The effect of ionic versus covalent functionalization of polyoxometalate hybrid materials with coordinating subunits on their stability and interaction with DNA.

Inorganic-organic hybrid materials that combine both Polyoxometalates (POMs) and metal ion coordinating subunits (CSUs) represent promising multifunctional materials. Though their individual components are often biologically active, utilization of hybrid materials in bioassays significantly depends on the functionalization method and thus resulting stability of the system. Quite intriguingly, these aspects were very scarcely studied in hybrid materials based on the Wells-Dawson POM (WD POM) scaffold and remain unknown. We chose two model WD POM hybrid systems to establish how the functionalization mode (ionic vs. covalent) affects their stability in biological medium and interaction with nucleic acids. The synthetic scope and limitations of the covalent POM-terpyridine hybrids were demonstrated and compared with the ionic Complex-Decorated Surfactant Encapsulated-Clusters (CD-SECs) hybrids. The nature of POM and CSU binding can be utilized to modulate the stability of the hybrid and the extent of DNA binding. The above systems show potential to behave as model cargo-platforms for potential utilization in medicine and pharmacy.

Correction: Computational study of linear carbon chain based organic dyes for dye sensitized solar cells.

[This corrects the article DOI: 10.1039/D2RA06767F.].

Correction: Predicting the dye-sensitized solar cell performance of novel linear carbon chain-based dyes: insights from DFT simulations.

Correction for 'Predicting the dye-sensitized solar cell performance of novel linear carbon chain-based dyes: insights from DFT simulations' by Giuseppe Consiglio et al., Dalton Trans., 2023, 52, 15995-16004, https://doi.org/10.1039/D3DT01856C.

MOF (UiO-66-NH2)@COF (TFP-TABQ) hybrids via on-surface condensation reactions for sustainable energy storage.

Core-shell MOF@COF hybrids were synthesized via subsequent modification of MOF UiO-66-NH2 with 1,3,5-triformylphloroglucinol (TFP) and 2,3,5,6-tetraaminobenzoquinone (TABQ). The hybrids exhibited significant surface area (236 m2 g-1) and outstanding electrochemical performance (103 F g-1 at 0.5 A g-1), surpassing both COFs and MOFs, thereby showcasing the potential of on-surface condensation reactions for developing high-performance energy storage devices.

Unexpected structural complexity of d-block metallosupramolecular architectures within the benzimidazole-phenoxo ligand scaffold for crystal engineering aspects.

Design of metallosupramolecular materials encompassing more than one kind of supramolecular interaction can become deceptive, but it is necessary to better understand the concept of the controlled formation of supramolecular systems. Herein, we show the structural diversity of the bis-compartmental phenoxo-benzimidazole ligand H3L1 upon self-assembly with variety of d-block metal ions, accounting for factors such as: counterions, pH, solvent and reaction conditions. Solid-state and solution studies show that the parent ligand can accommodate different forms, related to (de)protonation and proton-transfer, resulting in the formation of mono-, bi- or tetrametallic architectures, which was also confirmed with control studies on the new mono-compartmental phenoxo-benzimidazole H2L2 ligand analogue. For the chosen architectures, structural variables such as porous character, magnetic behaviour or luminescence studies were studied to demonstrate how the form of H3L1 ligand affects the final form of the supramolecular architecture and observed properties. Such complex structural variations within the benzimidazole-phenoxo-type ligand have been demonstrated for the first time and this proof-of-concept can be used to integrate these principles in more sophisticated architectures in the future, combining both the benzimidazole and phenoxide subunits. Ultimately, those principles could be utilized for targeted manipulation of properties through molecular tectonics and crystal engineering aspects.

Reactivity Prediction of Cu-Catalyzed Halogen Atom Transfer Reactions Using Data-Driven Techniques.

In catalysis, linear free energy relationships (LFERs) are commonly used to identify reaction descriptors that enable the prediction of outcomes and the design of more effective catalysts. Herein, LFERs are established for the reductive cleavage of the C(sp3)-X bond in alkyl halides (RX) by Cu complexes. This reaction represents the activation step in atom transfer radical polymerization and atom transfer radical addition/cyclization. The values of the activation rate constant, kact, for 107 Cu complex/RX couples in 5 different solvents spanning over 13 orders of magnitude were effectively interpolated by the equation: log kact = sC(I + C + S), where I, C, and S are, respectively, the initiator, catalyst, and solvent parameters, and sC is the catalyst-specific sensitivity parameter. Furthermore, each of these parameters was correlated to relevant descriptors, which included the bond dissociation free energy of RX and its Tolman cone angle θ, the electron affinity of X, the radical stabilization energy, the standard reduction potential of the Cu complex, the polarizability parameter π* of the solvent, and the distortion energy of the complex in its transition state. This set of descriptors establishes the fundamental properties of Cu complexes and RX that determine their reactivity and that need to be considered when designing novel systems for atom transfer radical reactions. Finally, a multivariate linear regression (MLR) approach was adopted to develop an objective model that surpassed the predictive capability of the LFER equation. Thus, the MLR model was employed to predict kact values for >2000 Cu complex/RX pairs.

Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma.

BACKGROUND: ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear. OBJECTIVE: To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC. METHODS: Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes. RESULTS: ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC. CONCLUSIONS: HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.

Trityl-Based Lanthanide-Supramolecular Assemblies Exhibiting Slow Magnetic Relaxation.

The triphenylmethane (trityl) group has been recognized as a supramolecular synthon in crystal engineering, molecular machine rotors and stereochemical chirality inductors in materials science. Herein we demonstrate for the first time how it can be utilized in the domain of molecular magnetic materials through shaping of single molecule magnet (SMM) properties within the lanthanide complexes in tandem with other non-covalent interactions. Trityl-appended mono- (HL1 ) and bis-compartmental (HL2 ) hydrazone ligands were synthesized and complexated with Dy(III) and Er(III) triflate and nitrate salts to generate four monometallic (1-4) and two bimetallic (5, 6) complexes. The static and dynamic magnetic properties of 1-6 were investigated, revealing that only ligand HL1 induces assemblies (1-4) capable of showing SMM behaviour, with Dy(III) congeners (1, 2) able to exhibit the phenomenon also under zero field conditions. Theoretical ab initio studies helped in determination of Dy(III) energetic levels, magnetic anisotropic axes and corroborated magnetic relaxation mechanisms to be a combination of Raman and quantum tunnelling in zero dc field, the latter being cancelled in the optimum non-zero dc field. Our work represents the first study of magneto-structural correlations within the trityl Ln-SMMs, leading to generation of slowly relaxing zero-field dysprosium complexes within the hydrogen-bonded assemblies.

New Anderson-Based Polyoxometalate Covalent Organic Frameworks as Electrodes for Energy Storage Boosted Through Keto-Enol Tautomerization.

The unique electrochemical properties of polyoxometalates (POMs) render them ideal components for the fabrication of next-generation high-performance energy storage systems. However, their practical applications have been hindered by their high solubility in common electrolytes. This problem can be overcome by the effective hybridization of POMs with other materials. Here we present the design and synthesis of two novel polyoxometalate-covalent organic frameworks (POCOF) via one-pot solvothermal strategy between an amino-functionalized Anderson-type POM and a trialdehyde-based building unit. We show that structural and functional complexity can be enriched by adding hydroxyl groups in the 2,4,6 position to the benzene-1,3,5-tricarbaldehyde allowing to exploit for the first time in POCOFs the keto-enol tautomerization as additional feature to impart greater chemical stability to the COFs and enhanced properties leading to large specific surface area (347 m2 /g) and superior electrochemical performance of the POCOF-1 electrodes, when compared with POCOF-2 electrodes that possess only imine-type linkage and with pristine POM electrodes. Specifically, POCOF-1 electrodes display remarkable specific, areal, and volumetric capacitance (125 F/g, 248 mF/cm2 and 41.9 mF/cm3 , respectively) at a current density of 0.5 A/g, a maximum energy density (56.2 Wh/kg), a maximum power density (3.7 kW/kg) and an outstanding cyclability (90 % capacitance retention after 5000 cycles).

High Selectivity and Sensitivity in Chemiresistive Sensing of Co(II) Ions with Liquid-Phase Exfoliated Functionalized MoS2 : A Supramolecular Approach.

Chemical sensing of water contamination by heavy metal ions is key as it represents a most severe environmental problem. Liquid-phase exfoliated two-dimensional (2D) transition metal dichalcogenides (TMDs) are suitable candidates for chemical sensing thanks to their high surface-to-volume ratio, sensitivity, unique electrical characteristics, and scalability. However, TMDs lack selectivity due to nonspecific analyte-nanosheet interactions. To overcome this drawback, defect engineering enables controlled functionalization of 2D TMDs. Here, ultrasensitive and selective sensors of cobalt(II) ions via the covalent functionalization of defect-rich MoS2 flakes with a specific receptor, 2,2':6',2″-terpyridine-4'-thiol is developed. A continuous network is assembled by healing of MoS2 sulfur vacancies in a tailored microfluidic approach, enabling high control over the assembly of thin and large hybrid films. The Co2+ cations complexation represents a powerful gauge for low concentrations of cationic species which can be best monitored in a chemiresisitive ion sensor, featuring a 1 pm limit of detection, sensing in a broad concentration range (1 pm - 1 µm) and sensitivity as high as 0.308 ± 0.010 lg([Co2+ ])-1 combined with a high selectivity towards Co2+ over K+ , Ca2+ , Mn2+ , Cu2+ , Cr3+ , and Fe3+ cations. This supramolecular approach based on highly specific recognition can be adapted for sensing other analytes through specific ad-hoc receptors.

Noncentrosymmetric Lanthanide-Based MOF Materials Exhibiting Strong SHG Activity and NIR Luminescence of Er3+: Application in Nonlinear Optical Thermometry.

Optically active luminescent materials based on lanthanide ions attract significant attention due to their unique spectroscopic properties, nonlinear optical activity, and the possibility of application as contactless sensors. Lanthanide metal-organic frameworks (Ln-MOFs) that exhibit strong second-harmonic generation (SHG) and are optically active in the NIR region are unexpectedly underrepresented. Moreover, such Ln-MOFs require ligands that are chiral and/or need multistep synthetic procedures. Here, we show that the NIR pulsed laser irradiation of the noncentrosymmetric, isostructural Ln-MOF materials (MOF-Er3+ (1) and codoped MOF-Yb3+/Er3+ (2)) that are constructed from simple, achiral organic substrates in a one-step procedure results in strong and tunable SHG activity. The SHG signals could be easily collected, exciting the materials in a broad NIR spectral range, from ≈800 to 1500 nm, resulting in the intense color of emission, observed in the entire visible spectral region. Moreover, upon excitation in the range of ≈900 to 1025 nm, the materials also exhibit the NIR luminescence of Er3+ ions, centered at ≈1550 nm. The use of a 975 nm pulse excitation allows simultaneous observations of the conventional NIR emission of Er3+ and the SHG signal, altogether tuned by the composition of the Ln-MOF materials. Taking the benefits of different thermal responses of the mentioned effects, we have developed a nonlinear optical thermometer based on lanthanide-MOF materials. In this system, the SHG signal decreases with temperature, whereas the NIR emission band of Er3+ slightly broadens, allowing ratiometric (Er3+ NIR 1550 nm/SHG 488 nm) temperature monitoring. Our study provides a groundwork for the rational design of readily available and self-monitoring NLO-active Ln-MOFs with the desired optical and electronic properties.

Markovnikov-selective double hydrosilylation of challenging terminal aryl alkynes under cobalt and iron catalysis.

Geminal bis(silanes) are unique compounds with interesting properties. The most straightforward way to access them is double hydrosilylation of alkynes, which was established only recently. Previous articles about transition metal-catalysed double hydrosilylation show that terminal aryl alkynes are a challenge. We report on cobalt(II) and iron(III) complexes with the easy-to-synthesise N,N,N-tridentate hydrazone ligand being active precatalysts in Markovnikov-selective double hydrosilylation of terminal aryl alkynes. The influence of the hydrazone ligand structure and the potential role of the sodium triethylborohydride activator were studied. Sets of geminal bis(silanes) with two identical or different silyl groups were synthesised, showing the applicability of the reported method.

Alternating Methyl Methacrylate/n-Butyl Acrylate Copolymer Prepared by Atom Transfer Radical Polymerization.

Poly(methyl methacrylate/n-butyl acrylate) [P(MMA/BA)] copolymer with an alternating structure was synthesized via an activator regenerated by electron transfer (ARGET) atom transfer radical (co)polymerization (ATRP) of 2-ethylfenchyl methacrylate (EFMA) and n-butyl acrylate (BA) with subsequent postpolymerization modifications (PPM). Due to the steric hindrance of the bulky pendant group of EFMA, as well as the low reactivity ratio of BA in copolymerization with methacrylates, copolymerization of EFMA and BA generated a copolymer with a high content of alternating dyads. A subsequent PPM procedure of the alternating EFMA/BA copolymer was comprised of the hydrolysis of a tertiary ester by trifluoroacetic acid and methylation by (trimethylsilyl)diazomethane. After the modifications, the architecture of the obtained alternating MMA/BA copolymers was compared with gradient and statistical copolymers with overall similar compositions, molecular weights, and dispersities. 13C NMR indicated the absence of either MMA/MMA/MMA or BA/BA/BA sequences, in contrast to an abundance of homotriads in either the statistical or especially in the gradient copolymer. All three copolymers had similar glass transition temperatures, as measured by differential scanning calorimetry (DSC), but the alternating copolymer had the narrowest range of glass transition.

Understanding the effect of structural changes on slow magnetic relaxation in mononuclear octahedral copper(II) complexes.

Current advances in molecular magnetism are aimed at the construction of molecular nanomagnets and spin qubits for their utilization as high-density data storage materials and quantum computers. Mononuclear coordination compounds with low spin values of S = ½ are excellent candidates for this endeavour, but knowledge of their construction via rational design is limited. This particularly applies to the single copper(II) spin center, having been only recently demonstrated to exhibit slow relaxation of magnetisation in the appropriate octahedral environment. We have thus prepared a unique organic scaffold that would allow one to gain in-depth insight into how purposeful structural differences affect the slow magnetic relaxation in monometallic, transition metal complexes. As a proof-of-principle, we demonstrate how one can construct two, structurally very similar complexes with isolated Cu(II) ions in an octahedral ligand environment, the magnetic properties of which differ significantly. The differences in structural symmetry effects and in magnetic relaxation are corroborated with a series of experimental techniques and theoretical approaches, showing how symmetry distortions and crystal packing affect the relaxation behaviour in these isolated Cu(II) systems. Our unique organic platform can be efficiently utilized for the construction of various transition-metal ion systems in the future, effectively providing a model system for investigation of magnetic relaxation via targeted structural distortions.

Toward Green Atom Transfer Radical Polymerization: Current Status and Future Challenges.

Reversible-deactivation radical polymerizations (RDRPs) have revolutionized synthetic polymer chemistry. Nowadays, RDRPs facilitate design and preparation of materials with controlled architecture, composition, and functionality. Atom transfer radical polymerization (ATRP) has evolved beyond traditional polymer field, enabling synthesis of organic-inorganic hybrids, bioconjugates, advanced polymers for electronics, energy, and environmentally relevant polymeric materials for broad applications in various fields. This review focuses on the relation between ATRP technology and the 12 principles of green chemistry, which are paramount guidelines in sustainable research and implementation. The green features of ATRP are presented, discussing the environmental and/or health issues and the challenges that remain to be overcome. Key discoveries and recent developments in green ATRP are highlighted, while providing a perspective for future opportunities in this area.

MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance.

Chemoresistance constitutes a major challenge in the treatment of triple-negative breast cancer (TNBC). Mixed-Lineage Kinase 4 (MLK4) is frequently amplified or overexpressed in TNBC where it facilitates the aggressive growth and migratory potential of breast cancer cells. However, the functional role of MLK4 in resistance to chemotherapy has not been investigated so far. Here, we demonstrate that MLK4 promotes TNBC chemoresistance by regulating the pro-survival response to DNA-damaging therapies. We observed that MLK4 knock-down or inhibition sensitized TNBC cell lines to chemotherapeutic agents in vitro. Similarly, MLK4-deficient cells displayed enhanced sensitivity towards doxorubicin treatment in vivo. MLK4 silencing induced persistent DNA damage accumulation and apoptosis in TNBC cells upon treatment with chemotherapeutics. Using phosphoproteomic profiling and reporter assays, we demonstrated that loss of MLK4 reduced phosphorylation of key DNA damage response factors, including ATM and CHK2, and compromised DNA repair via non-homologous end-joining pathway. Moreover, our mRNA-seq analysis revealed that MLK4 is required for DNA damage-induced expression of several NF-кB-associated cytokines, which facilitate TNBC cells survival. Lastly, we found that high MLK4 expression is associated with worse overall survival of TNBC patients receiving anthracycline-based neoadjuvant chemotherapy. Collectively, these results identify a novel function of MLK4 in the regulation of DNA damage response signaling and indicate that inhibition of this kinase could be an effective strategy to overcome TNBC chemoresistance.

High-sorption terpyridine-graphene oxide hybrid for the efficient removal of heavy metal ions from wastewater.

Pollution of wastewater with heavy metal-ions represents one of the most severe environmental problems associated with societal development. To overcome this issue, the design of new, highly efficient systems capable of removing such toxic species, hence to purify water, is of paramount importance for public health and environmental protection. In this work, novel sorption hybrid materials were developed to enable high-performance adsorption of heavy metal ions. Towards this end, graphene oxide (GO) exhibiting various C/O ratios has been functionalized with ad hoc receptors, i.e. terpyridine ligands. The maximum adsorption capacity of highly oxidized/terpyridine hybrids towards Ni(ii), Zn(ii) and Co(ii) was achieved at pH = 6 and 25 °C reaching values of 462, 421 and 336 mg g-1, respectively, being the highest reported in the literature for pristine GO and GO-based sorbents. Moreover, the uptake experiments showed that heavy metal ion adsorption on GO-Tpy and GOh-Tpy is strongly dependent on pH in the range from 2 to 10, as a result of the modulation of interactions at the supramolecular level. Moreover, the ionic strength was found to be independent of heavy metal ion adsorption on GO-Tpy and GOh-Tpy. Under ambient conditions, adsorption capacity values increase with the degree of oxidation of GO because dipolar oxygen units can both interact with heavy-metal ions via dipole-dipole and/or ionic interactions and enable bonding of more covalently anchored terpyridine units. Both adsorption isotherms and kinetics studies revealed that the uptake of the heavy metal ions occurs at a monolayer coverage, mostly controlled by the strong surface complexation with the oxygen of GO and nitrogen-containing groups of terpyridine. Furthermore, selectivity of the hybrid was confirmed by selective sorption of the above heavy metal ions from mixtures involving alkali (Na(i), K(i)) and alkaline Earth (Mg(ii), Ca(ii)) metal ions due to the chelating properties of the terpyridine subunits, as demonstrated with municipal drinking (tap) water samples. Our findings provide unambiguous evidence for the potential of chemical tailoring of GO-based materials with N-heterocyclic ligands as sorbent materials for highly efficient wastewater purification.

Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications.

Physicochemical, pharmacokinetic, and biopharmaceutical characterization tools play a key role in the assessment of nanopharmaceuticals' potential imaging analysis and for site-specific delivery of anti-cancers to neoplastic cells/tissues. If diagnostic tools and therapeutic approaches are combined in one single nanoparticle, a new platform called nanotheragnostics is generated. Several analytical technologies allow us to characterize nanopharmaceuticals and nanoparticles and their properties so that they can be properly used in cancer therapy. This paper describes the role of multifunctional nanoparticles in cancer diagnosis and treatment, describing how nanotheragnostics can be useful in modern chemotherapy, and finally, the challenges associated with the commercialization of nanoparticles for cancer therapy.

The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer.

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification.

ALK alterations in salivary gland carcinomas.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.