Exploration of the Existence Forms and Patterns of Dissolved Oxygen Molecules in Water.

The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds, and dissolved oxygen is one of the most important indicators for assessing water quality. In this work, distilled water with different concentration of dissolved oxygen were prepared, and a clear negative correlation between the size of water clusters and dissolved oxygen concentration was observed. Besides, a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled, suggesting that oxygen molecules predominantly exist at the interfaces of water clusters. Oxygen molecules can move rapidly through the interfaces among water clusters, allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and temperature. Further exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters. A semi-empirical formula relating the average number of water molecules in a cluster (n) to 17O NMR half-peak width (W) was summarized: n = 0.1 W + 0.85. These findings provide a foundation for exploring the structure and properties of water.

17 O nuclear magnetic resonance: Recent advances and applications.

The present review is focused on the most recent achievements in the application of liquid phase 17 O nuclear magnetic resonance (NMR) to inorganic, organic, and biochemical molecules focusing on their structure, conformations, and (bio)chemical behavior. The review is composed of four basic parts, namely, (1) simple molecules; (2) water and hydrogen bonding; (3) metal oxides, clusters, and complexes; and (4) biological molecules. Experimental 17 O NMR chemical shifts are thoroughly tabulated. They span a range of as much as almost 650 ppm (from -35.6 to +610.0 ppm) for inorganic and organic molecules, whereas this range is much wider for biological species being of about 1350 ppm (from -12 to +1332 ppm), and in the case of hemoproteins and heme-model compounds, isotropic chemical shifts of up to 2500 ppm were observed. The general prospects and caveats in the modern development of the liquid phase 17 O NMR in chemistry and biochemistry are critically discussed and briefly outlined in view of their future applications.

Magnetically aligned nanodiscs enable direct measurement of 17O residual quadrupolar coupling for small molecules.

The use of 17O in NMR spectroscopy for structural studies has been limited due to its low natural abundance, low gyromagnetic ratio, and quadrupolar relaxation. Previous solution 17O work has primarily focused on studies of liquids where the 17O quadrupolar coupling is averaged to zero by isotropic molecular tumbling, and therefore has ignored the structural information contained in this parameter. Here, we use magnetically aligned polymer nanodiscs as an alignment medium to measure residual quadrupolar couplings (RQCs) for 17O-labelled benzoic acid in the aqueous phase. We show that increasing the magnetic field strength improves spectral sensitivity and resolution and that each satellite peak of the expected pentet pattern resolves clearly at 18.8 T. We observed no significant dependence of the RQC magnitudes on the magnetic field strength. However, changing the orientation of the alignment medium alters the RQC by a consistent factor, suggesting that 17O RQCs measured in this way can provide reliable orientational information for elucidations of molecular structures.

17O NMR Spectroscopy: A Novel Probe for Characterizing Protein Structure and Folding.

Oxygen is a key atom that maintains biomolecular structures, regulates various physiological processes, and mediates various biomolecular interactions. Oxygen-17 (17O), therefore, has been proposed as a useful probe that can provide detailed information about various physicochemical features of proteins. This is attributed to the facts that (1) 17O is an active isotope for nuclear magnetic resonance (NMR) spectroscopic approaches; (2) NMR spectroscopy is one of the most suitable tools for characterizing the structural and dynamical features of biomolecules under native-like conditions; and (3) oxygen atoms are frequently involved in essential hydrogen bonds for the structural and functional integrity of proteins or related biomolecules. Although 17O NMR spectroscopic investigations of biomolecules have been considerably hampered due to low natural abundance and the quadruple characteristics of the 17O nucleus, recent theoretical and technical developments have revolutionized this methodology to be optimally poised as a unique and widely applicable tool for determining protein structure and dynamics. In this review, we recapitulate recent developments in 17O NMR spectroscopy to characterize protein structure and folding. In addition, we discuss the highly promising advantages of this methodology over other techniques and explain why further technical and experimental advancements are highly desired.

17 O NMR Studies of Yeast Ubiquitin in Aqueous Solution and in the Solid State.

We report a general method for amino acid-type specific 17 O-labeling of recombinant proteins in Escherichia coli. In particular, we have prepared several [1-13 C,17 O]-labeled yeast ubiquitin (Ub) samples including Ub-[1-13 C,17 O]Gly, Ub-[1-13 C,17 O]Tyr, and Ub-[1-13 C,17 O]Phe using the auxotrophic E. coli strain DL39 GlyA λDE3 (aspC- tyrB- ilvE- glyA- λDE3). We have also produced Ub-[η-17 O]Tyr, in which the phenolic group of Tyr59 is 17 O-labeled. We show for the first time that 17 O NMR signals from protein terminal residues and side chains can be readily detected in aqueous solution. We also reported solid-state 17 O NMR spectra for Ub-[1-13 C,17 O]Tyr and Ub-[1-13 C,17 O]Phe obtained at an ultrahigh magnetic field, 35.2 T (1.5 GHz for 1 H). This work represents a significant advance in the field of 17 O NMR studies of proteins.

Electrophilicity Scale of Activated Amides: 17 O†NMR and 15 N†NMR Chemical Shifts of Acyclic Twisted Amides in N-C(O) Cross-Coupling.

The structure and properties of amides are of tremendous interest in organic synthesis and biochemistry. Traditional amides are planar and the carbonyl group non-electrophilic due to nN →π*C=O conjugation. In this study, we report electrophilicity scale by exploiting 17 O NMR and 15 N NMR chemical shifts of acyclic twisted and destabilized acyclic amides that have recently received major attention as precursors in N-C(O) cross-coupling by selective oxidative addition as well as precursors in electrophilic activation of N-C(O) bonds. Most crucially, we demonstrate that acyclic twisted amides feature electrophilicity of the carbonyl group that ranges between that of acid anhydrides and acid chlorides. Furthermore, a wide range of electrophilic amides is possible with gradually varying carbonyl electrophilicity by steric and electronic tuning of amide bond properties. Overall, the study quantifies for the first time that steric and electronic destabilization of the amide bond in common acyclic amides renders the amide bond as electrophilic as acid anhydrides and chlorides. These findings should have major implications on the fundamental properties of amide bonds.

Functional stability of water wire-carbonyl interactions in an ion channel.

Water wires are critical for the functioning of many membrane proteins, as in channels that conduct water, protons, and other ions. Here, in liquid crystalline lipid bilayers under symmetric environmental conditions, the selective hydrogen bonding interactions between eight waters comprising a water wire and a subset of 26 carbonyl oxygens lining the antiparallel dimeric gramicidin A channel are characterized by 17O NMR spectroscopy at 35.2 T (or 1,500 MHz for 1H) and computational studies. While backbone 15N spectra clearly indicate structural symmetry between the two subunits, single site 17O labels of the pore-lining carbonyls report two resonances, implying a break in dimer symmetry caused by the selective interactions with the water wire. The 17O shifts document selective water hydrogen bonding with carbonyl oxygens that are stable on the millisecond timescale. Such interactions are supported by density functional theory calculations on snapshots taken from molecular dynamics simulations. Water hydrogen bonding in the pore is restricted to just three simultaneous interactions, unlike bulk water environs. The stability of the water wire orientation and its electric dipole leads to opposite charge-dipole interactions for K+ ions bound at the two ends of the pore, thereby providing a simple explanation for an ∼20-fold difference in K+ affinity between two binding sites that are ∼24 Šapart. The 17O NMR spectroscopy reported here represents a breakthrough in high field NMR technology that will have applications throughout molecular biophysics, because of the acute sensitivity of the 17O nucleus to its chemical environment.

Natural abundance 17O MAS NMR and DFT simulations: New insights into the atomic structure of designed micas.

Combining 17O Magic-Angle Spinning (MAS) NMR at natural abundance with DFT calculations is a promising methodology to shed light on the structure and disorder in tetrahedral sheets of designed micas with enhanced properties. Among brittle micas, synthetic mica is an important alternative to natural ones with a swelling sheet-like structure that results in many applications, by exploiting unique characteristics. Lowenstein's rule is one of the main chemical factor that determines the atomic structure of aluminosilicates and furthermore their properties. In the present article, 17O MAS NMR spectroscopy is used to validate (or not) the agreement of the Lowenstein's rule with the distribution of Si and Al sites in the tetrahedral sheets of synthetic micas. 17O MAS spectra of synthetic high-charged micas exhibit two regions of signals that revealed two distinguishable oxygen environments, namely Si-O-X (with X = Si, Altet, Mg) and Altet-O-Y (Y=Mg or Altet). DFT calculations were also conducted to obtain the 17O chemical shift and other NMR features like the quadrupolar coupling constant, CQ, for all of the oxygen environments encountered in the two model structures, one respecting the Lowenstein's rule and the other involving Altet-O-Altet and Si-O-Si environments. Our DFT calculations support the 17O assignment, by confirming that Altet-O-3Mg and Altet-O-Altet oxygen environments show chemical shifts under 30 ppm and more important, with quadrupolar coupling constants of about 1 MHz, in line with the spectral observation. By quantifying the 17O MAS NMR spectra at natural abundance, we demonstrate that one of the synthetic mica compositions does not meet the Lowenstein's rule.

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by 17O NMR spectroscopy.

Cyclic benziodoxole systems have become a premier scaffold for the design of electrophilic transfer reagents. A particularly intriguing aspect is the fundamental II-IIII tautomerism about the hypervalent bond, which has led in certain cases to a surprising re-evaluation of the classic hypervalent structure. Thus, through a combination of 17O NMR spectroscopy at natural abundance with DFT calculations, we establish a convenient method to provide solution-phase structural insights for this class of ubiquitous reagents. In particular, we confirm that Shen's revised, electrophilic SCF3-transfer reagent also adopts an "acyclic" thioperoxide tautomeric form in solution. After calibration, the approach described herein likely provides a more general and direct method to distinguish between cyclic and acyclic structural features based on a single experimental 17O NMR spectrum and a computationally-derived isotropic shift value. Furthermore, we apply this structural elucidation technique to predict the constitution of an electrophilic iodine-based cyano-transfer reagent as an NC-I-O motif and study the acid-mediated activation of Togni's trifluoromethylation reagent.

An 17 O NMR study of diamagnetic and paramagnetic lanthanide-tris(oxydiacetate) complexes in aqueous solution.

17 O-enriched complexes between oxydiacetate ligand and several diamagnetic and paramagnetic lanthanide(III) metal ions (Ln) were investigated by solution-state 17 O NMR spectroscopy. The bound-state signals of chelating (Oin ) and nonchelating (Oout ) oxygen atoms of the carboxylate groups were observed for all the samples investigated. The data indicate that the 17 O line width is dominated by contributions from both quadrupole relaxation and chemical exchange in the case of Pr and Nd complexes. Dissection of the chemical shift induced by metal ions on Oin  into Fermi contact and pseudocontact contributions was performed , and the hyperfine coupling constant (A/ℏ) was estimated. No evidence of structural changes within the series was detected.

Modeling short-range substitution order and disorder in crystals: Application to the Ga/Si distribution in a natrolite zeolite.

Atomic substitutions are a central feature of the physicochemical properties of an increasing number of solid-state materials. The complexity that this chemical disorder locally generates in otherwise crystalline solids poses a major challenge to the understanding of the relationships between the structure and properties of materials at the atomic and molecular level. Strategies designed to efficiently explore the ensemble of local chemical environments present in disordered crystals and predict their signatures in local spectroscopies such as solid-state nuclear magnetic resonance (NMR) are therefore essential. Focusing on the Ga/Si disorder in the framework of rubidium-exchanged gallosilicate natrolite zeolite (Rb-PST-1) with a high Ga content (SiGa=1.28), we show how the structure-generation approach implemented in the new program supercell (Okhotnikov et al. [26]) provides an excellent basis for the understanding of complex experimental spectroscopic data. Furthermore, we describe how exhaustive explorations of atomic configurations can be performed to seek local structural ordering and/or disordering factors. In the case of Rb-PST-1, we more specifically explore the possibility to form and to detect the presence of thermodynamically unfavorable Ga-O-Ga connectivities. While particularly adapted to the description of dense materials, we demonstrate that this approach may successfully be used to reproduce and interpret the distributions of local structural distortions (i.e., the geometrical disorder) resulting from the chemical disorder in systems as complex as microporous zeolites.

Structural roles of calcium in alkaline and alkaline-earth aluminosilicate glasses by solid-state 43Ca, 17O and 27Al NMR.

Structural roles of Ca in aluminosilicate glasses have been investigated by solid-state 43Ca, 17O, and 27Al NMR spectroscopy. In 15Al2O3-55SiO2-15CaO-15RO (R=Mg, Ca, Sr, and Na2) (mol%) glass systems wherein half of the alkaline plus alkaline-earth cations charge-compensate (AlO4)‒ tetrahedra and the other half modify the glass network, with decreasing cation field strength (CFS) in the order of Mg2+>Ca2+>Sr2+>Na+, the isotropic chemical shift (δiso) of 43Ca moves to a higher frequency and the quadrupolar coupling constant (PQ) of 43Ca decreases. The change in the δiso of 43Ca is more sensitive to the role of Ca than that in the PQ of 43Ca. The two possible roles (network modifier and charge compensator) of Ca in the glass with R=Ca are not distinguished in the 43Ca 3QMAS and 5QMAS spectra. The 17O 3QMAS results demonstrate that the cation with higher CFS (e.g., Mg2+ in the R=Mg glass and Ca2+ in the R=Na2 glass) dominantly creates non-bridging oxygen, even though there is slight cation mixing. With increasing CFS in the glass, the PQ of both 43Ca and 27Al also increases, indicating that the cation with higher CFS tends to degrade the structural symmetry.

Solid-state 17O NMR study of 2-acylbenzoic acids and warfarin.

We report synthesis and solid-state 17O NMR characterization of four site-specifically 17O-labeled 2-acylbenzoic acids (2-RC(O)C6H4COOH) where R=H and CH3): 2-[3-17O]formylbenzoic acid, 2-[1,2-17O2]formylbenzoic acid, 2-[3-17O]acetylbenzoic acid, and 2-[1,2,3-17O3]acetylbenzoic acid. In the solid state, both 2-formyl- and 2-acetyl-benzoic acids exist as the cyclic phthalide form each containing a five-membered lactone ring and a cyclic hemiacetal/hemiketal group. Static and magic-angle-spinning 17O NMR spectra were recorded at 14.1 and 21.1T for these compounds, from which the 17O chemical shift and nuclear quadrupolar coupling tensors were determined for each oxygen site. These results represent the first time that 17O NMR tensors are fully characterized for lactone, cyclic hemiacetal, and cyclic hemiketal functional groups. We also report solid-state 17O NMR data for the cyclic hemiketal group an anticoagulant drug, warfarin. Experimental 17O NMR tensors in these compounds were compared with computational results obtained with a periodic DFT code BAND.

Simple (17) O NMR method for studying electron self-exchange reaction between UO2 (2+) and U(4+) aqua ions in acidic solution.

(17) O NMR spectroscopy is proven to be suitable and convenient method for studying the electron exchange by following the decrease of (17) O-enrichment in U(17) OO(2+) ion in the presence of U(4+) ion in aqueous solution. The reactions have been performed at room temperature using I = 5 M ClO4 (-) ionic medium in acidic solutions in order to determine the kinetics of electron exchange between the U(4+) and UO2 (2+) aqua ions. The rate equation is given as R = a[H(+) ](-2) + R', where R' is an acid independent parallel path. R' depends on the concentration of the uranium species according to the following empirical rate equation: R' = k1 [UO(2 +) ](1/2) [U(4 +) ](1/2) + k2 [UO(2 +) ](3/2) [U(4 +) ](1/2) . The mechanism of the inverse H(+) concentration-dependent path is interpreted as equilibrium formation of reactive UO2 (+) species from UO2 (2+) and U(4+) aqua ions and its electron exchange with UO2 (2+) . The determined rate constant of this reaction path is in agreement with the rate constant of UO2 (2+) -UO2 (+) , one electron exchange step calculated by Marcus theory, match the range given experimentally of it in an early study. Our value lies in the same order of magnitude as the recently calculated ones by quantum chemical methods. The acid independent part is attributed to the formation of less hydrolyzed U(V) species, i.e. UO(3+) , which loses enrichment mainly by electron exchange with UO2 (2+) ions. One can also conclude that (17) O NMR spectroscopy, or in general NMR spectroscopy with careful kinetic analysis, is a powerful tool for studying isotope exchange reactions without the use of sophisticated separation processes. Copyright © 2015 John Wiley & Sons, Ltd.

Associating a negatively charged GdDOTA-derivative to the Pittsburgh compound B for targeting Aß amyloid aggregates.

We have conjugated the tetraazacyclododecane-tetraacetate (DOTA) chelator to Pittsburgh compound B (PiB) forming negatively charged lanthanide complexes, Ln(L4), with targeting capabilities towards aggregated amyloid peptides. The amphiphilic Gd(L4) chelate undergoes micellar aggregation in aqueous solution, with a critical micellar concentration of 0.68 mM, lower than those for the neutral complexes of similar structure. A variable temperature (17)O NMR and NMRD study allowed the assessment of the water exchange rate, k ex (298) = 9.7 × 10(6) s(-1), about the double of GdDOTA, and for the description of the rotational dynamics for both the monomeric and the micellar forms of Gd(L4). With respect to the analogous neutral complexes, the negative charge induces a significant rigidity of the micelles formed, which is reflected by slower and more restricted local motion of the Gd(3+) centers as evidenced by higher relaxivities at 20-60 MHz. Surface Plasmon Resonance results indicate that the charge does not affect significantly the binding strength to Aß1-40 [K d = 194 ± 11 µM for La(L4)], but it does enhance the affinity constant to human serum albumin [K a = 6530 ± 68 M(-1) for Gd(L4)], as compared to neutral counterparts. Protein-based NMR points to interaction of Gd(L4) with Aß1-40 in the monomer state as well, in contrast to neutral complexes interacting only with the aggregated form. Circular dichroism spectroscopy monitored time- and temperature-dependent changes of the Aß1-40 secondary structure, indicating that Gd(L4) stabilizes the random coil relative to the α-helix and ß-sheet. TEM images confirm that the Gd(L4) complex reduces the formation of aggregated fibrils.

Saturated amine oxides: part 10. hydroacridines: part 32. linear ¹7O/¹³C and ¹³C/¹³C chemical shift correlations between saturated azaheterocyclic N-methylamine N-oxides, and the methiodides of their parent amines.

Two kinds of good linear correlations were found between the chemical shifts of saturated six-membered azaheterocyclic N-methylamine N-oxides and the chemical shifts of the methiodides of their parent amines. One of the correlations occurs between the (17)O chemical shift of the N(+)-O(-) oxygen in the N-oxides and the (13)C chemical shift of the N(+)-CH3 methyl group analogously situated in the appropriate methiodide (r = 0.9778). This correlation enables unambiguous configuration assignment of the N(+)-O(-) bond, even if the experimentally observed (17)O chemical shift of only one N-epimer is available, provided the (13)C chemical shifts of both N(+)-CH3 groups in the methiodide are known and assigned; furthermore, it can be used also for the estimation of (17)O chemical shifts of the N(+)-O(-) oxygens in N-epimeric pairs of N-oxides, for which observed (17)O data hardly become available. The second correlation is observed between the (13)C chemical shift of the N(+)-CH3 methyl group in the N-oxides and the (13)C chemical shift of the N(+)-CH3 methyl group analogously situated in the appropriate methiodide (r = 0.9785). It can be used for safe configuration assignment of the N(+)-CH3 group and, indirectly, also of the N(+)-O(-) bond in an amine N-oxide, even if no (17)O NMR data, and the (13)C chemical shift of only one N-epimer is available.

Solid-state ¹7O NMR spectroscopy of paramagnetic coordination compounds.

High-quality solid-state (17)O (I=5/2) NMR spectra can be successfully obtained for paramagnetic coordination compounds in which oxygen atoms are directly bonded to the paramagnetic metal centers. For complexes containing V(III) (S=1), Cu(II) (S=1/2), and Mn(III) (S=2) metal centers, the (17)O isotropic paramagnetic shifts were found to span a range of more than 10,000 ppm. In several cases, high-resolution (17)O NMR spectra were recorded under very fast magic-angle spinning (MAS) conditions at 21.1 T. Quantum-chemical computations using density functional theory (DFT) qualitatively reproduced the experimental (17)O hyperfine shift tensors.

Entrapment of a neutral Tm(III)-based complex with two inner-sphere coordinated water molecules into PEG-stabilized vesicles: towards an alternative strategy to develop high-performance LipoCEST contrast agents for MR imaging.

Chemical exchange saturation transfer (CEST) probes issued from the encapsulation of a water proton paramagnetic shift reagent into the inner aqueous volume of lipid vesicles provide an emerging class of frequency-selective contrast agents with huge potential in the field of molecular magnetic resonance imaging (MRI). This work deals with the generation of such LipoCEST agents properly designed to optimize, under isotonic conditions, the chemical shift offset of the intra-liposomal water protons as well as the number of exchangeable protons under reasonably low radiofrequency (RF) fields of saturation. The strategy lies in the loading of poly(ethylene glycol)-stabilized nanosized liposomes with uncharged lanthanide chelates, binding more than one water molecule in the first hydration sphere, exemplified here by [Tm(III)-DO3A (H2 O)2 ] complex. The key properties of the probes are demonstrated by complementary NMR investigations. The residence lifetime of the water molecules coordinated to the lanthanide center was outstandingly short (9.5 ± 0.2 ns from (17) O NMR), and indeed relevant for effective LipoCEST responsiveness. The (1) H NMR CEST spectra (7.01 T magnetic field) prove that the theoretically expected optimal sensitivity can be approximated in the nanomolar concentration range, at reasonably low RF presaturation pulses (6.7-12 µT) and saturation frequency offsets of the intra-liposomal water protons beyond 10 ppm, making possible selective irradiation in biological environment. CEST-MRI images (7.01 T magnetic field and 10-12 µT RF pulse) explicitly confirm the interest of these newly conceived LipoCEST agents, indeed among the most efficient ones developed so far under isosmotic conditions.

Wobbling and Hopping: Studying Dynamics of CO2 Adsorbed in Metal-Organic Frameworks via (17)O Solid-State NMR.

Knowledge of adsorbed gas dynamics within microporous solids is crucial for the design of more efficient gas capture materials. We demonstrate that (17)O solid-state NMR (SSNMR) experiments allow one to obtain accurate information on CO2 dynamics within metal-organic frameworks (MOFs), using CPO-27-M (M = Mg, Zn) as examples. Variable-temperature (VT) (17)O SSNMR spectra acquired from 150 to 403 K yield key parameters defining the CO2 motions. VT (17)O SSNMR spectra of CPO-27-Zn indicate relatively weaker metal-oxygen binding and increased CO2 dynamics. (17)O SSNMR is a sensitive probe of CO2 dynamics due to the presence of both the quadrupolar and chemical shielding interactions, and holds potential for the investigation of motions within a variety of microporous materials.

Intramolecular interactions in ortho-methoxyalkylphenylboronic acids and their catechol esters.

Catechol esters of ortho-methoxyalkylphenylboronic acids have been synthesized and characterized by (17)O NMR spectroscopy. The results were compared with the data for the parent acids. The influence of intramolecular and intermolecular hydrogen bonds on the properties of the boronic acids has been discussed. The (17)O NMR data for the boronic esters proved that there are no O → B interactions in the investigated compounds. This fact is connected with weak Lewis acidity of the parent acids and their low sugars' receptors activity. Crystal structure of ortho-methoxyphenylboronic acid catechol ester was determined.