Modification of membrane heterogeneity by antipsychotic drugs: an X-ray diffraction comparative study

Lipid mixtures are used to mimic biological membranes as they allow characterization of lipid lateral domains defined by their specific lipid molecular organization. Therapeutic agents such as antipsychotic drugs (AP) that may interact with lipids arrangement are likely to modify membrane biological properties. The present study describes the effect of 2 typical and 5 atypical antipsychotic drugs on an aqueous co-dispersion of a lipid mixture made of egg phosphatidylcholine (PC)/brain sphingomyelin (SM)/cholesterol (1/1/1 mol/mol/mol). Lamellar liquid-ordered (Lo) and liquid-disordered (Ld) phase coexistence was identified in the control and antipsychotic-added mixtures at 37 degrees C using synchrotron small-angle X-ray scattering methods (XRD). Intensity of the Bragg peaks was used to generate electron density profiles (EDP) allowing bilayer thickness calculation. All antipsychotic except from amisulpride induced a Lo phase bilayer thickness (d(pp)) decrease. Chlorpromazine, haloperidol, amisulpride and 9-0H-risperidone induced a Ld d(pp) increase while ziprazidone, risperidone and clozapine induced a Ld d(pp) decrease, indicating that antipsychotic atypicality is not associated with a specific d(pp) modification on our lipid model mixture. Results are discussed in terms of competition of antipsychotic compounds with cholesterol and mode of reorganization of lateral domains. A pharmacological relevance of these changes is also discussed.     

Analysis of minor flavonoids in Piper hostmannianum var. berbicense using liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry

The fragmentations of hydroxylated flavanones, chalcones and dihydrochalcones were investigated by direct loop injection using an ion trap mass spectrometry equipped with atmospheric pressure chemical ionization (APCI) probe. Some of them have been isolated from the leaves of Piper hostmannianum var. berbicense and standards were used to confirm their fragmentation behaviour. In negative ion mode, fragmentations of these three types of flavonoids revealed specific diagnostic ions which allowed us to identify aglycones in a crude plant extract. The major fragment ion obtained in MS/MS experiment for methoxylated chalcones is the neutral loss of a methyl radical whereas a H(2)O molecule is lost in the case of methoxylated dihydrochalcones. Methoxylated chalcones and flavanones isomers could be differentiated by the relative intensity ratio of [M-H-CH(3)]*(-) and [M-H-C(2)H(2)O](-) ions. Based on UV and MS data, a decision tree that includes UV lambda(max) absorptions and MS/MS diagnostic ions was built in order to obtain structural information of unknown compounds present in the extract. This tree was used to identify flavonoids in the ethyl acetate extract of P. hostmannianum var. berbicense leaves after analysis by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionization ion trap multistage mass spectrometry. A total of 11 flavonoids were tentatively characterized based on the MS fragmentations pattern observed in MS(n) experiments.     

Electrochemical sensing of heavy metals in biological media: A review

Trace metals are required in the body as they play a significant role in several biochemical processes. Moreover, certain heavy metals are beneficial at appropriate levels. Copper (Cu), for example, is essential for red blood cell formation, bone strength, and infant growth. Despite these fundamental roles, Cu can become toxic at high levels. Other heavy metals such as lead (Pb), cadmium (Cd), manganese (Mn), and mercury (Hg), have been identified to cause acute and chronic health complications. For these reasons, rapid, real-time quantification of such metals in biological media is of interest to improving human health outcomes. Electrochemical methods offer numerous advantages, such as portability, capability to be miniaturized, low cost, and ease-of-use. In this review, we examine recent developments in electrochemical sensing for the detection of heavy metals in biological media. To meet the requirements for inclusion in this review, the electrochemical sensor must have been evaluated in biological media (blood, serum, sweat, saliva, urine, brain tissue/cells). Several applications are explored to examine recent advancements in electrochemical sensing within these matrices. Addressing the challenges through materials, device, and system innovations, it is expected that electrochemical sensing of heavy metals in biological media will facilitate future diagnoses and treatments in healthcare.     

Molecular analysis of the kirromycin biosynthetic gene cluster revealed beta-alanine as precursor of the pyridone moiety

Kirromycin is a complex linear polyketide that acts as a protein biosynthesis inhibitor by binding to the bacterial elongation factor Tu. The kirromycin biosynthetic gene cluster was isolated from the producer, Streptomyces collinus Tü 365, and confirmed by targeted disruption of essential biosynthesis genes. Kirromycin is synthesized by a large hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) encoded by the genes kirAI-kirAVI. This complex involves some very unusual features, including the absence of internal acyltransferase (AT) domains in KirAI-KirAV, multiple split-ups of PKS modules on separate genes, and swapping in the domain organization. Interestingly, one PKS enzyme, KirAVI, contains internal AT domains. Based on in silico analysis, a route to pyridone formation involving PKS and NRPS steps was postulated. This hypothesis was experimentally proven by feeding studies with [U-13C3(15)N]beta-alanine and NMR and MS analyses of the isolated pure kirromycin.     

Vibrational spectroscopy of nitroalkane chains using electron autodetachment and ar predissociation

If the binding energy of an excess electron is lower than some of the vibrational levels of its host anion, vibrational excitation can lead to autodetachment. We use excitation of CH stretching modes in nitroalkane anions (2700-3000 cm(-1)), where the excess electron is localized predominantly on the NO2 group. We present data on nitroalkane anions of various chain lengths, showing that this technique is a valid approach to the vibrational spectroscopy of such systems extending to nitroalkane anions at least the size of nitropentane. We compare spectra taken by using vibrational autodetachment with spectra obtained by monitoring Ar evaporation from Ar solvated nitroalkane anions. The spectra of nitromethane and nitroethane are assigned on the basis of ab initio calculations with a detailed analysis of Fermi resonances of CH stretching fundamentals with overtones and combination bands of HCH bending modes.     

On Optimal 4-Dimensional Metrics

We completely determine, up to homeomorphism, which simply connected compact oriented 4-manifolds admit scalar-flat, anti-self-dual Riemannian metrics. The key new ingredient is a proof that the connected sum of five reverse-oriented complex projective planes admits such metrics. Supported in part by NSF grant DMS-0604735.     

Self-assembled layers based on isomerizable stilbene and diketoarylhydrazone moieties

The ability to form self-assembled layers on gold (Au) using five organosulfur compounds that contain isomerizable groups has been investigated. The isomerizable groups are either stilbene or diketoarylhydrazone derivatives. To anchor them on a gold surface, the isomerizable groups have been combined with sulfur-containing groups (disulfide, 1,2-dithiolane, and thiophene). The resulting thin films assembled on gold were characterized by X-ray photoelectron spectroscopy (XPS), infrared (FTIR) reflectance spectroscopy, ellipsometry, and water contact angle measurements. Though all substances have the potential to form self-assembled monolayers (SAMs), only two of them, disulfanediyl-bis(ethane-2,1-diyl) bis(4-styrylbenzoate) (1) and 4-[(2,4-dioxo-3-pentylidene)diazane-2,2,1-triyl]phenyl thioctate (4), yield the expected structure, the latter one showing the possibility to incorporate diarylketohydrazone moieties into SAMs. The compound 4-[(2,4-dioxo-3-pentylidene)diazane-2,2,1-triyl]phenyl thiophene-2-carboxylate (5) does not self-assemble on gold, but 4-styrylphenyl thioctate (3) presumably forms multilayers. In the case of disulfanediyl-bis(ethane-2,1-diyl) bis[4-(p-nitrostyryl)benzoate] (2), we propose a structure with a fraction of the molecules bound to gold via the nitro group. The results show that the propensity of organosulfur compounds to self-assemble on gold not only is determined by the sulfur-containing group but also is affected by the complete molecule.     

Modulating the framework negative charge density in the system [BDT-TTP*+]/[Re6S5Cl9(1-)]/[Re6(S/Se)6Cl8(2-)]/[Re6S7Cl7(3-)]: templating by isosteric cluster anions of identical symmetry and shape, variations of incommensurate band filling, and electronic structure in 2D metals

A series of 2D metals, beta-(BDT-TTP)6[Re6Se6Cl8] x (CHCl2-CHCl2)2, 2; beta-(ST-TTP)6[Re6S6Cl8] x (CH2Cl-CHCl2)2, 3; beta-(BDT-TTP)7[Re6S6Cl8]0.5[Re6S7Cl7]0.5 x (CH2Cl2), 4; beta-(BDT-TTP)7[Re6Se6Cl8]0.5[Re6S7Cl7]0.5 x (CH2Cl2), 5; beta-(BDT-TTP)8[Re6S7Cl7] x (CH2Cl2)4, 6 (BDT-TTP and ST-TTP are 2,5-bis(1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentalene and 2-(1,3-diselenol-2-ylidene)-5(1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentalene, respectively) is reported to have one single beta-slab layered topology despite successive increases of the cluster anion negative charge. The charge density within the templating composite inorganic-neutral molecule slab is shown to remain above a threshold of ca. one negative charge per square nanometer, that is, for cluster anions with two negative charges and higher. Conversely, discrete stacks are shown to be stabilized instead in the semiconducting salts (BDT-TTP)2[Re6S5Cl9], 1 where the cluster anion bears one negative charge only. The electronic structure of salts 2-6 is shown to be very stable and kept almost intact across the series. The templating strategy is shown to fulfill its anticipated potential for deliberate installment of incommensurate band fillings in molecular metals. The deliberate admixture of the 6:1 and 8:1 structures yields novel phases with a 7:1 stoichiometry with the anticipated crystal and electronic structures. The action at the organic-inorganic interface triggered by changing the anion charge yet keeping its shape and volume identical, which ultimately governs the shape of the unit cell, is of paramount importance in defining the Fermi surface of these metallic salts. The present BDT-TTP salts thus provide a series of materials with strongly related but subtly different Fermi surfaces worthy of many physical studies. Shubnikov-de Haas measurements are expected to be particularly interesting since they are especially sensitive to the details of the Fermi surface.     

LC Using Two Different Cellulose Chiral Stationary Phases for Direct Enantioseparation of Benzoxazolinone Aminoalcohols and Aminoketones

A series of six benzoxazolinone aminoketones and height aminoalcohols has been synthetized as agonist and antagonist ligands for adrenergic receptors. For those benzoxazolinone derivatives which contain one or two chiral carbons, a stereoselective liquid chromatographic method, using silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H) or tris-4-methylbenzoate (Chiralcel OJ) as chiral stationary phase, has been developed. A better separation was achieved on cellulose carbamate phase compared to the cellulose ester phase. The effects of concentration of various aliphatic alcohols in the mobile phase were studied. The effects of structural features of the solutes on the discrimination between the enantiomers were examined.