Chemistry of Lipid A: At the Heart of Innate Immunity

In many Gram‐negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll‐like receptor 4/myeloid differentiation factor 2 (TLR4/MD‐2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock. Since the bioactivity of lipid A is strongly influenced by its primary structure, a broad range of chemical syntheses of lipid A derivatives have made an enormous contribution to the characterization of lipid A bioactivity, providing novel pharmacological targets for the development of new biomedical therapies. Here, we describe and discuss the chemical aspects regarding lipid A and its role in innate immunity, from the (bio)synthesis, isolation and characterization to the molecular recognition at the atomic level.     

Electrocatalysis of As(III) oxidation by cobalt oxide nanoparticles: measurement and modeling the effect of nanoparticle amount on As(III) oxidation potential

Journal of Solid State Electrochemistry - The performance of electrodes modified with electrochemically generated cobalt oxide nanoparticles for the oxidation of As(III) species was investigated by...     

Ultrasound-assisted extraction of capsaicinoids from peppers

The development of a rapid, reproducible and simple method of extraction of the majority capsaicinoids (nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin) present in hot peppers by the employment of ultrasound-assisted extraction is reported. The study has covered four possible solvents for the extraction (acetonitrile, methanol, ethanol and water), the optimum temperature for extraction (10–60 °C), the extraction time (2–25 min), the quantity of sample (0.2–2 g), and the volume of solvent (15–50 mL). Under the optimum conditions of the method developed, methanol is employed as solvent, at a temperature of 50 °C and an extraction time of 10 min. The repeatability and reproducibility of the method (R.S.D. < 3%) have been determined. The capsaicinoids extracted have been analysed by HPLC with fluorescence detection and using monolithic columns for the chromatographic separation. The method developed has been employed for the quantification of the various capsaicinoids present in different varieties of hot peppers cultivated in Spain.     

Decorated DNA-Based Scaffolds as Lateral Flow Biosensors

Here we develop Lateral Flow Assays (LFAs) that employ as functional elements DNA-based structures decorated with reporter tags and recognition elements. We have rationally re-engineered tile-based DNA tubular structures that can act as scaffolds and can be decorated with recognition elements of different nature (i.e. antigens, aptamers or proteins) and with orthogonal fluorescent dyes. As a proof-of-principle we have developed sandwich and competitive multiplex lateral flow platforms for the detection of several targets, ranging from small molecules (digoxigenin, Dig and dinitrophenol, DNP), to antibodies (Anti-Dig, Anti-DNP and Anti-MUC1/EGFR bispecific antibodies) and proteins (thrombin). Coupling the advantages of functional DNA-based scaffolds together with the simplicity of LFAs, our approach offers the opportunity to detect a wide range of targets with nanomolar sensitivity and high specificity.     

Squaraine Dyes: Interaction with Bovine Serum Albumin to Investigate Supramolecular Adducts with Aggregation‐Induced Emission (AIE) Properties

Bovine serum albumin (BSA)–squaraine supramolecular adducts with aggregation‐induced emission (AIE) properties were prepared and characterized by spectroscopic methods. While squaraine dyes showed a very low fluorescence quantum yield in water, a great enhancement in the fluorescence of the aggregated BSA adducts was achieved due to the abnormal aggregation‐induced emission properties of squaraines. The adducts formation was studied from a kinetic point of view showing unexpected structure–properties relationships.     

The fate of the tert-butylsulfinyl auxiliary after acid-promoted cleavage—a method for recycling t-BuSONH2

Ellman’s chiral auxiliary is converted into tert-butylsulfinyl chloride on sulfinamide deprotection with HCl and can be recovered in high yield upon treatment with ammonia. The enantiopure auxiliary can be obtained by trapping the sulfinyl chloride with a chiral alcohol followed by treatment of the resulting sulfinate ester with LiNH₂.     

Preparation and characterization of aryl or heteroaryl(3-indolyl)methylium o-benzenedisulfonimides

An initial study has been accomplished into the synthetic feasibility of the preparation of diarylcarbenium salt via the direct coupling of aryl (or heteroaryl) aldehydes and arenes (or heteroaryl analogues) in the presence of a strong organic Br?nsted acid. A number of stabilized aryl or heteroaryl(3-indolyl)carbenium ions, never previously prepared in the solid state, have been isolated in excellent yields as highly stable o-benzenedisulfonimide salts and have been fully characterized. Their purity has been proven by spectroscopic methods and chemical reduction with NaBH(4). An X-ray crystal structure analysis has been performed on one of the products: an azafulvenium species was shown to be the exclusive structure in the solid state.     

Intramolecular cyclization of tert-butyldiphenylallylsilane units and carbonyl groups: allylsilane terminated cyclization versus the ene reaction.

tert-Butyldiphenylsilylcopper reacts with allene to give an allylsilane-vinylcopper intermediate which upon treatment with alpha,beta-unsaturated ketones leads to allylsilane containing ketones resulting from conjugate addition. These oxoallylsilanes bearing the bulky tert-butyldiphenylsilyl group undergo highly selective intramolecular cyclizations when treated with Lewis acid affording unsaturated cyclopentanols. Two reactivity patterns are observed: allylsilane terminated cyclization involving elimination of silicon or an ene reaction without losing the silyl group. The pathway depends on the ability of a hydrogen beta to the carbonyl to be removed in an ene-type process. Alpha,beta-unsaturated acid chlorides lead to silylated cyclopentenones.     

Surface transitions in nematic liquid crystals oriented with Langmuir-Blodgett films

In this paper two types of surface transitions in nematic liquid crystals are theoretically analyzed with a simple model in which the anchoring energy is the result of both steric and electric interactions. The physical model is proper to explain both the transition temperature experimentally observed in homeotropically aligned nematic liquid crystals, and the change in the mean molecular direction due to the variation of the number of surfactant films, piled on the boundary surfaces with the Langmuir-Blodgett technique.Partially supported by the TEMPUS program     

Observation of time-dependent CP violation in B0 --> eta'K0 decays and improved measurements of CP asymmetries in B0 --> phiK0, KS0KS0KS0 and B0 --> J/psiK0 decays

We present improved measurements of CP-violation parameters in B(0) --> phiK(0), eta(')K(0), KS(0)KS(0)KS(0) decays based on a sample of 535 x 10(6) BB pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB energy-asymmetric e(+)e(-) collider. We obtain sin2phi1(eff)=+0.64+/-0.10(stat)+/-0.04(syst) for B(0) --> eta(')K(0), +0.50+/-0.21(stat)+/-0.06(syst) for B(0) --> phiK(0), and +0.30+/-0.32(stat)+/-0.08(syst) for B(0) --> KS(0)KS(0)KS(0) decays. We have observed CP violation in the B(0) --> eta(')K(0) decay with a significance of 5.6 standard deviations. We also perform an improved measurement of CP asymmetries in B(0) --> J/psiK(0) decays and obtain sin2phi1=+0.642+/-0.031(stat)+/-0.017(syst).