A comparative photophysical and photochemical study of nitropyrene isomers occurring in the environment

Ground state absorption, first excited-singlet state, and properties of reactive intermediates of mononitropyrene isomers encountered in the atmospheric aerosol have been studied under different conditions that could mimic the environment. The nitro group can present different orientations relative to the pyrene ring depending on its geometric location and could induce differences in the photochemistry of the isomers. The 2-NO(2)Py isomer has the largest red shift and lowest oscillator strength in the UV-visible band associated with the nitro group. The isomers show very low fluorescence yields (10(-3)-10(-4)). Only 1-NO(2)Py and 4-NO(2)Py have phosphorescence emission (Φ(p) ≈ 10(-4)), indicating that the lowest triplet state decays mainly through effective radiationless channels. Laser photolysis produces a low-lying triplet state (τ(T) = 10(-5)-10(-6) s), a long-lived pyrenoxy radical, and a PyNO(2)H radical in solvents in which the triplet can abstract a hydrogen atom. Similar triplet yields were calculated (0.1-0.6) for the isomers, while significant differences in the relative yield of the long-lived species were determined. Differences in the quenching rate constants of the triplet by water and phenols suggest a strong hydrogen-bond interaction with the nitro group in the C-2 position, which provides for radiationless deactivation routes.     

Morphology evolution of Cu(2-x)S nanoparticles: from spheres to dodecahedrons

An oriented attachment and growth mechanism allows an accurate control of the size and morphology of Cu(2-x)S nanocrystals, from spheres and disks to tetradecahedrons and dodecahedrons. The synthesis conditions and the growth mechanism are detailed here.     

Study of organo-hybrid layered double hydroxides by medium and near infrared spectroscopy

An Mg/Al layered double hydroxide (LDH) containing carbonate ion in its interlayer region was examined by medium infrared (MIR) and near infrared reflectance spectroscopy (NIRS). The MIR and NIR spectroscopy techniques was also used to study two organo-hybrid LDHs containing interlayer dodecylbenzenesulphonate (DBS) and dodecylsulphate (DS) ions, respectively. The NIR spectra for the latter solids were found to exhibit the overtone and combination bands for the hydroxyl groups in addition to those typical bands of the organic host functions.     

Schistosomicidal activity of the essential oil of Ageratum conyzoides L. (Asteraceae) against adult Schistosoma mansoni worms

The in vitro schistosomicidal effects of the essential oil of Ageratum conyzoides L. (Ac-EO) against adult worms of Schistosoma mansoni is reported in this paper. Concerning this activity, Ac-EO was considered to be active, but less effective than the positive control (praziquantel, PZQ) in terms of separation of coupled pairs, mortality, decrease in motor activity, and tegumental alterations. However, Ac-EO caused an interesting dose-dependent reduction in the number of eggs of S. mansoni. Precocene I (74.30%) and (E)-caryophyllene (14.23%) were identified as the two major constituents of Ac-EO. These compounds were tested individually and were found to be much less effective than Ac-EO and PZQ. A mixture of the two major compounds in a ratio similar to that found in the Ac-EO was also less effective than Ac-EO, thus revealing that there are no synergistic effects between these components. These results suggest that the essential oil of A. conyzoides is very promising for the development of new schistosomicidal agents.     

Modern drug discovery technologies: opportunities and challenges in lead discovery

The identification of promising hits and the generation of high quality leads are crucial steps in the early stages of drug discovery projects. The definition and assessment of both chemical and biological space have revitalized the screening process model and emphasized the importance of exploring the intrinsic complementary nature of classical and modern methods in drug research. In this context, the widespread use of combinatorial chemistry and sophisticated screening methods for the discovery of lead compounds has created a large demand for small organic molecules that act on specific drug targets. Modern drug discovery involves the employment of a wide variety of technologies and expertise in multidisciplinary research teams. The synergistic effects between experimental and computational approaches on the selection and optimization of bioactive compounds emphasize the importance of the integration of advanced technologies in drug discovery programs. These technologies (VS, HTS, SBDD, LBDD, QSAR, and so on) are complementary in the sense that they have mutual goals, thereby the combination of both empirical and in silico efforts is feasible at many different levels of lead optimization and new chemical entity (NCE) discovery. This paper provides a brief perspective on the evolution and use of key drug design technologies, highlighting opportunities and challenges.     

Probing lipid peroxidation by using linoleic acid and benzophenone

A thorough mechanistic study has been performed on the reaction between benzophenone (BZP) and a series of 1,4-dienes, including 1,4-cyclohexadiene (CHD), 1,4-dihydro-2-methylbenzoic acid (MBA), 1,4-dihydro-1,2-dimethylbenzoic acid (DMBA) and linoleic acid (LA). A combination of steady-state photolysis, laser flash photolysis (LFP), and photochemically induced dynamic nuclear polarization (photo-CIDNP) have been used. Irradiation of BZP and CHD led to a cross-coupled sensitizer-diene product, together with 6, 7, and 8. With MBA and DMBA as hydrogen donors, photoproducts arising from cross-coupling of sensitizer and diene radicals were found; compound 7 was also obtained, but 6 and o-toluic acid were only isolated in the irradiation of BZP with MBA. Triplet lifetimes were determined in the absence and in the presence of several diene concentrations. All three model compounds showed similar reactivity (k(q) ≈10(8) M(-1) s(-1)) towards triplet excited BZP. Partly reversible hydrogen abstraction of the allylic hydrogen atoms of CHD, MBA, and DMBA was also detected by photo-CIDNP on different timescales. Polarizations of the diamagnetic products were in full agreement with the results derived from LFP. Finally, LA also underwent partly reversible hydrogen abstraction during photoreaction with BZP. Subsequent hydrogen transfer between primary radicals led to conjugated derivatives of LA. The unpaired electron spin population in linoleyl radical (LA(.)) was predominantly found on H(1-5) protons. To date, LA-related radicals were only reported upon hydrogen transfer from highly substituted model compounds by steady-state EPR spectroscopy. Herein, we have experimentally established the formation of LA(.) and shown that it converts into two dominating conjugated isomers on the millisecond timescale. Such processes are at the basis of alterations of membrane structures caused by oxidative stress.     

Bijvoet in solution reveals unexpected stereoselectivity in a Michael addition

The absolute configuration of small crystallizable molecules can be determined with anomalous X-ray diffraction as shown by Bijvoet in 1951. For the majority of compounds that can neither be crystallized nor easily be converted into crystallizable derivatives, stereocontrolled organic synthesis is still required to establish their absolute configuration. In this contribution, a new fundamental methodology for resolving the absolute configuration will be presented that does not require crystallization. With residual dipolar coupling enhanced NMR spectroscopy, ensembles of a limited number of structures are created reflecting the correct conformations and relative configuration. Subsequently, from these ensembles, optical rotation dispersion (ORD) spectra are predicted by DFT calculations and compared to experimental results. The combination of these two steps reveals the absolute configuration of a flexible molecule in solution, which is a big challenge to chiroptical methods and DFT in the absence of NMR spectroscopy. Here the absolute stereochemistry of the product of a new Michael addition, synthesized via a niobium(V) chiral enolate, will be elucidated by using the new methodology.