Optimized 13C-TrEnDi Enhances the Sensitivity of Plasmenyl Ether Glycerophospholipids and Demonstrates Compatibility with Other Derivatization Strategies.

The identification and quantitation of plasmalogen glycerophospholipids is challenging due to their isobaric overlap with plasmanyl ether-linked glycerophospholipids, susceptibility to acid degradation, and their typically low abundance in biological samples. Trimethylation enhancement using diazomethane (TrEnDi) can be used to significantly enhance the signal of glycerophospholipids through the creation of quaternary ammonium groups producing fixed positive charges using 13C-diazomethane in complex lipid extracts. Although TrEnDi requires a strong acid for complete methylation, we report an optimized protocol using 10 mM HBF4 with the subsequent addition of a buffer solution that prevents acidic hydrolysis of plasmalogen species and enables the benefits of TrEnDi to be realized for this class of lipids. These optimized conditions were applied to aliquots of bovine liver extract (BLE) to achieve permethylation of plasmalogen lipids within a complex mixture. Treating aliquots of unmodified and TrEnDi-derivatized BLE samples with 80% formic acid and comparing their liquid chromatography mass spectrometry (LCMS) results to analogous samples not treated with formic acid, enabled the identification of 29 plasmalogen species. On average, methylated plasmalogen species from BLE demonstrated 2.81-fold and 28.1-fold sensitivity gains over unmodified counterparts for phosphatidylcholine and phosphatidylethanolamine plasmalogen species, respectively. Furthermore, the compatibility of employing 13C-TrEnDi and a previously reported iodoacetalization strategy was demonstrated to effectively identify plasmenyl-ether lipids in complex biological extracts at greater levels of sensitivity. Overall, we detail an optimized 13C-TrEnDi derivatization strategy that enables the analysis of plasmalogen glycerophospholipids with no undesired cleavage of radyl groups, boosting their sensitivity in LCMS and LCMS/MS analyses.

Direct mapping of kidney function by DCE-MRI urography using a tetrazinanone organic radical contrast agent.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, with clinical estimates providing a global assessment of kidney health without spatial information of kidney- or region-specific dysfunction. The addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to the anatomical imaging already performed would yield a 'one-stop-shop' for renal assessment in cases of suspected AKI and CKD. Towards urography by DCE-MRI, we evaluated a class of nitrogen-centered organic radicals known as verdazyls, which are extremely stable even in highly reducing environments. A glucose-modified verdazyl, glucoverdazyl, provided contrast limited to kidney and bladder, affording functional kidney evaluation in mouse models of unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN). Imaging outcomes correlated with histology and hematology assessing kidney dysfunction, and glucoverdazyl clearance rates were found to be a reliable surrogate measure of GFR.

Improved Chromatography and MS-Based Detection of Glyphosate and Aminomethylphosphonic Acid Using iTrEnDi.

Glyphosate (GLY), a synthetic, nonselective systemic herbicide that is particularly effective against perennial weeds, is the most used weedkiller in the world. There are growing concerns over GLY accumulation in the environment and the attendant human health-associated risks, and despite increased attention in the media, GLY and its breakdown product aminomethylphosphonic acid (AMPA) remain elusive to many analytical strategies. Chemical derivatization coupled with high-performance liquid chromatography-mass spectrometry (HPLC-MS) addresses the challenge of quantifying low levels of GLY and AMPA in complex samples. Here we demonstrate the use of in situ trimethylation enhancement using diazomethane (iTrEnDi) to derivatize GLY and AMPA into permethylated products ([GLYTr]+ and [AMPATr]+, respectively) prior to analysis via HPLC-MS. iTrEnDi produced quantitative yields and resulted in a 12-340-fold increases in HPLC-MS-based sensitivity for [GLYTr]+ and [AMPATr]+, respectively, compared with underivatized counterparts. The limits of detection of derivatized compounds were found to be 0.99 ng/L for [GLYTr]+ and 1.30 ng/L for [AMPATr]+, demonstrating significant sensitivity improvements compared to previously established derivatization techniques. iTrEnDi is compatible with the direct derivatization of Roundup formulations. Finally, as proof of principle, a simple aqueous extraction followed by iTrEnDi enabled the detection of [GLYTr]+ and [AMPATr]+ on the exterior of field-grown soybeans that were sprayed with Roundup. Overall, iTrEnDi ameliorates issues relating to low proton affinity and chromatographic retention, boosting HPLC-MS-based sensitivity and enabling the elucidation of elusive analytes such as GLY and AMPA within agricultural systems.

A cationic fcu-lanthanide MOF enhances the uptake of iodine vapour at room temperature.

The first example of a cationic cluster-based fcu-lanthanide metal-organic framework (MOF) bearing an asymmetric linker, herein named UOTT-4, has been designed and fully characterized. Compared to its rare-earth (RE) anionic counterpart (RE-UiO-66), UOTT-4 was found to significantly improve the performance towards adsorption of iodine vapour at room temperature, opening avenues for the design of the next-generation cationic porous materials for the beneficial uptake and confinement of target molecules.

Straightforward Mechanosynthesis of a Phase-Pure Interpenetrated MOF-5 Bearing a Size-Matching Tetrazine-Based Linker.

The archetypal metal-organic framework-5 (MOF-5 or IRMOF-1) has been explored as a benchmark sorbent material with untapped potential to be studied in the capture and storage of gases and chemical confinement. Several derivatives of this framework have been prepared using the multivariate (MTV) strategy through mixing size-matching linkers to isolate, for example, MIXMOFs that outperform same-linker congeners when employed as gas reservoirs. Herein, we describe a straightforward protocol that uses mechanosynthesis (solvent-free grinding) followed by mild activation in dimethylformamide (DMF)/CHCl3 (40 °C and ambient pressure) to synthesize a functional phase-pure interpenetrated MOF-5 (int-MOF-5) bearing the size-matching 1,4-benzene dicarboxylate (BDC) and 1,2,4,5-tetrazine-3,6-dicarboxylate (TZDC) linkers in the backbone of the interpenetrated MIXMOF. We found that the grinding involving a mixture of H2TZDC and H2BDC in a 1:4 ratio (20% of H2TZDC) in the presence of zinc(II) acetate yields a crystalline solid that upon activation forms a phase-pure int-MOF-5 herein referred to as 20%TZDC-MOF-5. The crystalline phase, thermal stability, and porous structure of 20%TZDC-MOF-5 were thoroughly characterized, and the gas adsorption performance of the MIXMOF was investigated through the isotherms of N2 and H2 at 77 K and CO2 at 273 and 296 K. The pore size distribution for 20%TZDC-MOF-5 was found to be very similar to that determined using single crystals of the same-linker int-MOF-5. The presence of TZDC in the MIXMOF led to a slight increase in the uptake values for both H2 and CO2, suggesting that beneficial interactions take place. To the best of our knowledge, this is the first report presenting a suitable protocol to yield a functionalized int-MOF-5 as a promising means of synergistically fine-tuning the confinement of small target molecules such as CO2 and H2.

iTrEnDi: In Situ Trimethylation Enhancement Using Diazomethane: Improved and Expanded Glycerophospholipid and Sphingolipid Analyses via a Microscale Autonomous Derivatization Platform.

Trimethylation enhancement using diazomethane (TrEnDi) is a derivatization technique that significantly enhances the signal intensity of glycerophospholipid species in mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses. Here, we describe a novel apparatus that is able to conduct in situ TrEnDi (iTrEnDi) by generating and immediately reacting small amounts of gaseous diazoalkane with analyte molecules. iTrEnDi allows complete and rapid methylation of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and sphingomyelin (SM) in a safe manner by removing any need for direct handling of dangerous diazoalkane solutions. iTrEnDi-modified PC ([PCTr]+) and PE ([PETr]+) showed similar sensitivity enhancements and fragmentation patterns compared to our previously reported methodology. iTrEnDi yielded dimethylated PA ([PATr]), which exhibited dramatically improved chromatographic behavior and a 14-fold increase in liquid chromatography MS (LCMS) sensitivity compared to unmodified PA. In comparison to in-solution-based TrEnDi, iTrEnDi demonstrated a modest decrease in sensitivity, likely due to analyte losses during handling. However, the enhanced safety benefits of iTrEnDi coupled with its ease of use and capacity for automation, as well as its accommodation of more-reactive diazoalkane species, vastly improve the accessibility and utility of this derivatization technique. Finally, as a proof of concept, iTrEnDi was used to produce diazoethane (DZE), a more-reactive diazoalkane than diazomethane. Reaction between DZE and PC yielded ethylated [PCTr]+, which fragmented via MS/MS to produce a high-intensity characteristic fragment ion, enabling a novel and highly sensitive precursor ion scan.

Surface chemistry of group 11 atomic layer deposition precursors on silica using solid-state nuclear magnetic resonance spectroscopy.

The use of chemical vapour deposition (CVD) and atomic layer deposition (ALD) as thin film deposition techniques has had a major impact on a number of fields. The deposition of pure, uniform, conformal thin films requires very specific vapour-solid reactivity that is largely unknown for the majority of ALD and CVD precursors. This work examines the initial chemisorption of several thin film vapour deposition precursors on high surface area silica (HSAS) using 13C, 31P, and quantitative 29Si nuclear magnetic resonance spectroscopy (NMR). Two copper metal precursors, 1,3-diisopropyl-imidazolin-2-ylidene copper (I) hexamethyldisilazide (1) and 1,3-diethyl-imidazolin-2-ylidene copper(I) hexamethyldisilazide (2), and one gold metal precursor, trimethylphosphine gold(III) trimethyl (3), are examined. Compounds 1 and 2 were found to chemisorb at the hydroxyl surface-reactive sites to form a ||-O-Cu-NHC surface species and fully methylated silicon (||-SiMe3, due to reactivity of the hexamethyldisilazane (HMDS) ligand on the precursor) at 150 °C and 250 °C. From quantitative 29Si solid-state NMR (SS-NMR) spectroscopy measurements, it was found that HMDS preferentially reacts at geminal disilanol surface sites while the copper surface species preferentially chemisorbed to lone silanol surface species. Additionally, the overall coverage was strongly dependent on temperature, with higher overall coverage of 1 at higher temperature but lower overall coverage of 2 at higher temperature. The chemisorption of 3 was found to produce a number of interesting surface species on HSAS. Gold(III) trimethylphosphine, reduced gold phosphine, methylated phosphoxides, and graphitic carbon were all observed as surface species. The overall coverage of 3 on HSAS was only about 10% at 100 °C and, like the copper compounds, had a preference for lone silanol surface reactive sites. The overall coverage and chemisorbed surface species have implications to the overall growth rate and purity of metal films grown with these precursors.

Copper iminopyrrolidinates: a study of thermal and surface chemistry.

Several copper(I) iminopyrrolidinates have been evaluated by thermogravimetric analysis (TGA) and solution based (1)H NMR studies to determine their thermal stability and decomposition mechanisms. Iminopyrrolidinates were used as a ligand for copper(I) to block previously identified decomposition routes of carbodiimide deinsertion and ß-hydrogen abstraction. The compounds copper(I) isopropyl-iminopyrrolidinate (1) and copper(I) tert-butyl-iminopyrrolidinate (2) were synthesized for this study, and compared to the previously reported copper(I) tert-butyl-imino-2,2-dimethylpyrrolidinate (3) and the copper(I) guanidinate [Me(2)NC((i)PrN)(2)Cu](2) (4). Compounds 1 and 2 were found to be volatile yet susceptible to decomposition during TGA. At 165 °C in C(6)D(6), they had half-lives of 181.7 h and 23.7 h, respectively. The main thermolysis product of 1 and 2 was their respective protonated iminopyrrolidine ligand. ß-Hydrogen abstraction was proposed for the mechanism of thermal decomposition. Since compound 3 showed no thermolysis at 165 °C, it was further studied by chemisorption on high surface area silica. It was found to eliminate an isobutene upon chemisoption at 275 °C. Annealing the sample at 350 °C showed further evidence of the decomposition of the surface species, likely eliminating ethene, and producing a surface bound methylene diamine.

Preventing thermolysis: precursor design for volatile copper compounds.

A copper(I) iminopyrrolidinate was synthesized and evaluated by thermal gravimetric analysis (TGA), solution based (1)H NMR studies and surface chemistry to determine its thermal stability and decomposition mechanism. Copper(I) tert-butyl-imino-2,2-dimethylpyrrolidinate (1) demonstrated superior thermal stability and showed negligible decomposition in TGA experiments up to 300 °C as well as no decomposition in solutions at 165 °C over 3 weeks.

Structure and dynamics of ammonium borohydride.

Synchrotron powder X-ray diffraction, ab initio molecular dynamics calculations and solid state (1)H and (2)H NMR are used to refine the structure of crystalline NH(4)BH(4) including H atoms. Rapid reorientations of both ions mean that on average half-hydrogens occupy the corners of a cube around B or N.

Mg-25 ultra-high field solid state NMR spectroscopy and first principles calculations of magnesium compounds.

Due to sensitivity problems, (25)Mg remains a largely under-explored nucleus in solid state NMR spectroscopy. In this work at an ultrahigh magnetic field of 21.1 T, we have studied at natural abundance the (25)Mg solid state (SS) NMR spectra for a number of previously unreported magnesium compounds with known crystal structures. Some previously reported compounds have been revisited to clarify the spectra that were obtained at lower fields and were either not sufficiently resolved, or misinterpreted. First principles calculations of the (25)Mg SS NMR parameters have been carried out using plane wave basis sets and periodic boundary conditions (CASTEP) and the results are compared with experimental data. The calculations produce the (25)Mg absolute shielding scale and give us insight into the relationship between the NMR and structural parameters. At 21.1 T the effects of the quadrupolar interactions are reduced significantly and the sensitivity and accuracy in determining chemicals shifts and quadrupole coupling parameters improve dramatically. Although T(1) measurements were not performed explicitly, these proved to be longer than assumed in much of the previously reported work. We demonstrate that the chemical shift range of magnesium in diamagnetic compounds may approach 200 ppm. Most commonly, however, the observed shifts are between -15 and +25 ppm. Quadrupolar effects dominate the (25)Mg spectra of magnesium cations in non-cubic environments. The chemical shift anisotropy appears to be rather small and only in a few cases could the contribution of the CSA be detected reliably. A good correspondence between the calculated shielding constants and experimental chemical shifts was obtained, demonstrating the good potential of computational methods in spectroscopic assignments of solid state (25)Mg NMR spectroscopy.