MicroRNAs-Dependent Regulation of PPARs in Metabolic Diseases and Cancers

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-dependent nuclear receptors, which control the transcription of genes involved in energy homeostasis and inflammation and cell proliferation/differentiation. Alterations of PPARs’ expression and/or activity are commonly associated with metabolic disorders occurring with obesity, type 2 diabetes, and fatty liver disease, as well as with inflammation and cancer. Emerging evidence now indicates that microRNAs (miRNAs), a family of small noncoding RNAs, which fine-tune gene expression, play a significant role in the pathophysiological mechanisms regulating the expression and activity of PPARs. Herein, the regulation of PPARs by miRNAs is reviewed in the context of metabolic disorders, inflammation, and cancer. The reciprocal control of miRNAs expression by PPARs, as well as the therapeutic potential of modulating PPAR expression/activity by pharmacological compounds targeting miRNA, is also discussed

Syntheses, structures, and infrared spectra of the hexa(cyanido) complexes of silicon, germanium, and tin

The rare octahedral EC6 coordination skeleton type is unknown for complexes with coordination centers consisting of group 14 elements. Here, the first examples of such EC6 species, the hexacoordinate homoleptic cyanido complexes E(CN)62–, E = Si, Ge, Sn, have been synthesized from element halides SiCl4, GeCl4 and SnF4 and isolated as salts with PPN counterions (PPN+ = (Ph3P)2N+) on a scale of 0.2–1 g. Characterization by spectroscopic techniques and by structure determination through single crystal crystallographic methods show that these pseudohalogen complexes have effective octahedral symmetry in solution and in the solid state. Infrared spectra obtained in solution reveal that the T1u symmetric IR-active vibrations in all three complexes have unusually small oscillator strengths. The observed reluctance of Si(CN)62–, Ge(CN)62–, and Sn(CN)62– to form from chloro-precursors was rationalized in terms of Gibbs free energies, which were found by ab initio calculations at the CCSD(T)-F12b/aug-cc-pVTZ(-PP)-F12 level of theory to be small or even positive. The work demonstrates that E(CN)62– complexes of silicon, germanium and tin are in fact stable at room temperature and exist as well-defined units in the presence of noncoordinating counterions. The results add to our understanding of the chemistry of pseudohalogens and structure and bonding

Structure and dynamics of iron pentacarbonyl

The dynamics of CO ligand scrambling in Fe(CO)5 has been investigated by linear infrared spectroscopy in supercritical xenon solution. The activation barrier for the Berry pseudorotation in Fe(CO)5 was determined experimentally to be Ea = 2.5 ± 0.4 kcal mol–1 by quantitative analysis of the temperature-dependent spectral line shape. This compares well with the range of Ea/(kcal mol–1) = 2.0 to 2.3 calculated by various DFT methods and the value of 1.6 ± 0.3 previously obtained from 2D IR measurements by Harris et al. ( Science 2008, 319, 1820). The involvement of Fe(CO)5···Xe interactions in the ligand scrambling process was tested computationally at the BP86-D3/AE2 level and found to be negligible

Synthesis of six-coordinate mono-, bis-, and tris(tetrazolato) complexes via [3 + 2] cycloadditions of nitriles to silicon-bound azido ligands

A convenient synthetic route to poly(tetrazolato) silicon complexes is described based on the four reactive centres of the N-rich, highly endothermic tetraazides of the type Si(N3)4(L2). Hypercoordinate azido(tetrazolato) silicon complexes Si(N3)2(N4C-R)2(L2), R = CH3, C6H5, 4-C6H4CH3 (4a, 5, 6, 7) and Si(N3)2(N4C-L)2 (9, L = 2-C5H4N), L2 = 2,2'-bipyridine, 1,10-phenanthroline, with SiN6 skeletons were synthesised via multiple [3 + 2] dipolar cycloaddition reactions starting from Si(N3)4(L2) and a nitrile. The isolated new complexes were characterised by standard analytical methods, single crystal X-ray diffraction and differential scanning calorimetry (4a,b). Tetrazolato ligand linkage isomerism was observed for complex 4a. The crystallographically characterised methyl tetrazolato complexes and plausible configurational and linkage isomers were evaluated by DFT calculations at the B3LYP/6-311G(d,p) level

Picosecond time-resolved infrared spectroscopy of rhodium and iridium azides

Picosecond time-resolved infrared spectroscopy was used to elucidate early photochemical processes in the diazido complexes M(Cp*)(N3)2(PPh3), M = Rh (1), Ir (2), using 266 nm and 400 nm excitation in THF, CH2Cl2, MeCN and toluene solutions. The time-resolved data have been interpreted with the aid of DFT calculations on vibrational spectra of the singlet ground states and triplet excited states and their rotamers. While the yields of phototransformations via N2 loss are low in both complexes, 2 cleaves a N3 ligand under 266 nm excitation. The molecular structure of 1 is also reported as determined by single crystal X-ray diffraction

Homoleptic Low-Valent Polyazides of Group 14 Elements

First examples of coordinatively unsaturated, homoleptic azido complexes of low-valent group 14 elements are reported. A simple strategy uses low-valent precursors, ionic azide transfer reagents and bulky cations to obtain salt-like compounds containing E(N3)3- of Ge(II)/Sn(II) which are fully characterised, including XRD. Remarkably, these compounds are kinetically stable at r.t. and isolable in sub-gram quantities

A Pathway to the Athermal Impact Initiation of Energetic Azides

Energetic materials (explosives, propellants and pyrotechnics) are used in a broad range of public and private sector applications. The design of novel, safe materials is therefore of critical importance. Until now, no physical mechanism has been described to rationalize the impact sensitivity properties of energetic materials. Investigation therefore has required lengthy synthesis and experimental testing. Based on knowledge of the effects of mechanical impact, an ab initio model is developed to rationalize and describe the impact sensitivity of a series of crystalline energetic azide materials. It is found that electronic excitation of the azido anion is sufficient for initiation of these materials. The athermal excitation can be achieved through consideration of non-adiabatic, vibronic processes. Across the series of azides studied here, the electronic structure of the azido anion is found to remain largely constant. By considering only the relative rates of vibrational energy transfer within the crystalline materials, it is found that a direct correlation exists between the relative impact sensitivity and the rate of energy up-conversion. Thus, the present contribution demonstrates a fully ab initio method to describe the athermal initiation of ideal, crystalline energetic materials, and predict their relative sensitivity. Without the need for any experimental input beyond a crystal structure, this method therefore offers a means to selectively design novel materials for targeted application

Taming Tin(IV) Polyazides

The first charge-neutral Lewis base adducts of tin(IV) tetraazide, [Sn(N3)4(bpy)], [Sn(N3)4(phen)] and [Sn(N3)4(py)2], and the salt bis{bis(triphenylphosphine)iminium} hexa(azido)stannate [(PPN)2Sn(N3)6] (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline; py = pyridine; PPN = N(PPh3)2) have been prepared using covalent or ionic azide-transfer reagents and ligand-exchange reactions. The azides were isolated on the 0.3 to 1 g scale and characterized by IR and NMR spectroscopies, microanalytical and thermal methods and their molecular structures determined by single-crystal XRD. All complexes have a distorted octahedral Sn[N]6 coordination geometry and possess greater thermal stability than their Si and Ge homologues. The nitrogen content of the adducts of up to 44 % exceed any SnIV compound known hitherto

Labile low-valent tin azides: syntheses, structural characterization, and thermal properties.

The first two examples of the class of tetracoordinate low-valent, mixed-ligand tin azido complexes, Sn(N3)2(L)2, are shown to form upon reaction of SnCl2 with NaN3 and SnF2 with Me3SiN3 in either pyridine or 4-picoline (2, L = py; 3, L = pic). These adducts of Sn(N3)2 are shock- and friction-insensitive and stable at r.t. under an atmosphere of pyridine or picoline, respectively. A new, fast, and efficient method for the preparation of Sn(N3)2 (1) directly from SnF2, and by the stepwise de-coordination of py from 2 at r.t., is reported that yields 1 in microcrystalline form, permitting powder X-ray diffraction studies. Reaction of 1 with a nonbulky cationic H-bond donor forms the salt-like compound {C(NH2)3}Sn(N3)3 (4) which is comparably stable despite its high nitrogen content (55%) and the absence of bulky weakly coordinating cations that are conventionally deemed essential in related systems of homoleptic azido metallates. The spectroscopic and crystallographic characterization of the polyazides 1-4 provides insight into azide-based H-bonded networks and unravels the previously unknown structure of 1 as an important lighter binary azide homologue of Pb(N3)2. The atomic coordinates for 1 and 2-4 were derived from powder and single crystal XRD data, respectively; those for 1 are consistent with predictions made by DFT-D calculations under periodic boundary conditions