Two polymorphs of 20‐desmethyl‐β‐carotene

Two polymorphs of 20‐desmethyl‐β‐carotene (systematic name: 20‐nor‐β,β‐carotene), C₃₉H₅₄, in monoclinic and triclinic space groups, were formed in the same vial by recrystallization from pyridine and water. Each polymorph crystallizes with the complete molecule as the asymmetric unit, and the two polymorphs show differing patterns of disorder. The β end rings of both polymorphs have the 6‐s‐cis conformation, and are twisted out of the plane of the polyene chain by angles of −53.2 (8) and 47.3 (8)° for the monoclinic polymorph, and −43.6 (3) and 56.1 (3)° for the triclinic polymorph. The cyclohexene end groups are in the half‐chair conformation, but the triclinic polymorph shows disorder of one ring. Overlay of the molecules shows that they differ in the degree of nonplanarity of the polyene chains and the angles of twist of the end rings. The packing arrangements of the two polymorphs are quite different, with the monoclinic polymorph showing short intermolecular contacts of the disordered methyl groups with adjacent polyene chain atoms, and the triclinic polymorph showing π–π stacking interactions of the almost parallel polyene chains. The determination of the crystal structures of the two title polymorphs of 20‐desmethyl‐β‐carotene allows information to be gained regarding the structural effects on the polyene chain, as well as on the end groups, versus that of the parent compound β‐carotene. The absence of the methyl group is known to have an impact on various functions of the title compound.     

A comparative study of the electrospray ionization response of β‐O‐4′ lignin model compounds

Electrospray ionization mass spectrometry has recently become the technique of choice for rapid characterization of lignin degradation products. However, the fundamental question of the relationship between lignin structure and ionization efficiency has not been explored. In this work, we studied the electrospray ionization response of five structurally similar β‐O‐4′ model lignin compounds using lithium cationization in the positive electrospray ionization mode. The studied compounds have the same β‐O‐4′ backbone structure but differ at the α‐position by increasing nonpolar side chains. Our results show a correlation between the ionization response and the length of the nonpolar side chain, with analytes having the longest side chain recording the highest ESI response in the full scan mode. Factors affecting the formation of analyte ions and analyte cluster ions were also studied. We have shown for the first time in this work that the introduction of a nonpolar group onto a β‐O‐4′ lignin compound can increase the lithium cationization ESI response in the positive ion mode.     

Mass spectrometry characterization of 3‐OH butyrated β‐cyclodextrin

Oligo(3‐OH butyrate)‐β‐cyclodextrin esters (PHB‐CD) were obtained through ring opening of β‐butyrolactone (β‐BL) in the presence of β‐cyclodextrin (CD) and (‐)‐sparteine (SP) as nucleophilic activator. The resulted reaction mixture was first separated in two fractions and then investigated through a deep mass spectrometry (MS) study performed on a liquid chromatography‐electrospray ionization‐quadrupole time of flight (LC‐ESI‐QTOF) instrument. LC MS and tandem MS structural assignment of the reaction products was completed by NMR. The performed analysis revealed that poly(3‐OH butyrate) homopolymers (PHB) are formed together with the PHB‐CD products. Secondary reactions resulting in the formation of crotonates were also proved to occur. A comparison between MS and NMR results demonstrated that more than one PHB oligomer is attached to the CD in the PHB‐CD product. The tandem MS fragmentation studies validated the proposed structure of CD derivatives. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Thermal degradation of polymers with phenylene units in the chain. I. Polyphenylenes and poly(phenylene oxides)

The thermal degradation of polyphenylenes and poly(phenylene oxides) was studied under vacuum at temperatures between 350 and 620°C. The volatile and solid degradation products were analyzed by mass spectroscopy, infrared spectroscopy, and elemental analysis. Overall mechanisms for the thermal breakdown have been proposed. Polyphenylene decomposes to form polymer carbon, while hydrogen is the major volatile product. Some ring breakdown occurs with evolution of methane. Poly(phenylene oxide) forms mainly low molecular weight chain fragments, partially with hydroxyl endgroups. Some of the ether linkages decompose with ring breakdown, yielding carbon monoxide, water, and some carbon dioxide. Pendent groups on polyphenylenes and poly(phenylene oxides) are removed at the lower temperatures. The hydroxyl group yields essentially carbon monoxide and dioxide (the carbon being supplied by the rings), the methyl group methane, and the methoxy group methane and some methanol.     

Carbamoyl Radical‐Mediated Synthesis and Semipinacol Rearrangement of β‐Lactam Diols

In an approach to the biologically important 6‐azabicyclo[3.2.1]octane ring system, the scope of the tandem 4‐exo‐trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring‐fused β‐lactams is evaluated. β‐Lactams fused to five‐, six‐, and seven‐membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β‐ or β,γ‐unsaturated lactams depending on both the methodology employed (base‐mediated or thermal) and the nature of the carbocycle fused to the β‐lactam. Fused β‐lactam diols, obtained from catalytic OsO₄‐mediated dihydroxylation of α,β‐unsaturated β‐lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto‐bridged bicyclic amides by exclusive N‐acyl group migration. A monocyclic β‐lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo‐ and stereoselective manipulation of the two carbonyl groups present in a representative 7,8‐dioxo‐6‐azabicyclo[3.2.1]octane rearrangement product are also reported.     

Reaction of benzohydroximinoyl chlorides and β‐(trifluoromethyl)‐acetylenic esters: Synthesis of regioisomeric (trifluoromethyl)‐isoxazolecarboxylate esters and oxime addition products

The triethylamine induced reaction of benzohydroximinoyl chlorides, precursors of nitrile oxides, with β‐trifluoromethylacetylenic esters gives rise to three products: 5‐trifluoromethyl‐4‐isoxozolecarboxylate esters, regioisomeric 4‐trifluoromethyl‐5‐isoxazolecarboxylate esters and an unexpected oxime 1,4‐addition adduct. Product distribution is rationalized in terms of two competing reaction modes, either 1,4 addition of the oxime anion to the acetylenic ester or formation of the nitrile oxide followed by 1,3‐dipolar cycloaddi‐tion. Anionic 1,4‐addition of the oximinoyl chloride to the acetylenic ester is preferred at low temperatures, while nitrile oxide formation followed by cycloaddition is preferred at temperatures above 0 °C. Regioisomeric products from addition of nitrile oxides to various perfluoroalkylacetylenes are compared and assigned by ¹³C NMR.     

Quantitative assessment of multi‐laboratory reproducibility of SDS‐PAGE assays: Digestion pattern of β‐casein and β‐lactoglobulin under simulated conditions

A digestion protocol was applied in triplicate by ten laboratories, simulating in vivo gastric and duodenal conditions. The intra‐ and inter‐laboratory variability in the kinetics of protein degradation was quantified, focussing on the digestion of β‐casein under gastric conditions, and of β‐lactoglobulin (β‐Lg) under duodenal conditions. The addition of surfactants such as phosphatidylcholine (PC) in the digestion mix was also evaluated. Identification and quantification of peptide bands on SDS‐PAGE gels formed the basis for analysis. An average intensity loss of 69% (SD=13.5) at 5 min (89% at 10 min, with SD=5.5) was observed for β‐casein, whereas the β‐Lg duodenal digestion showed an 82% loss at 30 min (SD=14.2). Constant rates of first‐order reactions showed that for fast reactions, inaccuracies in the time of first sampling contributed to the variability, which were also affected by image quality, saturation, and the splitting of time courses across gels. Breakdown products for β‐casein included ten other polypeptides, with four detected in all and two in most gels, and for β‐Lg ten polypeptides, with five detected in most, and two in two‐third of the cases. Addition of PC in the gastric phase led to β‐Lg intensity loss only a quarter as large as without PC and altered β‐Lg proteolysis in the duodenal compartment.     

Thermal decomposition of 4,4′-diaminodiphenylsulphone

The thermal decomposition of 4,4′-diaminodiphenylsulphone (DDS) was studied by thermogravimetry, differential scanning calorimetry and thermal volatilisation analysis. Solid residues, high-boiling and gaseous products of degradation were collected at each step of thermal decomposition and analysed by infrared spectroscopy and gas chromatography/mass spectrometry.

On programmed heating at normal pressure, DDS starts to evaporate at 250°C. Thermal decomposition, which probably proceeds through homolytic scission of the S-C bond is simultaneously observed. The resulting sulphonyl radicals provoke polymerisation and cross-linking of the solid residue which undergoes a limited degradation at 350°C with elimination of heteroatoms N and S as volatile moieties. Above 400°C, the residue undergoes a complex charring process leading to an aromatic char typical of carbonised aromatic polymers.     

The thermal degradation of cellulose triacetate—I. The reaction products

The fractionated volatile products arising from the stepwise thermal degradation of cellulose triacetate in vacuo are analysed by gas-solid chromatography, mass spectrometry, i.r. and NMR spectroscopy, and chemical tests. Gas evolution data resemble those reported for the thermal degradation of cellulose in vacuo; early evolution of large quantities of oxides of carbon indicates extensive breakdown of the pyranose rings. Acetic acid, attributed to thermal deacetylation reactions in the polymer chain, is a major product, and a portion undergoes further decomposition to keten and water. The tarry material appears to be a mixture of unsaturated mono- and diacetylated monosaccharides and oligomers.     

A study of the reaction between 2,4‐disubstituted‐2,3‐dihydro‐1,5‐benzothiazepines and ketenes generated in situ from chloro and dichloroacetyl chlorides

In the presence of triethyl amine, the reaction of 2,4‐disubstituted‐2,3‐dihydro‐1,5‐benzothiazepine with chloro and dichloroacetyl chlorides produced not only the expected β‐lactam derivative of the benzo‐thiazepine, but also the ring opening product. Different results were obtained when the substituent at 2‐position of the benxothiazepine varied from methyl to aryl, and the substituent on the chloroacetyl chloride varied from H to Cl, or when carrying out the reaction at different temperatures. The structures of the obtained products and the reaction mechanism are discussed.     

Thermal stability and degradation mechanisms of poly(acrylic acid) and its salts: Part 3—Magnesium and calcium salts

The magnesium and calcium salts of acrylic acid have been polymerised in aqueous solution using ammonium persulphate as initiator. Both polymers were also prepared by the neutralisation of poly(acrylic acid) with metal oxide in the same medium.

The thermal degradation behaviour of magnesium and calcium polyacrylate was studied using thermogravimetry (TG), differential thermal analysis (DTA) and thermal volatilisation analysis (TVA). Degradation products were investigated by IR spectroscopy, mass spectrometry and GC-MS techniques, the volatile product fraction having first been separated by subambient TVA.

The decompositions of these materials show some similarities to the behaviour of the alkali metal salts of poly(acrylic acid) and to that of the alkaline earth metal salts of poly(methacrylic acid), but there are also important differences. Acetone and carbon dioxide are the most important volatile products and, in addition, there are various other carbonyl containing products. More carbon dioxide, resulting from side group scission, is evolved from magnesium polyacrylate than from calcium polyacrylate, because of the lower thermal stability of magnesium carbonate.     

Utilization of thermodesorption coupled to GC-MS to study stability of different wood species to thermodegradation

Thermodesorption coupled to gas chromatography coupled to mass spectroscopy (TD-GC-MS) has been investigated to identify volatile degradation products generated during wood heat treatment by mild pyrolysis. For this purpose, wood samples of different softwood and hardwood species have been heat treated under nitrogen for different temperatures comprised between 180 and 230 °C during 15 min in the glass thermal desorption tube of the thermodesorber and the volatile wood degradation products trapped. The trapped products were then thermodesorbed and analysed by GC-MS. Chromatograms of the different samples indicated the formation of different products resulting from degradation of lignin and hemicelluloses. Hardwoods were shown to be more sensitive to thermodegradation than softwoods, for which degradation products appear at slightly higher temperature. The important formation of acetic acid is concomitant with the formation of most of degradation products and at the origin of the difference of reactivity observed between softwoods and hardwoods.     

Visible Light Promoted β‐C—H Alkylation of β‐Ketocarbonyls via a β‐Enaminyl Radical Intermediate

A 5πe carbonyl activation mode is reported on the basis of photo‐induced single‐electron‐transfer (SET) oxidation of a secondary enamine. The resultant β‐enaminyl radical intermediate was trapped by a wide range of Michael acceptors, producing β‐alkylation products of β‐ketocarbonyls in a highly efficient manner.     

Resonance Raman Spectral Imaging of Intracellular Uptake of β‐Carotene Loaded Poly(D,L‐lactide‐co‐glycolide) Nanoparticles

The use of nanoparticles for drug delivery has been drawing considerable attention in pharmaceutical research. With increasing diversity and potential of various carrier systems, it is important to study the impact of nanocarriers on sub‐cellular metabolic processes and organelles, since the delivery of a drug usually involves intra‐cellular internalization. Herein, we employ Raman microscopy as a non‐invasive method for cellular and sub‐cellular imaging, to monitor the uptake and translocation patterns of particles based on poly(D,L‐lactide‐co‐glycolide) over time. As the technique detects inherent signals from the molecules of interest, it does not rely on external labels or dyes, which is an advantage over fluorescence labeling. For this purpose, the particles were loaded with β‐carotene. The conjugated π‐system of the molecule has a large Raman scattering cross‐section and gives rise to resonance Raman effects, which can enhance the sensitivity by orders of magnitude. β‐Carotene as a provitamin is not soluble in water and is thus usually of low bioavailability, which is enhanced by encapsulation into the nanoparticles.     

End‐Group Identity and Its Effect on the Thermal Degradation of Poly(butyl cyanoacrylate)

Poly(butyl cyanoacrylate) was synthesised using triphenylphosphane and pyridine initiators. Matrix‐assisted laser desorption/ionisation time of flight mass spectrometry and NMR spectroscopy were used to confirm that the initiator remains as a chain end group. The prepared polymers were subjected to thermal degradation and re‐analysed with results that show the loss of the initiator end group for the pyridine‐initiated polymer, but not for that initiated with triphenylphosphane. Pyrolysis gas chromatography‐mass spectrometry was used to observe the presence of the pyridine initiator in the volatile degradation products.     

Thermal degradation of poly((E,E)-[6.2]paracyclophane-1,5-diene)

Thermal degradation of poly((E,E)-[6.2]paracyclophane-1,5-diene) is studied in inert and oxidative environments by using thermogravimetric analysis, pyrolysis GC/MS, pyrolysis GC/FT-IR, and variable temperature-diffuse reflectance infrared spectroscopy (VT-DRIFTS). Thermal degradation in helium begins by depolymerization yielding a volatile product capable of abstracting hydrogens from the polymer residue. Multiple hydrogen abstractions result in a variety of volatile species containing benzyl-benzyl bonds. In the presence of oxygen, polymer decomposition is dictated by reactions of peroxy and hydroperoxy radicals. At low temperatures, oxygenated species are the primary products. At higher temperatures, increased unsaturation is detected in the polymer residue. In both inert and oxidative environments, the strain associated with alignment of paracyclophane aromatic rings is lost during the initial stages of thermal degradation. © 1992 John Wiley & Sons, Inc.     

Gas‐phase fragmentation of γ‐lactone derivatives by electrospray ionization tandem mass spectrometry

Fragmentation reactions of β‐hydroxymethyl‐, β‐acetoxymethyl‐ and β‐benzyloxymethyl‐butenolides and the corresponding γ‐butyrolactones were investigated by electrospray ionization tandem mass spectrometry (ESI‐MS/MS) using collision‐induced dissociation (CID). This study revealed that loss of H₂O [M + H ?18]⁺ is the main fragmentation process for β‐hydroxymethylbutenolide (1) and β‐hydroxymethyl‐γ‐butyrolactone (2). Loss of ketene ([M + H ?42]⁺) is the major fragmentation process for protonated β‐acetoxymethyl‐γ‐butyrolactone (4), but not for β‐acetoxymethylbutenolide (3). The benzyl cation (m/z 91) is the major ion in the ESI‐MS/MS spectra of β‐benzyloxymethylbutenolide (5) and β‐benzyloxymethyl‐γ‐butyrolactone (6). The different side chain at the β‐position and the double bond presence afforded some product ions that can be important for the structural identification of each compound. The energetic aspects involved in the protonation and gas‐phase fragmentation processes were interpreted on the basis of thermochemical data obtained by computational quantum chemistry. Copyright © 2009 John Wiley & Sons, Ltd.     

Study of the forced degradation behavior of prasugrel hydrochloride by liquid chromatography with mass spectrometry and liquid chromatography with NMR detection and prediction of the toxicity of the characterized degradation products

Prasugrel was subjected to forced degradation studies under conditions of hydrolysis (acid, base, and neutral), photolysis, oxidation, and thermal stress. The drug showed liability in hydrolytic as well as oxidative conditions, resulting in a total of four degradation products. In order to characterize the latter, initially mass fragmentation pathway of the drug was established with the help of mass spectrometry/time‐of‐flight, multiple stage mass spectrometry and hydrogen/deuterium exchange data. The degradation products were then separated on a C₁₈ column using a stability‐indicating volatile buffer method, which was later extended to liquid chromatography‐mass spectrometry studies. The latter highlighted that three degradation products had the same molecular mass, while one was different. To characterize all, their mass fragmentation pathways were established in the same manner as the drug. Subsequently, liquid chromatography‐nuclear magnetic resonance (NMR) spectroscopy data were collected. Proton and correlation liquid chromatography with NMR spectroscopy studies highlighted existence of diastereomeric behavior in one pair of degradation products. Lastly, toxicity prediction by computer‐assisted technology (TOPKAT) and deductive estimation of risk from existing knowledge (DEREK) software were employed to assess in silico toxicity of the characterized degradation products.     

Engineering a β‐Helical d,l‐Peptide for Folding in Polar Media

β Helices—helices formed by alternating d,l ‐peptides and stabilized by β‐sheet hydrogen bonding—are found naturally in only a handful of highly hydrophobic peptides. This paper explores the scope of β‐helical structure by presenting the first design and biophysical characterization of a hydrophilic d,l ‐peptide, 1 , that forms a β helix in methanol. The design of 1 is based on the β‐hairpin/β helix—a new supersecondary that had been characterized previously only for hydrophobic peptides in nonpolar solvents. Incorporating polar residues in 1 provided solubility in methanol, in which the peptide adopts the expected β‐hairpin/β‐helical structure, as evidenced by CD, analytical ultracentrifugation (AUC), NMR spectroscopy, and NMR‐based structure calculations. Upon titration with water (at constant peptide concentration), the structure in methanol ( 1 m ) transitions cooperatively to an extended conformation ( 1 w ) resembling a cyclic β‐hairpin; observation of an isodichroic point in the solvent‐dependent CD spectra indicates that this transition is a two‐state process. In contrast, neither 1 m nor 1 w show cooperative thermal melting; instead, their structures appear intact at temperatures as high as 65 °C; this observation suggests that steric constraint is dominant in stabilizing these structures. Finally, the ¹H NMR CαH spectroscopic resonances of 1 m are downfield‐shifted with respect to random‐coil values, a hitherto unreported property for β helices that appears to be a general feature of these structures. These results show for the first time that an appropriately designed β‐helical peptide can fold stably in a polar solvent; furthermore, the structural and spectroscopic data reported should prove useful in the future design and characterization of water‐soluble β helices.     

Versatile Glycosyl Sulfonates in β‐Selective C‐Glycosylation

C‐Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics. We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β‐linked C‐glycosides. This reaction tolerates a range of acceptors and donors, including disaccharides. The resulting products can be readily derivatized into C‐glycoside analogues of β‐glycoconjugates, including C‐disaccharide mimetics.