Pressure-induced switching properties of the iron(iii) spin-transition complex [FeIII(3-OMeSalEen)2]PF6.

We investigated the effect of an externally applied pressure on the iron(iii) Schiff-base compound [Fe(3-OMeSalEen)2]PF6 (H-3-OMeSalEen, condensation product of 3-methoxy-substituted salicylaldehyde and N-ethylethylenediamine), which at ambient pressure displays a thermal spin transition with a 3 K wide hysteresis loop centered at 164 K. Raman spectrometry revealed the occurrence of a complete spin-state switching process for a pressure of P1/2 = 8-9 kbar at room temperature. The evolution of lattice parameters as a function of pressure was followed by X-ray diffraction measurements on single crystals, highlighting the important microscopic aspects at the origin of the pressure-induced transition, i.e. an anisotropic response and a high compressibility of the HS molecular lattice. Variable temperature magnetic susceptibility measurements at different applied pressures revealed the smoothening of the spin transition curves and a linear increase of the transition temperatures by ca. 16.4 (1.0) K kbar-1, in good agreement with the Clausius-Clapeyron law. The non-negligible influence of the pressure transmitting oils on the intrinsic transition properties was also evidenced and attributed to mechanical interactions between the particles and the solidified matrix.

Nanocrystals of Fe(phen)2(NCS)2 and the size-dependent spin-crossover characteristics.

We report on the size reduction of the neutral Fe(phen)2(NCS)2 prototypical compound exhibiting a cooperative spin-crossover associated with a first-order phase transition (at ca. 176 K). We use the [Fe(phen)3](NCS)2 ionic precursor and the solvent-assisted precipitation technique to prepare an array of crystalline objects with sizes varying over two orders of magnitude (from 15 up to 1400 nm). TEM, X-ray diffraction and IR measurements provide evidences for the formation of particles of neutral and ionic species, which results from the interplay between the relevant chemical equilibrium and the reaction kinetics (ligand extraction, complex precipitation), and the modulation of the latter by physico-chemical parameters. A thermal transformation of diamagnetic nanocrystals of [Fe(phen)3](NCS)2 leads to spin-crossover particles of Fe(phen)2(NCS)2 of a comparable size. Powders of nano-, micro- and polycrystals of Fe(phen)2(NCS)2 present X-ray diffractograms typical of the so-called polymorph II. The importance of size effects on the cooperative spin-crossover process was probed with magnetic, Mössbauer, Raman and IR spectroscopic measurements. Each sample exhibits spin-state switching of the Fe(ii) ions. The salient features are: a cooperativity preserved at the micrometric scale, a very limited downshift of the transition temperature and an asymmetric spreading of the thermal process (over ca. 100 K) with the size reduction. At temperatures close to room temperature, the process appears to be quasi complete whatever the size of the samples. This result, extracted from Raman data, was confirmed by Mössbauer measurements in the case of the largest objects (LS residue <5-10% for bulk and microparticles). Below 150 K, a very efficient low-spin to high-spin photoexcitation was induced by the Raman laser beam in all the samples which prevents the extraction of the high-spin fraction in this temperature range. However variable temperature IR spectra of the 29 nm particles indicate that the HS residue, that is close to zero in the case of microparticles, does not drastically increase (<30%) for the smallest particles. The processing of a number of related spin-crossover compounds in the form of nanoparticles may be achieved with this general approach.

Hyperactivation of constitutively dimerized oncogenic EGF receptors by autocrine loops.

The epidermal growth factor (EGF) receptor (EGFR) has a key role in normal embryonic development, adult tissue homeostasis and many pathological processes, in particular tumour formation. Aberrant EGFR activation occurs in many cancer types, and inhibition of this receptor is a promising anti-tumour strategy. Besides overexpression of the wild-type receptor, mutated oncogenic EGFR variants are often associated with malignant transformation. In human non-small-cell lung cancers, kinase mutants of the EGFR are rather common. Human glioblastoma often express the truncated EGFRvIII version as well as other dimerized and permanently activated mutants of the receptor, which are considered as tumour drivers. Similarly, the mutated and dimerized EGFR variant Xiphophorus melanoma receptor kinase (Xmrk) is causative for the development of malignant pigment cell tumours in medaka and Xiphophorus melanoma models. It is generally believed that oncogenic receptors that are active due to dimerizing mutations are ligand independent. Here, we show that different EGFR variants from fish and human efficiently induce autocrine loops by inducing EGFR ligands such as amphiregulin and HB-EGF. Importantly, the pre-dimerized oncogenic EGFR versions Xmrk from Xiphophorus and human EGFR(C600F), though already active in absence of ligands, respond to ligand stimulation with enhanced oncogenic signalling. In summary, our data show that autocrine or paracrine loops are still acting on pre-dimerized oncogenic EGFRs and contribute to their pro-tumorigenic signalling.