxide) composites. In each case, the impact of these changes in formulation on the local environment of the benzoxaboroles in the material (as determined by multinuclear solid state NMR), and on the kinetics of release in physiological media were analyzed, showing that a variety of release profiles could be achieved. Finally, cellular assays were carried out looking at the migration of MDA-MB-231 cancer cells. These tests revealed for the first time that benzoxaboroles like AN2690 and BBzx inhibited the migration of these cells. Moreover, the molecules incorporated in the films were found to remain active, and their effect on cancer cells was directly related to the release kinetics from the films. All in all, PLLA-based materials appear as highly versatile and attractive matrices for formulating benzoxaborole-based drugs.

Boronate ligands in materials: determining their local environment by using a combination of IR/solid-state NMR spectroscopies and DFT calculations.

Boronic acids (R-B(OH)(2)) are a family of molecules that have found a large number of applications in materials science. In contrast, boronate anions (R-B(OH)(3)(-)) have hardly been used so far for the preparation of novel materials. Here, a new crystalline phase involving a boronate ligand is described, Ca[C(4)H(9)-B(OH)(3)](2), which is then used as a basis for the establishment of the spectroscopic signatures of boronates in the solid state. The phase was characterized by IR and multinuclear solid-state NMR spectroscopy ((1)H, (13)C, (11)B and (43)Ca), and then modeled by periodic DFT calculations. Anharmonic OH vibration frequencies were calculated as well as NMR parameters (by using the Gauge Including Projector Augmented Wave--GIPAW--method). These data allow relationships between the geometry around the OH groups in boronates and the IR and (1)H NMR spectroscopic data to be established, which will be key to the future interpretation of the spectra of more complex organic-inorganic materials containing boronate building blocks.