A copper-catalyzed C-N bond formation involving sp-hybridized carbons. A direct entry to chiral ynamides via N-alkynylation of amides

A copper-catalyzed new C-N bond formation involving a sp-hybridized carbon is described here leading to a facile entry for syntheses of chiral ynamides. This direct N-alkynylation of amides should have a significant impact on the future development of synthetic methodologies employing ynamides.     

Characterization of the oxidation products of styryl-substituted terthiophenes and sexithiophenes using electronic absorption spectroscopy and time-dependent DFT

The electronic absorption spectra of a series of alkoxy-styryl substituted terthiophenes, their corresponding sexithiophenes, and the oxidation products of both have been measured. The terthiophenes studied sigma-dimerize to sexithiophenes during the oxidation process and there is clear evidence of sexithiophene radical cations, dications, and pi-dimers in the electronic absorption spectra. The oxidation of concentrated solutions produces predominantly pi-dimer bands, as expected. The absorption spectrum of the styryl-functionalized sexithiophene dication without alkoxy substitution closely resembles that of unsubstituted sexithiophene, while alkoxy substitution induces changes in the wavelength of the dication band maximum and the overall band shape. Time-dependent density functional theory (TDDFT) calculations have shown that styryl-based molecular orbitals are important in the transitions of the neutral molecules as well as the charged species, the dication in particular. Kinetics analyses confirm the stabilization effect induced by the alkoxy substituents. The presence of a reversible pi-dimer equilibrium was verified by cyclic voltammetry. It is clear from the experimental observations and the theoretical calculations that both the styryl and alkoxy groups are influencing the electronic properties of this class of molecules.     

Determination of the sulfur components of gasoline streams by capillary column gas chromatography with sulfur chemiluminescence detection

A method using a sulfur chemiluminescence detector (SCD) has been developed for the qualitative and quantitative determination of sulfur components in stabilized gasoline-range process streams, including blended gasolines containing between 1 and > 4000 ppm total sulfur. The detection limit per sulfur component was approximately 50 ppb. On-column injection was employed for optimum precision and accuracy. A new probe material was found which did not soften under FID operating conditions. A new method, using a hydrogen sulfide permeation tube, was developed for rapid alignment of the probe in the FID.     

Palladium salicylaldimine complexes containing boronate esters

Reactions of salicylaldehydes with boronate ester derivatives of aniline have been examined. Addition of these Schiff base ligands to palladium acetate or Na₂PdCl₄ afforded novel boron-containing trans-bis(N-arylsalicylaldiminato) palladium complexes.Condensation of salicylaldehyde (2-HOC₆H₄C(O)H) with H₂NC₆H₄Bpin (pin=1,2-O₂C₂Me₄) afforded the boron-containing Schiff bases, 2-HOC₆H₄C(H)=NC₆H₄Bpin (1–3a). Similar reactivity with 2-hydroxy-5-nitrobenzaldehyde and 2-hydroxy-1-naphthaldehyde gave the corresponding Schiff bases (1-3b) and (1-3c), respectively. Reaction of Schiff bases (2) and (3) with palladium acetate or Na₂PdCl₄ afforded complexes of the type PdL₂ (4,5), where L=deprotonated Schiff base. The molecular structure of the nitro-salicylaldehyde 4-Bpin palladium complex (5b) was characterized by an X-ray diffraction study. All new palladium compounds have been characterized fully and tested for their antifungal activity against Aspergillus niger and Aspergillus flavus.     

Quantum‐Chemical and Electrochemical Investigation of the Electrochemical Windows of Halogenated Carborate Anions

The range of electrochemical stability of a series of weakly coordinating halogenated (Hal=F, Cl, Br, I) 1‐carba‐closo‐dodecaborate anions, [1‐R‐CB₁₁X₅Y₆]^? (R=H, Me; X=H, Hal, Me; Y=Hal), has been established by using quantum chemical calculations and electrochemical methods. The structures of the neutral and dianionic radicals, as well as the anions, have been optimized by using DFT calculations at the PBE0/def2‐TZVPP level. The calculated structures are in good agreement with existing experimental data and with previous calculations. Their gas‐phase ionization energies and electron affinities were calculated based on their optimized structures and were compared with experimental (cyclic and square‐wave) voltammetry data. Electrochemical oxidation was performed in MeCN at room temperature and in liquid sulfur dioxide at lower temperatures. All of the anions show a very high resistance to the onset of oxidation (2.15–2.85 V versus Fc^0/+), with only a minor dependence of the oxidation potential on the different halogen substituents. In contrast, the reduction potentials in MeCN are strongly substituent dependent (?1.93 to ?3.32 V versus Fc^0/+). The calculated ionization energies and electron affinities correlate well with the experimental redox potentials, which provide important verification of the thermodynamic validity of the mostly irreversible redox processes that are observed for this series. The large electrochemical windows that are afforded by these anions indicate their suitability for electrochemical applications, for example, as supporting electrolytes.     

Development and validation of an ELISA kit for the detection of ricin toxins from biological specimens and environmental samples

Ricin is a toxin that can be easily extracted from seeds of Ricinus communis plants. Ricin is considered to be a major bio-threat as it can be freely and easily acquired in large quantities. A deliberate release of such toxin in civilian populations would very likely overwhelm existing public health systems, resulting in public fear and social unrest. There is currently no commercially available or FDA-approved prophylaxis such as vaccines, or therapeutic antitoxins or antidotes, available for ricin intoxication. Patient treatment is typically supportive care based on symptoms, often designed to reinforce the body’s natural response. This paper describes the development and validation of a robust ELISA test kit, which can be used to screen for ricin in biological specimens such as whole blood and faeces. Faecal specimens are shown in this study to have better diagnostic sensitivity and a wider diagnostic window compared to whole blood. From these results, it is concluded that faeces is the most suitable clinical specimen for diagnosis of ricin poisoning via the oral route. The ELISA test kit can also detect ricin in environmental samples. An advantage of this ELISA kit over other commercial off-the-shelf (COTS) detection kits currently on the market that are developed to screen environmental samples only is its ability to diagnose ricin poisoning from clinical specimens as well as detect ricin from environmental samples.     

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)–cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.     

The anxiolytic effects of midazolam during anticipation to pain revealed using fMRI

BACKGROUND AND PURPOSE: Functional neuroimaging can distinguish components of the pain experience associated with anticipation to pain from those associated with the experience of pain itself. Anticipation to pain is thought to increase the suffering of chronic pain patients. Inappropriate anxiety, of which anticipation is a component, is also a cause of disability. We present a pharmacological functional magnetic resonance imaging (fMRI) study in which we investigate the selective modulation by midazolam of brain activity associated with anticipation to pain compared to pain itself. METHODS: Eight right-handed male volunteers underwent fMRI combined with a thermal pain conditioning paradigm and midazolam (30 mug/kg) or saline administration on different occasions, with order randomized across volunteers. Volunteers learned to associate a colored light with either painful, hot stimulation or nonpainful, warm stimulation to the back of the left hand. RESULTS: Comparison of the period during thermal stimulation (pain-warm) revealed a network of brain activity commonly associated with noxious stimulation, including activities in the anterior cingulate cortex (ACC), the bilateral insular cortices (anterior and posterior), the thalamus, S1, the motor cortex, the brainstem, the prefrontal cortex and the cerebellum. Comparison of the periods preceding thermal stimulation (anticipation to pain-anticipation to warm) revealed activity principally in the ACC, the contralateral anterior insular cortex and the ipsilateral S2/posterior insula. Detected by a region-of-interest analysis, midazolam reduced the activity associated specifically with anticipation to pain while controlling for anticipation to warm. This was most significant in the contralateral anterior insula (P<.05). There were no significant drug effects on the activity associated with pain itself. CONCLUSION: In identifying a pharmacological effect on activity preceding but not during pain, we have successfully demonstrated an fMRI assay that can be used to study the action of anxiolytic agents in a relatively small cohort of humans.