A new approach to automated first‐order multiplet analysis

The dependence of the values of NMR spin–spin coupling constants on molecular conformation can be a valuable tool in the structure determination process. The continuing increase in the resonance frequency of modern NMR spectrometers allows an increasing number of resonances to be examined using first‐order multiplet analysis. While this can easily be done for the simplest patterns (doublets, triplets, quartets), more complex patterns can be extremely difficult to analyze. The task of deducing the coupling constant values from a multiplet is the reverse process of generating a conventional splitting tree from a single line (chemical shift) by sequential branching using a given set of coupling constants. We present a simple, straightforward method of deducing coupling constant values from first‐order multiplets based on a general inverted splitting tree algorithm but also including a peak intensity normalization procedure that utilizes multiplet symmetry and generates a set of possible first‐order intensity distribution patterns. When combined with an inverted splitting tree algorithm, it is possible to find an intensity pattern that allows the deduction of a proper set of coupling constants. Copyright © 2002 John Wiley & Sons, Ltd.     

Automated structure elucidation of organic molecules from (13)c NMR spectra using genetic algorithms and neural networks.

The automated structure elucidation of organic molecules from experimentally obtained properties is extended by an entirely new approach. A genetic algorithm is implemented that uses molecular constitution structures as individuals. With this approach, the structure of organic molecules can be optimized to meet experimental criteria, if in addition a fast and accurate method for the prediction of the used physical or chemical features is available. This is demonstrated using (13)C NMR spectrum as readily obtainable information. (13)C NMR chemical shift, intensity, and multiplicity information is available from (13)C NMR DEPT spectra. By means of artificial neural networks a fast and accurate method for calculating the (13)C NMR spectrum of the generated structures exists. The approach is limited by the size of the constitutional space that has to be searched and by the accuracy of the shift prediction for the unknown substance. The method is implemented and tested successfully for organic molecules with up to 20 non-hydrogen atoms.     

Molecular representation of coal-derived asphaltene based on high resolution mass spectrometry

The asphaltene separated by solubility in small molecular alkanes and toluene is the most structurally diverse and complex components in heavy oil, such as vacuum residue and coal tar. The coal-derived asphaltene is always regard as a succession of maltene fraction from small molecules to large molecules, and also a continuum of island- and archipelago-type structures, which is difficult to be identified accurately through current characterization methods. This limits the further study of molecular dynamics and reaction dynamics simulation of asphaltenes. In this work, a representation model of molecular composition and structure for coal-derived asphaltene is developed mainly based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) coupled with collision induced dissociation (CID) and traditional methods of nuclear magnetic resonance spectroscopy (¹³C NMR), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS). Island- and archipelago-type structures are considered qualitatively in the representation of asphaltene. The asphaltene molecules are systematic assembled using stochastic algorithms and optimized by simulated annealing algorithm according to the group contribution method. The bulk properties for simulating asphaltenes are in good agreement with the experimental results giving acceptable predictions for the composition and structure of the asphaltenes. Moreover, the representative average structure asphaltene molecules are obtained using the developed molecular similarity function, which could be applied in the further study of molecular aggregation simulation and reaction kinetics simulation.     

Genius: a genetic algorithm for automated structure elucidation from 13C NMR spectra

The automated structure elucidation of organic molecules from experimentally obtained properties is extended by an entirely new approach. A genetic algorithm is implemented that uses molecular constitution structures as individuals. With this approach, the structure of organic molecules can be optimized to meet experimental criteria, if in addition a fast and accurate method for the prediction of the used physical or chemical features is available. This is demonstrated using 13C NMR spectrum as readily obtainable information. By means of artificial neural networks a fast and accurate method for calculating the 13C NMR spectrum of the generated structures exists. The method is implemented and tested successfully for organic molecules with up to 18 non-hydrogen atoms.     

Slow diffusion of macromolecular assemblies by a new pulsed field gradient NMR method

The translational diffusion coefficient of an integral membrane protein/surfactant complex has been measured using a novel pulsed field gradient NMR method. In this new approach, the information about the localization of the molecules is temporarily stored in the form of longitudinal magnetization of isotopes with long spin-lattice relaxation times. This allows one to increase the duration of the diffusion interval by about 1 order of magnitude. Unlike standard proton NMR methods using pulsed field gradients and stimulated echoes, the new method can be applied to macromolecular assemblies with diffusion coefficients well below 10(-10) m(2) s(-1), corresponding to masses in excess of 25 kDa in aqueous solution at room temperature. The method was illustrated by application to a water-soluble complex of tOmpA, the hydrophobic transmembrane domain of bacterial outer membrane protein A, with the detergent octyl-tetraoxyethylene (C(8)E(4); overall mass of complex approximately 45 kDa). The diffusion coefficient was found to be D = (4.99 +/- 0.07) x 10(-11) m(2) s(-1), consistent with measurements by size exclusion chromatography and by ultracentrifugation. The method has also been applied to a solution of recombinant human tRNA(3)(Lys), which has a molecular mass of 24 kDa, and the diffusion coefficient D = (1.05 +/- 0.015) x 10(-10) m(2) s(-1).     

Potentiometric and spectrophotometric study of a new dipodal ligand N,N'-bis{2-[(2-hydroxybenzylidine)amino]ethyl}malonamide with Co(II), Ni(II), Cu(II) and Zn(II)

A new dipodal ligand, N,N'-bis{2-[(2-hydroxybenzylidine)amino]ethyl}malonamide (BHAEM) was synthesized by Schiff base condensation of N,N'-bis(2-aminoethyl)malonamide with two equivalent of salicylaldehyde and characterized on the basis of elemental analyses and various spectral (UV-vis, IR, (1)H NMR and (13)C NMR) data. The complexation reaction of the ligand with H(+), Co(II), Ni(II), Cu(II) and Zn(II) in solution was investigated by spectrophotometric and potentiometric method. Two protonation constants of BHAEM assigned for two hydroxyl groups of aromatic ring were determined and its hydrolysis mechanism was proposed through potentiometric result. In presence of metal ions, BHAEM shows different coordination properties. All metal ions form ML type complex where the ligand coordinates to the metal ion through two N-amine and two O-phenolate groups. In addition, Ni(II) and Cu(II) form additional complex species of the type MLH(-1) and MLH(-2), respectively due to ionization of amide protons. The molecular geometry of BHAEM was examined theoretically using the molecular mechanics MM3 force field followed by semi-empirical PM3 method and various spectral data UV-vis, IR and (1)H NMR were calculated from the energy-minimized structure applying semi-empirical ZINDO, PM3 and TNDO/2 method, respectively and compared with the experimental data. The probable structure of metal complexes in solution were proposed through calculated minimum strain energy by applying molecular mechanics MM(+) force field coupled with molecular dynamics simulation. Further the proposed structure of Cu(BHAEM) was refined through semi-empirical AM1/d method.     

Systematic fragmentation of large molecules by annihilation

A new version of systematic molecular fragmentation is presented which provides a hierarchy of estimates for the energy, and other properties, of large molecules with a computation time that scales linearly with the size of the molecule. This method is combined with an algorithm which ensures that the evaluation of the fragment compositions is efficient for very large molecules. The method is illustrated using protein structures derived from NMR spectroscopy.     

Molecular Dynamics and Chain Length of Edible Oil Using Low-Field Nuclear Magnetic Resonance

Nuclear magnetic resonance (NMR) techniques are widely used to identify pure substances and probe protein dynamics. Edible oil is a complex mixture composed of hydrocarbons, which have a wide range of molecular size distribution. In this research, low-field NMR (LF-NMR) relaxation characteristic data from various sample oils were analyzed. We also suggest a new method for predicting the size of edible oil molecules using LF-NMR relaxation time. According to the relative molecular mass, the carbon chain length and the transverse relaxation time of different sample oils, combined with oil viscosity and other factors, the relationship between carbon chain length and transverse relaxation time rate was analyzed. Various oils and fats in the mixed fluid were displayed, reflecting the composition information of different oils. We further studied the correlation between the rotation correlation time and the molecular information of oil molecules. The molecular composition of the resulting fluid determines its properties, such as viscosity and phase behavior. The results show that low-field NMR can obtain information on the composition, macromolecular aggregation and molecular dynamics of complex fluids. The measurements of grease in the free-fluid state show that the relaxation time can reflect the intrinsic properties of the fluid. It is shown that the composition characteristics and states of complex fluids can be measured using low-field nuclear magnetic resonance.     

Determining valine side-chain rotamer conformations in proteins from methyl 13C chemical shifts: application to the 360 kDa half-proteasome

A method is presented for determining Val side-chain χ(1) rotamer distributions in proteins based exclusively on measured (13)C(γ1) and (13)C(γ2) chemical shifts. The approach selects an ensemble of 20 χ(1) values, calculates average methyl (13)C(γ1,γ2) chemical shifts via theoretical quantum chemical calculations and maximizes the agreement with the experimentally measured shifts using a genetic algorithm. The methodology is validated with an application involving six proteins for which (13)C(γ) chemical shifts and three-bond methyl-backbone scalar couplings are available. The utility of the methodology is demonstrated with an application to the 360 kDa 'half-proteasome' where the χ(1) rotameric distributions of Val residues are calculated on the basis of chemical shifts. For the most part the χ(1) profiles so obtained compare very well with those generated from the high-resolution (2.3 ?) X-ray structure of the proteasome. Both NMR and X-ray distributions are cross-validated by comparing calculated (1)H-(13)C methyl residual dipolar couplings with measured values, and the level of agreement is at least as good for the NMR derived χ(1) values. Notably, as the resolution of the X-ray data improves (rotamer distributions from 3.4 and 2.3 ? X-ray structures are compared with the NMR data), the agreement with the NMR gets significantly better. This emphasizes the importance of NMR approaches for the study of high molecular weight complexes that can be recalcitrant to high resolution X-ray analysis.     

Study on inclusion behaviour of forsythiaside A with β-cyclodextrin

Inclusion behaviour of forsythiaside A with β-cyclodextrin (β-CD) was investigated by fluorescence spectrum, nuclear magnetic resonance (NMR) and molecular modelling. A ratio of 1:1 stoichiometry has been proposed for the inclusion complex of forsythiaside A with β-CD in aqueous media according to the continuous variation Job’s method based on the fluorescence spectroscopy data. The stability constant (K) of the inclusion complex was 669 M^?1. The pH, ionic strength and temperature of solution showed great effect on the formation of inclusion complex. The spatial configuration of complex demonstrated that the B ring of forsythiaside A might be embedded inside the lipophilic cavity of β-CD and the A ring of the forsythiaside A might be exposed outside the cavity of β-CD according to NMR spectra and molecular modelling.     

Sugar‐based Molecular Computing by Material Implication

A method to integrate an (in principle) unlimited number of molecular logic gates to construct complex circuits is presented. Logic circuits, such as half‐ or full‐adders, can be reinterpreted by using the functional completeness of the implication function (IMP) and the trivial FALSE operation. The molecular gate IMP is represented by a fluorescent boronic acid sugar probe. An external wiring algorithm translates the fluorescent output from one gate into a chemical input for the next gate on microtiter plates. This process is demonstrated on a four‐bit full adder.     

Palladium(II) complex with S-allyl-L-cysteine: new solid-state NMR spectroscopic measurements, molecular modeling and antibacterial assays

Nuclear magnetic resonance studies, molecular modeling and antibacterial assays of the palladium(II) complex with S-allyl-L-cysteine (deoxyalliin) are presented. Studies based on solid and solution 13C and 15N nuclear magnetic resonance (NMR) spectroscopy confirmed that the palladium(II) complex preserved the same structural arrangement in both states, with no modifications on coordination sphere when dissolved in water. Density functional theory (DFT) studies stated that the trans isomer is the most stable one. Antibacterial activities of S-allyl-L-cysteine and its palladium(II) complex were evaluated by antibiogram assays using the disc diffusion method. The palladium(II) complex showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive), Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial cells.     

Inclusion complex of N-nitroso,N-(2-chloroethyl), N′, N′-dibenzylsulfamid with β-Cyclodextrin: Fluorescence and molecular modeling

The inclusion complex of N-nitroso, N-(2-chloroethyl), N′, N′-dibenzylsulfamid with β-Cyclodextrin have been investigated using the spectrofluorescence technique ¹H NMR spectroscopy. The stoichiometric ratio of the complex was found to be 1:1 and the stability constant was evaluated using the Benesi-Hildebrand equation. In order to find the most favorable structure, molecular mechanics calculations were employed to study the inclusion of CENS-Dibenz in β-CD in vacuum and in the presence of water as a solvent. The driving forces for complexation are dominated by non-bonded van der Waals host-guest interactions with very little electrostatic contribution in both environments. After this stage of calculation, both the most stable complexes obtained by MM+ were re-optimized using semi-empirical and quantum mechanical calculations. It was found that the PM3 and the hybrid method ONIOM2 calculations predict the same mode of inclusion of the drug molecule in the host cavity. In the most stable conformation (i.e. Complex A), one of the two aromatic cycles is dipped within the relatively less polar cavity of β-cyclodextrin, while the other aromatic cycle as well as the active groupings (alkylating agent and nitroso group) are directed towards the exterior through the narrow rim of β-CD. This orientation is preferred because it is the most energetically favorable structure. Moreover, statistical thermodynamic calculations demonstrate that the formation of the inclusion complex is an enthalpy-driven process. A comparison between the experimental and theoretical values of ΔG⁰ proves that simulation of the complexes without an explicit treatment of the solvent leads to dubious results.     

免疫-遗传算法用于混合物重叠核磁共振信号解析

通过对免疫系统中抗体对外来抗原的识别、消除等过程的模拟,建立了一种新型的免疫算法模型.将标样信号作为抗体,混合物重叠信号作为抗原输入免疫算法模型,通过迭代运算,从抗原中消除抗体所表示的信息,当抗原被抗体完全消除时,即实现了混合物重叠信号的解析.对多组分混合氨基酸NMR谱图的解析结果证明,该算法可方便地用于多组分重叠信号的解析,为利用数据库解析混合物或生物大分子等物质的复杂NMR谱图开辟了一条全新的途径.     

Interpretation of substituent effects on 13C and 15N NMR chemical shifts in 6-substituted purines

A range of purine derivatives modified at position 6 of the basic purine skeleton exhibit a variety of biological activities. Several derivatives are used or tested nowadays for pharmacological treatments. The present work aims to analyze the effects of substituents on the electron distribution in the purine core as reflected by NMR chemical shifts. We collected a comprehensive set of experimental NMR data for a variety of 6-substituted purines (-NH(2), -NHMe, -NMe(2), -OMe, -Me, -CCH, and -CN) and determined the molecular and crystal structures of three derivatives (-NHMe, -CCH, and -CN) by X-ray diffraction. The density-functional methods calibrated in our recent study (Phys. Chem. Chem. Phys., 2010, 12, 5126) have been employed to enable understanding of the substituent-induced changes in the NMR chemical shifts of the atoms in the purine skeleton. Analyses of the nuclear shielding using localized molecular orbitals (LMOs), specifically the natural LMOs (NLMOs) and Pipek-Mezey LMOs, were used to break down the values of the isotropic (13)C and (15)N NMR chemical shifts and the chemical shift tensors into the contributions of the individual LMOs. The experimental and calculated trends in the chemical shift of the N-3 atom correlate nicely with the Hammett constants (σ(para)) and the calculated natural charges on N-3, whereas the contributions of the LMOs to the N-1 and C-6 chemical shifts are found to be more complex.     

六氟磷酸二(4,4'-二甲基-2,2'-联吡啶)·(2,2'-联吡啶-4,4'-二羧酸)合钌(Ⅱ)的二维核磁共振

用1H NMR和13C NMR谱研究了新型电化学发光探针六氟磷酸二(4,4'-二甲基-2,2'-联吡啶)·(4,4'-二羧酸-2,2'-联吡啶)合钌(Ⅱ)的立体结构,通过1H-1H COSY、13C-1H HETCOR谱对其氢谱和碳谱中的各谱峰进行了归属,并给出了氢谱和碳谱峰的化学位移值.     

A New Palladium Complex Containing the Mixture of Carbene and Phosphine Ligands: Synthesis,Crystal Structure and Spectral FT-IR,NMR and UV-Vis Researches

In this paper, a new Pd-based complex that contains N-heterocyclic carbene(NHC) and triphenylphosphine(PPh3) ligands was synthesized. The cis-(NHC)Pd Br_2(PPh3) complex has been prepared by the substitution of 3-chloropyridine ligand in(NHC)PdBr_2(3-chloropyridine) complex with triphenylphosphine. This complex has been characterized by using ~1H NMR, 31 P {~1H} NMR, ~(13)C {~1H} NMR, FTIR, UV-Vis spectroscopy and elemental analysis techniques. The molecular and crystal structures of the cis-(NHC)PdBr_2(PPh3) complex were determined by singlecrystal X-ray diffraction method.     

NMR characterization of the host-guest inclusion complex between beta-cyclodextrin and doxepin

The interaction between doxepin, a member of the tricyclic antidepressant (TCA) class of drugs, with beta-cyclodextrin (beta-CD) was investigated using NMR. Several TCAs have been reported to form a complex with beta-CD having 1:1 stoichiometry. Previous results from UV-visible spectroscopy, fluorescence measurements, and molecular modeling indicated that for imipramine, desipramine, and amitriptyline, the TCA aliphatic tail is included in the cyclodextrin cavity with apparently no interaction of the tricyclic ring. An alternative view of the doxepin-beta-CD complex is presented in this work using analysis of complexation-induced chemical shifts (CICSs), the method of continuous variation (Job's analysis), and analysis of ROESY spectra. The Job's plot derived from the NMR spectral data confirms that the complex formed has 1:1 stoichiometry. The largest changes in the CICS data were observed for the aromatic protons of one of the doxepin rings, with much smaller chemical shift changes observed for the protons of the other aromatic ring and the doxepin tail. Perhaps the most significant evidence for inclusion of the doxepin tricyclic ring is the strong ROESY cross peaks between the doxepin aromatic resonances and the protons located inside the beta-CD cavity. Changes in the doxepin (1)H NMR spectrum and the behavior of ROESY exchange cross peaks suggest that inclusion complex formation decreases the rate of internal motions of doxepin.     

衰减链转移(DT)聚合醋酸乙烯酯的动力学

在醋酸乙烯酯的普通自由基聚合体系中加入少量碘（质量分数为0.57%～0.86%）,用偶氮二异丁腈作引发剂合成聚醋酸乙烯酯,对其聚合反应的动力学及反应机理进行了研究。 考察了碘质量分数对聚合反应速率、聚合物分子量及分子量分布的影响,发现随着碘浓度的增加,聚合物分子量及分子量分布得到更好的控制;对聚合过程进行了核磁跟踪,考察了聚合过程中几种化合物的变化情况,特别是初级自由基与碘生成的加合物A-I（A来自引发剂分裂后产生的自由基）及单体加合物A-Mn-I（M代表单体单元）的变化情况;对聚合物结构作了详细的1H NMR分析,结果表明,聚合过程中分子量随时间延长而逐渐增大,分子量分布随单体转化率增加而变窄,聚合终期,单体转化率达到80%左右时,所得聚合物分子量分布窄（Mw/Mn≤1.41）,且含有碘端基。该方法的自由基聚合具有活性/可控的性质。