Synthesis and Analysis of Substituted Bullvalenes

Herein we detail a practical synthesis of bullvalene and a variety of mono‐ and disubstituted analogues through cobalt‐catalysed [6+2] cycloaddition of cyclooctatetraene to alkynes, followed by photochemical di‐π‐methane rearrangement. The application of isomer‐network analysis, coupled with quantum‐chemical calculations, provides a powerful automated tool for predicting the properties of bullvalene isomer networks.     

Optimization of the Ion Source-Mass Spectrometry Parameters in Non-Steroidal Anti-Inflammatory and Analgesic Pharmaceuticals Analysis by a Design of Experiments Approach

The flow rates of drying and nebulizing gas, heat block and desolvation line temperatures and interface voltage are potential electrospray ionization parameters as they may enhance sensitivity of the mass spectrometer. The conditions that give higher sensitivity of 13 pharmaceuticals were explored. First, Plackett-Burman design was implemented to screen significant factors, and it was concluded that interface voltage and nebulizing gas flow were the only factors that influence the intensity signal for all pharmaceuticals. This fractionated factorial design was projected to set a full 2² factorial design with center points. The lack-of-fit test proved to be significant. Then, a central composite face-centered design was conducted. Finally, a stepwise multiple linear regression and subsequently an optimization problem solving were carried out. Two main drug clusters were found concerning the signal intensities of all runs of the augmented factorial design. p-Aminophenol, salicylic acid, and nimesulide constitute one cluster as a result of showing much higher sensitivity than the remaining drugs. The other cluster is more homogeneous with some sub-clusters comprising one pharmaceutical and its respective metabolite. It was observed that instrumental signal increased when both significant factors increased with maximum signal occurring when both codified factors are set at level +1. It was also found that, for most of the pharmaceuticals, interface voltage influences the intensity of the instrument more than the nebulizing gas flowrate. The only exceptions refer to nimesulide where the relative importance of the factors is reversed and still salicylic acid where both factors equally influence the instrumental signal.

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Orthogonal Polynomials for Modified Chebyshev Measure of the First Kind

Given numbers \({n,s \in \mathbb{N}}\), \({n \geq 2}\), and the \({n}\)th-degree monic Chebyshev polynomial of the first kind \({\widehat T_n(x)}\), the polynomial system “induced” by \({\widehat T_n(x)}\) is the system of orthogonal polynomials \({\{p_{k}^{n,s} \}}\) corresponding to the modified measure \({d \sigma^{n,s}(x)=\widehat T^{2s}_n(x) d\sigma(x)}\), where \({d\sigma(x)=1/\sqrt{1-x^{2}}dx}\) is the Chebyshev measure of the first kind. Here we are concerned with the problem of determining the coefficients in the three-term recurrence relation for the polynomials \({p^{n,s}_{k}}\). The desired coefficients are obtained analytically in a closed form.     

Co(III) complex with (E)-2-(2-(pyridine-2-ylmethylene)hydrazinyl)-4-(4-tolyl)-1,3-thiazole: structure and activity against 2-D and 3-D cancer cell models

Co(III) complex with a 2-hydrazonylthiazole ligand was synthesized and characterized by single-crystal X-ray diffraction. In the inner sphere of the complex, two monoionic ligands are coordinated tridentately forming octahedral geometry around Co(III). Activity of the complex was investigated on MCF-7 breast cancer cell line, with cisplatin (CDDP) as a reference compound. Results showed that after 24-h incubation, Co(III) complex revealed stronger cytotoxic activity compared to CDDP. Treatment of MCF-7 3-D cell model with the complex at 10 μM concentration achieved complete suppression of spheroid growth in almost the same extent as at 100 μM. In combination treatments on MCF-7 spheroids, the complex acted synergistically with CDDP, while additive interaction type was achieved when the complex was applied together with paclitaxel.     

Structural analysis and biomedical potential of novel salicyloyloxy estrane derivatives synthesized by microwave irradiation

New estrane salicyloyloxy or D-homo derivatives were synthesized under microwave (MW) or conventional heating from estrane precursors and methyl salicylate. The MW technique provides advantages regarding product yield and reaction time, and represents a more environmentally friendly approach than conventional heating. Considering the biomedical potential of estrane compounds, we evaluated the antioxidant activity and cytotoxicity of synthesized estrane derivatives in a series of in vitro tests, as well as their 3β-hydroxysteroid dehydrogenase/Δ⁵ → Δ⁴ isomerase (3βHSD) and 17β-hydroxysteroid dehydrogenase types 1, 2 and 3 (17βHSD1, 17βHSD2 and 17βHSD3) inhibition potentials. In DPPH tests, 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate displayed antioxidant potential, while all compounds exhibited OH radical neutralization activity. 3-Oxoestr-4-en-17β-yl salicylate showed strong cytotoxicity against MDA-MB-231 breast cancer cells, while 17-oxoestra-1,3,5(10)-trien-3-yl salicylate, estra-1,3,5(10)-triene-3,17β-diyl 3-benzoate 17-salicylate and 3-benzyloxy-17-salicyloyloxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile showed the strongest inhibition of PC-3 prostate cancer cell growth. 3-Hydroxyestra-1,3,5(10)-trien-17β-yl salicylate was the best inhibitor of 17βHSD2, suggesting potential use in treating pathological conditions associated with estrogen depletion. For 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate and 3-oxoestr-4-en-17β-yl salicylate, X-ray crystal structure analysis and molecular energy optimization were performed to define their conformations and energy minima. Very good overlap in the region of the steroidal nucleus was observed for the molecular structures of each analyzed molecule in the crystalline state and after energy optimization, while conformer analysis indicates conformational flexibility in the form of rotation around the C17···O2 bond. Structural geometry analysis for these compounds shows that the region of ring A in steroids, and especially the C3 atom functional group, is important structural features concerning antiproliferative activity against MDA-MB-231 cells.

     

Diamagnetic Raman Optical Activity of Chlorine,Bromine, and Iodine Gases

Magnetic Raman optical activity of gases provides unique information about their electric and magnetic properties. Magnetic Raman optical activity has recently been observed in a paramagnetic gas (Angew. Chem. Int. Ed. 2012 , 51, 11058; Angew. Chem. 2012 , 124, 11220). In diamagnetic molecules, it has been considered too weak to be measurable. However, in chlorine, bromine and iodine vapors, we could detect a significant signal as well. Zeeman splitting of electronic ground‐state energy levels cannot rationalize the observed circular intensity difference (CID) values of about 10^?4. These are explicable by participation of paramagnetic excited electronic states. Then a simple model including one electronic excited state provides reasonable spectral intensities. The results suggest that this kind of scattering by diamagnetic molecules is a general event observable under resonance conditions. The phenomenon sheds new light on the role of excited states in the Raman scattering, and may be used to probe molecular geometry and electronic structure.     

Sensitizing DNA Towards Low‐Energy Electrons with 2‐Fluoroadenine

2‐Fluoroadenine (^2FA) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low‐energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in ^2FA are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion‐mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in ^2FA‐containing oligonucleotides upon irradiation with LEEs. The incorporation of ^2FA into DNA results in an enhanced strand breakage. The strand‐break cross sections are clearly energy dependent, whereas the strand‐break enhancements by ^2FA at 5.5, 10, and 15 eV are very similar. Thus, ^2FA can be considered an effective radiosensitizer operative at a wide range of electron energies.     

Using equality in the Krein conditions to prove nonexistence of certain distance-regular graphs

We prove the nonexistence of a distance-regular graph with intersection array {74,54,15;1,9,60} and of distance-regular graphs with intersection arrays

{4r³+8r²+6r+1,2r(r+1)(2r+1),2r²+2r+1;1,2r(r+1),(2r+1)(2r²+2r+1)}