One-step vs stepwise immobilization of 1-d coordination-based rh-rh molecular wires on gold surfaces

Reaction of dimeric [Rh(II)(2)(phen)(2)(μ-OAc)(2)(MeCN)(2)](BF(4))(2) (phen =1,10-phenanthroline) with pyrazine (pz) in a 1:2 ratio leads to the new 1-D metal-metal-bonded coordination oligomer {[Rh(II)(2)(phen)(2)(μ-OAc)(2)(pz)](BF(4))(2)}(n) (Rh-Rhpz)(n) (1), where each Rh atom of the dimeric unit (Rh-Rh) is coordinated in the equatorial plane to a nitrogen atom of a rigid and linear bifunctionalized organic linker (pz). Single X-ray diffraction analysis reveals the 1-D straight oligomeric chain structure (molecular wire, MW) consists of alternating (Rh-Rh) units and pz linking ligands with free BF(4)(-) as counteranions, and each metal center has a slightly distorted octahedral arrangement. The presence of accessible labile MeCN groups on both ends of these MWs ("free ends") enables functionalization of a 4-mercaptopyridine-gold coordinating platform (Au/MP) to form in one step a layer of coordination oligomer (Au/MP(Rh-Rhpz)(n); n ≈ 50). Furthermore (Rh-Rhpz)(n) (n = 1-6) MWs were grafted to Au/MP surfaces by a conventional step-by-step assembly construction involving coordination reactions between the Rh dimer ([Rh(2)(phen)(2)(μ-OAc)(2)(MeCN)(2)](BF(4))(2) (2)) and pz. A detailed physicochemical study (UV-vis, RAIR, QCM-D, ellipsometry, contact angle measurements, as well as impedance spectroscopy and cyclic voltammetry) has been made during both assembly methods to characterize the resulting surface-anchored coordination molecular wire (CMW) layers (Au/MP(Rh-Rhpz)(n)). The results indicate that the immobilized molecular assemblies (MAs) were successfully fabricated using both methods of assembly. The efficiency of the two methods is discussed.     

Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.     

ABAB homoleptic bis(phthalocyaninato)lutetium(III) complex: toward the real octupolar cube and giant quadratic hyperpolarizability

The concept of octupolar molecules has considerably enlarged the engineering of second-order nonlinear optical materials by giving access to 2D and 3D architectures. However, if the archetype of octupolar symmetry is a cube with alternating donor and acceptor groups at the corners, no translation of this ideal structure into a real molecule has been realized to date. This may be achieved by designing a bis(phthalocyaninato)lutetium(III) double-decker complex with a crosswise ABAB phthalocyanine bearing alternating electron-donor and electron-acceptor groups. In this communication, we present the first step toward this goal with the synthesis, crystal structure determination, and measurement of the molecular first-order hyperpolarizability β by harmonic light diffusion, of an original lutetium(III) sandwich complex displaying the required ABAB-type alternation for one face of the cube. This structure is characterized by an intense absorption in the near-IR due to an intervalence transition and exhibits the highest quadratic hyperpolarizability ever reported for an octupolar molecule, √<β(2)(HLS)> = 5750 × 10(-30) esu.     

Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering

The development of new antibiotics is imperative to fight increasing mortality rates connected to infections caused by multidrug-resistant (MDR) bacteria. In this context, Gram-negative pathogens listed in the WHO priority list are particularly problematic. Darobactin is a ribosomally produced and post-translationally modified bicyclic heptapeptide antibiotic selectively killing Gram-negative bacteria by targeting the outer membrane protein BamA. The native darobactin A producer Photorhabdus khanii HGB1456 shows very limited production under laboratory cultivation conditions. Herein, we present the design and heterologous expression of a synthetically engineered darobactin biosynthetic gene cluster (BGC) in Escherichia coli to reach an average darobactin A production titre of 13.4 mg L⁻¹. Rational design of darA variants, encoding the darobactin precursor peptide with altered core sequences, resulted in the production of 13 new ‘non-natural’ darobactin derivatives and 4 previously hypothetical natural darobactins. One of the non-natural compounds, darobactin 9, was more potent than darobactin A, and showed significantly improved activity especially against Pseudomonas aeruginosa (0.125 μg mL⁻¹) and Acinetobacter baumannii (1–2 μg mL⁻¹). Importantly, it also displayed superior activity against MDR clinical isolates of E. coli (1–2 μg mL⁻¹) and Klebsiella pneumoniae (1–4 μg mL⁻¹). Independent deletions of genes from the darobactin BGC showed that only darA and darE, encoding a radical forming S-adenosyl-l-methionine-dependent enzyme, are required for darobactin formation. Co-expression of two additional genes associated with the BGCs in hypothetical producer strains identified a proteolytic detoxification mechanism as a potential self-resistance strategy in native producers. Taken together, we describe a versatile heterologous darobactin platform allowing the production of unprecedented active derivatives in good yields, and we provide first experimental evidence for darobactin biosynthesis processes.

Heterologous expression of a synthetically engineered darobactin gene cluster in E. coli yields new darobactin derivatives with improved anti-Gram-negative activity. Targeted gene deletions provide first insights into biosynthetic steps.     

6,6′-Dimethyl-2,2′-bipyridine-4-ester: A pivotal synthon for building tethered bipyridine ligands

We describe an efficient and scalable synthesis of 4-carbomethoxy-6,6′-dimethyl-2,2′-bipyridine starting from easily available substituted 2-halopyridines and based on the application of modified Negishi cross-coupling conditions. This compound is a versatile starting material for the synthesis of 4-functionalized 2,2′-bipyridines bearing halide, alcohol, amine, and other functionalities, suitable for conjugation to biological material (2a-c, 3a-g). The utility of this compound in the construction of more complex architectures was further demonstrated by the synthesis of two bifunctional lanthanide chelators; an open chain ligand based on one 2,2′-bipyridine unit and a cryptand based on three 2,2′-bipyridine units [N₂(bpy)₃COOMe]. In the field of luminophoric biolabels, the photophysical properties of the corresponding Eu(III) cryptate are reported.     

Synthesis,Characterization, and Properties of Pentanitrobenzene C6H(NO2)5

The synthesis of the polynitroaromatic compound pentanitrobenzene was re‐examined by modern spectroscopic, structural and physicochemical methods. Originally prepared in 1979, this material could exhibit interesting properties as an oxygen‐rich energetic building block. The energies of formation were calculated with the GAUSSIAN program package and the detonation parameters were predicted using the EXPLO5 computer code. The performance data were determined and compared to the common oxidizer ammonium perchlorate. The crystal structure of pentanitrobenzene was determined by X‐ray crystallography, and those of 2,3,4,6‐tetranitroaniline and styphnic acid (trinitroresorcinol) were re‐determined.     

The Role of the Nucleotides in the Insertion of the bis-Molybdopterin Guanine Dinucleotide Cofactor into apo-Molybdoenzymes

The role of the GMP nucleotides of the bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor of the DMSO reductase family has long been a subject of discussion. The recent characterization of the bis-molybdopterin (bis-Mo-MPT) cofactor present in the E. coli YdhV protein, which differs from bis-MGD solely by the absence of the nucleotides, now enables studying the role of the nucleotides of bis-MGD and bis-MPT cofactors in Moco insertion and the activity of molybdoenzymes in direct comparison. Using the well-known E. coli TMAO reductase TorA as a model enzyme for cofactor insertion, we were able to show that the GMP nucleotides of bis-MGD are crucial for the insertion of the bis-MGD cofactor into apo-TorA.     

Phototoxicity of Some Bromine-Substituted Rhodamine Dyes: Synthesis, Photophysical Properties and Application as Photosensitizers

Abstract— The synthesis of some bromine-substituted rhodamine derivatives viz. , 4,5-dibromorhodamine methyl ester (dye 2) and 4,5-dibromorhodamine n -butyl ester (dye 3) are reported. These dyes were synthesized to promote a more efficient cancer cell photosensitizer for potential use in in vitro bone marrow purging in preparation for autologous bone marrow transplantation. Spectroscopic and photo-physical characterization of these dyes together with rhodamine 123 (dye 1) are reported in water, methanol, eth-anol and also in a microheterogeneous system, sodium dodecyl sulfate. The possible mechanism of photosensi-tization is characterized in terms of singlet oxygen efficiency of these dyes. Singlet oxygen quantum yields for bromine-substituted dyes are in the range of 0.3-0.5 depending on the solvent. For dye 1 no singlet oxygen production is found. The photodynamic actions of these dyes in different cell lines are tested. It was found that dye 2 and dye 3 are efficient photosensitizers and mediate eradication of K562, EM2, myeloid cell lines (CML) and the SMF-AI rhabdomyosarcoma line.     

Understanding glycine conformation through molecular orbitals

The four most stable C(s) conformers of glycine have been investigated using a variety of quantum-mechanical methods based on Hartree-Fock theory, density-functional theory (B3LYP and statistical average of orbital potential), and electron propagation (OVGF) treatments. Information obtained from these models were analyzed in coordinate and momentum spaces using dual space analysis to provide insight based on orbitals into the bonding mechanisms of glycine conformers, which are generated by rotation of C-O(H) (II), C-C (III), and C-N (IV) bonds from the global minimum structure (I). Wave functions generated from the B3LYP/TZVP model revealed that each rotation produced a unique set of fingerprint orbitals that correspond to a specific group of outer valence orbitals, generally of a' symmetry. Orbitals 14a', 13a', 12a', and 11a' are identified as the fingerprint orbitals for the C-O(H) (II) rotation, whereas fingerprint orbitals for the C-C (III) bond rotation are located as 16a' [highest occupied molecular orbital (HOMO)], 15a' [next highest molecular occupied molecular orbital (NHOMO)], 14a', and 12a' orbitals. Fingerprint orbitals for IV generated by the combined rotations around the C-C, C-O(H), and C-N bonds are found as 16a', 15a', 14a', 13a', and 11a', as well as in orbitals 2a" and 1a". Orbital 14a' is identified as the fingerprint orbital for all three conformational processes, as it is the only orbital in the outer valence region which is significantly affected by the conformational processes regardless rotation of which bond. Binding energies, molecular geometries, and other molecular properties such as dipole moments calculated based on the specified treatments agree well with available experimental measurements and with previous theoretical calculation.