Rotating-frame Overhauser Spectroscopy Research Articles

Yuccalechins A-C from the Yucca schidigera Roezl ex Ortgies Bark: Elucidation of the Relative and Absolute Configurations of Three New Spirobiflavonoids and Their Cholinesterase Inhibitory Activities.

The ethyl acetate fraction of the methanolic extract of Yucca schidigera Roezl ex Ortgies bark exhibited moderate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity (IC50 47.44 and 47.40 µg mL−1, respectively). Gel filtration on Sephadex LH-20 and further RP-C18 preparative HPLC of EtOAc fraction afforded 15 known and 3 new compounds, stereoisomers of larixinol. The structures of the isolated spirobiflavonoids 15, 26, and 29 were elucidated using 1D and 2D NMR and MS spectroscopic techniques. The relative configuration of isolated compounds was assigned based on coupling constants and ROESY (rotating-frame Overhauser spectroscopy) correlations along with applying the DP4+ probability method in case of ambiguous chiral centers. Determination of absolute configuration was performed by comparing calculated electronic circular dichroism (ECD) spectra with experimental ones. Compounds 26 and 29, obtained in sufficient amounts, were evaluated for activities against AChE and BChE, and they showed a weak inhibition only towards AChE (IC50 294.18 µM for 26, and 655.18 µM for 29). Furthermore, molecular docking simulations were performed to investigate the possible binding modes of 26 and 29 with AChE.

Supramolecular Interaction-Assisted Fluorescence and Tunable Stimuli-Responsiveness of l-Phenylalanine-Based Polymers.

Supramolecular host-guest interactions between randomly methylated β-cyclodextrin (RM β-CD) and side-chain phenylalanine (Phe) and Phe-Phe dipeptide-based homopolymers have been employed for the amplification of fluorescence emission of otherwise weakly fluorescent amino acid Phe. The host-guest complex has been characterized by 1H and 13C NMR spectroscopy, two-dimensional rotating-frame overhauser spectroscopy, Fourier-transform infrared spectroscopy, UV-visible spectroscopy, and fluorescence spectroscopy. To gain insights into the origin of fluorescence in homopolymers, density functional theory calculations were performed where phenyl moieties inside the less polar core of β-CD were observed to form a π-π coupled complex resulting in an enhanced emission. Furthermore, the complex-forming ability of Phe, the guest molecule, has been employed in tuning the cloud point temperature (TCP) of statistical copolymers derived from side-chain Phe/Phe-Phe-based methacrylate monomers and N-isopropylacrylamide. By varying the co-monomer feed ratios in the statistical copolymer and hence the concentration of RM β-CD throughout the polymer chain, host-guest interaction-assisted broad tunability in TCP of the supramolecular polymeric complex has been achieved.

Synthesis of Luminescent Platinum(II) 2,6-Bis(N-dodecylbenzimidazol-2′-yl)pyridine Foldamers and Their Supramolecular Assembly and Metallogel Formation

Dinuclear alkynylplatinum(II) metallofoldamers with an oligomeric m-phenyleneethynylene backbone have been designed with the incorporation of a sterically undemanding, π-conjugated, and hydrophobic 2,6-bis(N-dodecylbenzimidazol-2'-yl)pyridine pincer ligand. The complex with the optimal chain length has been found to exhibit gelation behavior via stabilization by noncovalent Pt···Pt and π-π stacking interactions in the hierarchical architecture constructed from the single-turn helix. The chain lengths of the complexes have been found to be a critical determinant for their gelation behavior, conformations, and morphologies. Such a gelation process has been found to undergo a cooperative assembly mechanism according to the nucleation-elongation model. Their self-assembly via the Pt···Pt and π-π stacking interactions has been studied by 1H NMR, 2D ROESY NMR (ROESY = rotating-frame Overhauser spectroscopy), electronic absorption, and emission spectroscopy, and density functional theory calculations have provided further insights into the folded state geometry of this class of metallofoldamers.

Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis.

Low selectivity of chemotherapy correlates with poor outcomes of cancer patients. To improve this issue, a novel agent, N-(1-[3-methoxycarbonyl-4-hydroxyphenyl]-β-carboline-3-carbonyl)-Trp-Lys-OBzl (PZL318), was reported here. The transmission electron microscopy, scanning electron microscopy, and atomic force microscopy images demonstrated that PZL318 can form nanoparticles. Fluorescent and confocal images visualized that PZL318 formed fluorescent nanoparticles capable of targeting cancer cells and tracing their interactions with cancer cells. In vitro, 40 μM of PZL318 inhibited the proliferation of tumorigenic cells, but not nontumorigenic cells. In vivo, 10 nmol/kg of PZL318 slowed the tumor growth of S180 mice and alleviated the thrombosis of ferric chloride-treated ICR mice, while 100 μmol/kg of PZL318 did not injure healthy mice and they exhibited no liver toxicity. By analyzing Fourier transform–mass spectrometry and rotating-frame Overhauser spectroscopy (ROESY) two-dimensional nuclear magnetic resonance spectra, the chemical mechanism of PZL318-forming trimers and nanoparticles was explored. By using mesoscale simulation, a nanoparticle of 3.01 nm in diameter was predicted containing 13 trimers. Scavenging free radicals, downregulating sP-selectin expression and intercalating toward DNA were correlated with the antitumor mechanism of PZL318.

Coadsorption of Low-Molecular Weight Aromatic and Aliphatic Alcohols and Acids with the Cationic Surfactant, CTAB, on Silica Surfaces

We have investigated the coadsorption of a range of small molecules with the cationic surfactant CTAB to silica surfaces over a range of concentrations and CTAB to solute ratios and compared the coadsorption with adsorption in the presence of the salicylate ion. We find that molecules with aromatic character and molecules with double bonds are most favorably adsorbed, and we attribute this to cation-π bonding between the surfactant headgroups and the π orbitals of the unsaturated bonds of the solute molecules. The adsorption is complex and depends on chemical interactions between the solute molecules and the surfactant, which are highly specific to the structure of the solute. To improve our understanding of the specifics of these interactions, we have performed one-dimensional rotating frame Overhauser spectroscopy (ROESY) nuclear magnetic resonance experiments. These experiments show the complexity of the intermolecular interactions and can be used to determine the position of the solute molecule with regard to the CTAB molecules in the adsorbed aggregates. The ROESY spectrum for the salicylate anion is distinct from those of the other solute molecules and suggests that the anions are dimerizing. Along with the cation-π bonding between the dimers, this provides a model for the strong influence that salicylate has on adsorption, micellar structure, and viscoelasticity. The ROESY data indicate that the catechol molecule interacts with all parts of the surfactant alkane chains such that they wrap around the molecule, but this has little effect on the interfacial curvature or aggregate shape. More intense isophthalic acid-CTAB intermolecular ROEs compared to those of other aromatic solutes are consistent with an interaction between isophthalic acid and the headgroups of two surfactant molecules that slows the intramicellar motion of isophthalic acid. Differences in interactions between solute molecules and the aliphatic surfactant chains do not result in changes in micelle structure.

Study of the complexation of risperidone and 9-hydroxyrisperidone with cyclodextrin hosts using affinity capillary electrophoresis and 1H NMR spectroscopy

The complexation of risperidone (Risp) and 9-hydroxyrisperidone (9-OH-Risp), atypical antipsychotics, with seven cyclodextrins (CDs) of pharmaceutical interest (native and hydroxypropylated (HP) α-, β-, γ-CDs and methyl (Me)-β-CD) was studied by affinity capillary electrophoresis (ACE) and nuclear magnetic resonance spectroscopy (NMR) for acidic pH 2.5 and physiological pH 7.4. The 1:1 stoichiometry of the complexes was established by 1H NMR spectroscopy using the continuous variation method developed by Job. The apparent binding constants of the 14 complexes at both pH were determined by ACE through the linear Scott's plots. The NMR spectroscopy investigation of the binding constants was achieved for the two CDs allowing the highest complexation: the β-CD and Me-β-CD. Both ACE and NMR spectroscopy studies provide similar conclusions by considering the influence of the 9-hydroxylation, the influence of the CD substitution and the influence of the pH. Moreover, the NMR spectroscopy results have allowed to suppose a pH-dependent inclusion mechanism. A thermodynamic study was then performed by ACE at both pH for the Risp·Me-β-CD and 9-OH-Risp·Me-β-CD complexes: the opposite signs of the entropic change (Δ S° < 0 at pH 2.5 and Δ S° > 0 at pH 7.4) confirms the influence of the pH on the complexation mechanism and the possible difference in the depth of the analyte inclusion in the hydrophobic cavity of the CD. Last, the two-dimensional ROESY (rotating-frame Overhauser spectroscopy) ( 1H– 1H) and HOESY (heteronuclear Overhauser effect spectroscopy) ( 19F– 1H) experiments have proved the inclusion of the aromatic part of the Risp and 9-OH-Risp in the hydrophobic CD cavity and lead us to propose a model of complexation.

Two-dimensional rotating-frame Overhauser spectroscopy (ROESY) and 13C NMR study of the interactions between maltodextrin and an anionic surfactant

Rotational frame nuclear Overhauser effect spectroscopy (ROESY) and 13C NMR measurements were carried out to study the molecular interaction between maltodextrin, a digestive byproduct of starch, and an anionic surfactant. Significant differences in chemical shifts were observed when sodium dodecyl sulfate (SDS) was introduced into the maltodextrin (DE 10) solutions. 13C NMR measurement indicated that there were downfield shifts and broadening of peaks, especially in the region of 75–81 and 100–103 ppm, which were assigned to carbons 1 and 4 of the d-glucopyranose residues of maltodextrin, respectively. ROESY spectra indicated cross-peaks between the SDS and maltodextrin protons. These peaks can arise only in the case of the designated SDS protons and maltodextrin protons being less than 0.5 nm apart for a substantial period of time. The most intense cross-peaks are those between the central CH 2 protons of SDS near 1.2 ppm and the maltodextrin protons ranging from 3.5 to 3.9 ppm. The SDS-H3 CH 2 protons were resolved from the bulk of the SDS protons, with peaks and shoulders at 1.25 ppm, which indicated an especially strong interaction of the SDS hydrophobic tail with MD6 and some less intense interactions with MD2, 4, and 5.

Conformational analysis of cyclic hexapeptides designed as constrained ligands for the SH2 domain of the p85 subunit of phosphatidylinositol-3-OH kinase.

The structures of the cyclic hexapeptide cyclo(-Gly-Tyr-Val-Pro-Met-Leu-) (1) and its phosphotyrosyl (pTyr) derivative cyclo[-Gly-Tyr(PO3H2)-Val-Pro-Met-Leu-] (2), designed as constrained models of a sequence that interacts with the src homology 2 (SH2) region of the p85 subunit of phosphatidylinositol-3-OH kinase (PI-3 kinase), were studied in methanol/water solutions by 500 MHz nmr spectroscopy. Compound 1 was found to exist as a 2:1 mixture of isomers about the Val-Pro bond (trans and cis prolyl) between 292-330 K in 75% CD3O(D,H)/(D,H)2O solutions. A third species of undetermined structure (ca. 5%) was also observed. Compound 2, a model of phosphorylated peptide ligand that binds to the PI-3 kinase SH2 domain, exhibited similar conformational isomerism. When either compound was dissolved in pure solvent [i.e., 100% CD3O(H,D) or (H,D)2O] the ratio of cis to trans isomers was ca 1:1. A battery of one- and two-dimensional nmr experiments at different temperatures and solvent compositions allowed a complete assignment of both the cis and trans forms of 1 and indicated the trans compound to be the major isomer. The spectral properties of the phophorylated derivative 2 paralleled those of 1, indicating like conformations for the two compounds. Analysis of rotating frame Overhauser spectroscopy data, coupling constants, amide proton temperature dependence, and amide proton exchange rates generated a set of constraints that were employed in energy minimization and molecular dynamics calculations using the CHARMM force field. The trans isomer exists with the tyrosine and C-terminal Tyr(+3) (Met) residues at opposite corners of the 18-membered ring separated by a distance of 16-18 A, in contrast with the cis isomer where the side chains of these residues are much closer in space (7-14 A). It was previously shown that the pTyr and the third amino acid C-terminal to this residue are the critical recognition elements for pTyr-peptide binding to the PI-3 kinase SH2 domain. Such cyclic structures may offer appropriate scaffolding for positioning important amino acid side chains of pTyr-containing peptides as a means of increasing their binding affinities to SH2 domains, and in turn provide a conceptual approach toward the design of SH2 domain directed peptidomimetics.