The renaissance of H/D exchange

The increasing demand for stable isotopically labeled compounds has led to an increased interest in H/D-exchange reactions at carbon centers. Today deuterium-labeled compounds are used as internal standards in mass spectrometry or to help elucidate mechanistic theories. Access to these deuterated compounds takes place significantly more efficiently and more cost effectively by exchange of hydrogen by deuterium in the target molecule than by classical synthesis. This Review will concentrate on the preparative application of the H/D-exchange reaction in the preparation of deuterium-labeled compounds. Advances over the last ten years are brought together and critically evaluated.     

微气相色谱法分析氢氘同位素组分气体

该文建立了聚变堆燃料循环系统中氢氘组分的微气相色谱定量分析方法.采用MnCl2溶液改性的氧化铝色谱柱(4～6m×0.53mm)为分离柱,考察了改性液含量、色谱柱长和载气流量对氢氘组分分析的影响,在液氮低温(77 K)条件下实现了H2、HD和D2混合物的分离.结果表明,19％MnCl2溶液处理的色谱柱分离氢同位素的效果优...     

供氢(氘)剂在减压渣油四组分裂化中的作用及其同位素效应

研究了辽河减渣四组分在微型高压釜内中临氮热裂化、临氢热裂化和临氢催化加氢反应,考察了供氢剂或供氘剂对上述反应的影响。结果表明,临氮热裂化时沥青质是大量生焦的物种,胶质的生焦能力不显著,芳香分、饱和分不生焦;临氢热裂化沥青质生焦量减少,胶质很少生焦,芳香分和饱和分不生焦;临氢催化加氢时,辽河减渣四组分在临氢反应基础之上,生焦量进一步降低。辽河减渣四组分在临氮热裂化、临氢热裂化和临氢催化加氢过程中添加供氢剂或供氘剂后,生焦反应得到显著抑制,相比之下供氢剂的作用更为明显。三种氢源都具有抑制渣油四组分缩合或缩聚反应的作用。渣油四组分从供氢剂或供氘剂中获得氢（氘）的能力不同,沥青质>胶质>芳香分≈饱和分。就同一组分而言,供氢剂或供氘剂的表观供氢（氘）率随反应条件不同而不同,临氮热裂化> 临氢热裂化>临氢催化加氢过程。供氢剂与供氘剂在所有的过程中都存在明显的动力学效应,并且这个动力学效应随加工环境的不同而变化,在临氮热裂化过程中动力学同位素效应明显。在临氢热裂化过程,尤其是催化加氢裂化过程中动力学效应逐渐变得不明显。2H-NMR分析表明,氘代四氢萘的环烷环中的α位比β位的脱氢选择性高,氘代四氢萘脱氢选择性大小的顺序为：临氮热裂化>临氢热裂化>临氢催化加氢过程。     

Controls over spatial and seasonal variations on isotopic composition of the precipitation along the central and eastern portion of Brazil

Based on Global Network Isotopes in Precipitation (GNIP) isotopic data set, a review of the spatial and temporal variability of δ¹⁸O and δ²H in precipitation was conducted throughout central and eastern Brazil, indicating that dynamic interactions between Intertropical and South Atlantic Convergence Zones, Amazon rainforest, and Atlantic Ocean determine the variations on the isotopic composition of precipitation over this area. Despite the seasonality and latitude effects observed, a fair correlation with precipitation amount was found. In addition, Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) air mass back trajectories were used to quantify the factors controlling daily variability in stable isotopes in precipitation. Through a linear multiple regression analysis, it was observed that temporal variations were consistent with the meteorological parameters derived from HYSPLIT, particularly precipitation amount along the trajectory and mix depth, but are not dependent on vapour residence time in the atmosphere. These findings also indicate the importance of convective systems to control the isotopic composition of precipitation in tropical and subtropical regions.     

Anilinolysis of O‐butyl phenyl phosphonochloridothioate in acetonitrile: Synthesis,characterization, kinetic study,and reaction mechanism

This paper describes a simple optimized method for the synthesis of O‐butyl phenyl phosphonochloridothioate ( 4 ) under mild conditions. The target compounds were characterized by ¹H‐nuclear magnetic resonance (NMR), ¹³C‐NMR, and ³¹P‐NMR spectroscopy, as well as mass spectroscopy. The apparent structure of 4 was confirmed by optimization using the B3LYP/6‐311 + G(d,p) level in the Gaussian 09 program in acetonitrile. The nucleophilic substitution reactions of 4 with X‐anilines (XC₆H₄NH₂) and deuterated X‐anilines (XC₆H₄ND₂) were investigated kinetically in acetonitrile at 55.0°C. The free energy relationship with X in the anilines looked biphasic concave upwards with a break region between X = H and X = 3‐MeO, giving large negative ρ_X and small positive β_X values. The deuterium kinetic isotope effects were secondary inverse (k_H/k_D < 1: 0.789‐0.995) and the magnitudes, (k_H/k_D), increased when the nucleophiles were changed from weakly basic to strongly basic anilines. A concerted S_N2 mechanism is proposed on the basis of the selectivity parameters and the variation trend of the deuterium kinetic isotope effects with X.     

Real‐time measurement of H/D exchange in a microdialysis Raman quartz cell

We present here a novel quartz cell for monitoring H/D exchange in biomolecules using Raman spectroscopy. This cell is combined with a syringe to pump heavy water through a hollow microdialysis fibre, which is inserted into the cell. The deuterium efflux into the sample has been studied as a function of the molecular weight cut‐off of the microdialysis fibre and compared with other microcell systems comprising conventional glass capillaries. The fastest D₂O efflux that we have obtained (k_d = 0.38 ± 0.008 min⁻¹) permits to measure exchange rates of 2.5 min⁻¹ or less. Application of this cell to deuterium exchange in glyceraldehyde‐3‐phosphate dehydrogenase reveals a class of H‐atoms highly resistant to deuteration, which is consistent with a previous infrared study on this protein. Copyright © 2009 John Wiley & Sons, Ltd.     

Online H/D exchange liquid chromatography as a support for the mass spectrometric identification of the oxidation products of melatonin

The hydrogen–deuterium exchange of protonated melatonin and its in vitro oxidation end‐products have been examined by liquid chromatography coupled with ion‐trap mass spectrometry. Specific H/D scrambling of protons in the C2 and C4 positions of the indole ring during gas‐phase fragmentation process was observed for both melatonin and its oxidation products. Collision‐induced dissociation spectra showed losses of variably deuterated NH₃, H₂O and CH₃CONH₂. In addition, a similar H/D scrambling behaviour was observed for the oxidation products, obtained from the opening of the indole ring by oxidative attack. Fragmentation pathways are proposed and H/D scrambling has been employed as a fingerprint, allowing identification of N¹‐acetyl‐5‐methoxykynurenin (AMK), N¹‐acetyl‐N²‐formyl‐5‐methoxykynurenin (AFMK), dehydro‐AFMK and hydroxymelatonin as the oxidation products of melatonin in vitro. Copyright © 2008 John Wiley & Sons, Ltd.     

Structural characterization of the regioisomers of di(hydroxybutyl) ether by GC‐EI MS and theoretical calculations

Di(hydroxybutyl) ether (DHBE), a liver protecting drug, is composed of a mixture of three regioisomers: 4‐(3‐hydroxybutoxy)‐2‐butanol (1), 3‐(4‐hydroxy‐2‐butoxy)‐1‐butanol (2), and 3‐(3‐hydroxybutoxy)‐1‐butanol (3). Unequivocal differentiation of each regioisomer of DHBE was rapidly obtained without isolation of the single components, using GC‐MS with electron ionization (EI). The mass spectrum of 1 showed a rearrangement ion at m/z 118, characteristic of the 3‐hydroxybutyl chain, deriving from loss of acetaldehyde from the molecular ion, whereas 2 and 3 were characterized by the ion at m/z 117, expected from α‐cleavage of the 4‐hydroxy‐2‐butyl chain. The species at m/z 118, in turn, loses a water molecule via a mechanism involving both alcohol hydrogens, as shown by deuterium exchange experiments. Both this finding and theoretical calculations support a mechanism in which the loss of acetaldehyde in 1 occurs via a cyclic intermediate, stabilized by a strong hydrogen bond between the alcohol oxygen bearing the charge and the other alcohol oxygen, and involves initial hydrogen transfer from the former to the latter. The EI spectrum of 2, having two 4‐hydroxy‐2‐butyl chains, showed the fragmentations expected from classical fragmentation rules of aliphatic ethers and alcohols, whereas the EI spectrum of 3, bearing one 4‐hydroxy‐2‐butyl and one 3‐hydroxybutyl chain, showed essentially the characteristic fragments of both chains. Copyright © 2009 John Wiley & Sons, Ltd.     

Efforts Toward the Direct Experimental Characterization of Enzyme Microenvironments: Tyrosine100 in Dihydrofolate Reductase

State secrets : Site‐specific deuteration and FTIR studies reveal that Tyr100 in dihydrofolate reductase plays an important role in catalysis, with a strong electrostatic coupling occuring between Tyr100 and the charge that develops in the hydride‐transfer transition state (see picture, NADP⁺ purple, Tyr100 green). However, relaying correlated motions that facilitate catalysis from distal sites of the protein to the hydride donor may also be involved.