Biophysical properties of dimeric phospholipids

A series of unusual bipolar and bis-phospholipids (dimeric phospholipids) have been studied. The structure, conformation, morphology and biophysical properties of the resulting phospholipid aggregates were investigated.Deuterium magnetic resonance spectroscopy ($sp2$H NMR) was used to study and characterize the conformation and acyl chain order in oriented bipolar lipid membranes. The $sp2$H-NMR studies indicated a large and constant value for the order parameter (S$rm sb{mol})$ for all positions along the bipolar lipid diacyl chain for mechanically oriented, magnetically oriented and unoriented samples. This indicates that the great majority ($>$90%) of the bipolar lipid exists in a highly ordered spanning conformation.Dimeric phospholipid aggregate morphologies were studied using $sp{31}$P NMR, small angle X-ray scattering, electron microscopy, differential scanning calorimetry, and the Langmuir film balance technique in order to study the relationship between lipid structure and aggregate morphology. Dimeric phospholipids favour a lamellar morphology. A number of lipid structure-dependent features have been observed including tri-lamellar structures, extended ripple phases and hexagonal phases.Dimeric and non-hydrolyzable phospholipids were used to study the phenomenon of interfacial activation of extracellular phospholipase A$sb2$ (EC. 3.1.1.4) (PLA$sb2)$ in relation to lipid phase, substrate conformation and mobility. Kinetic results and product analyses are consistent with a situation where the spanning conformer of bipolar phospholipids is resistant to PLA$sb2$-catalyzed hydrolysis but the hairpin conformer is readily hydrolyzed. Finally, an analysis of interfacial kinetics in non-hydrolyzable matrices indicated varying degrees of interfacial inhibition and hydrolysis product activation. This has not been explicitly recognized before and affects the choice of assay conditions for PLA$ sb2.

Mechanochemical Desymmetrization of Unbiased Bis- and Tris-alkynes to Access 3,5-Isoxazoles-Alkyne Adducts and Unsymmetrical Bis-3,5-isoxazoles

A mechanochemical desymmetrization of symmetrical bis- and tris-alkynes via a controlled 1,3-dipolar cycloaddition reaction with nitrile oxide dipoles has been developed. This convenient, efficient, and simple protocol allows access to 3,5-isoxazole-alkyne adducts from easily prepared or commercially available symmetrical bis- and tris-alkynes in moderate to excellent yield. The synthetic utility of 3,5-isoxazole-alkyne was demonstrated by developing a route to access β-ketoenamine-alkyne derivatives and the synthesis of unsymmetrical bis-3,5-isoxazoles products in good to excellent yields

On the Origin of Sugar Handedness: Facts, Hypotheses and Missing Links-A Review

By paraphrasing one of Kipling’s most amazing short stories (How the Leopard Got His Spots), this article could be entitled “How Sugars Became Homochiral”. Obviously, we have no answer to this still unsolved mystery, and this perspective simply brings recent models, experiments and hypotheses into the homochiral homogeneity of sugars on earth. We shall revisit the past and current understanding of sugar chirality in the context of prebiotic chemistry, with attention to recent developments and insights. Different scenarios and pathways will be discussed, from the widely known formose-type processes to less familiar ones, often viewed as unorthodox chemical routes. In particular, problems associated with the spontaneous generation of enantiomeric imbalances and the transfer of chirality will be tackled. As carbohydrates are essential components of all cellular systems, astrochemical and terrestrial observations suggest that saccharides originated from environmentally available feedstocks. Such substances would have been capable of sustaining autotrophic and heterotrophic mechanisms integrating nutrients, metabolism and the genome after compartmentalization. Recent findings likewise indicate that sugars’ enantiomeric bias may have emerged by a transfer of chirality mechanisms, rather than by deracemization of sugar backbones, yet providing an evolutionary advantage that fueled the cellular machinery

Pasteur made simple – mechanochemical transformation of racemic amino acid crystals into racemic conglomerate crystals

Conglomerate crystallization is required for many deracemization or enantioenrichment protocols. Here, we report the metal-mediated mechanochemical transformation of racemic compounds of some proteinogenic amino acids – valine, leucine and isoleucine – into their corresponding conglomerates. Specifically, ZnO has the ability to promote and stabilize the conglomerate phase of these amino acids to an extent where the racemic compound is not observed

Alkyl chain length effects on double-deck assembly at a liquid/solid interface

Controlled double-deck packing is an appealing means to expand upon conventional 2D self-assembly which is critical in crystal engineering, yet it is rare and poorly understood. Herein, we report the first systematic study of double-deck assembly in a series of alkylated aminoquinone derivatives at the liquid-solid interface. The competition between the fraction of alkyl chains adsorbed on the surface and the optimal conformation of the alkyl chains near the head group leads to a stepwise structural transformation ranging from complete double-deck packing to complete monolayer packing. Alkyl chains on the bottom or top layer of the double-deck assemblies were selectively visualized by carefully tuning the scanning tunneling microscopy settings. A method to easily identify mirror image domains was discovered based on the coincidence of domain boundaries with a graphite main axis. The effect of molecular symmetry and metal complexation on the formation of the double-deck assembly was also explored. Based on 2D crystal engineering principles, this bottom-up double-deck assembly can potentially provide an essential toehold for constructing precise 3D hierarchical structures.status: publishe

Revisiting homochiral versus heterochiral interactions through a long detective story of a useful azobis-nitrile and puzzling racemate

This paper documents and reinvestigates the solid-state and crystal structures of 4,4′-azobis-4-cyanopentanoic acid (ACPA), a water-soluble azobis-nitrile of immense utility as a radical initiator in living polymerizations and a labile mechanophore that can be embedded within long polymer chains to undergo selective scission under mechanical activation. Surprisingly, for such applications, both the commercially available reagent and their derivatives are used as “single initiators” when this azonitrile is actually a mixture of stereoisomers. Although the racemate and meso compounds were identified more than half a century ago and their enantiomers were separated by classical resolution, there have been confusing narratives dealing with their characterization, the existence of a conglomeratic phase, and fractional crystallization. Our results report on the X-ray crystal structures of all stereoisomers for the first time, along with further details on enantiodiscrimination and the always intriguing arguments accounting for the stability of homochiral versus heterochiral crystal aggregates. To this end, metadynamic (MTD) simulations on stereoisomer molecular aggregates were performed to capture the incipient nucleation events at the picosecond time scale. This analysis sheds light on the driving homochiral aggregation of ACPA enantiomers.</p

Oriented attachment by enantioselective facet recognition in millimeter-sized gypsum crystals

Crystal growth by oriented attachment involves the spontaneous self-assembly of adjoining crystals with common crystallographic orientations. Herein, we report the oriented attachment of gypsum crystals on agitation to form stereoselective mesoscale aggregates