CuSO4/sodium ascorbate catalysed synthesis of benzosuberone and 1,2,3-triazole conjugates: Design,synthesis and in vitro anti-proliferative activity

A novel series of conjugates of benzosuberone and 1,2,3-triazole i.e. 3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl-9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylic acids (8a-j) were synthesized in good to excellent yields catalysed by CuSO₄ under milder reaction conditions and evaluated for their anti-proliferative activity. The structural elucidation of the prepared compounds was carried out using IR, ¹H NMR, ¹³C NMR and Mass spectral analysis. The newly synthesized derivatives (8a-j) were evaluated for their anti-proliferative activity against four human cell lines and the novel derivatives showed moderate to excellent activity. The obtained results suggest that these compounds can be considered as new hits for anti-proliferative drug development programme and further SAR studies can help obtain better anticancer agents.     

Nitrile-Containing Fischerindoles from the Cultured Cyanobacterium Fischerella sp

Chemical investigation of the cultured cyanobacterium Fischerella sp. (SAG strain number 46.79) led to the isolation of four nitrile-containing indole alkaloids, namely 12-epi-fischerindole I nitrile (1), deschloro 12-epi-fischerindole I nitrile (2), 12-epi-fischerindole W nitrile (3), and deschloro 12-epi-fischerindole W nitrile (4) along with a known metabolite hapalosin. The structures were determined by detailed spectroscopic analyses on the basis of 1D and 2D NMR and HRESIMS data. All isolates were evaluated for cytotoxicity against human cancer cells and for 20S proteasome inhibition. Deschloro 12-epi-fischerindole I nitrile (2) was found to be weakly cytotoxic against HT-29 cells with an ED(50) value of 23 μM. Hapalosin showed weak cytotoxicity against HT-29 and MCF-7 cells with ED(50) values of 22 and 27 μM, respectively, as well as moderate 20S proteasome inhibition with an IC(50) value of 12 μM. Compounds 1-4 all contain a nitrile moiety instead of the isonitrile found in all fischerindoles reported to date. Compounds 3 and 4 also display a new carbon skeleton, in which a six-membered ring replaces the five-membered ring normally found in fischerindole-type alkaloids.     

PVM-AMBER: A parallel implementation of the AMBER molecular mechanics package for workstation clusters

A parallel version of the popular molecular mechanics package AMBER suitable for execution on workstation clusters has been developed. Computer-intensive portions of molecular dynamics or free-energy perturbation computations, such as nonbonded pair list generation or calculation of nonbonded energies and forces, are distributed across a collection of Unix workstations linked by Ethernet or FDDI connections. This parallel implementation utilizes the message-passing software PVM (Parallel Virtual Machine) from Oak Ridge National Laboratory to coordinate data exchange and processor synchronization. Test simulations performed for solvated peptide, protein, and lipid bilayer systems indicate that reasonable parallel efficiency (70–90%) and computational speedup (2–5 × serial computer runtimes) can be achieved with small workstation clusters (typically six to eight machines) for typical biomolecular simulation problems. PVM-AMBER is also easily and rapidly portable to different hardware platforms due to the availability of PVM for numerous computers. The current version of PVM-AMBER has been tested successfully on Silicon Graphics, IBM RS6000, DEC ALPHA, and HP 735 workstation clusters and heterogeneous clusters of these machines, as well as on CRAY T3D and Kendall Square KSR2 parallel supercomputers. Thus, PVM-AMBER provides a simple and cost-effective mechanism for parallel molecular dynamics simulations on readily available hardware platforms. Factors that affect the efficiency of this approach are discussed. © 1995 by John Wiley & Sons, Inc.     

Degradation and stabilization of polycyanoacrylates

Polycyanoacrylates were found to be inherently unstable. Even in the absence of a deliberately added strong base, their molecular weights decreased drastically on standing in solution in accord with observations by Ryan and McCann (Makromol Chem Rapid Commun 1996, 17, 217). The initial high molecular weight polymer disappeared over the course of a few hours in solution and was replaced by a much lower molecular weight material. For polymers made by anionic polymerization, the entire sample degraded, but for polymers made by free-radical polymerization, only a portion of the sample was affected. This behavior was consistent with the mechanism proposed by Ryan and McCann, in which the polymer chains are in dynamic equilibrium with their monomers and the polymer degrades from its chain terminus. Surprisingly, the degradation in molecular weight even occurred slowly in the solid state. The degradation was inhibited by acids and could be prevented by free-radical copolymerization with small amounts of more stable monomers. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4570–4581, 1999     

Diaryl ethers using Fischer chromium carbene mediated benzannulation

[formula: see text] The biological relevance and irresistible synthetic challenge of compounds containing the diaryl ether linkage encourages the development of new methodologies targeted toward this structural subunit. The syntheses of diaryl ethers 2 using a benzannulation strategy that formally involves a [3 + 2 + 1] cycloaddition between aryloxy-substituted Fischer carbenes 1 and alkynes are described. This methodology provides a neutral near ambient temperature formation of diaryl ethers.     

Raman study of SO2 at high pressure: aggregation,phase transformations,and photochemistry

We report Raman measurements made on SO₂ in a diamond cell up to 75 kbar showing two new phases, solid II and solid III, which differ from known, zero-pressure solid I. Spectra indicate that SO₂ molecules aggregate in solid III to possibly form a cyclical trimer; solid III is shown to be photochemically active to blue radiation.     

Computer simulation of liquid metal ion source optics

A numerical calculation of the electric field and current density distribution for a liquid metal ion (LMI) source has been carried out. If a field evaporation mechanism for ion formation is assumed an elongated Taylor cone shape emitter is required to account for the observed total currents. Trajectory calculations including the effect of uniform space charge have been carried out as a function of total current and particle mass. The predicted emission characteristics compare favorably with experimental results for Ga, however the homogeneous space charge model is unable to account for all of the experimentally observed increase in beam divergence with increasing mass and current.     

The combined use of SCF-MO calculations and experimental data in the evaluation of quadratic force fields: MOCIC potential functions for fluoroform,methyl acetylene,and methyl cyanide

A semiempirical method combining SCF-MO calculations and limited vibrational data has been employed to evaluate the completely general quadratic potential fields of fluoroform, methyl acetylene, and acetonitrile. MOCIC (molecular orbital constraint using interaction coordinates) potential fields are presented for gas phase molecules of intermediate size. Here general harmonic force fields or excellent approximations utilizing extensive experimental data are available as standards. A statistical evaluation of the interaction potentials shows that there is some improvement in going from MNDO or ab initio SCF-MO force fields to the MOCIC functions which reliably reproduce the off-diagonal vibrational potential constants in most instances. The MOCIC primary compliants are excellent approximations of their vibrational counterparts, as expected. Comparison of the calculated isotopic frequencies, Coriolis coupling constants, and centrifugal distortion constants for the SCF-MO, MOCIC, and vibrational spectroscopic potential fields with the corresponding experimental values also shows MOCICs reliability for molecules with many interaction potentials. There is substantial improvement in the calculated isotopic frequency shifts and centrifugal distortion constants in going from SCF-MO to MOCIC functions.     

Normal cones of monomial primes

We explicitly calculate the normal cones of all monomial primes which define the curves of the form , where . All of these normal cones are reduced and Cohen-Macaulay, and their reduction numbers are independent of the reduction. These monomial primes are new examples of integrally closed ideals for which the product with the maximal homogeneous ideal is also integrally closed.

Substantial use was made of the computer algebra packages Maple and Macaulay2.