Heteronuclear Overhauser Effect Spectroscopy Research Articles

Insight into the Molecular Structure, Interaction, and Dynamics of Aqueous Reline Deep Eutectic Solvent: A Nuclear Magnetic Resonance Investigation

Reline, which is composed of choline chloride (ChCl) and urea, is the first and most widely used deep eutectic solvent (DES) described by Abbot and co-workers. Due to the hygroscopic feature, traces of water are unavoidable, which significantly affect the physicochemical properties of reline. At present, the local structure of molecules and the impact from the presence of water are still the most significant questions in this field. Herein, reline and six aqueous dilutions with a controlled amount of water (from 3.2 to 50.0 wt %) were studied mainly by using a combination of nuclear magnetic resonance (NMR) techniques. According to 1D 35Cl NMR, 1D 15N NMR, and 2D 1H-15Cl heteronuclear Overhauser effect spectroscopy, we probed the interactions of urea···Cl- and Ch+···Cl- in pure reline, which gradually dissociated in the presence of water. Moreover, it was revealed that the dissociation rate altered when the water content reached 9.0 wt %, which is ascribed to the higher preference of hydration for Cl- ion compared to other species in the system. Furthermore, selected cross peaks in 1H-1H correlation spectroscopy spectra were analyzed. Accordingly, an enhanced correlation was observed for urea···Ch+ at a lower water fraction within 9.0 wt %. When the water content increased to 24.9 wt %, the water solvation of Ch+ and urea was also observed in COSY spectra. The interaction of H2O···Ch+ got continuously stronger when the water content increased from 24.9 to 50.0 wt %, while H2O···urea got enhanced when the water content reached 33.3 wt % and then diminished gradually from 33.3 to 50.0 wt %. 1H-1H nuclear Overhauser effect spectroscopy and 1H-1H rotating frame Overhauser effect spectroscopy experiments were also conducted for dynamics investigation. The τc value for the species in 9.0 wt % aqueous reline is very close to τccrit of 0.44 ns. For pure reline and the aqueous reline with a water fraction of less than 9.0 wt %, the τc value of the species is longer than 0.44 ns, while for the sample with water of 24.9 wt %, the τc value is much shorter than 0.44 ns. Based on our NMR study, we revealed that with the water amount increasing from 0 to 50.0 wt %, the species involved in the system behaved as the large molecules or molecules in viscous liquids transiting to the medium-sized molecules in nonviscous liquids and finally to small molecules in nonviscous liquids.

Use of Diethanolamine as a Viscous Solvent for Mixture Analysis by Multidimensional Heteronuclear ViscY NMR Experiments.

Diethanolamine/DMSO-d6 as a viscous binary solvent is first reported for the individualization of low-polarity mixture components by multidimensional heteronuclear ViscY NMR experiments under spin diffusion conditions. Solvent viscosity induces the slowing down of molecular tumbling, hence promoting magnetization transfer by dipolar longitudinal cross-relaxation. As a result, all 1H nuclei resonances within the same molecule may correlate in a 2D nuclear Overhauser effect spectroscopy (NOESY) spectrum, giving access to mixture analysis. We offer a new way to analyze mixtures by considering 3D heteronuclear heteronuclear single-quantum coherence-NOESY (HSQC-NOESY) experiments under viscous conditions. We state the individualization of four low-polarity chemical compounds dissolved in the diethanolamine/DMSO-d6 solvent blend using homonuclear selective 1D, 2D 1H-1H NOESY experiments and heteronuclear 1D, 2D 1H-19F heteronuclear Overhauser effect spectroscopy, 2D 1H-19F, 1H-31P HSQC-NOESY, and 3D 1H-19F-1H, 1H-31P-1H HSQC-NOESY experiments by taking profit from spin diffusion.

Using HOESY NMR Spectroscopy to Characterize Prenucleation Aggregates

Prenucleation aggregates are important species in the crystallization pathway. Here, we combine heteronuclear Overhauser effect spectroscopy (HOESY) and molecular dynamics calculations to study solute molecule association in a model system─benzoic acid/pentafluorobenzoic acid. Our findings indicate that HOEs arise from diffusion-limited prenucleation aggregates and that association is solvent dependent.

Anion-cation interactions in novel ionic liquids based on an asymmetric sulfonimide anion observed by NMR and MD simulations

The ion interactions in two novel ionic liquids containing the asymmetric sulfonimide anion, (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (DFTFSI), are investigated using 1H–19F Heteronuclear Overhauser Effect Spectroscopy (HOESY) nuclear magnetic resonance (NMR) in combination with relaxation measurements, and molecular dynamics (MD) simulations. These methods provide insights into how the different end groups of the anion interact with different regions of the IL cations. The 1H–19F cross-relaxation rates (σ) between different pairs of nuclei measured by HOESY are interpreted based on inter/intra molecular distances and dynamics. The results show that the protonated end of the DFTFSI anion (i.e., the CF2H group) preferentially interacts with the IL cations, while the MD simulations also show evidence of C-H…O hydrogen bonding interactions between DFTFSI and the methoxy-functionalised cation C2O1mpyr, thereby explaining the observed lower ionic conductivity and higher density in this IL as compared to the C3mpyr DFTFSI system.

Carbon-13 synthesis and NMR spectroscopic geometric isomer evaluation to support the filing of teriflunomide.

The two isotopomers of teriflunomide were synthesized starting from isotopically stable-labeled stocks of [13 C]potassium cyanide and [1-13 C]ethyl bromoacetate. The two 13 C-labeled compounds 1a, b were applied in several NMR studies to study the E/Z ratio in different matrices. In a solution, such as dimethyl sulfoxide (DMSO), a dynamic equilibrium between E/Z-isomers (ratio of 8:92) was determined by initial 13 C-carbon NMR experiments. To get insights into the E/Z ratio of teriflunomide under in vivo conditions, advanced heteronuclear NMR (heteronuclear Overhauser effect spectroscopy [HOESY]) in D2 O and mixtures of D2 O/plasma were performed. Whereas NMR experiments in mixtures of water and plasma failed owing to extreme line broadening, NMR spectra in water at pH 7.4 showed only the Z-isomer.

Probing the Interactions and Dynamics in an Ionic Liquid – Organic Solvent Hybrid Electrolyte System for Potential Application in Li-S Batteries

The depletion of fossil fuel and strict environmental regulation on carbon footprints has prompted a greater reliability on sustainable energy sources. Batteries represent an important energy storage option due to their wide range of applicability and portability, however, for certain applications such as transportation, a higher energy density battery is required. Beyond the conventional Li-ion battery system, current research is focusing on next-generation cost effective devices. Amongst them, the Li-S battery technology is very promising due to its high theoretical capacity and energy density [1]. However, the chemistry involved in the Li-S battery is a complex process with multiple consecutive electrochemical reactions. Despite having many advantages, its application is still limited by several issues, e.g., the dissolution and diffusion of intermediate polysulphides, unstable plating and stripping of Li metal, both resulting in rapid capacity fading [2]. Previously, we reported the application of a novel electrolyte system composed of N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)imide, C3mpyrFSI, ionic liquid (IL) and 1,2 dimethoxyethane (DME) in the presence of varying saturated lithium bis(fluorosulfonyl)imide, LiFSI which predominantly suppressed the polysulphide dissolution and diffusion while showing improved lithium plating and stripping behavior [3]. In order to expand our understanding on the role of DME and the lithium salt concentration; in this work, we have considered a similar ionic liquid based electrolyte system but at a constant concentration of LiFSI salt. The ionic interactions among different species of the electrolyte system have been extensively studied by nuclear magnetic resonance (NMR) spectroscopy using 1D chemical shift, PFG-NMR and Heteronuclear Overhauser Effect SpectroscopY (HOESY) measurements. We found that, when increasing the DME concentration in the system, a strong association of Li+ cation with the DME occurs due to the electronegative oxygen atoms present in the DME molecules which leads to strong coordination. This leads to a change of the chemical shift of 7Li nuclei due to them being increasingly de-shielded. Interestingly, we found that the diffusivity of both Li+ and DME species are very similar, which also confirms that a Li-DME complex is present with FSI anion associated in the next coordination sphere to counterbalance the positively charged Li complex. MD simulations are underway to better elucidate the molecular shell structure of the system. We have also carried out electrochemical characterizations of these hybrid electrolytes to determine their potential applicability in a lithium sulphur battery. It was apparent using cyclic voltammogram (CV) performed in a three electrode set-up, that an increasing amount of DME increases the ionic conductivity but decreases the lithium plating-stripping efficiency. A coin-cell study of Li/Li symmetrical cycling showed an excellent plating-stripping behaviour for 70%IL-30%DME composition. We have carried out a full cell cycling against sulphur cathode and the optimised electrolyte composition obtained a promising first discharge capacity of 1100mAh/g. Additionally, we have investigated the sulphur speciation in the presence of this ionic liquid in a three-electrode system where platinum mesh has been used as working electrode coupled with in-situ UV-vis spectroscopy. Finally, a time dependent bulk electrolysis study revealed the plausible intermediates formed during the charge-discharge cycle of sulphur redox reaction. From these studies it appears that the composition of this novel hybrid electrolyte system can be tuned to provide a system with improved transport, electrochemical and sulphur speciation properties which lend themselves to a higher performance, next generation lithium sulphur battery technology.

Investigating Intermolecular Interactions in a DME-Based Hybrid Ionic Liquid Electrolyte by HOESY NMR.

The intermolecular interactions in a hybrid electrolyte based on various compositions of the ionic liquid N-methyl-N-propyl pyrrolidinium bis-fluorosulfonylimide (C3mpyrFSI), LiFSI salt and an ether-based additive, 1,2-dimethoxy ethane (DME), have been investigated using the HOESY (Heteronuclear Overhauser Effect SpectroscopY) NMR experiment. This NMR technique allows a quantification of the intermolecular interactions in ionic liquids (ILs) by measuring the cross-relaxation rate (σ) between different pairs of nuclei. Thereby, we compare the cross-relaxation rates between the cations, anions and DME in these hybrid electrolyte systems using 1H-7Li and 1H-19F HOESY experiments, and interpret the measured parameters in terms of ionic and molecular associations. The results give insights into the local coordination environment of the Li+ cations and their solvation by the FSI anions and DME.

27Al NMR Study of the pH Dependent Hydrolysis Products of Al₂(SO₄)₃ in Different Physiological Media.

Soluble inorganic aluminium compounds like aluminium sulfate or aluminium chloride have been challenged by the European Chemical Agency to induce germ cell mutagenicity. Before conducting mutagenicity tests, the hydrolysis products in water and in physiological solutions should be determined as a function of the concentration and pH. We used different 27Al NMR spectroscopic techniques (heteronuclear Overhauser effect spectroscopy (HOESY), exchange spectroscopy (EXSY), diffusion ordered (DOSY)) in this work to gain the information to study the aluminium species in solutions with Al2(SO4)3 concentrations of 50.0, 5.0, and 0.5 g/L and their pH and time dependent transformation. At low pH, three different species were present in all physiological solutions and water: [Al(OH)n(H2O)6 − n](3 − n)+ (n = 0–2), [Al(H2O)5SO4]+, and [Al2(OH)2(H2O)8]4+. Increasing pH reduced the amounts of the two monomer species, with a complete loss at pH 5 for solutions with a concentration of 50.0 g/L and at pH 4 for solutions with a concentration of 5.0 g/L. The dimer species [Al2(OH)2(H2O)8]4+ is present in a pH range between 3 and 6. Less symmetric oligomeric and probably asymmetric aluminium species are formed at pH of 5 and 6. The pH value is the driving force for the formation of aluminium species in all media, whereas the specific medium had only minor effect. No conclusive information could be obtained at pH 7 due to signal loss related to fast quadrupole relaxation of asymmetric aluminium species. A slight reduction of the content of the symmetric aluminium species due to the formation of oligomeric species was observed over a period of 6 weeks. Reference 27Al NMR experiments conducted on saturated water solutions of AlCl3 and those with a concentration of 50 g/L show that the type of salt/counter ion at the same concentration and pH influences the hydrolysis products formed.

19F NMR Characterization of the Encapsulation of Emerging Perfluoroethercarboxylic Acids by Cyclodextrins.

Legacy perfluoroalkyl substances (PFASs) are known environmental pollutants with serious adverse health effects. Perfluoroethercarboxylic acids (PFECAs), emerging PFASs now being substituted for legacy PFASs, have recently been detected in the environment. Cyclodextrins (CDs) have been proposed as agents for the remediation of problematic pollutants, including legacy PFASs. The current study uses 19F NMR spectroscopy to measure the complexation of mono-, di-, and triether PFECAs by CDs for eventual environmental applications. Eight PFECAs were characterized by 19F and 13C NMR. The change in chemical shift of individual fluorines upon complexation of CDs at various stoichiometric ratios was used to determine the host-guest association constants. All studied PFECAs were most strongly encapsulated by β-CD, with association constants from 102-105 M-1 depending on chain length and number of ether functionalities. 19F-1H heteronuclear Overhauser effect spectroscopy (HOESY) NMR experiments were performed for the β-CD complexes of two branched monoethers, PFPrOPrA ("GenX") and PFDMMOBA, to elucidate the structural details of the complexes, determine the specific orientation, and position of β-CD along the PFAS chain, and assess the roles of hydrogen-bonding and PFECA branching on the host-guest interactions. The results give new understanding into the fundamental nature of the host-guest complex between cyclodextrins and perfluorinated surfactants.

Solubilization of Hexafluorobenzene by the Micellar Aromatic Core Formed from Aggregation of Amphiphilic (2,3-O-Dibenzyl-6-O-sulfobutyl) Cyclodextrins.

Aggregation colloids that possess an aromatic pseudophase in an aqueous system could provide new avenues of research including micellar catalysis, aqueous remediation, and emulsion polymerization studies. The apparent aggregation of two macrocyclic surfactants, hexakis (2,3-O-dibenzyl-6-O-sulfobutyl) cyclomaltohexaose (DBSBA) and heptakis (2,3-O-dibenzyl-6-O-sulfobutyl) cyclomaltoheptaose (DBSBB), was investigated using diffusion ordered nuclear magnetic resonance (NMR) spectroscopy (DOSY), conductivity, and pyrene fluorescence techniques. These amphiphiles were found to possess near spherical symmetry at critical micelle concentrations of approximately 0.1 mM in all techniques used to study the phenomenon. Aggregation of both surfactants was found to be entropically driven at low temperatures but enthalpically driven at higher temperatures. The calculated compensation temperatures of DBSBA and DBSBB were determined to be 317 and 307 K, respectively. These surfactants contain a high percentage of aromatic moieties in their structures, which affects the thermodynamics of aggregation and their interior micellar environment. The proposed aromatic micellar core was tested using hexafluorobenzene (HFB) as a molecular probe in (19)F NMR experiments. (19)F NMR relaxation and chemical shift studies found the HFB quantitatively partitioned into the micellar interiors. Global regression analysis found that HFB interaction with DBSBA micelles possessed at least two association constants, differing by an order of magnitude, the largest being in excess of 8300 M(-1). DBSBB micellar interactions with HFB were found to be weaker, although in excess of 1100 M(-1), with a subsequent association constant of similar magnitude. Benzyl substituents of DBSBB are required for solubilization of HFB. Heteronuclear Overhauser effect spectroscopy (HOESY, (19)F-(1)H) of the DBSBB:HFB complex revealed strong interaction of HFB with benzyl substituents but not the cyclodextrin cavity.

Diffusion NMR measurements on cationic linear gold(I) complexes

In the last years, it has been demonstrated that the anion plays a key role in gold(I) catalysis, affecting yield, regio- and stereo-selectivity of processes. In order to perform such activity, necessarily the anion has to locate itself close to the reaction center. In this contribution, the level of aggregation of cationic linear gold complexes bearing different ligands, such as phosphines and carbenes, is studied by diffusion PGSE (Pulsed field Gradient Spin Echo) NMR spectroscopy as a function of concentration and solvent. It is found that functional groups, which establish specific interactions with the anion, such as –NH or polarized –CH moieties, strongly influence the self-aggregation of gold(I) complexes: ion pairs are the predominant species in solution, but ion quadruples also form in apolar solvents only when –NH or polarized –CH moieties are present in the ligand. In the absence of those functional groups free ions are present in solution with a small amount of ion pairs. Interestingly, the presence of an extended aromatic group on the cation leads to dicationic adducts and ion triples, which are held together by π–π stacking interactions. When more than one functional group is present, 19F, 1H HOESY (Heteronuclear Overhauser Effect SpectroscopY) NMR experiments and DFT coulomb potential maps are used to check which group establishes the strongest interaction with the anion.

Fluorine-decoupled carbon spectroscopy for the determination of configuration at fully substituted, trifluoromethyl- and perfluoroalkyl-bearing carbons: comparison with 19F-1H heteronuclear Overhauser effect spectroscopy.

The synthesis of a series of α-trifluoromethylcyclohexanols and analogous trimethylsilyl ethers by addition of the Ruppert–Prakash reagent to substituted cyclohexanones is presented. A method for the assignment of configuration of such compounds, of related α-trifluoromethylcyclohexylamines and of quaternary trifluoromethyl-substituted carbons is described based on the determination of the 3JCH coupling constant between the fluorine-decoupled 13CF3 resonance and the vicinal hydrogens. This method is dubbed fluorine-decoupled carbon spectroscopy and abbreviated FDCS. The method is also applied to the configurational assignment of substances bearing mono-, di-, and perfluoroalkyl rather than trifluoromethyl groups. The configuration of all substances was verified by either 19F−1H heteronuclear Overhauser spectroscopy (HOESY) or X-ray crystallography. The relative merits of FDCS and HOESY are compared and contrasted. 2JCH, 3JCH, and 4JCH coupling constants to 19F decoupled CF3 groups in alkenes and arenes have also been determined and should prove to be useful in the structural assignment of trifluoromethylated alkenes and arenes.

A new rosane-type diterpenoid from Stachys parviflora and its density functional theory studies

A new rosane-type diterpenoid (1) has been isolated from the chloroform fraction of Stachys parviflora. Structure of 1 was proposed based on 1D and 2D NMR techniques including correlation spectroscopy, heteronuclear multiple quantum coherence, heteronuclear multiple bond correlation and nuclear Overhauser effect spectroscopy. A theoretical model for the electronic and spectroscopic properties of compound 1 is also developed. The geometries and electronic properties were modelled at B3LYP/6-31G* and the theoretical scaled spectroscopic data correlate nicely with the experimental data.

NMR Studies of Sulfonamide Based Deep Eutectic Lithium Electrolytes

LiPF6 solutions in organic carbonates, the present day battery industry state of the art lithium ion battery (LIBs) electrolytes, while providing adequate performance in LIBs for consumer applications, have some well-known and considerable drawbacks. LiPF6 hydrolyzes with HF formation and decomposes thermally at near-ambient temperatures, linear carbonates have high flammability and also generate flammable gases through their decomposition. Their replacement or materials-level mitigation measures for their deficiencies should target improved battery performance at both low and high temperatures, as well as increased battery durability. Ionic liquids (ILs) have been at the forefront of the search for improved LIB electrolytes. However; many ILs are very expensive and often exhibit specific conductivities lower by more than one order of magnitude compared to LiPF6in organic carbonates even at room temperature.Deep eutectic electrolytes1 (characterized by a significant depression in the freezing point for a mixture of two or more compounds at some composition) provide a much lower cost alternative to IL’s, while matching their low flammability. Our work focuses on the sulfonamide - lithium class binary deep eutectic electrolytes.2Besides discussing some of the physical properties which determine their suitability for LIBs (electrochemical window, conductivity, viscosity), we hereby present their detailed characterization by NMR. Such a study is particularly important for an in-depth understanding of their structure and properties, which should guide ongoing efforts towards improving their properties.Specialized NMR techniques can provide insight into both the transport properties and the local environment of these deep eutectic electrolytes. In particular, diffusion ordered spectroscopy (DOSY)3 can yield information on the diffusion coefficients and transference numbers of relevant nuclei in the sulfonamide component, cation and anion, i.e., 1H, 7Li, and 19F. We will show that NMR can provide diffusion coefficients over several orders of magnitude (Figure 1). Lithium transport numbers greater than 0.5 have been observed and are hereby reported. Changes in these parameters under applied electric potential are investigated through in-situ NMR imaging techniques, whose efficacy has been demonstrated previously.4 In particular, in situ 7Li imaging can map out the both spatial and temporal dependences of concentration gradients that develop in an electrochemical cells under an applied potential. Such data can then be used to obtain diffusion coefficients and transference numbers from a mathematical solution of the inverse transport problem for the system under study.5 To further probe the solvent structure surrounding the lithium cations, we utilized 1H-7Li and 19F-7Li heteronuclear Overhauser effect spectroscopy (HOESY).6 Our NMR results will be compared with those from molecular dynamics simulations.

ChemInform Abstract: Carbon‐13 Heteronuclear Longitudinal Spin Relaxation for Geometrical (and Stereochemical) Determinations in Small‐ or Medium‐Size Molecules

AbstractReview: 62 refs.

Ion Pairing and Salt Structure in Organic Salts through Diffusion, Overhauser, DFT and X‐ray Methods

Pulsed gradient spin-echo (PGSE) diffusion characteristics for a) the new [brucinium][X] salts 6 a-f [a: X = BF(4)(-); b: X = PF(6)(-); c: X = MeSO(3)(-), d: X = CF(3)SO(3)(-); e: X = BArF(-); f: X = PtCl(3)(C(2)H(4))(-)], b) 4-tert-butyl-N-benzyl analogue, 7 and c) the aryl carbocations (p-R-C(6)H(4))(2)CH 9 a (R = CH(3)O) and 9 b (R = (CH(3))(2)N), (p-CH(3)O-C(6)H(4))(x)CPh(3-x)(+) 10 a-c (x = 1-3, respectively) and (p-R-C(6)H(4))(3)C(+) 11 (R = (CH(3))(2)N) and 12 (R = H) all in several different solvents, are reported. The solvent dependence suggests strong ion pairing in CDCl(3), intermediate ion pairing in CD(2)Cl(2) and little ion pairing in [D(6)]acetone. (1)H, (19)F HOESY NMR spectra (HOESY: heteronuclear Overhauser effect spectroscopy) for 6 and 7 reveal a specific approach of the anion with respect to the brucinium cation plus subtle changes, which are related to the anion itself. Further, for carbocations 9-12, (all as BF(4)(-) salts) based on the NOE results, one finds marked changes in the relative positions of the BF(4)(-) anion. In these aryl cationic species the anion can be located either a) very close to the carbonium ion carbon b) in an intermediate position or c) proximate to the N or O atom of the p-substituent and remote from the formally positive C atom. This represents the first example of such a positional dependence of an anion on the structure of the carbocation. DFT calculations support the experimental HOESY results. The solid-state structures for 6 c and the novel Zeise's salt derivative, [brucinium][PtCl(3)(C(2)H(4))], 6 f, are reported. Analysis of (195)Pt NMR and other NMR measurements suggest that the eta(2)-C(2)H(4) bonding to the platinum centre in 6 f is very similar to that found in K[PtCl(3)(C(2)H(4))]. Field dependent T(1) measurements on [brucinium][PtCl(3)(C(2)H(4))] and K[PtCl(3)(C(2)H(4))], are reported and suggested to be useful in recognizing aggregation effects.

Diffusion and NOE NMR Studies on Multicationic DAB‐Organoruthenium Dendrimers: Size‐Dependent Noncovalent Self‐Assembly to Megamers and Ion Pairing

New multicationic organoruthenium dendrimers (RuPF(6)-Dabn, n = 2, 4, 8, 16) have been synthesized by coupling of [Ru(eta(6)-p-cymene)(kappa(3)-dpk-OCH(2)CH(2)OH)]X (1PF(6), dpk = 2,2'-dipyridyl ketone, X = PF(6)) with 1,4-diaminobutane (DAB) and polypropylenimine dendrimer DAB-dendr-(NH(2))(n) {n=4, 8, 16} mediated by 1,1'-carbonyldiimidazole (CDI). The intermediate in the synthesis, [Ru(eta(6)-p-cymene)(kappa(3)-dpk-OCH(2)CH(2)OC(O)Im]X (2PF(6), Im = imidazole, X = PF(6)) has been isolated and characterized by single-crystal XRD. The intra- and supramolecular structures in a solution of RuPF(6)-Dabn dendrimer have been investigated by multidimensional and multinuclear NMR techniques. Diffusion NMR experiments on dilute solutions indicated that the linear distance between two metal centers (14.9-22.1 A depending on the dendrimer generation) is much greater than the diameter of 1PF(6) (9.9 A). (19)F,(1)H-HOESY NMR experiments (HOESY = heteronuclear Overhauser effect spectroscopy) showed that the counterion is positioned on the surface of the dendrimers and assumes the same relative anion-cation orientation as in 2PF(6). Diffusion NMR experiments on RuPF(6)-Dabn dendrimers in CD(2)Cl(2) at different concentrations revealed a process of supramolecular assembly of dendrimers to megamers that is strongly favored for the highest generations. Megamer formation is coupled with an increased fraction of free ions (alpha) and a consequent reduction in ion-paired ruthenium centers. Graphs of alpha versus C(Ru) (the concentration of ruthenium centers) showed a minimum for RuPF(6)-Dab4, RuPF(6)-Dab8, and RuPF(6)-Dab16 at a position coinciding with the significant presence of supramolecular dendritic dimers. The tendency to ion pairing decreases as the dendrimer generation increases.

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.

Selective HOESY experiments for stereochemical determinations

Heteronuclear Overhauser effect spectroscopy (HOESY) is a powerful method for tracking geometrical proximities between two heteronuclei (for instance, (1)H and (13)C, as this will be the case here). The method is based on cross-relaxation arising from dipolar interactions. Sensitivity permitting, it is applied in the 2D mode yielding all spatial correlations in a single experiment. Whenever sensitivity is not sufficient, it can be applied in the one-dimensional mode by selectively inverting one particular proton. In that case, it yields, from the carbon-13 spectrum, remote spatial correlations. The method has been employed here for the discrimination between two possible E or Z isomers in a medium-size molecule.

Three new sesquiterpene hemiacetals from Achillea vermicularis

Three new sesquiterpene hemiacetals, tentatively named as achilleanone (1), vermiculone (2) and vermicularone (3) have been isolated from Achillea vermicularis, along with three other known compounds β-amyrin, oleonolic acid and β-sitosterol. The structure elucidation of new compounds was based primarily on two-dimensional (2D) NMR techniques including Nuclear Overhauser Effect/Enhancement (NOE), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond correlation (HMBC) and nuclear overhauser effect spectroscopy (NOESY) experiments. Compounds 1, 2 and 3 have displayed inhibitory potential against lipoxygenase enzyme in a concentration-dependent fashion with promising IC50 values.