Conformational analysis,part 43. A theoretical and LIS/NMR investigation of the conformations of substituted benzamides

A refined Lanthanide‐Induced‐Shift Analysis (LISA) is used with molecular mechanics and ab initio calculations to investigate the conformations of benzamide ( 1 ), N‐methylbenzamide ( 2 ), N,N‐dimethylbenzamide ( 3 ) and the conformational equilibria of 2‐fluoro ( 4 ), 2‐chloro ( 5 ) and N‐methyl‐2‐methoxy benzamide ( 6 ). The amino group in 1 is planar in the crystal but is calculated to be pyramidal with the CO/phenyl torsional angle (ω) of 20–25°. The LISA analysis gave acceptable agreement factors (Rcryst ≤ 1%) for the ab initio geometries when ω was decreased to 0°, the other geometries were not as good. In 2 , the N‐methyl is coplanar with the carbonyl group in all the geometries. Good agreement was obtained for the RHF geometries, with ω 25°, the other geometries were only acceptable with increased values of ω. In 3 , good agreement for the RHF and PCModel geometries was found when ω was changed from the calculated values of 40° (RHF) and 90° (PCModel) to ca. 60°, the X‐ray and B3LYP geometries were not as good. The two substituted compounds 4 , 5 and 6 are interconverting between the cis (O,X) and trans (O,X) conformers. The more stable trans conformer is planar in 4 and 6 but the cis form non‐planar. Both the cis and trans conformers of 5 are non‐planar. There is an additional degree of freedom in 6 due to the 2‐methoxy group, which can be either planar or orthogonal to the phenyl ring in both conformers. The conformer ratios were obtained from the LISA analysis to give Ecis‐Etrans in 4 > 2.3 kcal/mol (CDCl₃) and 1.7 kcal/mol (CD₃CN), in 5 0.0 kcal/mol (CD₃CN) and in 6 > 2.5 kcal/mol (CDCl₃) and 2.0 kcal/mol (CD₃CN). These values were used with the observed versus calculated ¹H shifts to determine the conformer ratios and energies in DMSO solvent to give Ecis‐Etrans 1.1, ?0.1 and 1.8 kcal/mol for ( 4 ), ( 5 ) and ( 6 ). Comparison of the observed versus calculated conformer energies show that both the MM and ab initio calculations overestimate the NH..F hydrogen bond in ( 4 ) by ca. 2 kcal/mol. Copyright © 2015 John Wiley & Sons, Ltd.     

Zuordnung offenkettiger Diastereomerer mittels lanthanoiden-induzierter Verschiebungen (LIS)

The LIS method has been tested for assignment purposes of acyclic diastereomers. After the estimation of the coordination geometry Eu ... O for some alkyl-methyl-ethers, the ground state conformations of the coordinated substrates have been determined and related to the free substrates. Due to obtained differences, the application of the LIS method for present assignment purposes should be limited to strained, less flexible stereoisomers.

     

Kinetics of Lisinopril degradation in solid phase

Summary The kinetics of degradation of lisinopril (LIS) in solid phase in presence of humidity at 343, 353, 358 and 363 K has been investigated. Changes of the LIS concentration were followed by an HPLC method with UV detection. The thermodynamic parameters at 293 K of degradation of LIS in solid phase E_a (kJ/mol) = 166 ± 47; H*(kJ/mol) = 163 ± 48; S*(J/(K × mol)) = 99 ± 135 for RH = 76.4% have been calculated. Identification of the product of LIS degradation in solid phase was carried out by HPLC-MS. Diketopiperazine derivative of LIS was the major product of its decomposition in the presence of humidity.     

1H NMR lanthanide-induced Shift investigations of highly flexible molecules III: Applications to alcohols,aldehydes, esters,and amines

Summary Two new methods (RANDOM-LIS and STEED-LIS) with random selection of up to ten dihedral angles were applied for the determination of preferred conformers of flexible molecules (alcohols, aldehydes, esters, and amines, respectively, with only one coordination site) by LIS studies. The results proved to be useful. The preferred complexation conformation was detected only in cases where conformational changes of the substrate took place to improve complexation to the LIS reagent. Force field calculations (RANDOM-PIMM) and Simple Hard Sphere Model calculations (RANDOM-SHSM and STEED-SHSM), using the same algorithm of randomly varying the dihedral angles, support the results obtained.For parts I and II, see Refs. [1] and [2]     

Nanosized thermometric NMR sensors based on the paramagnetic complex ion pairs of lanthanides(III) for temperature determinations in low-polar nonaqueous solutions

For temperature determination in solutions it is suggested that the temperature dependence of the paramagnetic lanthanide-induced shifts (LIS) in the NMR spectra on the ligand nuclei be used for [Ln(PTA)₂(18-crown-6)]⁺[Ln(PTA)₄]^? complex ion pairs formed in CCl₄, CDCl₃, CD₂Cl₂, CD₃C₆D₅, and C₂D₃N type low-polar solvents (Ln = La, Ce, Pr, Nd, Eu; PTA is the pivalyltrifluoroacetonato anion). It was found experimentally that the [Ln(PTA)₂(18-crown-6)]⁺ complex cation molecules (Ln = Ce and Pr) proved most suitable for use as nanosized (≈1.1 nm) probes for temperature determinations in nonaqueous solutions. A linear dependence of the LIS on the ¹H nuclei of different groups and the difference between the LIS corresponding to the CH₂ groups of the 18-crown-6 molecules and the CH groups of the PTA anions on the reciprocal temperature (1/T) was found. The LIS of the individual signals of different groups in Ln paramagnetic complexes (relative to the signals of the diamagnetic analogs, e.g., La or Lu) may be used for temperature control in the sample, although the temperature measurement error is smaller (≤ 0.04 K) when the difference between the LIS of the CH₂ and CH groups is used. Due to the high thermodynamic and kinetic stability combined with small sizes of [Ln(PTA)₂(18-crown-6)]⁺[Ln(PTA)₄]^? molecules in nonaqueous solutions, these compounds may be used as thermometric NMR sensors directly in reaction media for in situ control over temperature.     

Conformational analysis: Part 42. A modelling and LIS/NMR investigation of the conformations of some aromatic SO compounds

A refined Lanthanide‐Induced‐Shift Analysis (LISA), in which both the paramagnetic and the diamagnetic lanthanide induced chemical shifts are normalised separately, is used with molecular mechanics (MMFF94) and ab initio (RHF/6‐31G, RHF/6‐311G** and B3LYP/6‐311G**) calculations to investigate the conformations of methyl para‐tolyl sulphoxide 1 , sulphone 2 and sulphonate 3 and the conformational equilibria of methyl 2,4‐dimethylphenyl sulphoxide 4 and sulphone 5 . In 1 acceptable agreement factors (AFs) in the LISA analysis were only obtained when the SO/phenyl dihedral angle was increased from that (10–15°) of the computed geometries to 30–40°. The calculated geometries for 2 had the methyl group orthogonal to the phenyl ring and gave good AF in the LISA analysis. In both compounds, the AF were in the order MMFF94 ≤ B3LYP < RHF with the larger basis sets giving better agreement than the limiting 6‐31G* function. In 3 all the geometries again had the methoxy group orthogonal to the phenyl ring but, while the ab initio geometries still gave good AFs, the MMFF94 structure gave an AF which was only just acceptable. The unsymmetrical compounds 4 and 5 display conformational equilibria. In 4 two energy minima were found, both with the SMe group orthogonal to the phenyl ring, with the SO oxygen cis or trans to the 2‐methyl group. The energy difference (cis–trans) was calculated as 1.6 kcal/mol (MMFF94), 2.7 (6‐31G*), 1.9 (6‐311G**) but ?0.11 (DFT). The LISA analyses on the separate conformers gave poor agreement (ca. 3%) for the trans conformer but increasing the SO/Ph dihedral angle again gave an acceptable value (ca. 1.4%). Inclusion of even small amounts of the cis conformer in the LIS analysis gave poorer results. Thus, the LISA analysis confirms the MM and RHF prediction that the trans conformer is more stable and suggests that the conformer energy difference in solution is equal to or greater than the largest calculated value of 2.7 kcal/mol. In 5 all the calculations gave two mirror image conformations with the SMe orthogonal to the phenyl ring. The LISA analysis in this case is complicated by the fact that in the stable conformer the complexing oxygen atoms are not equivalent. This was resolved by considering both coordination sites in one Z‐matrix and varying the % coordination on each oxygen atom. This gave an acceptable AF of ca. 1.0% for all the geometries with ca. 2:1 coordination on the oxygen atoms trans and cis to the C2‐methyl. The difference in the geometries and conformer energies found by LISA for these molecules in solution compared to the theoretical values may be due to interactions with the chloroform solvent for these polar compounds. Copyright © 2010 John Wiley & Sons, Ltd.     

基于HL7的移动式微型临床实验室Mini Lis接口设计

由于移动式微型临床实验室集成了多种不同的医疗仪器,导致各应用系统之间难以实现数据信息交换与共享等问题。因此本文通过对微型临床实验室信息管理系统(Mini LIS)进行需求分析,研究了Mini LIS的接口设计。采用医疗信息行业国际前沿的HL7标准,结合XML编码方式,使用DOM技术实现对基于XML模式的HL7消息进行构建和解析,运用MQSeries信息传输系统作为中间件。实现了各仪器应用系统之间数据格式的统一,以及数据信息的交换与共享,解决了各应用系统间的通讯难题,成功集成了多种仪器,并在实际中取得了良好的应用效果。     

BCl3分子振动频率的同位素效应

利用密度泛函B3LYP方法与耦合簇CCSD方法,结合全电子高斯基函数,计算了¹⁰BCl₃和¹¹BCl₃分子的基态平衡几何和谐振频率,进而得到了分子伸缩振动模式的同位素位移.计算检验了芯-价电子关联、标量相对论效应,以及基组外推对分子几何结构、振动频率和同位素位移的影响;结果表明,高阶修正效应对同位素位移的影响很小,并分析了其原因.同时得到了不同Cl/B同位素分子体系的同位素位移.研究对激光分离同位素技术中激光中心波长的选择具有重要参考意义.     

Physical image vs structure relation: part 12 – structure of 2,2,5,5‐tetramethyl‐dihydro‐furan‐3‐one oxime and its protonated forms through isomerization and NMR spectra

The study of an isomeric A / B mixture of the title oxime 1 , by photolytic or thermal E,Z‐isomerization and NMR measurement including ¹H{¹H}‐NOE difference spectra, led to assignment of the E configuration to its predominating form A . The ¹H/¹³C data were interpreted in terms of steric overcrowding of both forms, especially of the thermolabile photoproduct B . Four classical (empirical) NMR methods of elucidating the oxime geometry were critically tested on these results. Unexpected vapor‐phase photoconversion A → B in the window glass‐filtered solar UV and spectroscopic findings on their protonated states were discussed, as well. The kinetically controlled formation of the N‐protonated species (Z)‐ 5 ⁺ was proved experimentally. In addition, some ¹H NMR assignments reported for structurally similar systems were rationalized ( 3 and 4 ) or revised ( 1 and 7–9 ) with the GIAO‐DFT(B3LYP) and/or GIAO‐HF calculational results. Copyright © 2007 John Wiley & Sons, Ltd.