Xenobiotica

Isocyanates differ from many other xenobiotics in their ability to form S-linked conjugates with glutathione (GSH) through direct nucleophilic addition reactions (e.g. without enzymatic "preactivation" and/or transferase activity), potentially predisposing them to metabolism via the mercapturic acid pathway. In vivo, mono-isocyanates are metabolized via the mercapturic acid pathway and excreted as N-acetylated cysteine conjugates, however, the metabolism of di-isocyanates remains unclear. We assessed the ability of purified human gamma-glutamyl transpeptidase-1 (GGT-1), a primary enzyme of the mercapturic acid pathway, to cleave S-linked GSH conjugates of 4,4'-methylene diphenyl diisocyanate (MDI) and 1,6-hexamethylene diisocyanate (HDI), two widely used industrial chemicals. A combination of liquid chromatography (LC), tandem mass spectrometry (MS/MS) and hydrogen-deuterium exchange studies confirmed GGT-1 mediated formation of the 607.2 and 525.2 m/z (M\ue2\u20ac\u2030+\ue2\u20ac\u2030H)(+)\ue2\u20ac\u2030ions corresponding to bis(cys-gly)-MDI and bis(cys-gly)-HDI, respectively, the cleavage products expected from the corresponding bis(GSH)-diisocyanate conjugates. Additional intermediate metabolites and mono(cys-gly)-conjugates with partially hydrolyzed diisocyanate were also observed. Consistent with GGT enzyme kinetics, metabolism proceeded more rapidly under conditions that favored transpeptidation versus hydrolytic mechanisms of cleavage. Together the data demonstrate the capacity of human GGT-1 to cleave GSH conjugates of both aromatic and aliphatic diisocyanates, suggesting a potential role in their metabolism.R21 OH010438/OH/NIOSH CDC HHS/United StatesR21 OH010494/OH/NIOSH CDC HHS/United States2016-08-01T00:00:00Z26678254PMC484813

Structure Elucidation of a Pyrrolobenzodiazepine Alkaloid and a Biologically Active Polyketide Produced by Rhodococcus sp. MTM3W5.2 via Two-Dimensional NMR Spectroscopy

As the battle against ever-increasing drug resistence bacteria rages on, novel and sometimes more complex natural products can be used to combat this. In this study, two-dimensional NMR techniques were utilized to collect a complete spectral data set for two natural products. The first structure, a synthesized Pyrrolobenzodiazepine alkaloid natural product was confirmed through these methods. The second, a strain of Rhodococcus, MTM3W5.2, produces a novel antibacterial molecule in broth cultures and the active compound was fractionated using a Sephedex LH-20 column. Chromatographic purification yielded a pure sample at 58.90 minutes, RT.58. HRMS data deduced an exact mass of 911.5490 Da, equivalent to a molecular formula of C52H78O13. Several major spin systems were constructed from the 2D-NMR spectra. However, due to limited sample quantity in compound with a large molecular weight and product instability, the long range HMBC signals needed to connect these fragments have not yet been obtained

Innovative mnemonics in chemical education: review article

In this review article, formulae based innovative mnemonics have been discussed to create interest and remove phobia of students in the field of chemical education. Educators can use these numerous mnemonics in their teaching style in the classroom lectures after discussing conventional methods to make chemistry intriguing. Here, I have tried to focus some time economic mnemonics by including thirty-three (33) new formulae in the field of chemical education. It will encourage students to solve multiple choice type questions (MCQs) at different competitive examinations in a time economic ground. This review article emphasizes chemical education in the light of a variety of mnemonic techniques to make it metabolic, time economic and intriguing for students because the use of mnemonics in classroom lectures is an essential tool to become a distinguished educator

Relationship between the molecular composition, visible light absorption, and health-related properties of smoldering woodsmoke aerosols

Organic aerosols generated from the smoldering combustion of wood critically impact air quality and health for billions of people worldwide; yet, the links between the chemical components and the optical or biological effects of woodsmoke aerosol (WSA) are still poorly understood. In this work, an untargeted analysis of the molecular composition of smoldering WSA, generated in a controlled environment from nine types of heartwood fuels (African mahogany, birch, cherry, maple, pine, poplar, red oak, redwood, and walnut), identified several hundred compounds using gas chromatography mass spectrometry (GCMS) and nano-electrospray high-resolution mass spectrometry (HRMS) with tandem multistage mass spectrometry (MSn). The effects of WSA on cell toxicity as well as gene expression dependent on the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) were characterized with cellular assays, and the visible mass absorption coefficients (MACvis) of WSA were measured with ultraviolet-visible spectroscopy. The WSAs studied in this work have significant levels of biological and toxicological activity, with exposure levels in both an outdoor and indoor environment similar to or greater than those of other toxicants. A correlation between the HRMS molecular composition and aerosol properties found that phenolic compounds from the oxidative decomposition of lignin are the main drivers of aerosol effects, while the cellulose decomposition products play a secondary role; e.g., levoglucosan is anticorrelated with multiple effects. Polycyclic aromatic hydrocarbons (PAHs) are not expected to form at the combustion temperature in this work, nor were they observed above the detection limit; thus, biological and optical properties of the smoldering WSA are not attributed to PAHs. Syringyl compounds tend to correlate with cell toxicity, while the more conjugated molecules (including several compounds assigned to dimers) have higher AhR activity and MACvis. The negative correlation between cell toxicity and AhR activity suggests that the toxicity of smoldering WSA to cells is not mediated by the AhR. Both mass-normalized biological outcomes have a statistically significant dependence on the degree of combustion of the wood. In addition, our observations support the fact that the visible light absorption of WSA is at least partially due to charge transfer effects in aerosols, as previously suggested. Finally, MACvis has no correlation with toxicity or receptor signaling, suggesting that key chromophores in this work are not biologically active on the endpoints tested

An Experimental Investigation Characterizing the Tribological Performance of Natural and Synthetic Biolubricants Composed of Carboxylic Acids for Energy Conservation and Sustainability

Over the last several decades the lubrication industry has been striving to bring bio-based lubricants known as biolubricants to prominence. The reasons for the increased environmental initiatives are due to depletion of oil reserves, increases in oil price, stringent government regulations on petroleum-based oils, and most importantly, concerns for protecting the environment. With an estimated, 50% of all lubricants entering the environment and much of these being composed of toxic mineral oils, biolubricants have begun to witness a resurgence. This experimental investigation seeks to develop a new class of ecofriendly biolubricants that are less toxic to the environment, derived from renewable resources, and provide feasible and economical alternatives to traditional petroleum-based lubricants. Advantages of biolubricants include their higher lubricity, lower volatility, higher shear stability, higher viscosity index, higher load carrying capacity, and superior detergency and dispersancy when compared to petroleum-based lubricants. This work highlights the evolution of biolubricants derived from natural oils and fats to green lamellar solid additives to a new class of greener functional fluids known as room temperature ionic liquids (RTILs). The attraction to biolubricants began with natural oils due to their low friction and wear characteristics owing to fatty acid monolayers that enable high lubricity. Despite these accolades, natural oils suffer from thermal-oxidative instability and high pour points. To improve upon the tribological properties, natural oils were combined with solid powders additives. Currently, RTIL lubricants derived from bio-based feedstock represent a more promising potential solution to many of the problems associated with previous biolubricants. In a final study the RTILs where shown to benefit from the use of solid powder additives to further improve upon their tribological performance. In this experimental investigation, friction and wear tests were carried out using a pin-on-disk tribometer under ambient and high temperature conditions to evaluate the tribological performance of the various natural and synthetic biolubricants. A thermogravimetric analysis (TGA) was conducted to study the thermal response of the lubricants in a high temperature oxygen-free environment. Scanning electron microscopy and surface profilometry studies were performed to assess the surface roughness. These experiments investigated the performance of natural oils as neat bio-based lubricants to understanding the effects that long chain fatty acids have on the tribological performance of natural oils. The experiments revealed that natural oils with low unsaturation numbers due to high concentrations of oleic acid demonstrated to have the superior friction and wear properties as well as high thermal-oxidative stability. Extensive testing of multiple natural oils with various particulate additives composed of a variety of types, sizes, and shapes revealed that natural oils benefit tremendously from nanometer-sized spherical shaped particles. However, this is not without its complexities as surface roughness, sphericity, particle size, and capillary effects all influenced the use and performance of particulate additives. In an effort to refine the natural oils composed of particulate additives, RTILs were chosen because of their ability to lubricate in boundary lubrication due to their inherent polar molecules; their ability to be tuned for specific applications; and most notably their lack of vapor pressure providing new opportunities for liquid lubricants. Investigations into the ionic liquid lubricants revealed that longer alkyl chains on the cations with aromatic carboxylate anions exhibited the most lubricity as neat lubricants i.e. lubricants with negligible additives. Again, these lubricants were subjected to particulate additivation and it was revealed that smaller nanometer sized particles independent of the particle type provided the greatest benefit to lowering friction and minimizing wear. The performance of the ionic liquids improved with the particulate additives and it was further verified that phosphonium and imidazolium cations combined with food grade carboxylate anions such as saccharinate, salicylate, or benzoate formed biolubricants that maintained superior tribological properties as well as maintained a high degree of thermal-oxidative stability. This experimental investigation has illuminated the potential of RTIL biolubricants to satisfy the growing environmental, health, economic, and performance concerns of modern lubricants. The mechanisms governing the chemical compositions, improved tribological performance, and thermal response of the lubricants are extensively discussed along with their viability as sustainable and renewable biolubricants

Cation-pi Interactions accelerate the living cationic ring-opening polymerization of unsaturated 2-alkyl-2-oxazolines

Cation-dipole interactions were previously shown to have a rate-enhancing effect on the cationic ring-opening polymerization (CROP) of 2-oxazolines bearing a side-chain ester functionality. In line with this, a similar rate enhancement-via intermolecular cation-pi interactions-was anticipated to occur when pi-bonds are introduced into the 2-oxazoline side-chains. Moreover, the incorporation of pi-bonds allows for facile postfunctionalization of the resulting poly(2-oxazoline)s with double and triple bonds in the side-chains via various click reactions. Herein, a combined molecular modeling and experimental approach was used to study the CROP reaction rates of 2-oxazolines with side-chains having varying degrees of unsaturation and side-chain length. The presence of cation-pi interactions and the influence of the degree of unsaturation were initially confirmed by means of regular molecular dynamics simulations on pentameric systems. Furthermore, a combination of enhanced molecular dynamics simulations, static calculations, and a thorough analysis of the noncovalent interactions was performed to unravel to what extent cation-pi interactions alter the reaction kinetics. Additionally, the observed trends were confirmed also in the presence of acetonitrile as solvent, in which experimentally the polymerization is performed. Most intriguingly, we found only a limited effect on the intrinsic reaction kinetics of the CROP and a preorganization effect in the reactive complex region. The latter effect was established by the unsaturated side-chains and the cationic center through a complex interplay between cation-pi, pi-pi, pi-induced dipole, and cation-dipole interactions. These findings led us to propose a two-step mechanism comprised of an equilibration step and a CROP reaction step. The influence of the degree of unsaturation, through a preorganization effect, on the equilibration step was determined with the following trend for the polymerization rates: n-ButylOx = PentynOx. The trend was experimentally confirmed by determining the polymerization rate constants

Extraction, Purification and Characterization of an Antibiotic-like Compound Produced by Rhodococcus sp. MTM3W5.2

The bacterium Rhodococcus is a potential source for novel antimicrobial metabolites. Recently, the Rhodococcus strain MTM3W5.2 was isolated from a soil sample collected from Morristown, East Tennessee and was found to produce an inhibitor molecule that is active against similar Rhodococcus species. The aim of this research is to extract, purify, and characterize the active compound. The compound was obtained from both agar and broth cultures of strain MTM3W5.2 and purified by primary fractionation of crude extract on a Sephadex LH-20 column, followed by semi-preparative reversed phase column chromatography. Final purification was achieved using multiple rounds of an analytical C18 HPLC column. Based on the results obtained from UV-Vis, FT-IR, and HR-MS, the molecule is a polyketide with a molecular formula of C52H78O13 and an exact mass of 911.5490 amu. The partial structure of this compound has been determined using 1D and 2D NMR spectroscopy

The application of ESCA to structure and bonding in polymer surfaces with particular reference to glow discharge polymerization

x-ray photoelectron spectroscopy is used to study structure, bonding and reactivity of materials, in particular polymeric materials, especially those prepared by 'glow discharge techniques'. The glow discharge polymers have been prepared predominantly in radiofrequency inductively coupled gas plasmas using fluorine containing monomers. Films of known thickness have been prepared in situ by plasma techniques from 1,1-difluoroethylene and the structure investigated by means of ESCA. Electron mean free paths have been measured at kinetic energies corresponding to photoemission from the F(_1s) (563 eV), C(_1s) (967 eV), Au(_4f7/2) (1170 eV) and F(_2s) (1220 eV) and found to be 7 ± 3Å, 10 ± 3Å, 17 ± 4Å and 25 ± 7Å respectively. Polymers produced by plasma techniques from three isomeric difluoroethylene monomers are examined by ESCA. The polymer produced from 1,1 difluoroethylene is discussed in some detail and compared with those for the two 1,2 difluoroethylene isomers. The kinetics of deposition and structures of the resultant plasma polymers are compared. Charge distribution for both the neutral molecules and their radical cations are calculated and a possible reaction scheme involving fluoroacetylene is outlined. This work is extended to include the results of polymerizations in microwave discharges. The perfluorocyclohexa compounds have been polymerized by plasmatechniques and the polymer studied in detail as a function of power input to the plasma and the operating pressure. The rates of deposition parallel the first ionization potentials of the monomers and are: C(_6)F(_6) > C(_6)F(_8) (1,3) ~ C(_6)F(_8) (1,4) > C(_6)F(_10) ~ C(_6)F(_12). C(_1s) spectra of the resultant polymer are shown to reflect the nature of the starting monomer. Through investigations of polymer deposited in non-glow regions reactive CF(_2) containing species are shown to be important. Fluorine incorporation into the polymer decreases with increasing working pressure and is explained in terms of an increase in molecular rearrangements at lower pressures. Preliminary studies of the vacuum U.V. transmission properties of a number of polymers show that all the systems investigated absorb strongly below 1700Å and the relative degree of absorption is: polystyrene > polyparaxylylene ~ polyvinylchloride > plasma polymerized C(_6)F(_6) > plasma polymerized C(_6)F(_12). A number of paint systems have been investigated by ESCA and the broad changes in surface chemistry monitored for weathering periods of 1, 3 and 6 months. Oxidation is shown to be an important process and erosion becomes important with long exposures. The relative sensitivities to degradation by weathering are made apparent. Selected polymers weathered for a fixed time are studied and oxidation is shown to be important. In some cases a mode of degradation is suggested and compared with other data. Differences in rates of modification are shown to be : polysulphone > polyphenylether > nylon 6,6 > low density polyethylene. Oxidation penetrates beyond the immediate surface except in the case of L.D.P.E. The angular dependence using a fixed X-ray and analyser arrangement for horizontally inhomogeneous samples is discussed and shown to be complex but reproducible. The changes in effective sampling area contribute to this. The angular dependent behaviour for vertically inhomogeneous samples is discussed and it is shown that for thin films (<20Å) the angular behaviour is distinct from that observed for a homogeneous sample. The angular behaviour of a composite probe with 18 electrically isolated points is described. The behaviour of off-axis points is complex and the area sampled on the probe tip is not symmetric

Computational Studies of Coordinatively Unsaturated Transition Metal Complexes

In this research the validity of various computational techniques has been determined and applied the appropriate techniques to investigate and propose a good catalytic system for C-H bond activation and functionalization. Methane being least reactive and major component of natural gas, its activation and conversion to functionalized products is of great scientific and economic interest in pure and applied chemistry. Thus C-H activation followed by C-C/C-X functionalization became crux of the synthesis. DFT (density functional theory) methods are well suited to determine the thermodynamic as well as kinetic factors of a reaction. The obtained results are helpful to industrial catalysis and experimental chemistry with additional information: since C-X (X = halogens) bond cleavage is important in many metal catalyzed organic syntheses, the results obtained in this research helps in determining the selectivity (kinetic or thermodynamic) advantage. When C-P bond activation is considered, results from chapter 3 indicated that C-X activation barrier is lower than C-H activation barrier. The results obtained from DFT calculations not only gave a good support to the experimental results and verified the experimentally demonstrated Ni-atom transfer mechanism from Ni=E (E = CH2, NH, PH) activating complex to ethylene to form three-membered ring products but also validated the application of late transition metal complexes in respective process. Results obtained supported the argument that increase in metal coordination and electronic spin state increases catalytic activity of FeIII-imido complexes. These results not only encouraged the fact that DFT and multi-layer ONIOM methods are good to determine geometry and thermodynamics of meta-stable chemical complexes, but also gave a great support to spectroscopic calculations like NMR and Mossbauer calculations