On molecular chirality within naturally occurring secondary organic aerosol particles from the central Amazon Basin

In this perspectives article, we reflect upon the existence of chirality in atmospheric aerosol particles. We then show that organic particles collected at a field site in the central Amazon Basin under pristine background conditions during the wet and dry seasons consist of chiral secondary organic material. We show how the chiral response from the aerosol particles can be imaged directly without the need for sample dissolution, solvent extraction, or sample preconcentration. By comparing the chiral-response images with optical images, we show that chiral responses always originate from particles on the filter, but not all aerosol particles produce chiral signals. The intensity of the chiral signal produced by the size resolved particles strongly indicates the presence of chiral secondary organic material in the particle. Finally, we discuss the implications of our findings on chiral atmospheric aerosol particles in terms of climate-related properties and source apportionment.

Chirality of reduced haloperidol in humans

In vitro, cytosolic human ketone reductases catalyse the stereospecific (i.e. >99%) formation of S(-) reduced haloperidol (RHP) from haloperidol (HP). Whether this situation is reflected in patients taking the drug is unknown. In this study in nine patients taking HP, only 73.2+/-18.2% of the RHP excreted in urine was the S(-) enantiomer. Thus, enzymes other than cytosolic ketone reductases must be responsible for the formation of the minor enantiomer. (C) 1998 Elsevier Science B.V./ECNP.

Insect chemistry and chirality

Examination of the chemistry of a number of Australian insect species provided examples of unusual structures and encouraged determinations of their absolute stereochemistry by stereocontrolled syntheses and chromatographic comparisons. Inter alia, studies with the fruit-spotting bug (Amblypelta nitida), certain parasitic wasps (Biosteres sp.), the aposematic shield bug (Cantao parentum), and various species of scarab grubs are summarized. The determination of enantiomeric excesses (ee's) for component epoxides, lactones, spiroacetals, and allenes are described. Stereochemical and related aspects of the biosynthesis of spiroacetals in certain fruit-fly species (Bactrocerae sp.) are also presented.

A fluorescente bicyclic Calix[4] Arene-Oxacyclophane with planar chirality: Resolution, chiroptical, properties, and absolute configuration.

A new inherently chiral calix[4]arene ICC 1 has been disclosed. The dissymmetry of 1 is generated from a chirality plane in the quinol moiety of a 1,3-bridged bicyclic calix[4]arene. ICC 1 has been resolved by enantioselective HPLC, and the chiroptical properties of both isolated antipodes (pS)-1 and (pR)-1 confirm their enantiomeric nature. The absolute configuration of the (pS)-1/(pR)-1 enantiomeric pair was established through time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (CD) spectra. (C) 2014 Elsevier Ltd. All rights reserved.

Inherently chiral calix[4]arenes with planar chirality: two new entries to the family

The synthesis of two new inherently chiral calix[4]arenes (ICCs, 1 and 2), endowed with electron-rich concave surfaces, has been achieved through the desymmetrization of a lower rim distal-bridged oxacyclophane (OCP) macrocycle. The new highly emissive ICCs were resolved by chiral HPLC, and the enantiomeric nature of the isolated antipodes proved by electronic circular dichroism (CD). Using time-dependent density functional calculations of CD spectra, their absolute configurations were established. NMR studies with (S)-Pirkle's alcohol unequivocally showed that the host-guest interactions occur in the chiral pocket comprehending the calix-OCP exo cavities and the carbazole moieties.

Chirality in the new generation of antidepressants: stereoselective analysis of the enantiomers of mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine by LC-MS.

Mirtazapine is an antidepressant that acts specifically on noradrenergic and sertonergic receptors. A LC-MS method was developed that allows the simultaneous analysis of the R-(-)- and S-(+)-enantiomers of mirtazapine (MIR), demethylmirtazapine (DMIR), and 8-hydroxymirtazapine (8-OH-MIR) in plasma of MIR-treated patients. The method involves a 3-step liquid-liquid extraction, an HPLC separation on a Chirobiotic V column, and MS detection in electrospray mode. The limit of quantification (LOQ) for all enantiomers was 0.5 ng/mL, and the intra- and interday CVs were within 3.3% to 11.7% (concentration ranges 5-50 ng/mL). A method is also presented for the quantitative analysis of glucuroconjugated MIR and 8-OH-MIR. S-(+)-8-OH-MIR is present in plasma mainly as its glucuronide. Preliminary data suggest that in all patients, except in those comedicated with CYP2D6 inhibitors such as fluoxetine and thioridazine, R-(-)-MIR concentrations were higher than those of S-(+)MIR. Moreover, fluvoxamine seems also to inhibit the metabolism of MIR. Therefore, this method seems to be suitable for the stereoselective assay of MIR and its metabolites in plasma of patients comedicated with MIR and other drugs for routine and research purposes.

Spontaneous mirror symmetry breaking in the limited enantioselective autocatalysis model: abyssal hydrotermal vents as scenario for the emergence of chirality in prebiotic chemistry

The emergence of chirality in enantioselective autocatalysis for compounds unable to transform according to the Frank-like reaction network is discussed with respect to the controversial limited enantioselectivity (LES) model composed of coupled enantioselective and non-enantioselective autocatalyses. The LES model cannot lead to spontaneous mirror symmetry breaking (SMSB) either in closed systems with a homogeneous temperature distribution or in closed systems with a stationary non-uniform temperature distribution. However, simulations of chemical kinetics in a two-compartment model demonstrate that SMSB may occur if both autocatalytic reactions are spatially separated at different temperatures in different compartments but coupled under the action of a continuous internal flow. In such conditions, the system can evolve, for certain reaction and system parameters, toward a chiral stationary state; that is, the system is able to reach a bifurcation point leading to SMSB. Numerical simulations in which reasonable chemical parameters have been used suggest that an ade- quate scenario for such a SMSB would be that of abyssal hydrothermal vents, by virtue of the typical temper- ature gradients found there and the role of inorganic solids mediating chemical reactions in an enzyme-like role. Key Words: Homochirality Prebiotic chemistry.

Spontaneous Emergence of Chirality in the Limited Enantioselectivity Model: Autocatalytic Cycle Driven by an External Reagent

The emergence of chirality in enantioselective autocatalysis for compounds unable to transform according to the Frank-like reaction network is discussed with respect to the controversial limited enantioselectivity (LES) model composed of coupled enantioselective and non-enantioselective autocatalyses. The LES model cannot lead to spontaneous mirror symmetry breaking (SMSB) either in closed systems with a homogeneous temperature distribution or in closed systems with a stationary non-uniform temperature distribution. However, simulations of chemical kinetics in a two-compartment model demonstrate that SMSB may occur if both autocatalytic reactions are spatially separated at different temperatures in different compartments but coupled under the action of a continuous internal flow. In such conditions, the system can evolve, for certain reaction and system parameters, toward a chiral stationary state; that is, the system is able to reach a bifurcation point leading to SMSB. Numerical simulations in which reasonable chemical parameters have been used suggest that an adequate scenario for such a SMSB would be that of abyssal hydrothermal vents, by virtue of the typical temperature gradients found there and the role of inorganic solids mediating chemical reactions in an enzyme-like role.

The stability of right- and left-handed alpha-helices as a function of monomer chirality

Poly-L-alanine forms stable right-handed alpha-helices, whereas Poly-D-alanine is stable as left-handed alpha helices.

Helices, chirality and interpenetration: the versatility and remarkable interconversion of silver-copper cyanide frameworks

The structural transformations between cesium silver-copper cyanides under modest conditions, both in solution and in the solid state, are described. Three new cesium silver(I) copper(I) cyanides with three-dimensional (3-D) framework structures were prepared as single crystals from a one-pot reaction initially heated under hydrothermal conditions. The first product to appear, Cs3Ag2Cu3(CN)(8) (I), when left in contact with the supernatant produced CsAgCu(CN)(3) (II) and CsAgCu(CN)(3)center dot 1/3H(2)O (III) over a few months via a series of thermodynamically controlled cascade reactions. Crystals of the hydrate (III) can be dehydrated to polycrystalline CsAgCu(CN)(3) (II) on heating at 100 degrees C in a remarkable solid-state transformation involving substantial breaking and reconnection of metal-cyanide linkages. Astonishingly, the conversion between the two known polymorphs of CsAg2Cu(CN)(4), which also involves a major change in connectivity and topology, occurs at 180 degrees C as a single-crystal to single-crystal transformation. Structural features of note in these materials include the presence of helical copper-cyanide chains in (I) and (II), which in the latter compound produce a chiral material. In (II) and (III), the silver-copper cyanide networks are both self- and interpenetrating, features also seen in the known polymorphs of CsAg2Cu(CN)(4).

Global and local expression of chirality in serine on the Cu{110} surface

Establishing a molecular-level understanding of enantioselectivity and chiral resolution at the organic−inorganic interfaces is a key challenge in the field of heterogeneous catalysis. As a model system, we investigate the adsorption geometry of serine on Cu{110} using a combination of low-energy electron diffraction (LEED), scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The chirality of enantiopure chemisorbed layers, where serine is in its deprotonated (anionic) state, is expressed at three levels: (i) the molecules form dimers whose orientation with respect to the substrate depends on the molecular chirality, (ii) dimers of l- and d-enantiomers aggregate into superstructures with chiral (−1 2; 4 0) lattices, respectively, which are mirror images of each other, and (iii) small islands have elongated shapes with the dominant direction depending on the chirality of the molecules. Dimer and superlattice formation can be explained in terms of intra- and interdimer bonds involving carboxylate, amino, and β−OH groups. The stability of the layers increases with the size of ordered islands. In racemic mixtures, we observe chiral resolution into small ordered enantiopure islands, which appears to be driven by the formation of homochiral dimer subunits and the directionality of interdimer hydrogen bonds. These islands show the same enantiospecific elongated shapes those as in low-coverage enantiopure layers.

Structure determination of proteins and peptides in solution: simulation, chirality and NMR studies

The study of protein fold is a central problem in life science, leading in the last years to several attempts for improving our knowledge of the protein structures. In this thesis this challenging problem is tackled by means of molecular dynamics, chirality and NMR studies. In the last decades, many algorithms were designed for the protein secondary structure assignment, which reveals the local protein shape adopted by segments of amino acids. In this regard, the use of local chirality for the protein secondary structure assignment was demonstreted, trying to correlate as well the propensity of a given amino acid for a particular secondary structure. The protein fold can be studied also by Nuclear Magnetic Resonance (NMR) investigations, finding the average structure adopted from a protein. In this context, the effect of Residual Dipolar Couplings (RDCs) in the structure refinement was shown, revealing a strong improvement of structure resolution. A wide extent of this thesis is devoted to the study of avian prion protein. Prion protein is the main responsible of a vast class of neurodegenerative diseases, known as Bovine Spongiform Encephalopathy (BSE), present in mammals, but not in avian species and it is caused from the conversion of cellular prion protein to the pathogenic misfolded isoform, accumulating in the brain in form of amiloyd plaques. In particular, the N-terminal region, namely the initial part of the protein, is quite different between mammal and avian species but both of them contain multimeric sequences called Repeats, octameric in mammals and hexameric in avians. However, such repeat regions show differences in the contained amino acids, in particular only avian hexarepeats contain tyrosine residues. The chirality analysis of avian prion protein configurations obtained from molecular dynamics reveals a high stiffness of the avian protein, which tends to preserve its regular secondary structure. This is due to the presence of prolines, histidines and especially tyrosines, which form a hydrogen bond network in the hexarepeat region, only possible in the avian protein, and thus probably hampering the aggregation.