Solution 1H NMR confirmation of folding in short o-phenylene ethynylene oligomers

Oligomers based on an o-phenylene ethynylene (oPE) backbone with polar substituents have been synthesized using Sonogashira methods. Folding of these extremely short oligomers was confirmed via 1D and 2D (NOESY) NMR methods. Utilizing electron-rich and electron-poor phenylene building blocks, variations of these oPE oligomers have been synthesized to determine the folded stability of pi-rich vs pi-poor vs pi-rich-pi-poor systems. Slight variations in temperature offer a route, aside from solvent denaturation, to probe the stability of the folded structure. This is the first report of an NMR solution characterization of folding for a PE backbone without hydrogen bonds.     

Solution structure of quinoline- and pyridine-derived oligoamide foldamers

The unambiguous elucidation of a new folded structure in solution may prove to be a very challenging task. The NMR protocols developed for solving the solution structures of alpha-peptides have been applied to aliphatic beta- and gamma-peptides but are not directly applicable to aromatic oligomers. In particular, the string of spin systems in an aromatic sequence cannot be reconstituted solely from correlations between protons. For aromatic oligomers, it is shown that the assignment of a large part of the 13C NMR spectrum through HMBC and HSQC experiments allows to unambiguously assign proton NMR spectra and in turn to interpret NOE correlations. This has been implemented both with quinoline- and pyridine-derived oligoamide foldamers, and should be applicable to a wide range of oligomers including various combinations of monomers. The NOE correlations allow the unambiguous solution structure elucidation of helical conformations of oligoamides derived from pyridine and quinoline monomers showing that, in these series, the solution structures correspond very well to the structures observed in the solid state.     

APPLICATION OF HMBC AND HMQC-TOCSY NMR METHODS TO ASSIGN THE STRUCTURES OF BICYCLIC-PEPTIDE MIMETICS

Abstract

The structures of representative bicyclic peptides are confirmed through the NMR methods of HMBC and HMQC-TOCSY. Complete assignment of proton and carbon resonances is afforded by these two-dimensional NMR methods. HMQC-TOCSY is especially useful for assigning spectra in molecules having extensive proton spin systems and in establishing connectivities between protonated carbons. Long-range proton-carbon connectivities obtained by HMBC confirm structure in molecules containing heteroatoms or non-protonated carbons that interrupt proton spin systems.     

Recent advances in arylene ethynylene folding systems: Toward functioning

Well-defined 3-dimensional architectures constitute the indispensable structural basis of the versatile, mind-boggling functions of biological macromolecules, such as proteins and nucleic acids. In the past few decades, diversified synthetic systems have been designed to mimic these biological entities in their capability of adopting such specific, higher order structures. The relevant research field presents one of the most rapidly developing areas related to supramolecular chemistry. The current contribution will focus on the most recent progress related to foldamers consisting of arylene ethynylene building blocks. Some of the work features developing novel functions based on previously established arylene ethynylene folding systems, and others have designed and synthesized new arylene ethynylene foldable structures that aim to realize previously uncharted properties.     

Phenylene Ethynylene‐Tethered Perylene Bisimide Folda‐Dimer and Folda‐Trimer: Investigations on Folding Features in Ground and Excited States

In this work, we have elucidated in detail the folding properties of two perylene bisimide (PBI) foldamers composed of two and three PBI units, respectively, attached to a phenylene ethynylene backbone. The folding behaviors of these new PBI folda‐dimer and trimer have been studied by solvent‐dependent UV/Vis absorption and 1D and 2D NMR spectroscopy, revealing facile folding of both systems in tetrahydrofuran (THF). In CHCl₃ the dimer exists in extended (unfolded) conformation, whereas partially folded conformations are observed in the trimer. Temperature‐dependent ¹H NMR spectroscopic studies in [D₈]THF revealed intramolecular dynamic processes for both PBI foldamers due to, on the one hand, hindered rotation around C?N imide bonds and, on the other hand, backbone flapping; the latter process being energetically more demanding as it was observed only at elevated temperature. The structural features of folded conformations of the dimer and trimer have been elucidated by different 2D‐NMR spectroscopy (e.g., ROESY and DOSY) in [D₈]THF. The energetics of folding processes for the PBI dimer and trimer have been assessed by calculations applying various methods, particularly the semiempirical PM6‐DH2 and the more sophisticated B97D approach, in which relevant dispersion corrections are included. These calculations corroborate the results of NMR spectroscopic studies. Folding features in the excited states of these PBI foldamers have been characterized by using time‐resolved fluorescence and transient absorption spectroscopy in THF and CHCl₃, exhibiting similar solvent‐dependent behavior as observed for the ground state. Interestingly, photoinduced electron transfer (PET) process from electron‐donating backbone to electron‐deficient PBI core for extended, but not for folded, conformations was observed, which can be explained by a fast relaxation of excited PBI stacks in the folded conformation into fluorescent excimer states.     

Solution structure determination of oligoureas using methylene spin state selective NMR at 13C natural abundance

Ability of N,N'-linked oligoureas containing proteinogenic side chains to adopt a stable helix conformation in solution has been described recently. NMR as well as circular dichroism (CD) spectroscopies were employed to gain insight into their specific fold. It is herein proposed to extend the structural information available on these peptidomimetics by an advantageous use of a methylene spin state selective NMR experiment. Homodecoupling provided by the pulse scheme made it possible to readily measure conformation-dependent (3)J(HH) constants that are difficult if not impossible to obtain with standard NMR experiments. Adding those couplings to the NMR restraints improved the quality of the structure calculations significantly, as judged by a ca 30% decrease of the root mean square deviation (RMSD) obtained over an ensemble of 20 structures. Moreover, accurate determination of individual (1)J(CH) couplings within each methylene group revealed uniform values throughout the oligourea sequence, with (1)J(CH) systematically slightly larger for the pro-S hydrogen than for the pro-R. As shown in this study, the methylene spin state selective NMR experiment displays a good intrinsic sensitivity and could therefore provide valuable structural information at (13)C natural abundance for peptidomimetic molecules and foldamers bearing diastereotopic methylene protons.     

寡肽Asterin B和C溶液构象的NMR研究1: ^1H NMR归属及构象特征

Asterin B和C是从紫菀中分得的两个寡肽, 本文利用2D-NMR技术归属了它们的^1H NMR谱线, 并讨论了它们的构象特征。为进一步采用NMR和分子动力学(MD)方法研究它们的溶液构象奠定了基础。     

2D NMR analysis for unambiguous structural elucidation of phenolic compounds formed through reaction between (+)‐catechin and glyoxylic acid

Various phenolic compounds were synthesized in an aqueous–alcoholic solution containing (+)‐catechin and glyoxylic acid which was used as a model of fruit‐derived food browning that usually occurs during aging. After purification by semi‐preparative HPLC, the isolated compounds were subjected to homo‐ and heteronuclear proton and carbon NMR analysis including COSY, TOCSY, ROESY, HSQC and HMBC techniques. These experiments allowed the structural elucidation and complete ¹H and ¹³C NMR assignment of the isolated compounds. The strategies followed for the assignment of all proton and carbon resonances in addition to the linkage site determination are discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

A Single-Scan Ultraselective Heteronuclear Polarization Transfer Method for Unambiguous Complex Structure Assignment

Complex nuclear magnetic resonance (NMR) signals of organic compounds containing multiple analogous substructures or mixtures pose a significant challenge to structural identification, thus resulting in frequent misassignment of structures. The GEMSTONE method, a single-scan technique that selectively excites a specific proton signal among the crowded NMR signals, was recently proposed as a solution. However, its extension to the polarization transfer method for heteronuclear spin systems was unsuccessful. Herein, we present an extension method that addresses the altered heteronuclear polarization transfer efficiency and enables the acquisition of ultraselective ¹³C and ¹H-¹³C correlation NMR subspectra with hertz-level signal selectivity in both dimensions. We demonstrate the effectiveness of this technique in the structural analysis of a chromopeptide pharmaceutical and a diastereomeric mixture of a fungicide.     

氧氟沙星的核磁共振波谱性质研究

结合1H, 13C NMR, DEPT, COSY, HSQC, HMBC谱和碳氟偶合裂分行为, 对酸性及碱性溶液中氧氟沙星(Ofloxacin, OFL)的1H和13C谱分别进行归属, 研究了哌嗪环亚甲基构成的AA'BB'复杂自旋体系中各H的化学位移. 发现噁嗪环上的甲基处于直立键; 5H在酸性溶液中化学位移移向低场, 这可能与形成C—H…O弱氢键有关; 在碱性溶液中, OFL的羧基变为羧酸根, 造成羧基和羰基周围碳原子上π电子重新分布, 导致相应C的化学位移和碳氟偶合常数发生明显变化.     

Synthesis and NMR assignment of pentacycloundecane precursors of potential pharmaceutical agents

The synthesis and complete NMR elucidation of eight novel pentacycloundecane (PCU) derivatives are reported. These compounds are precursors in the synthesis of PCU‐based anti‐tuberculosis (TB) agents and potential human immunodeficiency virus (HIV) protease inhibitors. Two‐dimensional (2D) NMR techniques were used to assign the NMR spectra for these compounds. Substitution of the cage molecule at (C‐8/11) further complicates the assignment, since some of the substituted alkyl chain groups overlap with the cage proton signals. The side chain heteroatoms also introduce a rare through‐space deshielding effect to some of the carbon atoms of the cage skeleton. Ring strain in the rigid cage skeleton appears to induce drastic electronic changes in some parts of the cage framework. This observation is more dramatic for the C‐4 methylene group of the cage diols and the cage ethers. Copyright © 2010 John Wiley & Sons, Ltd.     

选择性远程DEPT技术用于吡咯里西啶类生物碱的结构测定和核磁共振研究

本文从峨眉千里光中分得二个吡咯里西啶类生物碱.经测定,一个为阔叶千里光碱,另一个为新阔叶千里光碱.采用选择性远程^13CDEPT技术对这二个化合物的结构及其^1H和^13CNMR谱峰归属作了研究.     

Characterization of dimeric chiral lithium amide structures derived from N-isopropyl-O- triisopropylsilyl valinol

The dimeric structure is characterized for a chiral amide base complex consisting of an (S)-N-isopropyl-O-triisopropylsilyl valinol ligand and lithium. The complex is characterized by a variety of NMR techniques, including multinuclear one- and two-dimensional NMR experiments and diffusion-ordered NMR spectroscopy (DOSY) as well as diffusion coefficient-formula weight (D-fw) correlation analyses. Spartan calculations are presented which support the structural assignment. This structural characterization leads to an explanation of the behavior and the reactivity of these complexes in solution.     

Solid state separated-local-field NMR spectroscopy on half-integer quadrupolar nuclei: principles and applications to borane analysis

New multidimensional NMR methods correlating the quadrupolar and heteronuclear dipolar interactions affecting a half-integer quadrupolar spin in the solid state are introduced and exemplified. The methods extend separated-local-field magic-angle spinning (SLF MAS) NMR techniques that have been used successfully in spin-(1)/(2) spectroscopy to the study of S >/= (3)/(2) nuclei. In our implementation, these techniques avoid homonuclear proton decoupling requirements by relying on moderately fast MAS rates (6-15 kHz) and use rotor-synchronized constant-time pulse sequences to achieve nearly arbitrary amplifications of the apparent dipolar coupling strengths. The result is a suite of simple 2D NMR experiments, whose line shapes carry valuable information about the structure and dynamics of solids containing quadrupolar and proton nuclei. The potential of these sequences was exploited to gather new insight into the structure and dynamics of a variety of boron-containing samples. These experimental SLF schemes were also extended to 3D NMR experiments that incorporate multiple-quantum MAS, thus enabling the resolution needed to study multiple chemical sites in a solid and providing a useful tool for the assignment of inequivalent sites.     

选择性远程DEPT NMR技术用于萜类生物碱的结构测定

从中草药勒党根茎中分离出二个化合物, 其一为已知的萜类生物碱culamtraramine, 其二为它的差向立体异构体, 为新化合物, 定名为isoculantraramine。用选择性远程核磁共振技术测定了它们的结构。     

细胞色素b5突变体V45H NMR初步研究

通过分析在H2O和D2O中采集,DQF-COSY,TOCSY和NOESY等二维核磁共振波谱鉴定了细胞色素b5定点突变体V45H(残基Val^45突变为His^45)的大多数氨基酸残基的质子自旋系统,通过解析NOESY谱中的dNN(i,i+1),dαN(i,i+1),dαN(i,i+2),dαN(i,i+3),dαβ(i,i+3)和dβN(i,i+1)等NOE相关,完成了其序列特异性归属以及主链和侧链质子共振信号的全归属。突变体V45H的二级结构分析表明残基Val^45突变为His^45对分子的整体折叠影响不大。但是,与野生型细胞色素b5相比较,突变体V45H主链酰胺质子的化学位移指数提示突变使其血红素疏水腔的微环境受到扰动。以上实验结果为进一步测定V45H的溶液结构和分析残基Val^45在蛋白质中的作用提供了基础。     

Trifluoromethylated (tetrahydropyrrolo) quinazolinones by a new three‐component reaction and facile assignment of the regio‐ and stereoisomers formed by NMR spectroscopy

A new three‐component cyclisation reactions of methyl 3,3,3‐trifluoropyruvate, 2‐aminobenzylamine and oxo compounds afforded tetrahydropyrroloquinazolinones of the types 4 and 5 as mixtures of regio‐ and stereoisomers. Whereas standard 1D NMR spectroscopy was used for a facile assignment of the cyclization regioisomers, a combination of homo (proton–proton) and heteronuclear (proton–fluorine) NOE experiments allowed the determination of the relative configuration on stereogenic centres. The structure of some compounds was also confirmed by the X‐ray diffraction. Adaptation of the 1D double‐pulsed field‐gradient spin‐echo NOE for a heteronuclear case is presented. Copyright © 2010 John Wiley & Sons, Ltd.     

Carbon-13 NMR spectroscopy of the biological pigments luteoskyrin and rugulosin and some polyhydroxyanthraquinone analogues

The bianthraquinonic biological pigments luteoskyrin and rugulosin and five polyhydroxyanthraquinone derivatives are studied by carbon-13 NMR in DMSO solution. Peak assignment for the fourteen carbon atoms of these compounds is achieved by proton spin decoupling and by investigating the effect of ionisation of the hydroxyl groups upon the carbon chemical shifts. Carbon chemical shifts in the planar hydroxyanthraquinones can be rationalised in terms of conjugation and intramolecular hydrogen bonding. The latter is responsible for the relative acidity of the hydroxyl groups in the analogues, and for the different conformations proposed for luteoskyrin and rugulosin. Tautomeric equilibria occur in DMSO and water–DMSO solutions for the anionic species [LS]^2? and [RG]^2?. This can account for the binding of luteoskyrin and rugulosin to nucleic acids.     

NMR assignments of a di-pentacyclo-undecane cyclic ether

The X-ray structure of a di-pentacyclo-undecane cyclic ether was recently reported. As part of a programme to use NMR spectroscopy for the structure elucidation of cage compounds, the complete NMR assignments of the cyclic ether was attempted. Major overlap of proton and carbon signals of the two cages is observed. It was required to elucidate the fragment analogues that represent similar structural features of the cyclic ether in order to get an approximate but reasonable insight into the complex overlapping signals. Normal 2D NMR techniques were utilized to assign the various NMR signals.     

A new method for determining positions of phenolic hydroxyl groups through silylation and application of H(Si)C triple-resonance NMR experiments

Two-dimensional triple-resonance H(Si)C NMR experiments have been applied at natural abundance to assign ¹³C NMR signals in silylated phenols. The method showing its great potential in determining positions of hydroxyl groups is widely applicable to signal assignment and structure elucidation of synthetic and natural phenolic compounds.