Synthesis of 1-indolyl substituted β-carboline natural products and discovery of antimalarial and cytotoxic activities

A series of 1-indolyl substituted β-carbolines including the natural products hyrtiosulawesine, pityriacitrin and pityriacitrin B were prepared via Pictet–Spengler condensation—oxidation strategy from the corresponding indolyl-acetaldehydes and substituted tryptamines. Efforts to prepare the C-1 methylene-linked β-carboline analogues for structure–activity relationship studies were unsuccessful. Biological evaluation revealed two analogues (5 and 41) to exhibit weak inhibition of phospholipase A₂ (IC₅₀ 171 and 131 μM, respectively), two to act as antioxidants (3 and 43), and 12 analogues with activity towards a chloroquine-resistant strain (FcB1) of Plasmodium falciparum (IC₅₀ 1.0–23 μM). Testing against a panel of 60 human tumour cell lines revealed a general lack of cytotoxic effect for most of the compounds with the exception of β-carboline 42 exhibiting modest antileukaemic activity towards the HL-60(TB) cell line (LC₅₀ 4.2 μM). In addition, two novel structures (30 and 32) resulting from aldol condensation followed by Pictet–Spengler cyclisation displayed cytotoxicity with pronounced subpanel specificities towards colon cancer (COLO 205 and HCC-2998) cell lines.     

Preferential Solvation of Some Sulfonamides in Propylene Glycol + Water Solvent Mixtures According to the IKBI and QLQC Methods

The preferential solvation parameters, which represent differences between the local and bulk mole fractions of the solvents near to the solute, in solutions of some sulfonamides in propylene glycol + water binary mixtures are derived from their thermodynamic properties by means of the inverse Kirkwood?Buff integrals (IKBI) and the Quasi-Lattice Quasi-Chemical (QLQC) method. From solvent effect studies, it is found that sulfonamides are sensitive to solvation effects; the preferential solvation parameter, δx _PG,S, is negative in water-rich mixtures but positive in compositions from 0.20 to 1.00 in mole fraction of propylene glycol according to IKBI method and positive in all co-solvent compositions if the QLQC method is considered. It is conjecturable that in water-rich mixtures, hydrophobic hydration around the aromatic ring and/or other non-polar groups plays a relevant role in the solvation. The greater solvation by propylene glycol mixtures of similar solvent compositions and in co-solvent-rich mixtures could be due mainly to polarity effects and acidic behavior of the sulfonamides, in contrast to the more basic solvent propylene glycol.     

Cell‐level modeling of nutrient competition on the growth of microalgal biomass

Growth of microalgal biomass is driven by nutrient availability but also by species competition for these nutrients. In this study, a modeling procedure has been developed by means of which impacts of nutrient competition on microalgae cells can be investigated on a cell‐level. The goal of this modeling is to enhance the understanding of nutrient competition in a given biological environment and to enable predicting the biomass' species composition. These models are compared with experimental data and empirical assessments published earlier in this journal. Because these simulations have been built on very generic assumptions, transferring this chemometric methodology to other cell types is straightforward. Copyright © 2014 John Wiley & Sons, Ltd.     

Fundamental Change in the Nature of Chemical Bonding by Isotopic Substitution

Isotope effects are important in the making and breaking of chemical bonds in chemical reactivity. Here we report on a new discovery, that isotopic substitution can fundamentally alter the nature of chemical bonding. This is established by systematic, rigorous quantum chemistry calculations of the isotopomers BrLBr, where L is an isotope of hydrogen. All the heavier isotopomers of BrHBr, BrDBr, BrTBr, and Br⁴HBr, the latter indicating the muonic He atom, the heaviest isotope of H, can only be stabilized as van der Waals bound states. In contrast, the lightest isotopomer, BrMuBr, with Mu the muonium atom, alone exhibits vibrational bonding, in accord with its possible observation in a recent experiment on the Mu+Br₂ reaction. Accordingly, BrMuBr is stabilized at the saddle point of the potential energy surface due to a net decrease in vibrational zero point energy that overcompensates the increase in potential energy.     

Dynamics at conical intersections: the influence of O-H stretching vibrations on the photodissociation of phenol

Comparing the recoil energy distributions of the fragments from one-photon dissociation of phenol-d(5) with those from vibrationally mediated photodissociation shows that initial vibrational excitation strongly influences the disposal of energy into relative translation. The measurements use velocity map ion imaging to detect the H-atom fragments and determine the distribution of recoil energies. Dissociation of phenol-d(5) molecules with an initially excited O-H stretching vibration produces significantly more fragments with low recoil energies than does one-photon dissociation at the same total energy. The difference appears to come from the increased probability of adiabatic dissociation in which a vibrationally excited molecule passes around the conical intersection between the dissociative state and the ground state to produce electronically excited phenoxyl-d(5) radicals. The additional energy deposited in electronic excitation of the radical reduces the energy available for relative translation.     

Raman,infrared, SERS and theoretical study of 3‐(1‐phenylpropan‐2‐ylamino) propanenitrile,fenproporex

Infrared, Raman and surface‐enhanced Raman scattering (SERS) spectra of 3‐(1‐phenylpropan‐2‐ylamino)propanenitrile (fenproporex) have been recorded. Density functional theory (DFT) with the B3LYP functional was used for optimizations of ground state geometries and simulation of Raman and SERS vibrational spectra of this molecule. Bands of the vibrational spectra were assigned in detail. The comparison of SERS spectra obtained by using colloidal silver and gold nanoparticles with the corresponding Raman spectrum reveals enhancement and shifts in bands, suggesting a possible partial charge‐transfer mechanism in the SERS effect. Information about the orientation of fenproporex on the nanometer‐sized metal structures is also obtained. Copyright © 2011 John Wiley & Sons, Ltd.     

Photoisomerization and relaxation dynamics of a structurally modified biomimetic photoswitch

Recent experimental and theoretical studies on N-alkylated indanylidene pyrroline Schiff bases (NAIP) show that these compounds exhibit biomimetic photoisomerization analogous to that in the chromophore of rhodopsin. The NAIP compounds studied previously isomerize rapidly and often evolve coherently on the ground-electronic surface after reaction. We present the results of transient electronic absorption spectroscopy on dMe-OMe-NAIP, a newly synthesized NAIP analogue that differs from other NAIP compounds in the substituents on its pyrrolinium ring. Following excitation with 400 nm light, dMe-OMe-NAIP relaxes from the electronic-excited state in less than 500 fs, which is slower than in other analogues, and does not show the prominent oscillations observed in other NAIP compounds. A reduction in the amount of twisting between the rings caused by removal of the methyl group is likely responsible for the slower isomerization. Measurements in solvents of varying viscosity and structure suggest that intramolecular processes dominate the relaxation of nascent photoproducts.     

Transmissive olefination route to putative "morinol I" lignans

A series of morinol-type lignans were rapidly assembled using a Grignard-based transmissive olefination. In combination with palladium-catalyzed arylations, the strategy provides stereoselective access to (7Z,7'E), (7E,7'E), and (7E,7'Z) morinol diastereomers and the (7Z,8'E) and (7E,8'E) conjugated analogues. Critical for the E/Z stereoselectivity is a new, general method for converting alkenenitriles to alkenemethanols that circumvents the enal E/Z isomerization commonly encountered during conventional i-Bu(2)AlH reduction.