Heteronuclear Overhauser Effect Research Articles

A Comparison of Bonded and Nonbonded Zinc(II) Force Fields with NMR Data

Classical molecular dynamics (MD) simulations are widely used to inspect the behavior of zinc(II)-proteins at the atomic level, hence the need to properly model the zinc(II) ion and the interaction with its ligands. Different approaches have been developed to represent zinc(II) sites, with the bonded and nonbonded models being the most used. In the present work, we tested the well-known zinc AMBER force field (ZAFF) and a recently developed nonbonded force field (NBFF) to assess how accurately they reproduce the dynamic behavior of zinc(II)-proteins. For this, we selected as benchmark six zinc-fingers. This superfamily is extremely heterogenous in terms of architecture, binding mode, function, and reactivity. From repeated MD simulations, we computed the order parameter (S2) of all backbone N-H bond vectors in each system. These data were superimposed to heteronuclear Overhauser effect measurements taken by NMR spectroscopy. This provides a quantitative estimate of the accuracy of the FFs in reproducing protein dynamics, leveraging the information about the protein backbone mobility contained in the NMR data. The correlation between the MD-computed S2 and the experimental data indicated that both tested FFs reproduce well the dynamic behavior of zinc(II)-proteins, with comparable accuracy. Thus, along with ZAFF, NBFF represents a useful tool to simulate metalloproteins with the advantage of being extensible to diverse systems such as those bearing dinuclear metal sites.

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.

Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability.

HIV-1 capsid is comprised of over a hundred p24 protein molecules, arranged as either pentamers or hexamers. Three p24 mutants with amino acid substitutions in capsid N-terminal domain protein were examined: G60W (α3-4 loop), M68T (helix 4), and P90T (α4-5 loop), which exhibited no viability for biological activity. One common structural feature of the three p24 N-domain mutants, examined by NMR, was the long-range effect of more β-structures at the β2-strand in the N-terminal region compared with the wild-type. In addition, the presence of fewer helical structures was observed in M68T and P90T, beyond the broad area from helix 1 to the C-terminal part of helix 4. This suggests that both N-terminal beta structures and helices play important roles in the formation of p24 hexamers and pentamers. Next, compared with P90T, we examined cis-conformation or trans-conformation of wild-type adopted by isomerization at G89-P90. Since P90T mutant adopts only a trans-conformation, comparison of chemical shifts and signal intensities between each spectra revealed that the major peaks (about 85%) in the spectrum of wild-type correspond to trans-conformation. Furthermore, it was indicated that the region in cis-conformation (minor; 15%) was more stabilized than that observed in trans-conformation, based on the analyses of heteronuclear Overhauser effect as well as the order-parameter. Therefore, it was concluded that the cis-conformation is more favorable than the trans-conformation for the interaction between the p24 N-terminal domain and cyclophilin-A. This is because HIV-1 with a P90T protein, which adopts only a trans-conformation, is associated with non-viability of biological activity.

Evidence of C-F···H-C Attractive Interaction: Enforced Coplanarity of a Tetrafluorophenylene-Ethynylene-Linked Porphyrin Dimer.

The formation of C-F···H-C "hydrogen bonds" has been a controversial subject because, in principle, fluorine is hardly an acceptor for less acidic protons contrasting to the C-F···H-O and C-F···H-N hydrogen bonds. Nevertheless, the interaction is emerging as a powerful implement for confining the torsional rotation in the design of fully coplanar π-conjugated polymers. Heretofore, no evidence of the C-F···H-C interaction has been observed in solutions. We herein disclose comprehensive evidence that the C-F···H-C interaction produces an attractive force. A 19F-1H heteronuclear Overhauser effect experiment elucidated the close proximity of the F and H atoms in the doubly edge-facing C-F···H-C interactions of a meso-tetrafluorophenylene-ethynylene-conjugated porphyrin dimer (1). Extensive electronic and photophysical property investigations confirmed that all the aromatic units were torsionally restricted by the C-F···H-C interactions. Moreover, the enforced coplanarity invoked a markedly high π-staking propensity. Thus, we have firmly established the formation of a C-F···H-C interaction that produces a hydrogen-bond-like attractive force in solution.

Effects of Excipients on the Structure and Dynamics of Filgrastim Monitored by Thermal Unfolding Studies by CD and NMR Spectroscopy.

Product excipients are used to confer a number of desirable properties on the drug substance to maintain or improve stability and facilitate drug delivery. This is especially important for products where the active pharmaceutical ingredient (API) is a recombinant protein. In this study, we aimed to determine if excipients and formulation conditions affect the structure and/or modulate the dynamics of the protein API of filgrastim products. Samples of uniformly labeled 15N-Met-granulocyte-colony stimulating factor (GCSF) were prepared at 100 μM (near formulation concentration) with various concentrations of individual components (polysorbate-20 and -80, sorbitol) and three pH values. Nuclear magnetic resonance (NMR) spectroscopy techniques were applied to measure chemical shift perturbation (CSP) to detect structural changes, and relaxation parameters (T1, T2, and heteronuclear Overhauser effect) were measured to probe the effects on protein backbone motions. In parallel, the same solution conditions were subjected to protein thermal unfolding studies monitored by circular dichroism spectropolarimetry (CD). Detergents (polysorbate-20 and 80) do not induce any observable changes on the protein structure and do not modify its dynamics at formulation concentration. Lowering pH to 4.0, a condition known to stabilize the conformation of filgrastim, as well as the addition of sorbitol produced changes of the fast motion dynamics in the nanosecond and picosecond timescale. NMR-derived order parameters, which measure the local conformational entropy of the protein backbone, show that lowering pH leads to a compaction of the four-helix bundle while the addition of sorbitol relaxes helices B and C, thereby reducing the mobility of loop CD. CSPs and measurements of protein dynamics via NMR-derived order parameters provide a description in structural and motional terms at an atomic resolution on how formulation components contribute to the stabilization of filgrastim products.

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.

On the interference of urea with CO2/CO32- chemistry of cellulose model solutions in NaOH(aq)

The CO2/CO32− chemistry of the cellulose/NaOH(aq) solutions has been recently reported to comprise a CO2 incorporation through formation of a transient cellulose carbonate intermediate along with cellulose – CO32− interactions. This work explores on molecular interactions arising when this chemistry is brought together with urea, the most common stabiliser of these solutions. 1H, 13C and steady-state heteronuclear Overhauser effect NMR studies on the cellulose analogues (methyl-β-glucopyranoside (β-MeO-Glcp) and microcrystalline cellulose), combined with pH and ATR-FTIR measurements, reveal concurrent interactions of urea with both CO2 and CO32−– leading to increased uptake of CO2 and a buffering effect. Yet, regardless of the presence of urea, the route of conversion from CO2 to CO32-, whether going through reaction with the carbohydrate alkoxides or OH−, is likely to determine the chemical environment of the formed CO32-. These findings shed a new light on rather overlooked, albeit prominent, interactions in these solutions with the readily absorbed air CO2, essential for further development and implementation, whether towards regenerated and modified cellulose or CO2-capturing concepts.

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.

Deleterious effects of carbon-carbon dipolar coupling on RNA NMR dynamics.

Many regulatory RNAs undergo dynamic exchanges that are crucial for their biological functions and NMR spectroscopy is a versatile tool for monitoring dynamic motions of biomolecules. Meaningful information on biomolecular dynamics requires an accurate measurement of relaxation parameters such as longitudinal (R1) rates, transverse (R2) rates and heteronuclear Overhauser effect (hNOE). However, earlier studies have shown that the large 13C-13C interactions complicate analysis of the carbon relaxation parameters. To investigate the effect of 13C-13C interactions on RNA dynamic studies, we performed relaxation measurements on various RNA samples with different labeling patterns and compared these measurements with the computational simulations. For uniformly labeled samples, contributions of the neighboring carbon to R1 measurements were observed. These contributions increased with increasing magnetic field and overall correlation time ([Formula: see text]) for R1 rates, necessitating more careful analysis for uniformly labeled large RNAs. In addition, the hNOE measurements were also affected by the adjacent carbon nuclei. Unlike R1 rates, R1ρ rates showed relatively good agreement between uniformly- and site-selectively labeled samples, suggesting no dramatic effect from their attached carbon, in agreement with previous observations. Overall, having more accurate rate measurements avoids complex analysis and will be a key for interpreting 13C relaxation rates for molecular motion that can provide valuable insights into cellular molecular recognition events.

Exploring Protein Structures by DNP-Enhanced Methyl Solid-State NMR Spectroscopy.

Although the rapid development of sensitivity-enhanced solid-state NMR (ssNMR) spectroscopy based on dynamic nuclear polarization (DNP) has enabled a broad range of novel applications in material and life sciences, further methodological improvements are needed to unleash the full potential of DNP-ssNMR. Here, a new methyl-based toolkit for exploring protein structures is presented, which combines signal-enhancement by DNP with heteronuclear Overhauser effect (hetNOE), carbon-carbon-spin diffusion (SD) and strategically designed isotope-labeling schemes. It is demonstrated that within this framework, methyl groups can serve as dynamic sensors for probing local molecular packing within proteins. Furthermore, they can be used as "NMR torches" to selectively enlighten their molecular environment, e.g., to selectively enhance the polarization of nuclei within residues of ligand-binding pockets. Finally, the use of 13C-13C spin diffusion enables probing carbon-carbon distances within the subnanometer range, which bridges the gap between conventional 13C-ssNMR methods and EPR spectroscopy. The applicability of these methods is directly shown on a large membrane protein, the light-driven proton pump green proteorhodopsin (GPR), which offers new insight into the functional mechanism of the early step of its photocycle.

The CO2/CO32\u2212chemistry of the NaOH(aq) model system applicable to cellulose solutions

Molecular interactions governing the recently reported CO2/CO32− chemistry of cellulose/NaOH(aq) solutions are investigated using a cellulose analogue methyl-β-D-glucopyranoside in NaOH(aq) solutions under conditions feasible with cellulose dissolution. 1H, 13C and steady-state heteronuclear Overhauser effect NMR spectroscopy complemented by pH measurements reveal carbohydrate–CO32− interactions as an important component of this chemistry. However, depending on in which order carbohydrate and CO32− are brought together in NaOH(aq) this interaction is different with different implications on stability of the CO32− in the solution.

Influence of urea on methyl upbeta-D-glucopyranoside in alkali at different temperatures

The dissolution efficiency plays an important role on the properties of regenerated cellulose-based products. Urea is known to be one of the additives aiding to improve cellulose dissolution in the NaOH(aq) system. The acting mechanism caused by urea has been debated and one of the hypothesis is that urea could induce a conformational change on cellulose, which promotes dissolution. Here we used NMR spectroscopy on a model system for cellulose, namely, methyl upbeta-D-glucopyranoside (upbeta-MeO-Glcp) and compared chemical shifts and J couplings, which both are indicators for conformational changes, as a function of temperature and upon the addition of urea. We found that in NaOH(aq), the hydroxymethyl group changes its conformation in favour of the population of the gt rotamer, while the presence of urea induced temperature dependent conformational changes. Heteronuclear Overhauser effect experiments showed that urea associates with cellulose but in a non-specific manner. This suggests that urea rather than binding to the carbohydrate, changes the chemical environment inducing a change in conformation of upbeta-MeO-Glcp and likely also for cellulose when dissolved in NaOH(aq) with urea.

Mobility of Histidine Side Chains Analyzed with 15N NMR Relaxation and Cross-Correlation Data: Insight into Zinc-Finger-DNA Interactions.

Due to chemical exchange, the mobility of histidine (His) side chains of proteins is typically difficult to analyze by NMR spectroscopy. Using an NMR approach that is uninfluenced by chemical exchange, we investigated internal motions of the His imidazole NH groups that directly interact with DNA phosphates in the Egr-1 zinc-finger-DNA complex. In this approach, the transverse and longitudinal cross-correlation rates for 15N chemical shift anisotropy and 15N-1H dipole-dipole relaxation interference were analyzed together with 15N longitudinal relaxation rates and heteronuclear Overhauser effect data at two magnetic field strengths. We found that the zinc-coordinating His side chains directly interacting with DNA phosphates are strongly restricted in mobility. This makes a contrast to the arginine and lysine side chains that retain high mobility despite their interactions with DNA phosphates in the same complex. The entropic effects of side-chain mobility on the molecular association are discussed.

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.

Optimization of signal-to-noise ratio in the in vivo31P magnetic resonance spectra of the human brain

The main problem in 31P magnetic resonance spectroscopy is a low signal-to-noise ratio (SNR) of spectra acquired with clinical magnetic resonance imaging (MRI) scanners. Using spin-spin phosphorus-proton (31P-1H) decoupling and heteronuclear Overhauser effect and taking into account the effect of the longitudinal relaxation time T1 on the SNR, the method for localization and excitation of the region of interest (Image Selected in vivo Spectroscopy pulse sequence) was optimized to increase the SNR in the 31P magnetic resonance spectra of the human brain to ~50% without increasing signal acquisition time.

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.