NMR and IR investigations of biologically active peptides in solution

Summary Nuclear-magnetic-resonance and infra-red spectroscopic features in solution have been investigated for the delineation of conformation and dynamics of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine. The main conformation is unfolded and characterized by a certain degree of weak intermolecular hydrogen bounding. The steric hindrance of neighbouring side chains limits the motional averaging of the several possible conformers by excluding some of the rotamers. Dipolar and scalar connectivities, as detected by 2D NMR spectroscopy, point to a cis configuration of the H−N−C−H_α moiety in the case of leucine and trans in the cases of methionine and phenylalanine.

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Riassunto Per il chiarimento della conformazione e della dinamica molecolare del peptide chemotattico formil-L-metionil-L-leucil-L-fenilalanina sono stati studiati i parametri spettroscopici di risonanza magnetica nucleare ed infrarosso in soluzione. La conformazione principale è distesa e caratterizzata da un certo grado di deboli legami a idrogeno intermolecolari. L’impedimento sterico di catene laterali vicine limita la possibilità che i vari conformeri possibili siano mediati dai moti molecolari, escludendo alcuni rotameri. Le connettività dipolari e scalari, messe in evidenza dalla spettroscopia 2D NMR, suggeriscono una configurazione cis del residuo H−N−C−H_α nel caso della leucina e trans nei casi della metionina e della fenila lanina.

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Реэюме Исследуются ядерный магнитный резонанс и инфра-красные спектроскопические характеристики в растворе с целью описания конформации и динамики хемотактичного пептида формия-Л-метионил-Л-лейцил-Л-фенилаланина. Основная конформация явлется раэвернутой и характериэуется определенной степенью слабой межмолекулярной водородной связй. Стерическое припятствие для соседних боковых цепей ограничивает динамическое усреднение для некоторых конформаций, исключая некоторые ротамеры. Дипольнье и скалярные связности, зарегистрированные с помощью 2D ЯМР-спектроскопии, указывают на цис-конфигурацию H−N−C−H_α в случае лейцина и на транс-конфигурацию в случаях метионина и фенилаланина.

     

Combinatorial chemistry and high-throughput screening in drug discovery: Different strategies and formats

Different strategies for the discovery of novel leadsinteracting with therapeutically relevant targets are thoroughlypresented and discussed, using also three recent examples.Emphasis is given to approaches which do not require extensiveresources and budgets, but rather prove how cleverness andcreativity can provide active compounds in drug discovery.     

Probing spatial correlations in the inhomogeneous glassy state of the cuprates by Cu NMR

We discuss the crossover of the form of the Cu Nuclear magnetic resonance (NMR) spin echo decay at the onset of Cu wipeout in lanthanum cuprates. Experimentally, the echo decay undergoes a crossover from Gaussian to exponential form below the temperature where the Cu NMR intensity drops. The wipeout and the change in behavior both arise because the nuclei experience spatially inhomogeneous spin fluctuations at low temperatures. We argue that regions where the spin fluctuations remain fast are localized on length scales of order 1-2 lattice spacings. The inhomogeneity is characterized by the local activation energy E_a(r); we estimate the functional form of E_a(r) for points where E_a>(r)∼0.     

75As, 63Cu NMR and NQR characterization of selected arsenic minerals

The direct measurement and identification of solid state arsenic phases using ⁷⁵As NMR is made difficult by the simultaneous conditions of large quadrupole moment and low coordination symmetry in many compounds. However, specific arsenic minerals can efficiently be detected and discriminated via nuclear quadrupolar resonance (NQR). We report on the first NMR and NQR measurements in the natural minerals enargite (Cu₃AsS₄), niccolite (NiAs), arsenopyrite (FeAsS) and loellingite (FeAs₂). The NQR frequencies have been determined from both high-field NMR powder patterns and via zero-field frequency sweeps. Density functional theory (DFT) based ab initio calculations support the experimental results. The compounds studied here are common in terms of the known set of As-containing minerals. They are sometimes encountered in the context of base metal or gold mining. The study represents a significant addition to the list of arsenic minerals that can now be detected with NQR techniques.     

Defects and impurities in nanodiamonds: EPR, NMR and TEM study

EPR, ¹³C NMR and TEM study of ultradisperse diamond (UDD) samples is reported. The compounds show a high concentration of paramagnetic centers (up to 10²⁰ spin/g), which are due to structural defects (dangling C-C bonds) on the diamond cluster surface. The anomalous reduction in the spin-lattice relaxation time of ¹³C (from several hours in natural diamond to ∼150 ms in UDD clusters) is attributed to the interaction between the unpaired electrons of the paramagnetic centers and nuclear spins. ¹³C NMR line-width reflects the fact that the structure of the UDD surface is distorted in comparison to the ‘bulk’ diamond structure.     

Overview-the role of NMR spectroscopy in epilepsy

Nuclear magnetic resonance (NMR) spectroscopy permits noninvasive, serial measurements of several metabolites with important neurobiologic roles in localized brain regions in vivo. Over the last decade, this technique has been applied to investigations of both animals and humans with epilepsy. Several nuclei that include specific proton, phosphorus, and carbon isotopes provide NMR signals that measure specific compounds in vivo. This paper reviews the studies that have used these multinuclear NMR techniques to investigate the role of these methods in the diagnosis and pathogenesis of epilepsy.     

Adsorption effects and NMR properties: Continuous chain approach

The NMR properties of nuclei linked to long linear polymer molecules are sensitive to the influence of hard walls. In this context, the residual energy of tensorial spin-spin interactions is calculated using a path integral approach. Several thermodynamic quantities of the polymer system (free energy, equation of state,...) are also expressed, taking chain stiffness effects and the presence of two repulsive walls into consideration.     

NMR frequency and magnetic dipole moment of (3)He nucleus

We present new gas-phase NMR spectra which relate the resonance frequency of (3)He nucleus to the resonance frequency of the proton in tetramethylsilane (TMS). We discuss the dependence of (3)He resonance frequency on the density of the solvent gas, and we consider in detail the absolute shielding scales of both nuclei. Finally, we analyse the accuracy of the results, using the relationship between the resonance frequencies, absolute shielding constants and magnetic dipole moments of (1)H and (3)He nuclei.     

Cd MAS and static NMR study of halogenocadmate crystals

¹¹³Cd magic-angle spinning (MAS) and static NMR spectra are measured using 23 kinds of halogenocadmate crystals with known structures to determine the isotropic chemical shifts (δ_iso), chemical shift anisotropies (Δδ), and asymmetry parameters η and then to discuss the relationship among these NMR parameters and the halide-anion co-ordination environments around Cd²⁺. The δ_iso(MAS) values of halide-anion co-ordination polyhedra of Cd²⁺ largely change with the kind of halide-anion and the halide-anion co-ordination number. The |Δδ| and η in halogenocadmate crystals is largely dependent on the structure type of crystal, but is independent of the halide-anion co-ordination number of Cd²⁺.     

Anisotropy of hyperfine interactions as a tool for interpretation of NMR spectra in magnetic materials

Approach for interpretation of nuclear magnetic resonance (NMR) spectra in magnetic materials is presented, consisting in employing the anisotropy of hyperfine interaction. The anisotropic parts of hyperfine magnetic fields on ⁵⁷Fe nuclei are calculated ab initio for a model example of lithium ferrite and utilized to assign the experimental NMR spectral lines to iron sites in the crystal structure.     

Novel superconducting phases in copper oxides and iron-oxypnictides: NMR studies

We reexamine the novel phase diagrams of antiferromagnetism (AFM) and high-T_c superconductivity (HTSC) for a disorder-free CuO₂ plane based on an evaluation of local hole density (p) by site-selective Cu-NMR studies on multilayered copper oxides. Multilayered systems provide us with the opportunity to research the characteristics of the disorder-free CuO₂ plane. The site-selective NMR is the best and the only tool used to extract layer-dependent characteristics. Consequently, we have concluded that the uniform mixing of AFM and SC is a general property inherent to a single CuO₂ plane in an underdoped regime of HTSC. The T=0 phase diagram of AFM constructed here is in quantitative agreement with the theories in a strong correlation regime which is unchanged even with mobile holes. This Mott physics plays a vital role for mediating the Cooper pairs to make T_c of HTSC very high. By contrast, we address from extensive NMR studies on electron-doped iron-oxypnictides La1111 compounds that the increase in T_c is not due to the development of AFM spin fluctuations, but because the structural parameters, such as the bond angle α of the FeAs₄ tetrahedron and the a-axis length, approach each optimum value. Based on these results, we propose that a stronger correlation in HTSC than in FeAs-based superconductors may make T_c higher significantly.     

B NMR relaxation in superconductors: YRuB2 and LuRuB2

To investigate the electronic states in YRuB₂ and LuRuB₂, we have carried out ¹¹B NMR measurements. In the normal state, the spin-lattice relaxation rates 1/T₁'s in these compounds are proportional to the temperature T. 1/T₁'s show a small coherence peak just below the superconducting transition temperature T_c and decrease exponentially well below T_c. YRuB₂ and LuRuB₂ are found to be BCS superconductors with the energy gap 2Δ(0)=3.52 k_BT_c.     

N NMR in AlN and BN

A characterisation by ¹⁴N NMR of the binary nitrides AlN and BN is presented. Both the static and magic angle spinning (MAS) lineshapes have been investigated in order to determine, or set upper limits on, the nuclear quadrupole coupling (C_q) at the nitrogen site. Additional data are given for the C_q values at the Al and B sites. A comparison is made with other similar (mainly wurtzite) binary compounds for which C_q is known at each atomic site.     

A multiple-field (23)Na NMR study of sodium species in porous carbons

The sodium environments in porous carbon materials prepared from NaOH activation of a char were investigated by means of multiple-field solid-state ²³Na NMR measurements, carried out at magnetic fields of 4.7, 8.45 and 14.1 T, with single-pulse excitation and magic angle spinning (MAS). The recorded spectra showed a relatively featureless resonance with linewidth and peak shift strongly dependent on the magnetic field strength and on the hydration level of the samples. The existence of second-order quadrupolar effects was inferred, although the structural disorder and the mobile character associated with the Na environment precluded the direct observation of typical quadrupolar features in the MAS NMR spectra. The analysis of the spectra collected at multiple magnetic fields yielded the values of −2.8 ppm for the isotropic chemical shift and 1.8 MHz for the quadrupole coupling constant, which were interpreted as due to Na⁺ ions bonded to oxygenated groups at the edges of the graphene planes within the carbon pore network.     

直肠组织的高分辨魔角旋转核磁共振波谱研究

文章对6例直肠癌变及正常组织进行高分辨魔角旋转核磁共振波谱研究,结果显示直肠癌变和正常组织的核磁共振氢谱存在明显差异。这可以通过特征峰面积与0.88处峰积分面积的比值上的差异看出：（1）在化学位移0.75～1.55之间,癌组织各种氨基酸[缬氨酸,异亮氨酸,亮氨酸]与脂肪酸甲基的比值（I₂/I₁）,癌组织乳酸盐与脂肪酸甲基的比值(I₄/I₁)都明显增大。（2）在化学位移1.55～2.90之间,癌变组织中亮氨酸、赖氨酸、异亮氨酸与脂肪酸甲基的比值（I₇/I₁）, 谷氨酸、谷氨酰胺、缬氨酸、琥珀酸与脂肪酸甲基的比值((I₉+I₁₁)/I₁)、天冬氨酸与脂肪酸甲基的比值((I₁₂+I₁₄)/I₁)都较正常组织明显增大。（3）在化学位移2.90～3.49之间,癌变组织氨基酸与脂肪酸甲基的比值（I₁₅/I₁）、胆碱类与脂肪酸甲基的比值((I₁₆+I₁₇)/I₁)、牛磺酸与脂肪酸甲基的比值((I₁₈+I₁₉)/I₁)都较正常组织明显增大。（4）在化学位移3.49～4.50之间,其他代谢物与脂肪酸甲基的比值（I₂₀/I₁）,以及甘油基与脂肪酸甲基的比值（I₂₂/I₁）在癌变组织中都有增大的趋势。（5）化学位移4.5～10之间,癌变组织的核苷酸发生了变化,癌变组织的不饱和脂肪酸与脂肪酸甲基的比值（I₂₄/I₁）明显减小。（6）在化学位移-8～0.75之间,癌变组织的谱峰有减少的趋势。通过上述分析可知,通过癌变与正常组织代谢物NMR谱峰的差异,可以区分癌变和正常组织。说明核磁共振波谱技术可能发展成为一种诊断直肠癌的新方法。     

Route to and from the NMR chaos in diamagnets

The route to and from the chaos via period doubling bifurcations in nuclear spin system with dipole-dipole interactions is investigated. The transition points are found. It is shown that route from the chaos proceeds according the Feigenbaum scenario. Received 19 August 1998 and Received in final form 15 December 1998