Synthesis and determination of the absolute configuration of fugomycin and desoxyfugomycin: CD spectroscopy and fungicidal activity of butenolides

The dibromoalkenes (S)-3 and (R)- and (S)-4 are intermediates in the syntheses of the naturally occurring fungicidal butenolides fugomycin (1) and desoxyfugomycin (2), respectively. The stereoselective bromine-lithium exchange that leads to the carbenoid 12 and the vinyllithium reagent 17 a on the one hand, and palladium-catalyzed coupling reactions of the dibromoalkene 3 and the bromolactone 22 on the other are key steps en route to the butenolides 1 and 2. The chiral building blocks (S)-3, (R)-4, and (S)-4 are readily available from (R)-isopropylideneglyceraldehyde 5, isobutyl (R)-lactate 6 a, and ethyl (S)-lactate 6 b, respectively. The synthetic procedure adopted here permits the absolute configuration of the natural products fugomycin (1) and desoxyfugomycin (2) to be assigned by comparison of their chiroptical properties with those of the synthetic products. The CD spectra of the bromolactone 22, calculated by two different density functional methods (TDDFT, DFT/MRCI), are found to be in good agreement with the measured spectra. On the basis of these calculations, the two CD bands observed could be assigned to n-pi* and pi-pi* transitions, respectively. Fugomycin (1) and the synthetic butenolide 20 displayed high fungicidal activity against botrytis in greenhouse experiments, whereas the saturated lactone 21 was practically inactive.     

π-olefin-iridium-komplexe: XII. Umsetzung von chloro-cyclooctadien-methyl-imidazoyl-iridium mit methyl- oder phenyllithium; ungewöhnliche bildung eines iridacyclopentadienyl-komplexes

Reaction of CH₃li with (cod)Ir(mid)Cl (I) (cod = 1,5-cyclooctadiene; mid = 1-methylimidazole) in hexano yields a $\text{1}\text{1}$ mixture of two geometric isomers of [(cod)IrL]₂ (IIa, IIb) where L is a μ-2,3-dihydro-1H-imidazole-1,2,2-triyl ligand. From the reaction of I with C₆H₅Li a mixture is obtained of IIa, IIb, and a dinuclear complex containing a dibenzoiridacyclopentadienyl unit; the latter has been characterized crystallographically.     

Shearinines D-K, new indole triterpenoids from an endophytic Penicillium sp. (strain HKI0459) with blocking activity on large-conductance calcium-activated potassium channels

A chemical examination of the endophytic fungus Penicillium sp. isolated from the mangrove plant Aegiceras corniculatum resulted in the isolation and characterization of eight new indole triterpenes named shearinines D-K (1-8), along with shearinine A (9), paspalitrem A (10), and paspaline (11). Their stereostructures were determined by extensive spectroscopic data analyses and quantum chemical circular dichroism calculations. The biosynthetic relationship of all 11 alkaloids is suggested. Shearinines D (1), E (2), and (with reduced potency) G (4) exhibit significant in vitro blocking activity on large-conductance calcium-activated potassium channels.     

Interactions between the chloride anion and aromatic molecules: infrared spectra of the Cl- -C6H5CH3, Cl- -C6H5NH2 and Cl- -C6H5OH complexes

The Cl- -C6H5CH3*Ar, Cl- -C6H5NH2*Ar, and Cl- -C6H5OH*Ar anion complexes are investigated using infrared photodissociation spectroscopy and ab initio calculations at the MP2/aug-cc-pVDZ level. The results indicate that for Cl- -C6H5NH2 and Cl- -C6H5OH, the Cl- anion is attached to the substituent group by a single near-linear hydrogen bond. For Cl--C6H5CH3, the Cl- is attached to an ortho-hydrogen atom on the aromatic ring and to a hydrogen atom on the methyl group by a weaker hydrogen bond. The principal spectroscopic consequence of the hydrogen-bonding interaction in the three complexes is a red-shift and intensity increase for the CH, NH, and OH stretching modes. Complexities in the infrared spectra in the region of the hydrogen-bonded XH stretch band are associated with Fermi resonances between the hydrogen-stretching vibrational modes and bending overtone and combination levels. There are notable correlations between the vibrational red-shift, the elongation of the H-bonded XH group, and the proton affinity of the aromatic molecule's conjugate base.     

Stimulated Raman scattering microscopy with spectral phasor analysis: applications in assessing drug–cell interactions

Statins have displayed significant, although heterogeneous, anti-tumour activity in breast cancer disease progression and recurrence. They offer promise as a class of drugs, normally used for cardiovascular disease control, that could have a significant impact on the treatment of cancer. Understanding their mode of action and accurately assessing their efficacy on live cancer cells is an important and significant challenge. Stimulated Raman scattering (SRS) microscopy is a powerful, label-free imaging technique that can rapidly characterise the biochemical responses of live cell populations following drug treatment. Here, we demonstrate multi-wavelength SRS imaging together with spectral phasor analysis to characterise a panel of breast cancer cell lines (MCF-7, SK-BR-3 and MDA-MB-231 cells) treated with two clinically relevant statins, atorvastatin and rosuvastatin. Label-free SRS imaging within the high wavenumber region of the Raman spectrum (2800–3050 cm⁻¹) revealed the lipid droplet distribution throughout populations of live breast cancer cells using biocompatible imaging conditions. A spectral phasor analysis of the hyperspectral dataset enables rapid differentiation of discrete cellular compartments based on their intrinsic SRS characteristics. Applying the spectral phasor method to studying statin treated cells identified a lipid accumulating phenotype in cell populations which displayed the lowest sensitivity to statin treatment, whilst a weaker lipid accumulating phenotype was associated with a potent reduction in cell viability. This study provides an insight into potential resistance mechanisms of specific cancer cells towards treatment with statins. Label-free SRS imaging provides a novel and innovative technique for phenotypic assessment of drug-induced effects across different cellular populations and enables effective analysis of drug–cell interactions at the subcellular scale.

Stimulated Raman scattering microscopy with spectral phasor analysis provides a label-free approach for phenotypic evaluation of drug-induced effects.     

Photopolymerization in water of diacetylenes chemisorbed onto noble metal nanoparticles: a spectroscopic study

Gold and silver nanoparticles of different size, decorated by a diacetylenic monomer having a COOH anchor group, were prepared in aqueous dispersions. Topochemical polymerization of the colloidal suspensions was obtained by UV irradiation and studied by means of spectroscopic techniques (UV–visible absorption, IR and Raman spectroscopies). A variety of polymer phases were found in the case of silver nanohybrids. The main contribution for this investigation was supplied by the Raman spectra, which provide detailed information on the polymer forms and on the preferred conformation of the alkylic side chains. Copyright © 2009 John Wiley & Sons, Ltd.