Breaking Symmetry Relaxes Structural and Magnetic Restraints, Suppressing QTM in Enantiopure Butterfly Fe2 Dy2 SMMs*.

The {Fe2 Dy2 } butterfly systems can show single molecule magnet (SMM) behaviour, the nature of which depends on details of the electronic structure, as previously demonstrated for the [Fe2 Dy2 (µ3 -OH)2 (Me-teaH)2 (O2 CPh)6 ] compound, where the [N,N-bis-(2-hydroxyethyl)-amino]-2-propanol (Me-teaH3 ) ligand is usually used in its racemic form. Here, we describe the consequences for the SMM properties by using enantiopure versions of this ligand and present the first homochiral 3d/4 f SMM, which could only be obtained for the S enantiomer of the ligand for [Fe2 Dy2 (µ3 -OH)2 (Me-teaH)2 (O2 CPh)6 ] since the R enantiomer underwent significant racemisation. To investigate this further, we prepared the [Fe2 Dy2 (µ3 -OH)2 (Me-teaH)2 (O2 CPh)4 (NO3 )2 ] version, which could be obtained as the RS-, R- and S-compounds. Remarkably, the enantiopure versions show enhanced slow relaxation of magnetisation. The use of the enantiomerically pure ligand suppresses QTM, leading to the conclusion that use of enantiopure ligands is a "gamechanger" by breaking the cluster symmetry and altering the intimate details of the coordination cluster's molecular structure.

miRNAs 484 and 210 regulate Pax-5 expression and function in breast cancer cells.

Recent studies have enabled the identification of important factors regulating cancer progression, such as paired box gene 5 (Pax-5). This transcription factor has consistently been associated to B-cell cancer lesions and more recently solid tumors including breast carcinoma. Although Pax-5 downstream activity is relatively well characterized, aberrant Pax-5 expression in a cancer-specific context is poorly understood. To investigate the regulation of Pax-5 expression, we turned to micro RNAs (miRNAs), small non-coding RNA molecules that regulate key biological processes. Extensive studies show that miRNA deregulation is prevalent in cancer lesions. In this study, we aim to elucidate a causal link between differentially expressed miRNAs in cancer cells and their putative targeting of Pax-5-dependent cancer processes. Bioinformatic prediction tools indicate that miRNAs 484 and 210 are aberrantly expressed in breast cancer and predicted to target Pax-5 messenger RNA (mRNA). Through conditional modulation of these miRNAs in breast cancer cells, we demonstrate that miRNAs 484 and 210 inhibit Pax-5 expression and regulate Pax-5-associated cancer processes. In validation, we show that these effects are probably caused by direct miRNA/mRNA interaction, which are reversible by Pax-5 recombinant expression. Interestingly, miRNAs 484 and 210, which are both overexpressed in clinical tumor samples, are also modulated during epithelial-mesenchymal transitioning and hypoxia that correlate inversely to Pax-5 expression. This is the first study demonstrating the regulation of Pax-5 expression and function by non-coding RNAs. These findings will help us better understand Pax-5 aberrant expression within cancer cells, creating the possibility for more efficient diagnosis and treatments for cancer patients.

Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors.

Pax-5, an essential transcription factor in B cell development, is aberrantly expressed in various B cell cancer lesions and solid tumors such as breast carcinoma. We have recently shown that Pax-5 regulates NF-κB activity which lead to the modulation of breast cancer phenotypic features (EMT-MET). NF-κB is known as a central mediator in inflammation, stress response as well as being a gatekeeper of pro-tumorigenic activity. However, little is known as to how Pax-5 affects this modulation. We thus turned our attention to microRNAs as potential regulatory effectors. In this study, we set out to elucidate the regulatory network between differential Pax-5 expression and NF-κB activity which dictate breast cancer malignancy. Through next-generation sequencing (NGS) of breast cancer cells conditionally expressing Pax-5, we profile significantly upregulated microRNAs; including microRNA-155, a known regulator of pathological processes and suppressor of malignant growth. Through the conditional expression of microRNA-155 in breast cancer models, we identify and validate IKKε (IKBKE) as a downstream target and an essential effector of Pax-5-mediated suppression of NF-κB signaling. Using rescue experiments, we also confirm that Pax-5 modulates NF-κB activity via IKKε downregulation. Interestingly, we also show that microRNA-155, in turn, supresses Pax-5 expression, indicative of an auto-regulatory feedback loop. Altogether, we demonstrate that Pax-5 inhibits NF-κB signalling through the regulation of microRNA-155 and its downstream target IKKε. The elucidation of this signaling network is relevant as Pax-5 and NF-κB are potent transcriptional regulators of breast cancer aggressivity. In addition, IKKε is relevant oncogene aberrantly expressed in 30% of breast carcinomas. Further insight into the regulatory pathways of breast cancer progression will eventually identify strategic therapeutic and prognostic targets to improve cancer patient outcome.

A platform with connections in many directions - further remarkable facets to the multifaceted methylbiquinoxen dication.

The N,N'-dimethyl-3,3'-biquinoxalinium "methylbiquinoxen" dicationic platform is revealed to have even more fascinating possibilities than we originally thought in terms of its chemical versatility. In addition to its rich redox chemistry and coordination abilities, we have now unveiled an unexpected Lewis acid/base chemistry linked with a tuneable switching of its luminescence properties. This, amongst other things, allows for the facile fluorescent covalent labelling of hydroxyl-terminated materials. This platform provides intriguing chemical prospects realised in molecular systems such as porphyrins as well as an easy alternative functionalisation methodology to that provided by click-chemistry.

Self-Assembly of a Giant Tetrahedral 3 d-4 f Single-Molecule Magnet within a Polyoxometalate System.

A giant tetrahedral heterometallic polyoxometalate (POM) [Dy30 Co8 Ge12 W108 O408 (OH)42 (OH2 )30 ](56-) , which shows single-molecule magnet (SMM) behavior, is described. This hybrid contains the largest number of 4f ions of any polyoxometalate (POM) reported to date and is the first to incorporate two different 3d-4f and 4f coordination cluster assemblies within same POM framework.

Large spontaneous polarization and clear hysteresis loop of a room-temperature hybrid ferroelectric based on mixed-halide [BiI3Cl2] polar chains and methylviologen dication.

The search for hybrid organic-inorganic materials, which have the great advantage that they can be synthesized at moderate temperature (T < 200 °C), remains a great challenge in the field of ferroelectrics. Here, a room-temperature ferroelectric material with interesting characteristics, (MV)[BiI(3)Cl(2)] (MV(2+) = methylviologen), is reported. Its structure is based on polar inorganic chains resulting from a remarkable Cl/I segregation induced by methylviologen entities, which coincide with the fourfold polar axis of the tetragonal structure. Of great importance is that this room-temperature hybrid ferroelectric displays a clear electrical hysteresis loop with a large spontaneous polarization (>15 µC·cm(-2)).

Photochromism, electrical properties, and structural investigations of a series of hydrated methylviologen halobismuthate hybrids: influence of the anionic oligomer size and iodide doping on the photoinduced properties and on the dehydration process.

Syntheses, X-ray structural analyses, thermal behaviors, photochromism, and electrical properties of a series of methylviologen (MV(2+)) halobismuthate hybrids, namely, (MV)(3)[Bi(4)Cl(18)](H(2)O)(y) (1a, y approximately = 1.7), (MV)(4)[Bi(6)Cl(26)](H(2)O)(y) (2a, y approximately = 1.7), (MV)(4)[Bi(6)Cl(25.6)I(0.4)](H(2)O)(y) (3a, y approximately = 1.5), and (MV)(4)[Bi(6)Cl(24.6)I(1.4)](H(2)O)(y) (4a, y approximately = 1.3), are reported. Because of the thermal effect of a UV lamp or as a result of being heated up to 100 degrees C, all of the above compounds undergo a complete (1a, 2a, and 3a) or a partial (4a) dehydration together, in 2a and 3a, with an impressive structural reorganization involving a 90 degrees rotation of methylviologen dimers and, in 3a, a new Cl/I distribution, finally leading to (MV)(3)[Bi(4)Cl(18)] (1b), (MV)(4)[Bi(6)Cl(26)] (2b), (MV)(4)[Bi(6)Cl(25.6)I(0.4)] (3b), and (MV)(4)[Bi(6)Cl(24.6)I(1.4)](H(2)O)(x) (4a, x approximately = 0.65), respectively. In its turn, 4a (x approximately = 0.65) undergoes an abrupt structural change at 160 degrees C when water molecules are completely removed, leading to (MV)(4)[Bi(6)Cl(24.6)I(1.4)] (4b). Obviously, the two first dehydrated phases can be considered as the n = 2 (1b) and n = 3 (2b) members of the (MV)((2n+2)/2)[Bi(2n)Cl(8n+2)] family, and the ultimate member (n = infinity) with an infinite 1D double-chain inorganic framework, namely, (MV)[Bi(2)Cl(8)], has already been reported. According to the results of structural refinements, some positions of the Cl atoms in the [Bi(6)Cl(26)](8-) anionic cluster of 3a and 4a have been occupied by I atoms, finally leading to iodide-doped materials of the 2a type (percentage of doping: 3a, 1.5%; 4a, 5.4%). Upon UV irradiation, yellow crystals of 2a and 3a (which become 2b and 3b because of the thermal effect of the UV lamp) or yellow crystals of 2b, 3b, and 4a undergo a color change to black crystals (in the case of 2b), as observed in (MV)[Bi(2)Cl(8)], or light-brown crystals (in the cases of 3b and 4a). These photochromic properties are probably due to the photoinduced electron transfer from the anionic part to the methylviologen dications. In contrast, no color change is observed when yellow crystals of 1a or 1b and the iodide-doped (MV)[Bi(2)Cl(8-epsilon)I(epsilon)] material are irradiated. Because the relative positions of methylviologen to the host anionic frameworks are comparable in all structures (the N...Cl distances are about 3.4 A), these results indicate that such kinds of photochemical reactions depend on the dimension of the anionic networks, as well as the iodide doping. The single-crystal electrical conductivity measurements of 2b before and after irradiation were carried out between 150 and 393 K. The results prove that both of them are semiconductors with weak room temperature conductivity and that the band gap of the irradiated crystal (2b, 0.35 eV) is much smaller than that of the original hybrid 2a (1.0 eV).

Detection of low dose of piroxicam polymorph in pharmaceutical tablets by surface-enhanced Raman chemical imaging (SER-CI) and multivariate analysis.

This study demonstrates, for the first time, the ability of surface-enhanced Raman chemical imaging (SER-CI) combined with multivariate analysis to detect low levels (0.1% (w/w)) of a polymorphic form in a pharmaceutical mixture. In the studied formulation, piroxicam was used as a model molecule to develop this approach. Piroxicam is a widely available non-steroidal anti-inflammatory drug, exhibiting an interesting case of polymorphism, with two most commonly observed forms (ß and α2). In this work, the SERS spectra of piroxicam polymorphic forms ß and α2 are presented. These forms showed clear spectral differences in terms of band position and intensity. From a crystallographic point of view, the difference of exaltation between both forms was correlated with a preferred orientation of crystallites of form α2 making its SERS detection difficult compared to form ß. A preferred orientation of the (1k0) crystallographic planes of α2 was demonstrated in samples, not promoting an appropriate molecular orientation onto the metallic surface. Additionally, a semi-quantitative approach using SER-CI combined with chemometric tools was developed enabling to detect crystallites of form ß below the detection limit of conventional Raman microscopy. The exaltation of the Raman signal in the presence of silver nanoparticles allowed a higher sensitivity and a reduction of the acquisition time by a factor of 6.

Pax-5 Inhibits Breast Cancer Proliferation Through MiR-215 Up-regulation.

BACKGROUND/AIM: In breast cancer, Pax-5 promotes pro-epithelial features and suppresses malignant cancer processes. However, the molecular mechanism of this antitumor activity remains largely unknown. This study aimed to identify the cellular roles of Pax-5-regulated miRNAs in breast cancer progression. MATERIALS AND METHODS: After transient transfection of Pax-5 in MDA-MB-231 breast cancer cells, Pax-5-regulated miRNA expression was examined by next-generation sequencing. The identified Pax-5-regulated miRNAs were then validated by qRT-PCR and examined for the roles they play in breast cancer cells. RESULTS: Pax-5 was shown to be an effective modulator of miR-215-5p and its target genes. MiR-215 inhibited cell proliferation and migration of breast cancer cells, but not cell invasion. More importantly, Pax-5-induced suppression of cancer cell proliferation and migration was found to be miR-215-dependent. Interestingly, miR-215 profiling in clinical tumor samples showed that miR-215 expression was lower in cancer tissues in comparison to healthy controls. CONCLUSION: Pax-5 reduces breast cancer proliferation and migration through up-regulation of the tumor suppressor miR-215. This result supports the use of miR-215 as a prognostic marker for breast cancer.

A fascinating multifaceted redox-active chelating ligand: introducing the N,N'-dimethyl-3,3'-biquinoxalinium "methylbiquinoxen" platform.

To intimately combine a chelating ligand function with the numerous properties of a viologen-like redox-active centre would offer a rare possibility to design controllable multi-redox states, whose properties arise from strongly correlated phenomena between the organic ligand as well as with any metalloid coordinated centres. Such a concept previously proved to be feasible, however is not widely applicable owing to challenges in terms of synthesis, isolation, and aerial sensitivity of both the ligand and its metal complexes. Here we report the first stable example of such a redox-active molecule, N,N'-dimethyl-3,3'-biquinoxalinium2+/˙+/0 "methylbiquinoxen, MBqn2+/˙+/0", which shows a rich redox chemistry and chelates a metal ion in the case of the metal complex [CdCl2(MBqn0)]. This goes beyond what is possible to achieve using viologens, which are limited by not providing chelation as well as having no accessible biradicaloid state, corresponding to the neutral direduced MBqn0 open-shell behaviour we observe here.

Approaching the limit of Cu(II)/Cu(I) mixed valency in a Cu(I)Br2-N-methylquinoxalinium hybrid compound.

A novel 1D hybrid salt (MQ)[CuBr2]∞ (MQ = N-methylquinoxalinium) is reported. Structural, spectroscopic and magnetic investigations reveal a minimal Cu(II) doping of less than 0.1%. However it is not possible to distinguish Cu(I) and Cu(II). The unusually close packing of the organic moieties and the dark brown colour of the crystals suggest a defect electronic structure.

Unprecedented stacking of MV2+ dications and MV˙+ radical cations in the mixed-valence viologen salt (MV)2(BF4)3 (MV = methylviologen).

Using a slow liquid-gas diffusion method, the mixed-valence viologen salt (MV)2(BF4)3 (1) and the radical cation salt (MV)(BF4) (2) are crystallized. Both structures contain regular stacks of MV˙(+) radical cations (2) or alternating MV˙(+) and MV(2+) entities (1). A short intrastack intermolecular separation (3.23 Å) unprecedently reveals strong interactions between MV(2+) and MV˙(+) in 1.