NOE NMR Spectroscopy Research Articles

Multiple binding modes of an N-terminal CCR5-peptide in complex with HIV-1 gp120.

The N-terminal segment of CCR5 contains four tyrosine residues, sulphation of two of which is essential for high-affinity binding to gp120. In the present study, the interactions of gp120YU2 with a 27-residue N-terminal CCR5 peptide sulphated at position Y10 and Y14, i.e. Nt-CCR5, were studied using 13 C-edited-HMQC methyl-NOESY [1 H(13 C)-1 H], combined with transferred NOE NMR spectroscopy. A large number of pairwise interactions were observed between the methyl protons of methionine, threonine, valine and isoleucine residues of gp120, and the aromatic tyrosine-protons of Nt-CCR5. M434, V120 and V200 of gp120 were found to interact with all four tyrosine residues, Y3, sY10, sY14 and Y15. Particularly intriguing was the observation that Y3 and Y15 interact with the same gp120 methyl protons. Such interactions cannot be explained by the single cryo-EM structure of gp120/CD4/CCR5 complex published recently (Nature, 565, 318-323, 2019). Rather, they are consistent with the existence of a dynamic equilibrium involving two or more binding modes of Nt-CCR5 to gp120. These different modes of binding can coexist because the surface of gp120 contains two sites that can optimally interact with a sulphated tyrosine residue and two sites that can interact favorably with a non-sulphated tyrosine residue. Modelling of gp120YU2 complexed with the Nt-CCR5 peptide or with the entire CCR5 receptor provides an explanation for the NMR observations and the existence of these different binding modes of the disordered N-terminus of CCR5. The data presented extend our understanding of the two-step model and suggest a more variable binding mode of Nt-CCR5 with gp120.

Donor-Acceptor Boron-Ketoiminate Complexes with Pendent N-Heterocyclic Arms: Switched-on Luminescence through N-Heterocycle Methylation.

A series of intramolecular, donor-stabilized BF2 complexes supported by phenanthridinyl-decorated, β-ketoiminate chelating ligand scaffolds is described, along with their characterization by spectroscopy and X-ray diffraction. In solution, the relative orientation of the pendent phenanthridinyl arm is fixed despite not coordinating to the boron center, and a well-resolved through-space interaction between a phenanthridinyl C-H and a single fluorine atom can be observed by 19F-1H NOE NMR spectroscopy. The neutral compounds are nonetheless only weakly luminescent in fluid solution, ascribed to nonradiative decay pathways enabled by rotation of the N-heterocyclic unit. Methylation of the phenanthridinyl nitrogen restricts this rotation, "switching on" comparably strong emission in solution. Modeling by density functional theory (DFT) and time-dependent DFT (TDDFT) indicates that the character of the lowest energy excitation changes upon methylation, with shallow calculated potential energy surfaces of the neutral complexes consistent with their lack of significant radiative decay.

Determination of inter-ionic and intra-ionic interactions in a monofluorinated imidazolium ionic liquid by a combination of X-ray crystallography and NOE NMR spectroscopy.

We report the very first application of a Transient 1D 1 H{19 F} NOE NMR experiment in neat ionic liquids. In comparison with classical 2D HOESY NMR spectroscopy, a substantial reduction in measurement time is gained with comparable quality and information content of the spectra. In combination with classical X-ray crystallography, we have applied this technique for the determination of inter-ionic distances (i.e. probabilities of presence) utilizing an ionic liquid containing a monofluorinated imidazolium cation. Copyright © 2017 John Wiley & Sons, Ltd.

Chirality Control in Enzyme-Catalyzed Dynamic Kinetic Resolution of 1,3-Oxathiolanes.

The origin of enantioenrichment in enzyme-catalyzed dynamic kinetic resolution of 1,3-oxathiolane derivatives, key intermediates for asymmetric lamivudine synthesis, was elucidated. The chirality control could be determined by chiral HPLC and NOE NMR spectroscopy using a modified 1,3-oxathiolane compound obtained through enzyme-catalyzed selective hydrolysis. Solvent-dependent stereoselectivity was observed under biphasic conditions using different organic solvents with phosphate buffer.

Designing foldamer-foldamer interactions in solution: the roles of helix length and terminus functionality in promoting the self-association of aminoisobutyric acid oligomers.

The biological activity of antibiotic peptaibols has been linked to their ability to aggregate, but the structure-activity relationship for aggregation is not well understood. Herein, we report a systematic study of a class of synthetic helical oligomer (foldamer) composed of aminoisobutyric acid (Aib) residues, which mimic the folding behavior of peptaibols. NMR spectroscopic analysis was used to quantify the dimerization constants in solution, which showed hydrogen-bond donors at the N terminus promoted aggregation more effectively than similar modifications at the C terminus. Elongation of the peptide chain also favored aggregation. The geometry of aggregation in solution was investigated by means of titrations with [D6]DMSO and 2D NOE NMR spectroscopy, which allowed the NH protons most involved in intermolecular hydrogen bonds in solution to be identified. X-ray crystallography studies of two oligomers allowed a comparison of the inter- and intramolecular hydrogen-bonding interactions in the solid state and in solution and gave further insight into the geometry of foldamer-foldamer interactions. These solution-based and solid-state studies indicated that the preferred geometry for aggregation is through head-to-tail interactions between the N and C termini of adjacent Aib oligomers.

Interaction between hydrophobically modified 2-hydroxyethyl cellulose and sodium dodecyl sulfate studied by viscometry and two-dimensional NOE NMR spectroscopy.

Interaction between an anionic surfactant, sodium dodecyl sulfate (SDS), and a nonionic polymer, 2-hydroxyethyl cellulose (HEC) hydrophobically modified with benzoyl chloride (bmHEC), is studied by viscometry and two-dimensional nuclear Overhauser effect NMR spectroscopy (2D NOESY) in a semidilute regime of bmHEC. The hydrophobicity of bmHEC was varied with different substitution of benzoyl group to HEC macromolecules. In general, the low-shear viscosity of 1 wt % bmHEC aqueous solution is increased with added SDS surfactant having concentration from 0 to 0.5 wt %, and then decreased significantly with a further addition of surfactant to 3 wt %. The activation energy of transient network formation in 1 wt % bmHEC aqueous solution present with SDS surfactant is found to be dependent with SDS concentration, which varies from 32.7 to 69.80 kJ/mol. The maximum activation energy takes place when 0.5 wt % SDS is added, which coincides with that of the maximal viscosity. The 2D NOESY displays that the surfactants actually interact with bmHEC not only on the hydrophobes, namely benzoyl groups, but also the polymer backbone, i.e., glucose units. In contrast, no interaction is revealed by 2D NOESY in the aqueous system containing SDS surfactant and HEC polymer.

ChemInform Abstract: Ligand Effects on Bonding and Ion Pairing in Cationic Gold(I) Catalysts Bearing Unsaturated Hydrocarbons

AbstractReview: < 60 refs.

NHC-Gold-Alkyne Complexes: Influence of the Carbene Backbone on the Ion Pair Structure

We have studied the ion pair structure of [NHC-Au(η2-3-hexyne)][BF4] (NHC = nitrogen-heterocyclic carbene) by solution NOE NMR spectroscopy and relativistic DFT calculation. The neutral complexes [...

Ligand Effects on Bonding and Ion Pairing in Cationic Gold(I) Catalysts Bearing Unsaturated Hydrocarbons

AbstractWe critically review recent experimental and theoretical investigations into some key aspects of the chemistry of gold(I) complexes of the type [L–Au–S]+X– (L = NHC carbenes and phosphanes, S = alkenes and alkynes, and X– = weakly coordinating counterion). These systems are important intermediates formed during gold‐catalyzed nucleophilic additions to an unsaturated substrate, and their specific activity is largely governed by two fundamental factors: the nature of the gold–substrate bond and the role of the ion‐pair structure in solution. Both are crucially influenced by the nature and properties of the auxiliary ligand L, and on this interplay we focus our discussion. The relative anion–cation orientation, investigated by NOE NMR spectroscopy and DFT calculations, shows that the exact position of the counterion is determined by the natures of the ancillary ligand and substrate: the counterion is located near the substrate in the phosphane complexes, while for the NHC complexes the preferred position of the counterion is near the ligand. This tunable interionic structure opens the way to greater control over the properties and activity of these catalysts. The bond between AuI and the unsaturated substrate is investigated using an original and powerful theoretical method of analysis. Our approach permits a rigorous definition and assessment of the charge‐displacement (CD) components at the heart of the Dewar–Chatt–Duncanson model: substrate‐to‐metal (σ donation) and metal‐to‐substrate (π back‐donation) and how these change with different ligands. The results consistently reveal that π back‐donation is a large and crucially important component of the AuI–substrate bond in all systems: π back‐donation penetrates the external side of coordinated alkynes, where nucleophile attack is directed, thus partially mitigating the electron depletion caused by σ donation.

Spatial structure of felodipine dissolved in DMSO by 1D NOE and 2D NOESY NMR spectroscopy

Small organic molecules in dissolved state exist as an ensemble of conformers. In this work conformation of felodipine in dimethyl sulphoxide was studied and dominant stable conformers were determined. Effective interatomic distances were obtained by means of NOE spectroscopy. Fractions of different conformers were estimated by comparing effective distances and those obtained from quantum-chemical calculation [8]; averaging of distances was made following the N-site jump model.

Synthesis of aryl-substituted or aryl-fused N-hydroxyethyl and N-hydroxymethypyrazole derivatives as potential ligands for the estrogen receptor

A new series of N-hydroxyethylpyrazole (12a–f) and N-hydroxymethylpyrazole derivatives (15a–f) were designed for their estrogenic activities, having a 11.0 ± 0.5 A distance between their two hydroxyl groups, aliphatic–OH and phenolic–OH similar to 17β-estradiol (E2) as an endogenous hormone. To synthesize the title compounds, the key intermediate 1,3-dicarbonyl derivatives (2 and 8), were treated with hydrazine hydrate to produce the pyrazole ring 5 and 9. Further hydroxyalkylation of the latter produced the title pyrazoles. The position of hydroxyethyl or hydroxymethyl substituents in the products was determined through 2D NOE NMR spectroscopy.

ChemInform Abstract: Absolute Configuration and Synthesis of 2-Hydroxy-2-(1-hydroxyethyl)-3- methyl-γ-butyrolactone, a Presumed Pheromone of Ithomiine Butterflies.

2-Hydroxy-2-(1-hydroxyethyl)-3-methyl-γ-butyrolactone (1) is a constituent of scent glands of male ithomiine butterflies. All diastereomers and the respective (3R)-enantiomers were synthesized by starting from rac- or (3S)-3-methyl-γ-butyrolactone 3. Their relative configurations were determined by difference NOE-NMR spectroscopy or by X-ray diffraction analysis. The absolute configuration of the natural product was determined by gas chromatography on a chiral stationary phase of the respective dioxolane derivatives. The natural lactone could be shown to be the (1′S,2S,3R)-enantiomer [(1′S,2S,3R)-1a, ithomiolide A]. In addition, the corresponding ketone, (2S,3R)-2-acetyl-2-hydroxy-3-methyl-γ-butyrolactone [(2S,3R)-5a, ithomiolide B], could be identified as a new natural product from Prittwitzia hymaenea.

Synthesis and photochemistry of two quinoline analogs of the perimidinespirohexadienone family of photochromes

We report the detailed synthesis and photochemistry of two analogs (specifically 3,5-di- tert-butyl-7′-methyl- and 3,5-di- tert-butyl-7′,9′-dimethyl-1′,3′-dihydrospirocyclohexa[2,5]diene-1,2′-pyrido[4,3,2-de]quinazolin-4-one) of the perimidinespirohexadienone (3,5-di- tert-butyl-1′,3′-dihydrospirocyclohexa[2,5]diene-1,2′-perimidin-4-one) family of photochromes in which the naphthalene moiety of the parent is replaced by a quinoline, and compare them to the parent compound. Molar absorptivities of both the short wavelength spirocyclic isomer (SW) and long wavelength quinonimine isomer (LW) of each were determined by a combination of proton NMR and UV–vis spectroscopy in solvents of varying polarity. Quantum yield measurements for photoisomerization of SW to LW are reported in those same solvents, with qualitative extrapolation to additional solvents. The position and rate of the thermal equilibrium reverting LW to SW is estimated for these compounds. The 9′-methyl in SW (6-methyl in LW) is found to be essential for complete reversion of LW to SW in the dark. Finally one-dimensional NOE NMR spectroscopy was used to conclusively determine the structure of LW for the quinoline analogs as the 4-(5-aminoquinolin-4-ylimino)-2,6-di- tert-butylcyclohexa-2,5-dienone resulting from opening toward the quinoline nitrogen, rather than the 4-(4-aminoquinolin-5-ylimino) structure that would result from spirocyclic ring opening away from the quinoline nitrogen which had been initially proposed by Minkin et al. for very similar compounds [V.I. Minkin, V.N. Komissarov, V.A. Kharlanov, Perimidinespirocyclohexadienones, in: J.C. Crano, R.J. Guglielmetti (Eds.), Organic Photochromic and Thermochromic Compounds, vol. 1, Plenum Press, New York, 1999, pp. 315–340, and references therein].

New Insights into the Interactions between Dendrimers and Surfactants by Two Dimensional NOE NMR Spectroscopy

The interactions between polyamidoamine dendrimers and different surfactants including sodium dodecyl sulfate (SDS) and dodecyltrimethyl ammonium bromide in aqueous solutions have been investigated by a NOESY NMR technique. Strong NOE cross-peaks between hydrophobic chain protons of SDS and methylene protons of cationic dendrimers were found, suggesting a strong tendency for the long hydrophobic tails of SDS to associate with the hydrophobic pockets of dendrimers. The hydrophilic head of SDS localizes near the core or the boundary of each generation of dendrimers, and the hydrophobic chain of SDS localizes in the relative nonpolar pockets of dendrimers. The encapsulation of surfactant monomers by dendrimers is dependent on the charge type of the surfactants, the surface functionality, and the generation of dendrimers. The NOESY analysis provides a new insight into interactions between dendrimers and surfactants in comparison with previous investigations.

Self‐Aggregation Tendency of Zirconocenium Ion Pairs Which Model Polymer‐Chain‐Carrying Species in Aromatic and Aliphatic Solvents with Low Polarity

From pairs to double pairs: Zirconocene ion pairs bearing an aliphatic chain of variable length were synthesized and investigated by means of NOE and diffusion NMR spectroscopy experiments. The presence of long aliphatic chains allowed an unprecedented investigation of their self‐aggregation tendency in cyclohexane (see figure), which has a dielectric constant similar to that of isoparaffins used in industrial plants.

Interactions between Poly(N-vinylformamide) and Sodium Dodecyl Sulfate As Studied by Fluorescence and Two-Dimensional NOE NMR Spectroscopy

The interaction of poly(N-vinylformamide) (PNVF) with anionic surfactant, sodium dodecyl sulfate (SDS), has been studied by pyrene fluorescence and two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY). With use of pyrene as the probe, from low to high concentration of SDS, the pyrene I1/I3 plot exhibits three stages of association of PNVF with SDS. The I1/I3 plot vs [SDS] shows a well-defined plateau (I1/I3 = 1.47) at SDS concentrations ranging between 3 and 10 mM, indicating that in this range of SDS concentrations the sizes of polymer-bound SDS aggregates are approximately identical. The ambiguity in determining the critical aggregation concentration (cac) of SDS from the I1/I3 plot vs [SDS], which resembles the typical profile of surface tension vs surfactant concentration, has been clarified by the 2D NOESY experiment. Also, just beyond the cac ([SDS] = 3 mM), definite proof of formation of the PNVF−SDS complex bound on the polymer chain is provided by the 2D NOESY experiments. On the bas...

Interionic Structure of Ion Pairs and Ion Quadruples of Half-Sandwich Ruthenium(II) Salts Bearing α-Diimine Ligands

The interionic structure of complexes [Ru(η6-Arene){(2-R-C6H4)NC(Me)−C(Me)N(2-R-C6H4)}Cl]X was investigated by an integrated experimental (PGSE diffusion and NOE NMR spectroscopy and X-ray single-crystal studies) and theoretical (DFT and ONIOM calculations) approach. PGSE NMR experiments indicated that ion pairing is the main aggregative process in CD2Cl2 and solvents with higher relative permittivity. They also showed that the tendency to ion pairing for isodielectric solvents is higher when the latter are protic. NOE interionic contacts were observed in 2-propanol-d8 even for BARF- salts. Ion pairing was favored by more coordinating counterions and an increase in concentration. An equilibrium between ion pairs and ion quadruples was observed by PGSE measurements in chloroform-d and benzene-d6. Such equilibrium is shifted toward ion quadruples by an increase in the concentration or when least coordinating counterions are used. For small fluorinated counterions, NOE studies located the anion in ion pairs ...

Microwave-Assisted Synthesis of Tricarbonyl Rhenacarboranes: Steric and Electronic Effects on the 1,2 → 1,7 Carborane Cage Isomerization

A series of tricarbonyl rhenacarboranes {[M][Re(CO)3(RR'C2B9H9)]} (M = Na, K) were synthesized in water using microwave radiation with reaction times of less than 15 min. The novel complexes were isolated in good yields (57-94%) as either 3,1,2-(R = H: R' = CH2Pyr 6; R' = CH2Cy, 20) or 2,1,8-(R = H: R' = H, 4; R' = CH2PyrMe 12; R' = CH2PyrH, 13; R' = Pyr, 15; R' = Ph, 17; R = R' = Bn, 19) metallacarboranes and characterized by multinuclear (1H, 11B, 13C) and NOE NMR spectroscopy, IR spectroscopy, mass spectrometry, and X-ray crystallography in the case of compounds 12 and 13. Carborane cage isomerization from the original 1,2 configuration to the 1,7 orientation occurred in cases where significant steric crowding was present at the metal center. Incorporation of a methylene spacer between the carborane cage and the six-membered ring as in 7 and 20 decreased steric strain such that the 3,1,2 configuration was maintained. Conversion of the 3,1,2 complex 6 to the 2,1,8 isomers 12 and 13 takes place at room temperature upon methylation or protonation of the pyridyl ring, indicating that electronic effects also play a significant role in the isomerization process.

Resorcinarenes are hexameric capsules in solution

The host-guest complexes of resorcin[4]arenes with small molecules in organic solutions are examined using modern NMR spectroscopic methods. The complexation of glutaric acid and beta-methyl d-glucopyranoside in chloroform were investigated through 2D COSY, 2D NOESY, 1D NOE, and diffusion-ordered NMR spectroscopy (DOSY) techniques. These methods indicate that the complex is a self-assembled capsule composed of six resorcinarenes that surround six guest molecules of glutaric acid or three molecules of beta-methyl d-glucopyranoside inside. The multiplicity of guest proton signals shows that the capsule provides an asymmetric magnetic environment that persists on the (1)H NMR time scale. The encapsulation of these guests and common solvents suggests that the phenomenon of reversible encapsulation in chemistry may be a century old.

Synthesis and conformational analysis of chiral ureas incorporatingN‐1‐phenylethyl groups. Manifestation of allylic 1,3‐strain

AbstractThe synthesis of novel chiral ureas (R,R)‐2, (S,S)‐3and (R)‐6incorporating the α‐phenylethyl group is described. Conformational analysis of these ureas, and of previously reported (R,R)‐1, was carried out computationally, both at semiempirical (AM1 and PM3) andab initio(HF and B3LYP) levels, and experimentally from x‐ray crystallographic analysis of (R,R)‐2and (S,S)‐3, and in the case of (R)‐6by means of NOE NMR spectroscopy. A substantial preference of 1.5–2.6 kcal mol−1in favor of conformations withsyn‐periplanar arrangements between the CH bond at the α‐phenylethylN‐substituent and the NC(O) segment was found, and this observation confirms the relevance of allylic A1,3strain in this system. The possibility of hydrogen bonding in thesyn‐periplanar CH···OCN arrangement was discarded in the light of topological analysis of (R,R)‐1, within the frame of Bader's atoms in molecules theory. Copyright © 2005 John Wiley & Sons, Ltd.