Chemistry of nitrated lipids: remarkable instability of 9-nitrolinoleic acid in neutral aqueous medium and a novel nitronitrate ester product by concurrent autoxidation/nitric oxide-release pathways

Despite the mounting interest in nitrolinoleic acids and related nitrated polyunsaturated fatty acids as a novel class of bioactive signaling lipids, their chemistry and metabolic fate have remained poorly elucidated. Herein, we report an expedient nitroselenenylation/oxidation route to 9-nitrolinoleic acid (1) and 10-nitrolinoleic acid (2), which enabled comparative product studies under physiologically relevant conditions. Under biomimetic conditions, 1 decayed at an unusually fast rate to give the hydroxy-, keto-, and nitronitrate ester derivatives 3, 4, and 5 as main products, identified by ESI-MS and 2D NMR spectroscopy, including (1)H, (15)N HMBC experiments on the (15)N-labeled derivatives. The 13-nitrato functionality in 5 suggested partitioning of 1 between concurrent peroxidation and nitric oxide (NO)-release pathways. Lipid 2 decayed at a much slower rate giving only the hydroxynitro derivative 6 as an isolable product. Diphenylpicrylhydrazide (DPPH) radical quenching experiments and DFT computations concurred to support a higher H-atom donating ability of 1 versus 2, due to more effective stabilization of the resulting pentadienyl radical by the terminal nitro group. The markedly different stability of isomeric nitrolinoleic acids disclosed in the present study may provide an explanation for the previous identification of 2, but not 1, in body fluids and offers a key for future insights into the biological activities of nitrated lipids.     

Design and Stereoselective Synthesis of ProM‐2: A Spirocyclic Diproline Mimetic with Polyproline Type II (PPII) Helix Conformation

With the aim of developing polyproline type II helix (PPII) secondary‐structure mimetics for the modulation of prolin‐rich‐mediated protein–protein interactions, the novel diproline mimetic ProM‐2 was designed by bridging the two pyrrolidine rings of a diproline (Pro–Pro) unit through a Z‐vinylidene moiety. This scaffold, which closely resembles a section of a PPII helix, was then stereoselectively synthesized by exploiting a ruthenium‐catalyzed ring‐closing metathesis (RCM) as a late key step. The required vinylproline building blocks, that is, (R)‐N‐Boc‐2‐vinylproline (Boc=tert‐butyloxycarbonyl) and (S,S)‐5‐vinylproline‐tert‐butyl ester, were prepared on a gram scale as pure stereoisomers. The difficult peptide coupling of the sterically demanding building blocks was achieved in good yield and without epimerization by using 2‐(1H‐7‐azabenzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate (HATU)/N,N‐diisopropylethylamine (DIPEA). The RCM proceeded smoothly in the presence of the Grubbs II catalyst. Stereostructural assignments for several intermediates were secured by X‐ray crystallography. As a proof of concept, it was shown that certain peptides containing ProM‐2 exhibited improved (canonical) binding towards the Ena/VASP homology 1 (EVH1) domain as a relevant protein interaction target.     

Full-field separation of principal stresses by combined thermo- and photoelasticity

The combined use of thermoelastic stress analysis and full-field reflection photoelasticity based on the phase-stepping technique has been developed for twodimensional problems. The first method determines the sum of the principal stresses, the latter evaluates the difference of the principal stresses. Thus the principal stresses were separated at each point in the field of view without reference to neighboring points. An evaluation of this approach has been performed using a tensile plate with a central circular hole. The results show that the analysis carried out combining thermo- and photoelasticity incurred errors no larger than those of each system working independently.     

Trichocyanines: a Red-Hair-Inspired Modular Platform for Dye-Based One-Time-Pad Molecular Cryptography

Current molecular cryptography (MoCryp) systems are almost exclusively based on DNA chemistry and reports of cryptography technologies based on other less complex chemical systems are lacking. We describe herein, as proof of concept, the prototype of the first asymmetric MoCryp system, based on an 8-compound set of a novel bioinspired class of cyanine-type dyes called trichocyanines. These novel acidichromic cyanine-type dyes inspired by red hair pigments were synthesized and characterized with the aid of density functional theory (DFT) calculations. Trichocyanines consist of a modular scaffold easily accessible via an expedient condensation of 3-phenyl- or 3-methyl-2H-1,4-benzothiazines with N-dimethyl- or o-methoxyhydroxy-substituted benzaldehyde or cinnamaldehyde derivatives. The eight representative members synthesized herein can be classified as belonging to two three-state systems tunable through four different control points. This versatile dye platform can generate an expandable palette of colors and appears to be specifically suited to implement an unprecedented single-use asymmetric molecular cryptography system. With this system, we intend to pioneer the translation of digital public-key cryptography into a chemical-coding one-time-pad-like system.     

Multi-Analytical Characterization and Radiocarbon Dating of a Roman Egyptian Mummy Portrait

Fayum mummy portraits, painted around 2000 years ago, represent a fascinating fusion of Egyptian and Graeco-Roman funerary and artistic traditions. Examination of these artworks may provide insight into the Roman Empire’s trade and economic and social structure during one of its most crucial yet still hazy times of transition. The lack of proper archaeological documentation of the numerous excavated portraits currently prevents their chronological dating, be it absolute or relative. So far, their production period has been defined essentially on the basis of the relevant differences in their pictorial style. Our study introduces the use of Accelerator Mass Spectrometry (AMS) to assess the age of a fragment of an encaustic painting belonging to the corpus of the Fayum portraits. The unexpected age resulting from ¹⁴C analysis suggests the need to reconsider previous assumptions regarding the period of production of the Fayum corpus. Furthermore, our multi-analytical, non-invasive approach yields further details regarding the fragment’s pictorial technique and constituting materials, based on spectral and morphological analysis and cross-sectional examination.     

Thermodynamic Stability of Ribonuclease B

The thermodynamic stability of pancreatic ribonuclease B (RNase B), which possesses identical protein structure of pancreatic ribonuclease A (RNase A), but differs by the presence of a carbohydrate chain attached to Asn 34, was studied by means of differential scanning calorimetry (DSC) at different pH conditions. The comparison between the two proteins has shown a little but significant stabilization of RNase B with respect to the unglycosylated one at pH values higher than 7.0. The thermodynamic analysis reveals the carbohydrate moiety to have a small stabilization effect of 3 kJ mol^–1 at pH 8.0 and 63°C on the protein. This revised version was published online in July 2006 with corrections to the Cover Date.     

Understanding the role of stereoelectronic effects in determining collagen stability. 1. A quantum mechanical study of proline, hydroxyproline, and fluoroproline dipeptide analogues in aqueous solution.

The importance of local (intraresidue) effects in determining the stability of the collagen triple helix has been investigated with special reference to the role played by hydroxyproline. To this end the dipeptide analogues of L-proline (ProDA), 4(R)-hydroxy-L-proline (HypDA), and 4(R)-fluoro-L-proline (FlpDA) have been studied by means of quantum mechanical ab initio calculations, taking into account solvent effects by the polarizable continuum model (PCM). Our results confirm that the relative stability of up puckerings of the pyrrolidine ring increases with the electronegativity of the 4(R) substituent (X), whereas down puckerings are favored by 4(S) electronegative substituents. Calculations on model compounds show that this effect is due to the interaction between vicinal C-H bonding and C-X antibonding orbitals. Electronegative substituents on the pyrrolidine ring affect cis-trans isomerism around the peptidic bond, with trans isomers stabilized by 4(R) substituents and cis isomers by 4(S) substituents. Also the hydrogen bonding power of the carbonyl moiety following the pyrrolidine ring is affected by 4(R) substituents, but this effect is tuned by the polarity of the embedding medium. Finally, up puckering favors smaller values of the backbone dihedrals phi and psi. All these results strongly support the proposal that the stability of triple helices containing fluorinated or hydroxylated prolines in Y positions is related to the necessity of having up puckerings in those positions.     

Implementation of a graphical user interface for the virtual multifrequency spectrometer: The VMS‐Draw tool

This article presents the setup and implementation of a graphical user interface (VMS‐Draw) for a virtual multifrequency spectrometer. Special attention is paid to ease of use, generality and robustness for a panel of spectroscopic techniques and quantum mechanical approaches. Depending on the kind of data to be analyzed, VMS‐Draw produces different types of graphical representations, including two‐dimensional or three‐dimesional (3D) plots, bar charts, or heat maps. Among other integrated features, one may quote the convolution of stick spectra to obtain realistic line‐shapes. It is also possible to analyze and visualize, together with the structure, the molecular orbitals and/or the vibrational motions of molecular systems thanks to 3D interactive tools. On these grounds, VMS‐Draw could represent a useful additional tool for spectroscopic studies integrating measurements and computer simulations. © 2014 Wiley Periodicals, Inc.