NMR Probe Research Articles

How Solid Surfaces Control Stability and Interactions of Supported Cationic CuI(dppf) Complexes─A Solid-State NMR Study

Organometallic complexes are frequently deposited on solid surfaces, but little is known about how the resulting complex-solid interactions alter their properties. Here, a series of complexes of the type Cu(dppf)(Lx)+ (dppf = 1,1'-bis(diphenylphosphino)ferrocene, Lx = mono- and bidentate ligands) were synthesized, physisorbed, ion-exchanged, or covalently immobilized on solid surfaces and investigated by 31P MAS NMR spectroscopy. Complexes adsorbed on silica interacted weakly and were stable, while adsorption on acidic γ-Al2O3 resulted in slow complex decomposition. Ion exchange into mesoporous Na-[Al]SBA-15 resulted in magnetic inequivalence of 31P nuclei verified by 31P-31P RFDR and 1H-31P FSLG HETCOR. DFT calculations verified that a MeCN ligand dissociates upon ion exchange. Covalent immobilization via organic linkers as well as ion exchange with bidentate ligands both lead to rigidly bound complexes that cause broad 31P CSA tensors. We thus demonstrate how the interactions between complexes and functional surfaces determine and alter the stability of complexes. The applied Cu(dppf)(Lx)+ complex family members are identified as suitable solid-state NMR probes for investigating the influence of support surfaces on deposited inorganic complexes.

Praseodymium Metallacrown-Based NMR Probe for Enantioselective Discrimination of Mandelate Anions in Water.

Recently, the enhanced interest in water-soluble aminohydroximate Ln(III)-Cu(II) metallacrowns (MC) is largely due to their fascinating structural chemistry, diverse properties and ease of synthesis. We examined the water-soluble praseodymium(III) alaninehydroximate complex Pr(H2O)4[15-MCCu(II)Alaha-5]·3Cl (1) as a highly effective chiral lanthanide shift reagent for NMR analysis of the biologically relevant (R/S)-mandelate (MA) anions in aqueous media. The R-MA and S-MA enantiomers can be easily discriminated in the presence of small (1.2-6.2 mol %) amounts of MC 1 by the 1H NMR signals of multiple protons exhibiting an enantiomeric shift difference (ΔΔδ) of 0.06 ppm up to 0.31 ppm. Additionally, a possibility of coordination of MA to the metallacrown was investigated by the ESI-MS technique and a Density Functional Theory modeling of the molecular electrostatic potential and noncovalent interactions.

Determination of accessibility and spatial distribution of chiral Rh diene complexes immobilized on SBA-15 via phosphine-based solid-state NMR probe molecules

We reveal a method to quantify accessibility and location of molecular catalysts, immobilized on SBA-15 and applied in 1,2-additions.

Oligonucleotide Containing 8-Trifluoromethyl-2'-Deoxyguanosine as a Z-DNA Probe.

Z-DNA structure is a noncanonical left-handed alternative form of DNA, which has been suggested to be biologically important and is related to several genetic diseases and cancer. Therefore, investigation of Z-DNA structure associated with biological events is of great importance to understanding the functions of these molecules. Here, we described the development of a trifluoromethyl labeled deoxyguanosine derivative and employed it as a 19F NMR probe to study Z-form DNA structure in vitro and in living cells.

1H chemical shift anisotropy: a high sensitivity solid-state NMR dynamics probe for surface studies?

Dynamics play significant roles in chemistry and biochemistry-molecular motions impact both large- and small-scale chemical reactions in addition to biochemical processes. In many systems, including heterogeneous catalysts, the characterization of dynamics remains a challenge. The most common approaches involve the solid-state NMR measurement of anisotropic interactions, in particular 2H quadrupolar coupling and 1H-X dipolar coupling, which generally require isotope enrichment. Due to the high sensitivity of 1H NMR, 1H chemical shift anisotropy (CSA) is a particularly enticing, and underexplored, dynamics probe. We carried out 1H CSA and 1H-13C dipolar coupling measurements in a series of model supported complexes to understand how 1H CSA can be leveraged to gain dynamic information for heterogeneous catalysts. Mathematical descriptions are given for the dynamic averaging of the CSA tensor, and its dependence on orientation and asymmetry. The variability of the orientation of the tensor in the molecular frame, in addition to its magnitude and asymmetry, negatively impacts attempts to extract quantitative dynamic information. Nevertheless, 1H CSA measurements can reveal useful qualitative insights into the motions of a particularly dilute site, such as from a surface species.

A compact permanent magnet for microflow NMR relaxometry

We design and demonstrate a compact, robust, and simple to assemble and tune permanent magnet suitable for NMR relaxometry measurements of microfluidic flows. Soft-magnetic stainless-steel plates, incorporated inside the magnet airgap, are key for obtaining substantially improved and tunable field homogeneity. The design is scalable for different NMR probe sizes with the region of suitable field homogeneity, less than 200 ppm, achievable in a capillary length of about 50 % of the total magnet length. The built physical prototype, having 3.5x3.5x8.0 cm3 in size and 5 mm high airgap, provides a field strength of 0.5 T and sufficient field homogeneity for NMR relaxometry measurements in capillaries up to 1.6 mm i.d. and 20 mm long. The magnet was used for test flow rate measurements in a wide range, from 0.001 ml/min to 20 ml/min.

Structural Parameters of the Interaction between Ciprofloxacin and Human Topoisomerase-II β Enzyme: Toward New 19F NMR Chemical Shift Probes

New tools for cancer diagnosis are being studied since early diagnosis can be crucial for a successful treatment. In this context, the use of NMR probes constitutes an efficient method of diagnosis. In this study, we investigated the use of ciprofloxacin to indirectly label the overexpression of topoisomerase-II enzymes by changes in 19F NMR chemical shifts of ciprofloxacin. Increased topoisomerase-II expression has been associated with cancer occurrence, mainly with aggressive forms of breast cancer, thus constituting a promising molecular target for new tumor cell identifiers. Using DFT calculations, we performed a spectroscopy analysis of ciprofloxacin in different chemical environments and evaluated the solvent and enzymatic effects. Our results show that ciprofloxacin forms a stable complex with the enzyme, and the main intermolecular interactions between ciprofloxacin and human topoisomerase-IIβ are hydrogen bonds, followed by π-π stacking and electrostatic interactions. Additionally, a shift of 6.04 ppm occurs in the 19F NMR signal when ciprofloxacin interacts with the human topoisomerase-IIβ enzyme, and this parameter may be an indirect marker indicating the overexpression of these enzymes in the body.

Development of temperature-responsive suspension stabilizer and its application in cementing slurry system

To solve the problem of cement slurry suspension instability caused by a geothermal gradient in low-pressure and leakage formation, a hydrophobically associating long-chain polymer (PSAN) was designed as a suspension stabilizer by introducing hydrophilic monomer acrylamide (AM), temperature-resistant monomer 2-acrylamide-2-methyl propane sulfonic acid (AMPS), hydrophobic monomer styrene (St) and temperature-sensitive monomer N-vinyl caprolactam (NVCL). The synthesis conditions of PSAN were optimized by orthogonal response surface method. The structure and performance of PSAN were characterized and tested by IR, 1H NMR, GPC, SEM, TG, high-temperature rheology, and fluorescent probes. The research and analysis showed that PSAN had a good temperature response. At 30–65 ℃, the apparent viscosity of PSAN aqueous solution increased with the increase of temperature. At 65 ℃, the hydrophobically associating ability of PSAN was enhanced, and the retention rate of the apparent viscosity of its aqueous solution at 65–110 ℃ was still more than 83%. The good temperature response of PSAN was conducive to the suspension stability of cement slurry under the condition of large temperature differences. When 1% bwoc (percentage of cement mass) was added to the cement slurry, the free liquid of the cement slurry was 0, the water loss was less than 90 mL, and the density difference between the upper and lower sections of the cement stone column was less than 0.01 g/cm3. SEM analysis showed that there was a network structure formed by hydrophobic association between PSAN molecules in cement. In a word, under the condition of 30–110 ℃ (80 ℃ large temperature difference), the suspension stabilizer PSAN can effectively alleviate the floating of light materials and the sinking of heavy materials in cementing slurry through the hydrophobic association between molecules, and ensure the suspension stability of cementing slurry, thus contributing to the safety of cementing construction and improving the quality of cementing.

Regioselective Aromatic Perfluoro-tert-butylation Using Perfluoro-tert-butyl Phenyl Sulfone and Arynes.

The selective introduction of perfluoro-tert-butyl group (PFtB, the bulkier analogue of CF3 group) into arenes has long been sought after but remains a formidable task. We herein report the first general synthetic protocol to realize aromatic perfluoro-tert-butylation. The key to the success is the identification of PFtB phenyl sulfone as a new source of PFtB anion, which reacts with arynes in a highly regioselective manner to afford perfluoro-tert-butylated arenes in high yields. The application of the method is demonstrated by the preparation of sensitive 19F-labeled NMR probes with an extraordinary resolving ability.

NMR instrumentation- a primer

This primer covers de-bugging NMR hardware, at the level of major components (not the circuit board level). It is intended for users of NMR who are unlikely to build their own spectrometer, but will need to localize the malfunction to individual small sub-systems. Brand names and some part numbers of appropriate test equipment and lab-gadgets are given. But many users will find themselves in need of special purpose NMR probes, so construction of a dedicated probe is not beyond consideration. Thus, simple single-resonance probe circuits are discussed at greater length. The need for tuning and coupling of the probe tuned circuit is treated as an exercise in impedance matching.

4′‐SCF3‐Labeling Constitutes a Sensitive 19F NMR Probe for Characterization of Interactions in the Minor Groove of DNA

AbstractFluorinated nucleotides are invaluable for 19F NMR studies of nucleic acid structure and function. Here, we synthesized 4′‐SCF3‐thymidine (T ) and incorporated it into DNA by means of solid‐phase DNA synthesis. NMR studies showed that the 4′‐SCF3 group exhibited a flexible orientation in the minor groove of DNA duplexes and was well accommodated by various higher order DNA structures. The three magnetically equivalent fluorine atoms in 4′‐SCF3‐DNA constitute an isolated spin system, offering high 19F NMR sensitivity and excellent resolution of the positioning of T within various secondary and tertiary DNA structures. The high structural adaptability and high sensitivity of T make it a valuable 19F NMR probe for quantitatively distinguishing diverse DNA structures with single‐nucleotide resolution and for monitoring the dynamics of interactions in the minor groove of double‐stranded DNA.

4'-SCF3 -Labeling Constitutes a Sensitive 19 F NMR Probe for Characterization of Interactions in the Minor Groove of DNA.

Fluorinated nucleotides are invaluable for 19 F NMR studies of nucleic acid structure and function. Here, we synthesized 4'-SCF3 -thymidine (T ) and incorporated it into DNA by means of solid-phase DNA synthesis. NMR studies showed that the 4'-SCF3 group exhibited a flexible orientation in the minor groove of DNA duplexes and was well accommodated by various higher order DNA structures. The three magnetically equivalent fluorine atoms in 4'-SCF3 -DNA constitute an isolated spin system, offering high 19 F NMR sensitivity and excellent resolution of the positioning of T within various secondary and tertiary DNA structures. The high structural adaptability and high sensitivity of T make it a valuable 19 F NMR probe for quantitatively distinguishing diverse DNA structures with single-nucleotide resolution and for monitoring the dynamics of interactions in the minor groove of double-stranded DNA.

Real-Time 1H and 31P NMR spectroscopy of the copolymerization of cyclic phosphoesters and trimethylene carbonate reveals transesterification from gradient to random copolymers

Copolymerization is the general approach to combine properties of different polymers in a single material. We prepared the first trimethylene carbonate (TMC) phosphoester (PE) copolymers by statistical copolymerization using either stannous octanoate or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the respective catalyst. Variation of comonomer feed, reaction temperature and solvent, resulted in a library of copolymers with molar masses of up to 83,000 g/mol and moderate molar mass dispersities (<1.8). The monomer consumptions during the copolymerizations were followed by real-time 1H and 31P NMR spectroscopy in solution and in the bulk. As ring-opening copolymerization of cyclic esters often leads to gradient copolymers, also TMC and PE copolymerizations resulted in gradient copolymers, i.e. P(TMC-grad-PE)s, with different gradient strength depending on the copolymerization conditions. If a suitable transesterification catalyst like stannous octanoate was used, randomization of the gradient copolymer occurred. The 31P NMR shift of incorporated phosphoester units was used as a probe to monitor the randomization of the gradient copolymers in real-time by 31P NMR spectroscopy. The P-comonomer acts as an ideal NMR probe for in situ monitoring the changes of the copolymers’ microstructure during the transesterification by following the evolution of diads and triads. This paper focusses on the randomization procedure and gives detailed information about the copolymer structure and the kinetics of the copolymerization. The data give the possibility to understand randomization processes on a molecular scale and to fine-tune properties of polycarbonate-polyphosphoester copolymers in future applications.

19F fast MAS (60–111 kHz) dipolar and scalar based correlation spectroscopy of organic molecules and pharmaceutical formulations

19F magic angle spinning (MAS) NMR spectroscopy is a powerful tool for characterization of fluorinated solids. The recent development of 19F MAS NMR probes, operating at spinning frequencies of 60–111 kHz, enabled analysis of systems spanning from organic molecules to pharmaceutical formulations to biological assemblies, with unprecedented resolution. Herein, we systematically evaluate the benefits of high MAS frequencies (60–111 kHz) for 1D and 2D 19F-detected experiments in two pharmaceuticals, the antimalarial drug mefloquine and a formulation of the cholesterol-lowering drug atorvastatin calcium. We demonstrate that 1H decoupling is essential and that scalar-based, heteronuclear single quantum coherence (HSQC) and heteronuclear multiple quantum coherence (HMQC) correlation experiments become feasible and efficient at the MAS frequency of 100 kHz. This study opens doors for the applications of high frequency 19F MAS NMR to a wide range of problems in chemistry and biology.

129Xe NMR analysis of pore structures and adsorption phenomena in rare-earth element phosphates

Rare-earth elements (REEs) are indispensable in various applications ranging from catalysis to batteries and they are commonly found from phosphate minerals. Xenon is an excellent exogenous NMR probe for materials because it is inert and its 129Xe chemical shift is very sensitive to its local physical or chemical environment. Here, we exploit, for the first time, 129Xe NMR for the characterization of porous structures and adsorption properties of REE phosphates (REEPO4). We study four different REEPO4 samples (REE = La, Lu, Sm and Yb), including both light (La and Sm) and heavy (Lu and Yb) as well as diamagnetic (La and Lu) and paramagnetic (Sm and Yb) REEs. 129Xe resonances are very sensitive to the porous structures and moisture content of the REEPO4 samples. In the samples treated at a lower temperature (80 °C), free water hinders the access of hydrophobic xenon into small mesopores, but the treatment at a higher temperature (200 °C) removes the free water and allows xenon to explore the mesopores. Based on a standard two-site exchange model analysis of the variable-temperature 129Xe chemical shifts, as well as its proposed, novel modification for paramagnetic materials, the average mesopore sizes were determined. The size was the largest (79 nm) for the La sample with mixed monazite (70%) and rhabdophane (30%) phases and the smallest (6 nm) for the Yb sample with pure xenotime phase. The mesopore sizes of the Lu and Yb samples (12 and 6 nm) differed by a factor of two regardless of their similar xenotime phase. The 129Xe NMR analysis revealed that the heats of adsorption of the samples are similar, varying between 8.7 and 10.1 kJ/mol. For diamagnetic samples, computational modelling confirmed the order of magnitude of the chemical shifts of Xe adsorbed on surfaces and therefore the validity of the two-site exchange model analysis. Overall, 129Xe NMR provides exceptionally versatile information about the pore structures and adsorption properties of REEPO4 materials, which may be very useful for developing the extraction processes and applications of REEs.

Double-crossed radiofrequency coil with improved uniformity for rodent MRI at 7 T

A transceiver volume coil for High Field Magnetic Resonance Imaging was developed based on Temnikov’s NMR probe coil. The critical advantage of this design is that requires only one trimmer capacitor for both tuning and matching. Electromagnetic simulations of our coil were compared to a four-rung birdcage coil to evaluate their performances. A transceiver coil prototype, called the double-cross coil and a birdcage coil were built to compare and contrast their feasibility. Both coil prototypes were operated in the linear mode. Experimental quality factors were Qu/Ql=101/45 for the double-cross coil and Qu/Ql=105/43 for the birdcage coil. Phantom images were acquired to test the viability of each coil for high field magnetic resonance imaging applications. The signal-to-noise ratios, noise factors and uniformity values were also calculated: 85.26/0.74/44.48 for the double-cross coil and 76.54/1.9/65.65 for the birdcage coil. These volume coils showed similar performance, but the double-cross coil has better uniformity and a slightly lower noise figure than the birdcage coil. A remarkable agreement of experimental and simulated B1 was obtained for the double-cross coil. These experimental and numerical results demonstrate the feasibility of the double-cross volume coil with better uniformity for rodent magnetic resonance imaging at 7 T.

Development of Magnetic Field Mapping System for the MuSEUM Experiment With High Precision Using CW-NMR Probes

The MuSEUM experiment is planned at J-PARC to measure the hyperfine structure of a muonium at 1.7 T. The aim is to test the standard theory by precisely measuring the hyperfine structure of a muonium in the ground state. An important parameter is the magnetic field uniformity, which is required to be smaller than 0.2 ppm (peak-to-peak) in a rotating ellipsoid region with a diameter of 20 cm and a major axis length of 30 cm. To perform magnetic field shimming and verify the uniformity of the magnetic field, We are developing a magnetic field distribution measurement system using a CW (Continuous Wave)-NMR probe with a resolution of smaller than 10 ppb. In the present design, twenty-four CW-NMR probes are arranged in a semicircular circumference for quick measurement. Because each probe is located at a short distance, the effect of a crosstalk among probes should be minimised. Parameters of each probe has been determined and operation with multiple channels has been tested. Moreover, an influence of iron shims has been measured accurately with a eight-channel system.

Software Architecture and Hardware Organization in Mu2e Solenoid Field Mapping System

The Mu2e field mapping system is designed to produce high accuracy field maps of the detector solenoid used in the experiment. The data acquisition system is mobile and uses a self-propelled mapper with rotating arms equipped with 3D Hall probes. The measurements require not only accurate magnetic field readouts, but also accurate locations of all Hall probes while measuring data. The latter is accomplished by using the laser tracker to measure positions of several retroreflectors on the field mapper during data acquisition. The measurement process requires scanning the whole space inside the large solenoid and takes many hours to complete, which necessitates its full automation. The automation software includes control of the mapper, readout of Hall and NMR probes and control of a laser tracker, including prediction of retroreflector positions and execution of quality control checks. The software architecture and data acquisition hardware of the field mapping system are described, with special attention given to control of the laser tracker and its integration with the rest of the system.

Highly cytotoxic palladium(ii) complexes with 1,2,4-triazole-derived carbene ligands

Two novel palladium(ii) complexes, trans-[PdBr2(tz-Mes)2] and trans-[PdBr2(tz-Dipp)2] featuring less explored 1,2,4-triazole-derived N-heterocyclic carbene (tz) have been synthesized. In solution, they exist both as trans-syn and trans-anti rotamers while their syn/anti ratios can be determined by 1H NMR harnessing the built-in aromatic rings as NMR probes. Complex trans-[PdBr2(tz-Mes)2] is highly cytotoxic toward A549, MCF-7, LNCaP and HT-29 cancerous cells.

Environment-Sensitive Nucleoside Probe Unravels the Complex Structural Dynamics of i-Motif DNAs.

Although evidence for the existence and biological role of i-motif (iM) DNA structures in cells is emerging, probing their structural polymorphism and identifying physiologically active conformations using currently available tools remain a major challenge. Here, we describe the development of an innovative device to investigate the conformation equilibrium of different iMs formed by C-rich telomeric repeat and oncogenic B-raf promoter sequences using a new conformation-sensitive dual-purpose nucleoside probe. The nucleoside is composed of a trifluoromethyl-benzofuran-2-yl moiety at the C5 position of 2'-deoxyuridine, which functions as a responsive fluorescent and 19F NMR probe. While the fluorescent component is useful in monitoring and estimating the folding process, the 19F label provides spectral signatures for various iMs, thereby enabling a systematic analysis of their complex population equilibrium under different conditions (e.g., pH, temperature, metal ions, and cell lysate). Distinct 19F signals exhibited by the iMs formed by the human telomeric repeat helped in calculating their relative population. A battery of fluorescence and 19F NMR studies using native and mutated B-raf oligonucleotides gave valuable insights into the iM structure landscape and its dependence on environmental conditions and also helped in predicting the structure of the major iM conformation. Overall, our findings indicate that the probe is highly suitable for studying complex nucleic acid systems.