New heteroleptic bis-phenanthroline copper(I) complexes with dipyridophenazine or imidazole fused phenanthroline ligands: spectral, electrochemical, and quantum chemical studies

Two new sterically challenged diimine ligands L(1) (2,9-dimesityl-2-(4'-bromophenyl)imidazo[4,5-f][1,10]phenanthroline) and L(2) (3,6-di-n-butyl-11-bromodipyrido[3,2-a:2',3'-c]phenazine) have been synthesized with the aim to build original heteroleptic copper(I) complexes, following the HETPHEN concept developed by Schmittel and co-workers. The structure of L(1) is based on a phen-imidazole molecular core, derivatized by two highly bulky mesityl groups in positions 2 and 9 of the phenanthroline cavity, preventing the formation of a homoleptic species, while L(2) is a dppz derivative, bearing n-butyl chains in α positions of the chelating nitrogen atoms. The unambiguous formation of six novel heteroleptic copper(I) complexes based on L(1), L(2), and complementary matching ligands (2,9-R(2)-1,10-phenanthroline, with R = H, methyl, n-butyl or mesityl) has been evidenced, and the resulting compounds were fully characterized. The electronic absorption spectra of all complexes fits well with DFT calculations allowing the assignment of the main transitions. The characteristics of the emissive excited state were investigated in different solvents using time-resolved single photon counting and transient absorption spectroscopy. The complexes with ligand L(2), bearing a characteristic dppz moiety, exhibit a very low energy excited-state which mainly leads to fast nonradiative relaxation, whereas the emission lifetime is higher for those containing the bulky ligand L(1). For example, a luminescence quantum yield of about 3 × 10(-4) is obtained with a decay time of about 50 ns for C2 ([Cu(I)(nBu-phen)(L(1))](+)) with a weak influence of strong coordinating solvent on the luminescence properties. Overall, the spectral features are those expected for a highly constrained coordination cage. Yet, the complexes are stable in solution, partly due to the beneficial π stacking between mesityl groups and vicinal phenanthroline aromatic rings, as evidenced by the X-ray structure of complex C3 ([Cu(I)(Mes-phen)(L(2))](+)). Electrochemistry of the copper(I) complexes revealed reversible anodic behavior, corresponding to a copper(I) to copper(II) transition. The half wave potentials increase with the steric bulk at the level of the copper(I) ion, reaching a value as high as 1 V vs SCE, with the assistance of ligand induced electronic effects. L(1) and L(2) are further end-capped by a bromo functionality. A Suzuki cross-coupling reaction was directly performed on the complexes, in spite of the handicapping lability of copper(I)-phenanthroline complexes.     

Naphthalene-fused metallo-porphyrins--synthesis and spectroscopy

Oxidative aromatic coupling of meso-substituted porphyrins bearing one electron-rich naphthalene unit has been studied in detail. After thorough optimization of oxidant, naphthalene-fused porphyrins were prepared in high yield without contamination from chlorinated side-products using Fe(ClO(4))(3)·2H(2)O. Copper and nickel complexes were successfully transformed into π-expanded porphyrins in 40-83% yield.     

Complexes of lanthanide nitrates with tri tert butylphosphine oxide

Reaction of lanthanide nitrates with (t)Bu(3)PO (=L) lead to the isolation of complexes Ln(NO(3))(3)L(2)·H(2)O·nEtOH (Ln = La (1), Nd(2)), Ln(NO(3))(3)L(2)?·nEtOH (Sm(3), Eu(4)), and Ln(NO(3))(3)L(2) (Dy(5), Er(6), Lu(7)). These have been characterized by elemental analysis, infrared and NMR((1)H, (13)C and (31)P) spectroscopy and single-crystal X-ray diffraction. The structures show L to be positioned on opposite sides of the metal with the nitrates forming an equatorial band. When Ln = Dy, Er, and Lu two distinct molecules are present in the unit cell. A major isomer (70%) has a (P)O-Ln-O(P) angle of less than 180° with one of the nitrate ligands twisted out of the plane of the other nitrates while the lower abundance isomer is more symmetric with the (P)O-Ln-O(P) angle of 180° and the nitrate ligands coplanar giving a hexagonal bipyramidal geometry. These isomers cannot be observed by variable temperature solution (31)P NMR measurements but are clearly seen in the solid-state NMR spectrum of the Lu complex. Variable temperature solid-state NMR indicates that the isomers do not interconvert at temperatures up to 100 °C. Attempts to prepare cationic species [Ln(NO(3))(2)L(3)](+)[PF(6)](-) have not been totally successful and led to the isolation of crystals of Lu(NO(3))(3)L(2) and Tb(NO(3))(3)L(2).CH(3)CN (8).     

Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers

Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use.     

Semipinacol rearrangement of cis-fused β-lactam diols into keto-bridged bicyclic lactams

The 6-azabicyclo[3.2.1]octane ring system, prevalent in a range of biologically active molecules, is prepared through a novel semipinacol rearrangement utilizing a cyclic phosphorane or sulfite intermediate. The rearrangement proceeds with exclusive N-acyl group migration of a β-lactam ring and results in carbonyl functionality at the 7- and bridging 8-position of the bicycle. Precursor ring-fused β-lactam diols are prepared through a sequence of 4-exo trig carbamoyl radical cyclization, regioselective dithiocarbamate group elimination, and dihydroxylation.     

Controlled production of subradiant states of a diatomic molecule in an optical lattice

We report the successful production of subradiant states of a two-atom system in a three-dimensional optical lattice starting from doubly occupied sites in a Mott insulator phase of a quantum gas of atomic ytterbium. We can selectively produce either a subradiant 1(g) state or a superradiant 0(u) state by choosing the excitation laser frequency. The inherent weak excitation rate for the subradiant 1(g) state is overcome by the increased atomic density due to the tight confinement in a three-dimensional optical lattice. Our experimental measurements of binding energies, linewidth, and Zeeman shift confirm the observation of subradiant levels of the 1(g) state of the Yb(2) molecule.     

Intrinsic Ultracontractivity for Stable Semigroups on Unbounded Open Sets

We study the intrinsic ultracontractivity of the semigroup of the isotropic stable process on an unbounded open set. A two-sided estimate of the first eigenfunction of the semigroup is derived. We obtain general geometric conditions for intrinsic ultracontractivity which yield a necessary and sufficient condition for non-degenerate horn-shaped sets. The research was supported by KBN grant 1 P03A 020 28.     

Effect of Ellagic Acid on Seizure Threshold in Two Acute Seizure Tests in Mice

Ellagic acid (EA) is a natural dietary polyphenol that has many beneficial properties, including anti-inflammatory, antioxidant, antiviral, antibacterial, and neuroprotective effects. Studies have revealed that EA may modulate seizure activity in chemically induced animal models of seizures. Therefore, the aim of the present study was to investigate the effect of EA on the seizure threshold in two acute seizure tests in male mice, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test and in the maximal electroshock seizure threshold (MEST) test. The obtained results showed that EA (100 mg/kg) significantly elevated the threshold for both the first myoclonic twitch and generalized clonic seizure in the i.v. PTZ seizure test. At the highest dose tested (200 mg/kg), EA increased the threshold for tonic hindlimb extension in the MEST test. EA did not produce any significant changes in motor coordination (assessed in the chimney test) or muscular strength (investigated in the grip-strength test). The plasma and total brain concentration-time profiles of EA after intraperitoneal and oral administration were also determined. Although further studies are necessary to confirm the anticonvulsant activity of EA, our findings suggest that it may modulate seizure susceptibility in animal models.     

Effects of surface functionalization of hydrophilic NaYF<Subscript>4</Subscript> nanocrystals doped with Eu<Superscript>3+</Superscript> on glutamate and GABA transport in brain synaptosomes

Specific rare earth doped nanocrystals (NCs), a recent class of nanoparticles with fluorescent features, have great bioanalytical potential. Neuroactive properties of NaYF₄ nanocrystals doped with Eu³⁺ were assessed based on the analysis of their effects on glutamate- and γ-aminobutyric acid (GABA) transport process in nerve terminals isolated from rat brain (synaptosomes). Two types of hydrophilic NCs were examined in this work: (i) coated by polyethylene glycol (PEG) and (ii) with OH groups at the surface. It was found that NaYF₄:Eu³⁺-PEG and NaYF₄:Eu³⁺-OH within the concentration range of 0.5–3.5 and 0.5–1.5 mg/ml, respectively, did not influence Na⁺-dependent transporter-dependent l-[¹⁴C]glutamate and [³H]GABA uptake and the ambient level of the neurotransmitters in the synaptosomes. An increase in NaYF₄:Eu³⁺-PEG and NaYF₄:Eu³⁺-OH concentrations up to 7.5 and 3.5 mg/ml, respectively, led to the (1) attenuation of the initial velocity of uptake of l-[¹⁴C]glutamate and [³H]GABA and (2) elevation of ambient neurotransmitters in the suspension of nerve terminals. In the mentioned concentrations, nanocrystals did not influence acidification of synaptic vesicles that was shown with pH-sensitive fluorescent dye acridine orange, however, decreased the potential of the plasma membrane of synaptosomes. In comparison with other nanoparticles studied with similar methodological approach, NCs start to exhibit their effects on neurotransmitter transport at concentrations several times higher than those shown for carbon dots, detonation nanodiamonds and an iron storage protein ferritin, whose activity can be registered at 0.08, 0.5 and 0.08 mg/ml, respectively. Therefore, NCs can be considered lesser neurotoxic as compared to above nanoparticles.     

Synthesis of Polycyclic Monothioimides via a Domino Reaction of β-Aminocycloalkenethioamides

Summary. Tricyclic cyclopenta[b]pyrrolo[3,4-c]pyridine-3,5-dione and pyrrolo[3,4-d]quinoline-3,5-diones with stable hemiaminal function or bicyclic azaspiro[4.4]nonanes and azaspiro[4.5]decanes were obtained in a domino reaction of cycloalkenecarbothioamides with maleimides. The proposed mechanism involves Michael addition, ring transformation, aqueous hydrolysis of the imine, and additional ring closure which is observed exclusively for one diastereoisomer.