Large-Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N-Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context

A large-scale synthesis of known Ru olefin metathesis catalyst VII featuring an unsymmetrical N-heterocyclic carbene (NHC) ligand with one 2,5-diisopropylphenyl (DIPP) and one thiophenylmethylene N-substituent is reported. The optimised procedure does not require column chromatography in any step and allows for preparation of up to 0.5 kg batches of the catalyst from simple precursors. The application profile of the obtained catalyst was studied in environmentally friendly dimethyl carbonate (DMC). Although VII exhibited low efficiency in cross-metathesis (CM) with electron-deficient partners, good to excellent results were noted for substrates featuring easy to isomerise C−C double bonds. This includes polyfunctional substrates of medicinal chemistry interest, such as analogues of psychoactive 5F-PB-22 and NM-2201 and two PDE5 inhibitors—Sildenafil and Vardenafil. Finally, a larger scale ring-closing metathesis (RCM) of a Vardenafil derivative was conducted in DMC, allowing for straightforward isolation of the expected product (23 g) in high yield and with low Ru contamination level (7.7 ppm).     

Special chaotic systems

The European Physical Journal Special Topics - This topical issue collects contributions related to recent achievements and scientific progress in special chaotic systems. The individual papers...     

L-argininato copper(II) complexes in solution exert significant selective anticancer and antimicrobial activities

A search for new drugs that overcome the multidrug resistance of microorganisms or are effective against cancer cells prompted us to investigate the binary and ternary Cu(II) complexes containing L-arginine, [CuCl(L-Arg)(phen)]Cl·2H₂O (phen = 1,10-phenanthroline) ( 1 ) and [Cu(L-Arg)₂(H₂O)]C₂O₄·6H₂O ( 2 ), for which crystal and molecular structures were characterized previously. In order to discuss the biological function, the complexes have been screened for their antitumor activity against A549 (human lung cancer cells), HepG2 (human liver hepatocellular carcinoma cells) and antimicrobial activity. To identify the complexes forms existing in the solutions of 1 and 2 crystals, the results obtained from EPR, NIR–Vis–UV and MS (mass spectrometry) measurements were correlated with those from analysis of potentiometric titration of Cu(II)―L-Arg and Cu(II)―L-Arg―phen systems. This comprehensive study indicated that the [Cu(L-Arg)(phen)]²⁺ and [Cu(L-Arg)₂]²⁺ species are dominant in the solution. Complexes 1 and 2 were found to present specific ligand-dependent cytotoxic and antiproliferative potential against cancer cells. They also show antibacterial activity against Gram-positive and Gram-negative bacteria as well as display antifungal properties.     

Kinetics and Characterization of Degradation Products of Dihydralazine and Hydrochlorothiazide in Binary Mixture by HPLC-UV,LC-DAD and LC–MS Methods

Dihydralazine and hydrochlorothiazide were stored at high temperature and humidity, under UV/Vis light and different pH, as individual drugs and the mixture. Then, a sensitive and selective HPLC-UV method was developed for simultaneous determination of dihydralazine and hydrochlorothiazide in presence of their degradation products. Finally, the degradation products were characterized through LC-DAD and LC–MS methods. Dihydralazine was sensitive to high temperature and humidity, UV/Vis light and pH?≥?7. At the same time, it was resistant to acidic conditions. Hydrochlorothiazide was sensitive to high temperature and humidity, UV/Vis light and changes in pH. Its highest level of degradation was observed in 1 M HCl. Degradation of the drugs was higher when they were stressed in the mixture. In the case of dihydralazine, the percentage degradation was 5–15 times higher. What is more, dihydralazine became sensitive to acidic conditions. Hydrochlorothiazide was shown to be more sensitive to UV/Vis light and pH?>?4. Degradation of dihydralazine and hydrochlorothiazide followed first-order kinetics. The quickest degradation of dihydralazine was found to be in 1 M NaOH while of hydrochlorothiazide was in 1 M HCl (individual hydrochlorothiazide) or at pH 7–10 (hydrochlorothiazide in the mixture). A number of new degradation products were detected and some of them were identified by our LC-DAD and LC–MS methods. In the stressed individual samples, (phenylmethyl)hydrazine and 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide were observed for the first time. Interactions between dihydralazine and hydrochlorothiazide in the mixture were confirmed by additional degradation products, e.g., 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1,4-trioxide.     

Operator geometric stable laws

Operator geometric stable laws are the weak limits of operator normed and centered geometric random sums of independent, identically distributed random vectors. They generalize operator stable laws and geometric stable laws. In this work we characterize operator geometric stable distributions, their divisibility and domains of attraction, and present their application to finance. Operator geometric stable laws are useful for modeling financial portfolios where the cumulative price change vectors are sums of a random number of small random shocks with heavy tails, and each component has a different tail index.     

On special rational curves in Grassmannians

Numerical and geometric characterizations, among all morphisms , of those which are -equivalent to the canonical morphism induced by the Morita equivalence –, are presented. The author was partially supported by KBN grants 1P03A 036 26 and 115/E-343/SPB/6.PR UE/DIE 50/2005-2008. Received: 10 September 2005     

Dual pairs and Kostant-Sekiguchi correspondence. II. Classification of nilpotent elements

We classify the homogeneous nilpotent orbits in certain Lie color algebras and specialize the results to the setting of a real reductive dual pair. For any member of a dual pair, we prove the bijectivity of the two Kostant-Sekiguchi maps by straightforward argument. For a dual pair we determine the correspondence of the real orbits, the correspondence of the complex orbits and explain how these two relations behave under the Kostant-Sekiguchi maps. In particular we prove that for a dual pair in the stable range there is a Kostant-Sekiguchi map such that the conjecture formulated in [6] holds. We also show that the conjecture cannot be true in general.     

On the multi‐colored Ramsey numbers of cycles

For a graph L and an integer k≥2, R_k(L) denotes the smallest integer N for which for any edge‐coloring of the complete graph K_N by k colors there exists a color i for which the corresponding color class contains L as a subgraph. Bondy and Erdos conjectured that, for an odd cycle C_n on n vertices, They proved the case when k = 2 and also provided an upper bound R_k(C_n)≤(k+ 2)!n. Recently, this conjecture has been verified for k = 3 if n is large. In this note, we prove that for every integer k≥4, When n is even, Sun Yongqi, Yang Yuansheng, Xu Feng, and Li Bingxi gave a construction, showing that R_k(C_n)≥(k?1)n?2k+ 4. Here we prove that if n is even, then © 2011 Wiley Periodicals, Inc. J Graph Theory 69: 169‐175, 2012