Substituent Effects on 13C NMR and 1H NMR Chemical Shifts of CH=N in Multi-substituted Benzylideneanilines

Fifty-three samples of multi-substituted benzylideneanilines XArCH=NArYs （abbreviated XBAYs） were synthesized and their NMR spectra were determined. An extensional study of substituent effects on the 1H NMR chemical shifts （δH（CH=N）） and 13C NMR chemical shifts （δc（CH=N）） of the CH=N bridging group from di-substituted to multi-substituted XBAYs was made based on a total of 182 samples of XBAYs, together with the NMR data of other 129 samples of di-substituted XBAYs quoted from literatures. The results show thatthe substituent specific cross-interaction effect parameter （△（∑σ）2） plays an important role in quantifying the δc（CH=N） values of XBAYs, but it is negligible for quantifying the δH （CH=N） values; the other substituent parameters also present different influences on the δc （CH=N） and （δH （CH=N）. On the whole, the contributions of X and Y to the δc （CH=N） of XBAYs are balanced, but the δH（CH=N） values of XBAYs mainly rely on the contributions of X.

Relative Chemical Shifts for Obtaining Accurate Chemical Shifts of Hydrogen Atoms in CH Groups

Accurate chemical shifts of hydrogen atoms in CH groups are difficult to obtain. To solve this problem, relative chemical shifts are introduced. Internal and external standard methods were used to measure the chemical shifts in a whole-concentration of N-methylacetamide- water system. Determination of the chemical shifts of hydrogen atoms, especially those of CH groups, according to the two methods yielded significant differences. Relative chemical shifts were proven to be independent of the reference and may be applied to other systems.

Prediction of the ^(13)C NMR Chemical Shifts of Stilbene Analogues by GIAO Method

After the geometry optimization at B3LYP/6-31＋G（d,p） level,the calculations of the NMR chemical shifts of a series of stilbene analogues were carried out by means of Gauge Including Atomic Orbitals（GIAO） method at HF/6-31＋G（d） level and B3LYP/6-311G＋（2d,p） level,respectively.The 13C NMR chemical shifts calculated at both HF/6-31＋G（d） and B3LYP/6-31＋G（d,p） levels are in agreement with the observed values.By virtue of a series of linear correction equations（δpred.=a＋bδcalcd.） of the 13C chemical shifts,accurate prediction of 13C chemical shifts was achieved for the new stilbene compounds.For the 13C NMR chemical shifts calculated at HF/6-31＋G（d） level,the linear correlation of δpred.with δexptl.is excellent,and the square of correlation coefficient,r2,is 0.9985.The maximum absolute difference between δpred.and δexptl.,Δδ,is 2.3,and the root-mean-square error between δpred.and δexptl.is 0.98.In the meantime,for those obtained at B3LYP/6-31＋G（d,p） level,the linear correlation of δpred.with δexptl.is also excellent,and the square of correlation coefficient,r2,is up to 0.9987.The maximum absolute difference between δpred.and δexptl.,Δδ,is 2.2,and the root-mean-square error between δpred.and δexptl.is only 0.88.

Prediction of the ^(13)C NMR Chemical Shifts of Fluorenone Analogues by the GIAO Method

After the geometry optimization at B3LYP/6-31＋G（d,p） level,the NMR calcula-tions of a series of fluorenone analogues have been carried out by GIAO method at HF/6-31＋G（d） level and B3LYP/6-311G＋（2d,p） level,respectively.The 13C NMR chemical shifts calculated at HF/6-31＋G（d） level show better agreement with the observed values.By a series of linear correction equations （δpred=a ＋ bδcalc）,accurate prediction of 13C chemical shifts was achieved for the new fluorenone compound.The linear correlation of δpred with δexptl is excellent,and the square of correlation coefficient,r2,is up to 0.994.The maximum absolute difference between δpred and δexptl,Δδ,is 4.6 ppm,and the root-mean-square error between δpred and δexptl is only 2.6 ppm.

DFT Studies on Thermal Stabilities,Electronic Structures,and ^(13)C Chemical Shifts of C_(24)O_2 Based on Fullerene C_(24)(D_6)

Quantum chemical calculations on some possible equilibrium geometries of C24O2 isomers derived from C24 （D6） and C24O have been performed using density functional theory （DFT） method. The geometric and electronic structures as well as the relative energies and thermal stabilities of various C24O2 isomers at the ground state have been calculated at the B3LYP/6-31G（d） level of theory. And the 1,4,2,5-C24O2 isomer was found to be the most stable geometry where two oxygen atoms were added to the longest carbon-carbon bonds in the same pentagon from a thermodynamic point of view. Based on the optimized neutral geometries, the vertical ionization potential and vertical electron affinity have been obtained. Meanwhile, the vibrational frequencies, IR spectrum, and 13C chemical shifts of various C24O2 isomers have been calculated and analyzed.

Correlation of ^1H NMR Chemical Shift for Aqueous Solutions by Statistical Associating Fluid Theory Association Model

1H NMR chemical shifts of binary aqueous mixtures of acylamide, alcohol, dimethyl sulphoxide (DMSO), and acetone are correlated by statistical associating fluid theory (SAFT) association model. The comparison between SAPT association model and Wilson equation shows that the former is better for dealing with aqueous solutions. Finally, the specialties of both models are discussed.

Simulation of ^(13)C NMR chemical shifts of carbinol carbon atoms using quantitative structure-spectrum relationships

A quantitative structure-spectrum relationship (QSSR) model was developed to simulate 13C nuclear magnetic resonance (NMR) spectra of carbinol carbon atoms for 55 alcohols. The proposed model,using multiple linear regression,contained four descriptors solely extracted from the molecular structure of compounds. The statistical results of the final model show that R2= 0.982 4 and S=0.869 8 (where R is the correlation coefficient and S is the standard deviation). To test its predictive ability,the model was further used to predict the 13C NMR spectra of the carbinol carbon atoms of other nine compounds which were not included in the developed model. The average relative errors are 0.94% and 1.70%,respectively,for the training set and the predictive set. The model is statistically significant and shows good stability for data variation as tested by the leave-one-out (LOO) cross-validation. The comparison with other approaches also reveals good performance of this method.

Substituent Effect on Mercury-199 Chemical Shifts in Some Bisarylmercurials and Aryl(2-benzothiazolylthio) mercurials

The present paper covers the 199 Hg NMR chemical shifts of 24 substituted diphenylmercurials and phenyl(2-benzothiazolylthio)mercurials. There is a good linear relationship between the chemical shift and the Hammett constant of the substituents for both series of compounds, and electron donating substituents cause the chemical shift towards downfield.

Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds

AIM To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds(Cho).METHODS Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2 D chemical shift imaging(CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation(CV), repeatability coefficient(RC), and intraclass correlation coefficient(ICC) were used to assess the repeatability. RESULTS The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test. CONCLUSION It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.

Structures and Hydrogen Bonding Interactions in Urea-water System Studied by All-atom MD Simulation and Chemical Shifts in NMR Spectrum

The interactions and structures of the urea-water system are studied by an all-atom molecular dynamics （MD） simulation. The hydrogen-bonding network and the radial distribution functions are adopted in MD simulations. The structures of urea-water mixtures can be classified into different regions from the analysis of the hydrogen-bonding network. The urea molecule shows the certain tendency to the self-aggregate with the mole fraction of urea increasing. Moreover, the results of the MD simulations are also compare with the chemical shifts and viscosities of the urea aqueous solutions, and the statistical results of the average number hydrogen bonds in the MD simulations are in agreement with the experiment data such as chemical shifts of the hydrogen atom and viscosity.

SUBSTITUENT CHEMICAL SHIFT (SCS) AND THE SEQUENCE STRUCTURE OF ETHYLENE-VINYL ALCOHOL COPOLYMERS

Three ethylene-vinyl alcohol copolymers were studied by means of the substituent chemical shift (SCS) method. The SCS parameters of hydroxy (-OH) in two different solvents were obtained: in deuterium oxide/phenol (20/80 W/W ) the parameters are S_1 = 42.77±0.08ppm, S_2 = 7.15±0.06 ppm, S_3 (s)= -4.08±0.02ppm, S_3 (t) =-3.09±0.20ppm,S_4 = 0.48±0.03ppm, S_5 = 0.26±0.05ppm. In o-dichloro-benzen-d_4 S_1(s)=44.79±0.61ppm, S_2=7.40±0.00ppm, S_3(s)=-4.51±0.17ppm, S_3(t)=-3.13 ±0.00 ppm, S_4 =0.63±0.04ppm, S_5=0.36±0.00ppm.Simultaneously the ^(13)CNMR spectra of EVA copolymers were assigned by using the SCS parameters obtained.

Prediction of the ^(13)C NMR Chemical Shifts of 9,10-Dihydrophenanthrene Analogues by the GIAO Method

After the geometry optimizations at the B3LYP/6-31＋G（d,p） level, the NMR calculations of a series of 9,10-dihydrophenanthrene analogues have been carried out by GIAO method at the HF/6-31＋G（d） level. The calculated ^13C NMR chemical shifts are in agreement with the observed values. By a series of linear correlation equations （δpred = a ＋ bδcal.c） of the ^13C chemical shifts, accurate prediction of ^13C chemical shifts was achieved for the new 9,10- dihydrophenanthrene compound, for which the predicted ^13C NMR chemical shifts are in quite good agreement with the experimental values. The linear correlation between δpred and δexptl is excellent, and the square of correlation coefficient, r^2, is up to 0.9973. The maximum absolute difference between δpred and δexptl, △δ, is 4.5 ppm, and the rms error between δpred and δexpt is 2.55 ppm. In the meantime, according to the theoretical predicted result, we could confirm that the new 9,10-dihydrophenanthrene analogue is erianthridin （2,7-dihydroxy-3,4-dimethoxy-9,10-dihydro- phenanthrene）.

Ab Initio Prediction of ^(29)Si-NMR Chemical Shifts

The ability of several ab initio models to predict experimental 29Si-NMR chemical shift is examined. The shielding values of trimethylsilyl chloride (A), t-butyldimethylsilyl chloride (B) and allyltrimethylsilane (C) are calculated by GIAO , CSGT and IGAIM methods, using HF/6-31G*, B3LYP/6-31G*, HF/6-311+G **, B3LYP/6-311+G ** and MPW1PW91/6-311+G ** models respectively. The 29Si chemical shifts calculated by GIAO method using HF/6-311+G ** model are highly in agreement with those obtained experimentally. All of the models above reproduce the trends of chemical shifts in all cases studied, suggesting that the models are of practical value.

ACCEPT-NMR: A New Tool for the Analysis of Crystal Contacts and Their Links to NMR Chemical Shift Perturbations

We have developed an open-source cross-platform software toolkit entitled ACCEPT-NMR (Automated Crystal Contact Extrapolation/Prediction Toolkit for NMR) as a helpful tool to automate many of the complex tasks required to find and visualize crystal contacts in structures of biomolecules and biomolecular assemblies. This toolkit provides many powerful features geared toward NMR spectroscopy and related disciplines, such as isotopic labeling, advanced visualization options, and reporting tools. Using this software, we have undertaken a survey of available chemical shift data in the literature and deposited in the BMRB, and show that the mere presence of one or more crystal contacts to a residue confers an approximately 65% likelihood of significant chemical shift perturbations (relative to solution NMR chemical shifts). The presence of each additional crystal contact subsequently increases this probability, resulting in predictive accuracies in excess of 80% in many cases. Conversely, the presence of a significant experimental chemical shift perturbation indicates a >60% likelihood of finding one or more crystal contacts to a particular residue. Pinpointing sites likely to experience large CSPs is critical to mapping solution NMR chemical shifts onto solid-state NMR data as a basis for preliminary assignments, and can thus simplify the assignment process for complex biomolecules. Mapping observed CSPs onto the molecular structure, on the other hand, can indicate the presence of crystal interfaces where no crystal structure is available. Finally, by detecting sites critical to intermolecular interfaces, ACCEPT-NMR can help guide experimental approaches (e.g. isotopic labeling schemes) to detect and probe specific inter-subunit interactions.

Anomeric Proton and Carbon (H1-C1) NMR Chemical Shifts of Antigenic Mannans Obtained from Pathogenic Yeast <i>Candida tropicalis</i>

On two dimensional maps of 1H-13C correlation spectroscopy (H-C COSY) analysis for the mannan of Candida tropicalis, nine cross peaks of anomeric proton and carbon were useful for the purpose of obtaining information on the chemical structure of this molecule. Namely, the mannans was comb-like structure constructed with the linear α-1,6-linked polymannnosyl backbone and several oligomannnosyl side chains composed of α-1,2-, α-1,3-, and β-1,2-linkages. Therefore, in the structural investigation of comb-like mannan, two-dimensional H-C COSY analysis is as useful as two-dimensional nuclear Hartmann-Hahn (HOHAHA) analysis.

不同MR设备CSE MR序列定量骨髓质子密度脂肪分数的一致性分析

目的探讨以单体素氢质子磁共振波谱成像(MRS)为参照,验证不同厂家3T化学位移编码水/脂分离MR序列(CSE-MRI)定量腰椎骨髓质子密度脂肪分数(PDFF)的可重复性与一致性。方法选取38例受试者进行腰椎MRS(PDFF_(MRS))、联影CSE-MRI(PDFF_(FACT))与西门子CSE-MRI(PDFF_(Dixion))扫描。以均方根误差(RMSE)和均方根变异系数(RMS-CV)评价CSE-MRI定量PDFF的精密度及可重复性。使用组内相关系数(ICC)评估不同观察者及观察者内测定PDFF值的一致性。采用Linear regression及Bland-Altman分析评价不同CSE-MRI序列与MRS定量PDFF的可代替性及不同公司间CSE-MRI序列定量PDFF的一致性。结果PDFF_(MRS)、PDFF_(FACT)及PDFF_(Dixion)定量骨髓PDFF值分别为58.2%(38.7%,67.0%)、56.7%(37.2%,66.6%)、56.3%(36.8%,65.4%)。PDFF_(FACT)与PDFF_(Dixion)RMSE分别为1.48%、1.57%,RMS-CV分别为2.37%、2.25%,可重复性良好。观察者内及观察者间测定PDFF具有实质性的一致性,ICC均大于0.99。MRS、FACT及Dixon VIBE序列定量骨髓PDFF之间的线性回归分析,R^(2)=0.985~0.989,差异有统计学意义(P<0.001)。Bland-Altman分析PDFF_(FACT)与PDFF_(MRS)差值97.4%的点落在95%可信区间内,PDFFDixon与PDFF_(MRS)差值92.1%的点落在95%可信区间内,PDFF_(FACT)与PDFFDixon差值92.1%的点落在95%可信区间内,显示了良好的一致性。结论联影与西门子CSE MR序列定量腰椎PDFF可重复性良好,其准确性可等同于MRS。

二氧化硅颗粒堆积空隙中氢气分子的核磁共振谱学特征研究

本文研究了一系列不同尺寸二氧化硅小球堆积空隙中氢气分子的核磁共振信号特征,观察到氢气分子化学位移随着小球堆积空隙尺寸减小逐渐向高场变化的现象.结合变温氢谱、氢气自扩散系数测量及扫描电镜等实验结果,认为两个因素的共同作用是该现象产生的原因,即:1)抗磁性的二氧化硅小球所导致的磁场不均匀性分布随小球尺寸变化而变化;2)处在小球空隙内不同位置的氢气分子间存在快速交换.本文结果展示了氢气作为探针分子用于微纳空隙尺寸测量的可能性.

腹部脂肪组织脂肪酸组分的MRI定量检测及其在直肠癌中的应用价值初探

目的:利用化学位移编码磁共振成像(chemical-shift-encoded magnetic resonance imaging,CSE-MRI)技术定量检测脂肪组织脂肪酸组分,分析直肠癌患者不同部位脂肪酸组分变化情况,探讨该技术应用于评价脂肪酸影响直肠癌发生、发展的价值。方法:对2021年10月—2022年12月于复旦大学附属华东医院经术后病理学检查证实的直肠腺癌患者术前行直肠常规MRI扫描和多回波梯度回波CSE-MRI检查以测定直肠系膜、肠系膜和臀部皮下3个部位的脂肪组织脂肪酸组分[包括饱和脂肪酸分数(fraction of saturated fatty acid,fSFA)、单不饱和脂肪酸分数(fraction of monounsaturated fatty acid,fMUFA)和多不饱和脂肪酸分数(fraction of polyunsaturated fatty acid,fPUFA)]。同期入组与年龄性别相匹配的对照组非直肠癌患者20例。分析直肠癌组与对照组间以及直肠癌患者中各部位脂肪组织脂肪酸组分变化,评价脂肪酸在肿瘤发生发展过程中的作用;分别分析直肠癌淋巴血管侵犯(lymphovascular invasion,LVI)、周围神经侵犯(peripheral nerve invasion,PNI)阳性组和阴性组各部位脂肪组织脂肪酸组分变化,评价脂肪酸对肿瘤侵袭性的影响。脂肪酸分数参数测量的观察者间一致性通过组内相关系数(intraclass correlation coefficient,ICC)评估。两组间差异分析用独立样本t检验或Mann-Whitney U检验;多组间差异分析用单因素方差分析(One-Way ANOVA)或Kruskal-Wallis H(K)检验。结果:共纳入56例直肠腺癌患者,包括男性36例,女性20例,平均(65.1±10.1)岁;LVI阳性11例(19.6%),PNI阳性10例(17.9%)。对照组20例,其中男性12例,女性8例,平均(66.3±8.8)岁。观察者间各部位各脂肪酸分数的测量相关性良好,ICC均>0.60。直肠癌组中直肠系膜脂肪组织fSFA高于对照组(37.2±4.2 vs 35.0±2.7,P=0.035);直肠癌患者中直肠系膜、肠系膜与臀部皮下脂肪组织中的fMUFA(分别为37.5±2.4、37.3±8.1和40.6±8.7,P=0.003)和fPUFA(分别为24.9±4.1、26.3±4.9和21.5±4.7,P<0.001)的差异均有统计学意义;LVI(+)直肠癌直肠系膜脂肪中fMUFA高于LVI(-)组(38.8±1.5 vs 37.1±2.5,P=0.035);PNI(+)/(-)直肠癌组间各部位脂肪组织各脂肪酸分数差异均无统计学意义(P>0.05)。结论:①直肠癌患者直肠系膜脂肪SFA分数与正常对照组存在差异;②直肠癌患者直肠系膜和肠系膜脂肪的fMUFA和fPUFA与皮下脂肪组织之间存在差异;③直肠癌患者直肠系膜脂肪fMUFA与LVI存在关联。