Creating a fatty acid methyl ester database for lipid profiling in a single drop of human blood using high resolution capillary gas chromatography and mass spectrometry

Capillary gas chromatography (CGC) in combination with mass spectrometry (MS) was optimized for the separation and detection of the fatty acids occurring in the lipid fraction of blood. A fingertip blood sample (ca. 50 microL) was transesterified into the methyl esters and analyzed on a 100 m x 0.25 mm ID column coated with a biscyanopropyl polysiloxane (HP-88) stationary phase. The method was retention time locked. Programmed temperature vaporization injection (PTV) in the solvent venting mode was applied to minimize the sample size, while maintaining high sensitivity. The total analysis time was ca. 60 min. Retention times and both electron impact (EI) and positive chemical ionization (PCI) mass spectrometry were combined to elucidate the fatty acids according to alkyl chain, degree of unsaturation and position of the double bonds. Using extracted ion chromatograms about 100 fatty acids and related compounds were detected in blood samples and most of them were identified. This work resulted in a very large fatty acid methyl esters database, containing retention time and mass spectral information that will be applied to metabolomic studies.     

Ring-fused cyclobutanes via cycloisomerization of alkylidenecyclopropane acylsilanes

A novel Lewis acid-catalyzed cycloisomerization of alkylidenecyclopropane acylsilanes is disclosed. The readily available starting materials participate in tandem Prins addition/ring expansion/1,2-silyl shift to grant access to bicyclo[4.2.0]octanes and bicyclo[3.2.0]heptanes, which are common motifs in terpenoid natural products. Notably, the transformation relies on the ability of acylsilanes to act sequentially as acceptors and donors on the same carbon atom.

A novel Lewis acid-catalyzed cycloisomerization of alkylidenecyclopropane acylsilanes is disclosed that involves tandem Prins addition/ring expansion/1,2-silyl shift to grant access to bicyclo[4.2.0]octanes and bicyclo[3.2.0]heptanes.     

Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens

Due to the emergence of multidrug-resistant pathogens, it is necessary to develop options to fight infections caused by these agents. Lactoferrin (Lf) is a cationic nonheme multifunctional glycoprotein of the innate immune system of mammals that provides numerous benefits. Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects. Lactoferrin is present in colostrum and milk and is also produced by the secondary granules of polymorphonuclear leukocytes, which store this glycoprotein and release it at sites of infection. Lf is also present in many fluids and exocrine secretions, on the surfaces of the digestive, respiratory and reproductive systems that are commonly exposed to pathogens. Apo-Lf (an iron-free molecule) can be microbiostatic due to its ability to capture ferric iron, blocking the availability of host iron to pathogens. However, apo-Lf is mostly microbicidal via its interaction with the microbial surface, causing membrane damage and altering its permeability function. Lf can inhibit viral entry by binding to cell receptors or viral particles. Lf is also able to counter different important mechanisms evolved by microbial pathogens to infect and invade the host, such as adherence, colonization, invasion, production of biofilms and production of virulence factors such as proteases and toxins. Lf can also cause mitochondrial and caspase-dependent regulated cell death and apoptosis-like in pathogenic yeasts. All of these mechanisms are important targets for treatment with Lf. Holo-Lf (the iron-saturated molecule) can contain up to two ferric ions and can also be microbicidal against some pathogens. On the other hand, lactoferricins (Lfcins) are peptides derived from the N-terminus of Lf that are produced by proteolysis with pepsin under acidic conditions, and they cause similar effects on pathogens to those caused by the parental Lf. Synthetic analog peptides comprising the N-terminus Lf region similarly exhibit potent antimicrobial properties. Importantly, there are no reported pathogens that are resistant to Lf and Lfcins; in addition, Lf and Lfcins have shown a synergistic effect with antimicrobial and antiviral drugs. Due to the Lf properties being microbiostatic, microbicidal, anti-inflammatory and an immune modulator, it represents an excellent natural alternative either alone or as adjuvant in the combat to antibiotic multidrug-resistant bacteria and other pathogens. This review aimed to evaluate the data that appeared in the literature about the effects of Lf and its derived peptides on pathogenic bacteria, protozoa, fungi and viruses and how Lf and Lfcins inhibit the mechanisms developed by these pathogens to cause disease.     

One-pot synthesis of novel photochromic oxazine compounds

A one-pot domino synthesis of photochromic 2,2-diarylphenanthro-(9,10)-[2H]-[1,4]-oxazines in excellent yield is described starting with acrylic acid derivatives. The reaction mechanism was studied by ReactIR and UV-vis. The cascade sequence of the reactions involves five transformations, namely, acyl azide formation, Curtius rearrangement, arsonium ylide formation, aza-Wittig, and final cyclization to the title compounds.     

Anharmonic vibrational calculations modeling the raman spectra of intermediates in the photoactive yellow protein (PYP) photocycle

The role of anharmonic effects in the vibrational spectroscopy of the dark state and two major chromophore intermediates of the photoactive yellow protein (PYP) photocycle is examined via ab initio vibrational self-consistent field (VSCF) calculations and time-resolved resonance Raman spectroscopy. For the first time, anharmonicity is considered explicitly in calculating the vibrational spectra of an ensemble consisting of the PYP chromophore surrounded by model compounds used as mimics of the important active-site residues. Predictions of vibrational frequencies on an ab initio corrected semiempirical potential energy surface show remarkable agreement with experimental frequencies for all three states, thus shedding light on the potential along the reaction path. For example, calculated frequencies for vibrational modes of the red-shifted intermediate, PYPL, exhibit an overall average error of 0.82% from experiment. Upon analysis of anharmonicity patterns in the PYP modes we observe a decrease in anharmonicity in the C8-C9 stretching mode nu29 (trans-cis isomerization marker mode) with the onset of the cis configuration in PYPL. This can be attributed to the loss of the hydrogen-bonding character of the adjacent C9-O2 to the methylamine (Cys69 backbone). For several of the modes, the anharmonicity is mostly due to mode-mode coupling, while for others it is mostly intrinsic. This study shows the importance of the inclusion of anharmonicity in theoretical spectroscopic calculations, and the sensitivity of experiments to anharmonicity. The characterization of protein active-site residues by small molecular mimics provides an acceptable chemical structural representation for biomolecular spectroscopy calculations.     

Oligothiophene-linked bisnaphthopyrans: sequential and temperature-dependent photochromism

Photochromic bisnaphthopyrans linked with oligothiophenes were synthesized and their photochromic behavior studied. Sequential and temperature-dependent photochromism was observed in the oligothiophene linked bisnaphthopyrans. The kinetics of photo and thermal processes in bisnaphthopyrans in comparison with naphthopyrans were studied. Substituent and linking effects on the photochromic properties are discussed. We demonstrate that the cross-talk between the two photochromophores is dependent on the length of the oligothiophene linker. The presence of the bithiophene linker led to high colorability and high quantum yield of coloration.     

Synthesis and Biological Evaluation of Bromo‐ and Fluorodanicalipin A

We disclose the syntheses of (+)‐bromodanicalipin A as well as (±)‐fluorodanicalipin A. The relative configuration and ground‐state conformation in solution of both molecules was secured by J‐based configuration analysis which revealed that these are identical to natural danicalipin A. Furthermore, preliminary toxicological investigations suggest that the adverse effect of danicalipin A may be due to the lipophilicity of the halogens.