Copper single-site engineering in MOF-808 membranes for improved water treatment.

MOF-808, a metal-organic framework containing Zr6O8 clusters, can serve as a secure anchoring point for stabilizing copper single-sites with redox activity, thus making it a promising candidate for catalytic applications. In this study, we target the incorporation of Cu-MOF-808 into a mixed-matrix membrane for the degradation of tyrosol, an emerging endocrine-disrupting compound commonly found in water sources, through Fenton reactions, developing innovative technologies for water treatment. We successfully demonstrate the effectiveness of this approach by preparing catalytic membranes with minimal metal leaching, which is one of the primary challenges in developing copper-based Fenton heterogeneous catalysts. Furthermore, we utilized advanced synchrotron characterization techniques, combining X-ray absorption spectroscopy and pair distribution function analysis of X-ray total scattering, to provide evidence of the atomic structure of the catalytic copper sites within the membranes. Additionally, we observed the presence of weak interactions between the MOF-808 and the organic polymer, potentially explaining their enhanced stability.

How Reproducible is the Synthesis of Zr-Porphyrin Metal-Organic Frameworks? An Interlaboratory Study.

Metal-organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal structures can often be accessed from the same building blocks, which complicates the phase selectivity. Likewise, the high sensitivity to slight changes in synthesis conditions may cause reproducibility issues. This is crucial, as it hampers the research and commercialization of affected MOFs. Here, it presents the first-ever interlaboratory study of the synthetic reproducibility of two Zr-porphyrin MOFs, PCN-222 and PCN-224, to investigate the scope of this problem. For PCN-222, only one sample out of ten was phase pure and of the correct symmetry, while for PCN-224, three are phase pure, although none of these show the spatial linker order characteristic of PCN-224. Instead, these samples resemble dPCN-224 (disordered PCN-224), which has recently been reported. The variability in thermal behavior, defect content, and surface area of the synthesised samples are also studied. The results have important ramifications for field of metal-organic frameworks and their crystallization, by highlighting the synthetic challenges associated with a multi-variable synthesis space and flat energy landscapes characteristic of MOFs.

ß-Turn Induction by a Diastereopure Azepane-Derived Quaternary Amino Acid.

ß-Turns are one of the most common secondary structures found in proteins. In the interest of developing novel ß-turn inducers, a diastereopure azepane-derived quaternary amino acid has been incorporated into a library of simplified tetrapeptide models in order to assess the effect of the azepane position and peptide sequence on the stabilization of ß-turns. The conformational analysis of these peptides by molecular modeling, NMR spectroscopy, and X-ray crystallography showed that this azepane amino acid is an effective ß-turn inducer when incorporated at the i + 1 position. Moreover, the analysis of the supramolecular self-assembly of one of the ß-turn-containing peptide models in the solid state reveals that it forms a supramolecular helical arrangement while maintaining the ß-turn structure. The results here presented provide the basis for the use of this azepane quaternary amino acid as a strong ß-turn inducer in the search for novel peptide-based bioactive molecules, catalysts, and biomaterials.

Synergistic binding sites in a metal-organic framework for the optical sensing of nitrogen dioxide.

Luminescent metal-organic frameworks are an emerging class of optical sensors, able to capture and detect toxic gases. Herein, we report the incorporation of synergistic binding sites in MOF-808 through post-synthetic modification with copper for optical sensing of NO2 at remarkably low concentrations. Computational modelling and advanced synchrotron characterization tools are applied to elucidate the atomic structure of the copper sites. The excellent performance of Cu-MOF-808 is explained by the synergistic effect between the hydroxo/aquo-terminated Zr6O8 clusters and the copper-hydroxo single sites, where NO2 is adsorbed through combined dispersive- and metal-bonding interactions.

Ultrasmall Copper Nanoclusters in Zirconium Metal-Organic Frameworks for the Photoreduction of CO2.

Encapsulating ultrasmall Cu nanoparticles inside Zr-MOFs to form core-shell architecture is very challenging but of interest for CO2 reduction. We report for the first time the incorporation of ultrasmall Cu NCs into a series of benchmark Zr-MOFs, without Cu NCs aggregation, via a scalable room temperature fabrication approach. The Cu NCs@MOFs core-shell composites show much enhanced reactivity in comparison to the Cu NCs confined in the pore of MOFs, regardless of their very similar intrinsic properties at the atomic level. Moreover, introducing polar groups on the MOF structure can further improve both the catalytic reactivity and selectivity. Mechanistic investigation reveals that the CuI sites located at the interface between Cu NCs and support serve as the active sites and efficiently catalyze CO2 photoreduction. This synergetic effect may pave the way for the design of low-cost and efficient catalysts for CO2 photoreduction into high-value chemical feedstock.

Revisiting Vibrational Spectroscopy to Tackle the Chemistry of Zr6O8 Metal-Organic Framework Nodes.

The metal-organic framework MOF-808 contains Zr6O8 nodes with a high density of vacancy sites, which can incorporate carboxylate-containing functional groups to tune chemical reactivity. Although the postsynthetic methods to modify the chemistry of the Zr6O8 nodes in MOFs are well known, tackling these alterations from a structural perspective is still a challenge. We have combined infrared spectroscopy experiments and first-principles calculations to identify the presence of node vacancies accessible for chemical modifications within the MOF-808. We demonstrate the potential of our approach to assess the decoration of MOF-808 nodes with different catechol-benzoate ligands. Furthermore, we have applied advanced synchrotron characterization tools, such as pair distribution function analyses and X-ray absorption spectroscopy, to resolve the atomic structure of single metal sites incorporated into the catechol groups postsynthetically. Finally, we demonstrate the catalytic activity of these MOF-808 materials decorated with single copper sites for 1,3-dipolar cycloadditions.

Layered Copper-Metallated Covalent Organic Frameworks for Huisgen Reactions.

Covalent organic frameworks (COFs) are porous materials formed through condensation reactions of organic molecules via the formation of dynamic covalent bonds. Among COFs, those based on imine and ß-ketoenamine linkages offer an excellent platform for binding metallic species such as copper to design efficient heterogeneous catalysts. In this work, imine- and ß-ketoenamine-based COF materials were modified with catalytic copper sites following a metallation method, which favored the formation of binding amine defects. The obtained copper-metallated COF materials were tested as heterogeneous catalysts for 1,3-dipolar cycloaddition reactions, resulting in high yields and recyclability.

Unravelling the local structure of catalytic Fe-oxo clusters stabilized on the MOF-808 metal organic-framework.

Stabilizing catalytic iron-oxo-clusters within nanoporous metal-organic frameworks (MOFs) is a powerful strategy to prepare new active materials for the degradation of toxic chemicals, such as bisphenol A. Herein, we combine pair distribution function analysis of total X-ray scattering data and X-ray absorption spectroscopy, with computational modelling to understand the local structural nature of added redox-active iron-oxo clusters bridging neighbouring zirconia-nodes within MOF-808.

Applications of pair distribution function analyses to the emerging field of non-ideal metal-organic framework materials.

Pair distribution function, PDF, analyses are emerging as a powerful tool to characterize non-ideal metal-organic framework (MOF) materials with compromised ordering. Although originally envisaged as crystalline porous architectures, MOFs can incorporate defects in their structures through either chemistry or mechanical stress, resulting in materials with unpredicted novel properties. Indeed, a wide variety of current non-ideal MOFs have disorder in their structures to some extent, thereby often lacking crystals. Typically, PDF experiments are performed using high-energy synchrotron X-rays or neutrons to achieve a superior high atomic resolution in short times. The PDF technique analyses both Bragg and diffuse scattering signals simultaneously, without being restricted to crystalline materials. This characteristic makes PDF analyses a powerful probe to address the structural characterization of non-ideal MOF materials both at the local and intermediate range scales, including under in situ conditions relevant to MOF synthesis, activation and catalysis.

Unveiling the Local Structure of Palladium Loaded into Imine-Linked Layered Covalent Organic Frameworks for Cross-Coupling Catalysis.

Layered covalent organic frameworks (2D-COFs), composed of reversible imine linkages and accessible pores, offer versatility for chemical modifications towards the development of catalytic materials. Nitrogen-enriched COFs are good candidates for binding Pd species. Understanding the local structure of reacting Pd sites bonded to the COF pores is key to rationalize interactions between active sites and porous surfaces. By combining advanced synchrotron characterization methods with periodic computational DFT modeling, the precise atomic structure of catalytic Pd sites attached to local defects is resolved within an archetypical imine-linked 2D-COF. This material was synthesized using an in situ method as a gel, under which imine hydrolysis and metalation reactions are coupled. Local defects formed in situ within imine-linked 2D-COF materials are highly reactive towards Pd metalation, resulting in active materials for Suzuki-Miyaura cross-coupling reactions.

Safety of eribulin as third-line chemotherapy in HER2-negative, advanced breast cancer pre-treated with taxanes and anthracycline: OnSITE study.

Eribulin is active and safe in heavily pre-treated metastatic breast cancer patients. Few safety data have been published in third line. We aimed to report the specific safety profile on third line beyond taxanes and anthracyclines in advanced breast cancer (ABC). A multicenter phase II, prospective study was conducted in anthracyclines and taxanes pre-treated HER2-negative ABC, programmed to receive eribulin as third-line chemotherapy. Adverse events (AEs) were assessed and classified according to CTCAE. In addition, efficacy, in terms of overall survival (OS) and progression-free survival (PFS), and the dynamics of circulating tumor cells (CTCs) during treatment were assessed. 59 patients fulfilled the criteria. All but one showed AEs with a cumulative number of 598 AEs. The most frequent grade 3/4 drug-related AEs were neutropenia (1.7%), febrile neutropenia (0.5%), leukopenia (0.5%), alopecia (0.5%), asthenia (0.3%), elevated gamma glutamyl transferase levels (0.2%), and respiratory tract infection (0.2%). Median PFS was 4 months (95% CI 3.1-5.9) and median OS was 13.6 months (11.8-not reached). The mean number of CTCs in peripheral blood was significantly reduced from baseline to cycle 2 (16.8 vs 5.4 CTCs; P < 0.001). Median OS was significantly longer in <5 baseline CTC patients compared to ≥5 baseline CTC patients (13.1 months [95% CI: 11.8-not reached] vs 12.5 months [95% CI: 7.6-not reached]; P = 0.045). A significant correlation (P = 0.0129) was observed between CTC levels at cycle 2 and death when CTCs were analyzed using cox regression. Eribulin chemotherapy is effective and safe as third line in advanced HER2-negative breast cancer. CTC levels correlate with overall survival.

Factors Associated with the Selection of First-line Bevacizumab plus Chemotherapy and Clinical Response in HER2-negative Metastatic Breast Cancer: ONCOSUR AVALOX Study.

AIM: To evaluate factors associated with the selection of first-line bevacizumab plus chemotherapy and clinical response in HER2-negative metastatic breast cancer (MBC) in clinical practice in Spain. PATIENTS AND METHODS: All consecutive adult female patients with HER2-negative MBC who had received first-line bevacizumab plus chemotherapy for at least 3 months were enrolled in the present study. RESULTS: A total of 292 evaluable patients were included; 25% had triple-negative breast cancer (TNBC) and 75% had hormone receptor-positive breast cancer (HRPBC). Nearly 40% of patients had ≥3 metastatic sites, mainly located in the bone (48%) and liver (40%). Bevacizumab was mostly combined with paclitaxel (67.1%). ER-positive tumors were only identified as an independent factor associated with the choice of treatment (odds ratio (OR): 0.538; p=0.02). The overall response rate (ORR) was 63.7% (TNBC: 57.5%; HRPBC: 65.9%). Patients aged 36-50 years (OR: 3.03; p=0.028) and those with metastases at sites other than the bone (OR: 0.38; p=0.001) and ≥3 metastatic sites (OR: 1.41; p=0.018) were more likely to achieve objective responses. CONCLUSION: First-line bevacizumab plus chemotherapy, mainly paclitaxel, is an effective and well-tolerated treatment option for HER2-negative MBC, particularly in more aggressive disease.

Raman microspectroscopic analysis of decorative pigments from the Roman villa of El Ruedo (Almedinilla, Spain).

In this work, we analysed the preparatory layer and paintings in the hypocaustum of the Roman villa of El Ruedo (Almedinilla, southern Spain). The specimens studied were from the III and IV centuries. Raman microscopy was for the first time used here to examine Roman pictures in the south of the Iberian peninsula. The results obtained allowed us to establish the chemical nature of the different pigments used by the Roman artists. All were applied over a preparatory layer consisting of limewash. The different colours used (black, white, red, yellow, green and blue) were obtained by using carbon, calcite, gypsum, hematite, goethite, green earth and Egyptian blue. Some exhibited various hues that were obtained by mixing the previous compounds. Worth special note is the incipient presence of blue pigments, which were rarely used in Roman Hispania owing to their scarcity and high price.

Molecular subtypes of breast cancer: metabolic correlation with ¹8F-FDG PET/CT.

PURPOSE: To determine whether the metabolic features of breast tumours differ among molecular subtypes. METHODS: This prospective study included 168 women diagnosed with locally advanced breast cancer. PET/CT was requested in the initial staging before neoadjuvant treatment (multicentre study, FISCAM grant). All patients underwent an ¹8F-FDG PET/CT scan with a dual time-point acquisition. Both examinations (PET-1 and PET-2) were evaluated qualitatively and semiquantitatively with calculation of SUVmax (SUV-1 and SUV-2, respectively), and the percentage variation in the SUVs and retention indexes (RI) between PET-1 and PET-2 in the breast tumour were calculated. Biological prognostic parameters, including the steroid receptor status, HER-2 expression, proliferation rate (Ki-67) and grading, were determined from primary tumour tissue. Tumour subtypes were classified following the recommendations of the 12th International Breast Conference, by immunohistochemical surrogates as luminal A, luminal B-HER2(-), luminal B-HER2(+), HER2(+) or basal. Metabolic semiquantitative parameters and molecular subtypes were correlated. RESULTS: Of the 168 tumours, 151 were classified: 16 were luminal A, 53 were luminal B-HER2(-), 29 were luminal B-HER2(+), 18 were HER2(+) and 35 were basal. There were significant differences between SUV-1 and SUV-2 and the different subtypes, with higher SUVs in HER2(+) and basal tumours. No significant differences were found with respect to RI. CONCLUSION: Semiquantitative metabolic parameters showed statistically significant differences among the molecular subtypes of the tumours evaluated. Therefore, there seems to be a relationship between molecular and glycolytic phenotypes.

Semi-quantitative lymph node assessment of (18)F-FDG PET/CT in locally advanced breast cancer: correlation with biological prognostic factors.

PURPOSE: The aim of this study was to analyse the correlation between dual-time-point (18)F-2-deoxy-2-fluoro-D-glucose (FDG) uptakes in lymph nodes assessed by positron emission tomography (PET)/CT and histopathological and immunohistochemical prognostic factors. METHODS: Seventy-five women with locally advanced breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to adjuvant chemotherapy (multicentre study). All of the patients underwent (18)F-FDG PET/CT with a dual-time-point acquisition. Both examinations were evaluated qualitatively and semi-quantitatively with calculation of maximum standardized uptake values (SUV(max)) in PET-1 (SUV-1) and in PET-2 (SUV-2) and the percentage variation of the SUV or retention index (RI) between PET-1 and PET-2 in lymph nodes with the greater (18)F-FDG uptake. The biological prognostic parameters such as the steroid receptor status, p53 and HER2 expression, proliferation rate (Ki-67) and grading were determined from tissue of the primary tumour. Metabolic and biological parameters were correlated using Spearman's rank-order correlation coefficient and Mann-Whitney U and Kruskal-Wallis tests. RESULTS: Negative receptor status was correlated with higher SUV-1, SUV-2 and RI in lymph nodes. The results were significant for progesterone receptor status. p53 over-expression and triple-negative status were associated with greater semi-quantitative parameters in lymph nodes. Higher tumoural grades were related with greater semi-quantitative parameters (p > 0.05). CONCLUSION: Biological factors of bad prognosis were correlated with higher semi-quantitative metabolic values in lymph nodes. Therefore these results appear to reveal biological significance of lymph node (18)F-FDG accumulation.

18F-FDG retention index and biologic prognostic parameters in breast cancer.

AIM: To analyze the correlation between [(18)F]-fluoro-2-deoxy-D-glucose (F-FDG) uptake assessed by positron emission tomography/computed tomography (PET/CT) in breast tumors and histopathologic and immunohistochemical prognostic factors. MATERIAL AND METHODS: Sixty-eight women with breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to neoadjuvant chemotherapy (multicentric study).All the patients underwent a standard (18)F-FDG PET/CT followed by a delayed acquisition, 1 hour (PET-1) and 3 hours (PET-2) after FDG administration. Both examinations were evaluated qualitatively and semiquantitatively (SUV(max) values) in PET-1 (SUV-1) and in PET-2 (SUV-2). The percentage variation of the standard uptake values (retention index) between PET-1 and PET-2 was calculated.Clinical and metabolic stages were assessed according to TNM classification. All biologic prognostic parameters, such as the receptor status, p53 and c-erbB-2 expression, proliferation rate (Ki-67), and grading were determined from tissue of the primary tumor. Metabolic, clinical, and biologic parameters were correlated. RESULTS: A positive relationship was found between the SUV(max), tumor size, clinical, and metabolic stages. SUV-1 and SUV-2 values showed significant statistical correlation (P < 0.05) with PET stage and tumor size assessed by PET. On the contrary, the retention index showed relation with clinical stage (P < 0.05).When related to the biologic parameters, retention index showed the best results, with positive and significant relation (P < 0.05), with histologic grade, and Ki-67 and c-erbB-2 expression. Isolated SUV values only showed significant relation to Ki-67 expression. CONCLUSION: The retention index showed the best relation with biologic and clinical parameters compared with isolated SUVmax values for what could be a predictive marker of tumor biologic behavior.

Mediastinal extravasation of doxorubicin.

A 48-year-old woman with a diagnosis of breast carcinoma was treated with adjuvant chemotherapy through a central venous catheter with subcutaneous reservoir (Port-A-Cath). While doxorubicin was administered, the patient presented thoracic pain and breathing distress due to superior vena cava perforation by the central catheter and subsequent extravasation of the drug into the mediastinum. The patient recovered without sequelae with conservative therapy. Cytostatic extravasation via central catheter is an uncommon complication in clinical practice. In this paper we present the first doxorubicin extravasation through a central catheter in adults and review the only ten cases found in the literature.