Stannylenes and Germylenes Stabilized by Tetradentate Bis(amidine) Ligands with a Rigid Naphthalene Backbone.

An unusual series of germylenes and stannylenes stabilized by new tetradentate bis(amidine) ligands RNC(R')N-linker-NC(R')NR with a rigid naphthalene backbone has been prepared by protonolysis reaction of Lappert's metallylenes [M(HMDS)] (M = Ge or Sn). Germylenes and stannylenes were fully characterized by NMR spectroscopy and X-ray diffraction analysis. DFT calculations have been performed to clarify the structural and electronic properties associated with tetradentate bis(amidine) ligands.

Synthesis and Characterization of Iridium(III) Complexes with Substituted Phenylimidazo(4,5-)1,10-phenanthroline Ancillary Ligands and Their Application in LEC Devices.

In this work, we report on the synthesis and characterization of six new iridium(III) complexes of the type [Ir(C^N)(N^N)] using 2-phenylpyridine (-) and its fluorinated derivative (-) as cyclometalating ligands (C^N) and R-phenylimidazo(4,5-)1,10-phenanthroline (R = H, CH, F) as the ancillary ligand (N^N). These luminescent complexes have been fully characterized through optical and electrochemical studies. In solution, the - series exhibits quantum yields (Ф) twice as high as the - series, exceeding 60% in dichloromethane and where MLCT/LLCT and LC emissions participate in the phenomenon.

Air- and Water-Stable Heteroleptic Copper (I) Complexes Bearing Bis(indazol-1-yl)methane Ligands: Synthesis, Characterisation, and Computational Studies.

A series of four novel heteroleptic Cu(I) complexes, bearing bis(1-indazol-1-yl)methane analogues as , ligands and DPEPhos as the ligand, were synthesised in high yields under mild conditions and characterised by spectroscopic and spectrometric techniques. In addition, the position of the carboxymethyl substituent in the complexes and its effect on the electrochemical and photophysical behaviour was evaluated. As expected, the homoleptic copper (I) complexes with the , ligands showed air instability.

Predicting the effect of CRISPR-Cas9-based epigenome editing.

Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models to predict gene expression from histone post-translational modifications (PTMs), achieving transcriptome-wide correlations of ~ 0.70 - 0.

Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.

Engineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR-Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors.

Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae.

Multidrug-resistant bacteria, such as ESBL producing-Klebsiella pneumoniae, have increased substantially, encouraging the development of complementary therapies such as photodynamic inactivation (PDI). PDI uses photosensitizer (PS) compounds that kill bacteria using light to produce reactive oxygen species. We test Ru-based PS to inhibit K.

The sound of silence: Transgene silencing in mammalian cell engineering.

To elucidate principles operating in native biological systems and to develop novel biotechnologies, synthetic biology aims to build and integrate synthetic gene circuits within native transcriptional networks. The utility of synthetic gene circuits for cell engineering relies on the ability to control the expression of all constituent transgene components. Transgene silencing, defined as the loss of expression over time, persists as an obstacle for engineering primary cells and stem cells with transgenic cargos.

Multiplex Base-Editing Enables Combinatorial Epigenetic Regulation for Genome Mining of Fungal Natural Products.

Genome mining of cryptic natural products (NPs) remains challenging, especially in filamentous fungi, owing to their complex genetic regulation. Increasing evidence indicates that several epigenetic modifications often act cooperatively to control fungal gene transcription, yet the ability to predictably manipulate multiple genes simultaneously is still largely limited. Here, we developed a multiplex base-editing (MBE) platform that significantly improves the capability and throughput of fungal genome manipulation, leading to the simultaneous inactivation of up to eight genes using a single transformation.

Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription.

To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers and genes connected by loops exhibit stronger correlations between histone H3K27 acetylation and expression than can be explained by genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes in acetylation at distal enhancers precede changes in gene expression.

Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays.

We designed, synthesized, and evaluated novel 2,6,9-trisubstituted purine derivatives for their prospective role as antitumor compounds. Using simple and efficient methodologies, 31 compounds were obtained. We tested these compounds in vitro to draw conclusions about their cell toxicity on seven cancer cells lines and one non-neoplastic cell line.

(-)-Shikimic Acid as a Chiral Building Block for the Synthesis of New Cytotoxic 6-Aza-Analogues of Angucyclinones.

We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene , with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and one non-tumoral cell line, human colon epithelial cells (CCD841 CoN). Our results showed that most 6-azadiene derivatives exhibited significant cytotoxic activities, which was demonstrated by their IC values (less than 10 μM), especially for the most sensitive cells, PC-3 and HT-29.

New imidoyl-indazole platinum (II) complexes as potential anticancer agents: Synthesis, evaluation of cytotoxicity, cell death and experimental-theoretical DNA interaction studies.

Four new neutral N,N imidoyl-indazole ligands (L1, L3, L6, L7) and six new Pt(II)-based complexes (C1-5 and C7) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6, L7, C3, C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively.

Fluorescence properties of aurone derivatives: an experimental and theoretical study with some preliminary biological applications.

In this paper, we explored the fluorescence properties of eight aurone derivatives bearing methoxy groups and bromine atoms as substituents in the benzene rings. All derivatives showed strong solvatochromic absorption and emission properties in solvents of different polarities. Some of them showed high fluorescence quantum yields, which make them potential compounds for sensing applications.

Synthesis of new asymmetric substituted boron amidines - reactions with CO and transfer hydrogenations of phenylacetylene.

The syntheses of the new asymmetric substituted boron amidines [N'-(2,6-diisopropylphenyl)-N-(pentafluorophenyl)acetimidamide]bis(pentafluorophenyl)borate () and [N'-(2,6-diisopropylphenyl)-N-(4-cyanophenyl)acetimidamide]bis(pentafluorophenyl)borate () were achieved by reaction of one equivalent of HB(C6F5)2 and the respective amidines and . These adducts, bearing electron withdrawing groups, showed thermally induced H2 elimination forming the four-membered cyclic diazaborate derivatives and . These new species were characterized by spectroscopic methods.

Synthesis of [(π-cyano-P-nacnac)Cp] and [(π-cyano-nacnac)Cp]-zirconium complexes, and their remote activation for ethylene polymerization.

In this contribution the synthesis and characterization of two distinct, yet similar, zirconium complexes, [(π-P-nacnac-CN)Cp] and [(π-nacnac-CN)Cp] zirconium dichloride were discussed. In addition to the complexes, Lewis acid adducts [B(C(6)F(5))(3)] of the complexes were isolated and characterized as well. It was found that while structurally similar, the complexes behave distinctly upon adduct formation and in their ethylene polymerizations.