Adaptive optimization of the OXPHOS assembly line partially compensates lrpprc-dependent mitochondrial translation defects in mice

Mouse models of genetic mitochondrial disorders are generally used to understand specific molecular defects and their biochemical consequences, but rarely to map compensatory changes allowing survival. Here we took advantage of the extraordinary mitochondrial resilience of hepatic Lrpprc knockout mice to explore this question using native proteomics profiling and lipidomics. In these mice, low levels of the mtRNA binding protein LRPPRC induce a global mitochondrial translation defect and a severe reduction (>80%) in the assembly and activity of the electron transport chain (ETC) complex IV (CIV). Yet, animals show no signs of overt liver failure and capacity of the ETC is preserved. Beyond stimulation of mitochondrial biogenesis, results show that the abundance of mitoribosomes per unit of mitochondria is increased and proteostatic mechanisms are induced in presence of low LRPPRC levels to preserve a balance in the availability of mitochondrial- vs nuclear-encoded ETC subunits. At the level of individual organelles, a stabilization of residual CIV in supercomplexes (SCs) is observed, pointing to a role of these supramolecular arrangements in preserving ETC function. While the SC assembly factor COX7A2L could not contribute to the stabilization of CIV, important changes in membrane glycerophospholipid (GPL), most notably an increase in SC-stabilizing cardiolipins species (CLs), were observed along with an increased abundance of other supramolecular assemblies known to be stabilized by, and/or participate in CL metabolism. Together these data reveal a complex in vivo network of molecular adjustments involved in preserving mitochondrial integrity in energy consuming organs facing OXPHOS defects, which could be therapeutically exploited.

Synthesis and Structural Studies of Two New Anthracene Derivatives

Anthracene derivatives are an interesting class of compounds and modifications in the anthracene ring, producing different compounds with different properties. Structural analysis of anthracene derivatives with modifications in position 9,10 of the aromatic ring is necessary in order to obtain information about its properties. The introduction of groups with polar substituents increases the possibility to modify the molecule lipophilicity, corroborating its use as bioimaging probes. Anthracene derivatives are used in many biochemical applications. These compounds can react with molecular singlet oxygen [O2 (1Δg)], a reactive oxygen species, through the Diels–Alder reaction [4 + 2] to form the respective endoperoxide and to be used as a chemical trap in biological systems. Thus, the structural and crystalline characterizations of two anthracene derivatives are presented in this work to obtain information about their physical-chemical properties. The compounds were characterized by Fourier-transform infrared spectroscopy, thermogravimetric analyses and scanning electron microscopy. The molecular structures of the compounds were studied by the Density Functional Theory, M06-2X/6-311++G(d,p) level of theory in the gas phase. From the results obtained for the frontier molecular orbitals, HOMO and LUMO, and from the Molecular Electrostatic Potential map, it was possible to predict the chemical properties of both compounds. The supramolecular arrangements were also theoretically studied, whose molecules were kept fixed in their crystallographic positions, through the natural bonding orbitals analysis to check the stability of interactions and the quantum theory of atoms in molecules to verify the type of intermolecular interaction between their molecules, as well as how they occur.

Exploration of CH⋯F & CF⋯H mediated supramolecular arrangements into fluorinated terphenyls and theoretical prediction of their third-order nonlinear optical response

Three novel fluorinated terphenyls were synthesized by a Suzuki Miyaura method. DFT and TDDFT were performed to explore FMO, DOS analysis and third-order NLO properties. This may provide new ways to utilise fluorinated terphenyl compounds as advanced functional materials.

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

Transition metal-based compounds have shown promising uses as therapeutic agents. Among their unique characteristics, these compounds are suitable for interaction with specific biological targets, making them important potential drugs to treat various diseases. Copper compounds, of which Casiopeinas® are an excellent example, have shown promising results as alternatives to current cancer therapies, in part because of their intercalative properties with DNA. Vanadium compounds have been extensively studied for their pharmacological properties and application, mostly in diabetes, although recently, there is a growing interest in testing their activity as anti-cancer agents. In the present work, two compounds, [Cu(Metf)(bipy)Cl]Cl·2H2O and [Cu(Impy)(Gly)(H2O)]VO3, were obtained and characterized by visible and FTIR spectroscopies, single-crystal X-ray diffraction, and theoretical methods. The structural and electronic properties of the compounds were calculated through the density functional theory (DFT) using the Austin–Frisch–Petersson functional with dispersion APFD, and the 6-311 + G(2d,p) basis set. Non-covalent interactions were analyzed using Hirshfeld surface analysis (HSA) and atom in molecules analysis (AIM). Additionally, docking analysis to test DNA/RNA interactions with the Casiopeina-like complexes were carried out. The compounds provide metals that can interact with critical biological targets. In addition, they show interesting non-covalent interactions that are responsible for their supramolecular arrangements.

Background reduction in STED-FCS using coherent-hybrid STED

Fluorescence correlation spectroscopy (FCS) is a valuable tool to study the molecular dynamics of living cells. When used together with a super-resolution stimulated emission depletion (STED) microscope, STED-FCS can measure diffusion processes at the nanoscale in living cells. In twodimensional (2D) systems like the cellular plasma membrane, a ring-shaped depletion focus is most commonly used to increase the lateral resolution, leading to more than 25-fold decrease in the observation volumee, reaching the relevant scale of supramolecular arrangements. However, STED-FCS faces severe limitations when measuring diffusion in three dimensions (3D), largely due to the spurious background contributions from undepleted areas of the excitation focus that reduce the signal quality and ultimately limit the resolution. In this paper, we investigate how different STED confinement modes can mitigate this issue. By simulations as well as experiments with fluorescent probes in solution and in cells, we demonstrate that the coherent-hybrid (CH) depletion pattern reduces background most efficiently and thus provides superior signal quality under comparable reduction of the observation volume. Featuring also the highest robustness to common optical aberrations, CH-STED can be considered the method of choice for reliable STED-FCS based investigations of 3D diffusion on the sub-diffraction scale.

Bis(μ2-benzoato-κ2 O,O′)bis(benzoato-κO)bis(ethanol-κO)bis(μ3-hydroxido)hexakis(μ-pyrazolato-κ2 N,N′)hexacopper(II) ethanol disolvate

Trinuclear copper–pyrazolate entities are present in various Cu-based enzymes and nanojar supramolecular arrangements. The reaction of copper(II) chloride with pyrazole (pzH) and sodium benzoate (benzNa) assisted by microwave radiation afforded a neutral centrosymmetric hexanuclear copper(II) complex, [Cu6(C7H5O2)4(OH)2(C3H3N2)6(C2H5OH)2]·2C2H5OH. Half a molecule is present in the asymmetric unit that comprises a [Cu3(μ3-OH)(pz)3]2+ core with the copper(II) atoms arranged in an irregular triangle. The three copper(II) atoms are bridged by an O atom of the central hydroxyl group and by three bridging pyrazolate ligands on each of the sides. The carboxylate groups show a chelating mode to one and a bridging syn,syn mode to the other two CuII atoms. The coordination environment of one CuII atom is square-planar while it is distorted square-pyramidal for the other two. Two ethanol molecules are present in the asymmetric unit, one binding to one of the CuII atoms, one as a solvent molecule. In the crystal, stabilization arises from intermolecular O—H...O hydrogen-bonding interactions.

Synthesis, characterization and cytotoxic activity of tioconazole coordination compounds with nickel(II), palladium(II) and platinum(II)

Coordination compounds of nickel(II), palladium(II) and platinum(II) with tioconazole (tcnz) were synthesized and characterized by infrared, UV-Vis-NIR, elemental analysis, molar conductivity, magnetic susceptibility, mass spectrometry, NMR spectroscopy and X- ray diffraction. Tioconazole presented a monodentate coordination mode, through the nitrogen atom of the imidazolic ring. The NiII compounds stabilized an octahedral geometry. In [Ni(tcnz)2(NO3)2].H2O the coordinated nitrate presented a bidentate coordination mode, while for the [Ni(tcnz)2(OAc)2].3H2O compound, the acetate behaves as a bridging ligand. When different molar ratios were used on the reaction synthesis, three or six ligands were coordinate to the nickel(II) atom, [Ni(tcnz)3Br2(H2O)], [Ni(tcnz)6]Cl2 and [Ni(tcnz)6]Br2. The palladium(II) and platinum(II) compounds, [Pd(tcnz)2Cl2], [Pt(tcnz)2Cl2].2H2O and [Pd(tcnz)2(OAc)2], stabilized a trans-square planar geometry. The compounds [Ni(tcnz)6]X2 give place to 3D supramolecular arrangements through hydrogen bonding (X∙∙∙H, X = Cl and Br) and p∙∙∙p stacking interactions, between the six membered rings of neighbouring molecules. The in vitro cytotoxic activity of the synthesized compounds was studied in four different human carcinoma cell lines: HCT-15 (colon), HeLa (cervix-uterine), MCF-7 (breast) and PC-3 (prostate).