Rational Design of [13C,D14]Tert‐butylbenzene as a Scaffold Structure for Designing Long‐lived Hyperpolarized 13C Probes

Dynamic nuclear polarization (DNP) is a technique to polarize the nuclear spin population. As a result of the hyperpolarization, the NMR sensitivity of the nuclei in molecules can be dramatically enhanced. Recent application of the hyperpolarization technique has led to advances in biochemical and molecular studies. A major problem is the short lifetime of the polarized nuclear spin state. Generally, in solution, the polarized nuclear spin state decays to a thermal spin equilibrium, resulting in loss of the enhanced NMR signal. This decay is correlated directly with the spin‐lattice relaxation time T₁. Here we report [¹³C,D₁₄]tert‐butylbenzene as a new scaffold structure for designing hyperpolarized ¹³C probes. Thanks to the minimized spin‐lattice relaxation (T₁) pathways, its water‐soluble derivative showed a remarkably long ¹³C T₁ value and long retention of the hyperpolarized spin state.     

Nuclear Spin Singlet States in Photoactive Molecules: From Fluorescence/NMR Bimodality to a Bimolecular Switch for Spin Singlet States

Nuclear spin singlet states are silent states in nuclear magnetic resonance (NMR). However, they can be probed indirectly and offer great potential for the development of contrast agents for magnetic resonance imaging (MRI). Introduced here are two novel concepts: Firstly, the bimodal NMR/fluorescence properties of ¹³C₂‐tetraphenylethylene. It possesses a long‐lived singlet state in organic solvents, and it shortens upon the addition of water. This simultaneously increases the aggregation‐induced emission (AIE) of the molecule, resulting in a substantial enhancement of fluorescence. Secondly, introduced is a bimolecular switch for singlet states based on 3‐²H‐coumarin containing an isolated proton. Upon UV‐light exposure, a dimer forms, leading to a coupling between two previously isolated protons. A nuclear spin singlet state can now be populated. Excitation with a wavelength of 254 nm results in partial ring cleavage of the molecule back to its monomer.     

Hydrophilic domain structure in polymer exchange membranes: Simulations of NMR spin diffusion experiments to address ability for model discrimination

We detail the development of a flexible simulation program (NMR_DIFFSIM) that solves the nuclear magnetic resonance (NMR) spin diffusion equation for arbitrary polymer architectures. The program was used to explore the proton (¹H) NMR spin diffusion behavior predicted for a range of geometrical models describing polymer exchange membranes. These results were also directly compared with the NMR spin diffusion behavior predicted for more complex domain structures obtained from molecular dynamics (MD) simulations. The numerical implementation and capabilities of NMR_DIFFSIM were demonstrated by evaluating the experimental NMR spin diffusion behavior for the hydrophilic domain structure in sulfonated Diels‐Alder Poly(Phenylene) (SDAPP) polymer membranes. The impact of morphology variations as a function of sulfonation and hydration level on the resulting NMR spin diffusion behavior were determined. These simulations allowed us to critically address the ability of NMR spin diffusion to discriminate between different structural models, and to highlight the extremely high fidelity experimental data required to accomplish this. A direct comparison of experimental double‐quantum‐filtered ¹H NMR spin diffusion in SDAPP membranes to the spin diffusion behavior predicted for MD‐proposed morphologies revealed excellent agreement, providing experimental support for the MD structures at low to moderate hydration levels. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 62–78     

Discrepancy between the Spin Distribution and the Magnetic Ground State for a Triaminoxyl Substituted Triphenylphosphine Oxide Derivative

The magnetic interaction and spin transfer via phosphorus have been investigated for the tri‐tert‐butylaminoxyl para‐substituted triphenylphosphine oxide. For this radical unit, the conjugation existing between the π* orbital of the NO group and the phenyl π orbitals leads to an efficient delocalization of the spin from the radical to the neighboring aromatic ring. This has been confirmed by using fluid solution high‐resolution EPR and solid state MAS NMR spectroscopy. The spin densities located on the atoms of the molecule could be probed since ¹H, ¹³C, ¹⁴N, and ³¹P are nuclei active in NMR and EPR, and lead to a precise spin distribution map for the triradical. The experimental investigations were completed by a DFT computational study. These techniques established in particular that spin density is located at the phosphorus (ρ=?15×10^?3 au), that its sign is in line with the sign alternation principle and that its magnitude is in the order of that found on the aromatic C atoms of the molecule. Surprisingly, whereas the spin distribution scheme supports ferromagnetic interactions among the radical units, the magnetic behavior found for this molecule revealed a low‐spin ground state characterized by an intramolecular exchange parameter of J=?7.55 cm^?1 as revealed by solid state susceptibility studies and low temperature EPR. The X‐ray crystal structures solved at 293 and 30 K show the occurrence of a crystallographic transition resulting in an ordering of the molecular units at low temperature.     

Complete 1H NMR spectral analysis of ten chemical markers of Ginkgo biloba

The complete and unambiguous ¹H NMR assignments of ten marker constituents of Ginkgo biloba are described. The comprehensive ¹H NMR profiles (fingerprints) of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, bilobalide, quercetin, kaempferol, isorhamnetin, isoquercetin, and rutin in DMSO‐d₆ were obtained through the examination of 1D ¹H NMR and 2D ¹H,¹H‐COSY data, in combination with ¹H iterative full spin analysis (HiFSA). The computational analysis of discrete spin systems allowed a detailed characterization of all the ¹H NMR signals in terms of chemical shifts (δ_H) and spin‐spin coupling constants (J_HH), regardless of signal overlap and higher order coupling effects. The capability of the HiFSA‐generated ¹H fingerprints to reproduce experimental ¹H NMR spectra at different field strengths was also evaluated. As a result of this analysis, a revised set of ¹H NMR parameters for all ten phytoconstituents was assembled. Furthermore, precise ¹H NMR assignments of the sugar moieties of isoquercetin and rutin are reported for the first time. Copyright © 2012 John Wiley & Sons, Ltd.     

Studies on the phase structure of ethylene‐vinyl acetate copolymers by solid‐state 1H and 13C NMR

The phase structure of a series of ethylene‐vinyl acetate copolymers has been investigated by solid‐state wide‐line ¹H NMR and solid‐state high‐resolution ¹³C NMR spectroscopy. Not only the degree of crystallinity but the relative contents of the monoclinic and orthorhombic crystals within the crystalline region varied with the vinyl acetate (VA) content. Biexponential ¹³C NMR spin–lattice relaxation behavior was observed for the crystalline region of all samples. The component with longer ¹³C NMR spin–lattice relaxation time (T₁) was attributed to the internal part of the crystalline region, whereas the component with shorter ¹³C NMR T₁ to the mobile crystalline component was located between the noncrystalline region and the internal part of the crystalline region. The content of the mobile crystalline component relative to the internal part of the crystalline region increased with the VA content, showing that the ¹³C NMR spin–lattice relaxation behavior is closely related to the crystalline structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 2199–2207, 2002     

Solid‐state cross‐polarization magic angle spinning 13C and 15N NMR characterization of Sepia melanin,Sepia melanin free acid and Human hair melanin in comparison with several model compounds

This paper presents the high‐resolution ¹³C and ¹⁵N cross‐polarization magic angle spinning (CP/MAS) NMR spectra of three natural melanin solids: Sepia officinalis melanin, Sepia officinalis melanin free acid (MFA) and Human hair melanin. The functional group characterization of Human hair melanin by NMR is the first to date and the ¹³C CP/MAS NMR spectra reported here show improved resolution of chemically inequivalent sites. The observed spectral regions of the solid melanin samples can be assigned to the postulated structural unit of the polymer chain of Sepia MFA derived from solution‐state NMR studies. To assist in the assignment of functional groups in the spectra, the solid‐state CP/MAS NMR spectra are compared with high‐resolution ¹³C and ¹⁵N CP/MAS spectra of four model compounds, L ‐dopa, dopamine, 2‐methoxycarbonyl‐3‐ethoxycarbonyl‐4‐methylpyrrole and ethyl 5,6‐dimethoxyindole‐2‐carboxylate. To aid further in the assignment of protonated and non‐protonated carbon atoms, CP contact time dependence and non‐quaternary carbon suppression (NQS) experiments were performed on the melanin samples. The ¹⁵N CP/MAS spectra of the melanin samples confirm the presence of indole and pyrrole units in the melanin polymer chain. The NMR peaks observed in all of the melanin samples are relatively broad, presumably owing to the presence of free radicals. Electron spin resonance (ESR) data shows that all three melanin samples contain localized free radicals (g = 2.007), with the Sepia melanin containing a 10‐fold higher free radical density than Human hair melanin. Copyright © 2003 John Wiley & Sons, Ltd.     

Observation of Diastereotopic Signals in 15N NMR Spectroscopy

The first example in the literature of a compound showing anisochronous ¹⁵N atoms resulting from diastereotopicity is described. Racemic 1,3‐dimethyl‐2‐phenyloctahydro‐1H‐benzimidazole was prepared and studied by ¹H, ¹³C and ¹⁵N NMR spectroscopy. If convenient conditions were used (monitored by theoretical calculations of ²J_N‐H spin–spin coupling constants), two ¹⁵N NMR signals were observed and corresponded to the diastereotopic atoms. GIAO/density‐functional calculations of chemical shifts were not only in good agreement with the experimental values but also served as prediction tools. This study suggests that ¹⁵N NMR spectroscopy could be used to probe chirality.     

Annealing‐induced increase of permeability and amorphous‐phase mobility in an ethylene–vinylacetate copolymer

The 50% increased permeability after annealing of semicrystalline poly(ethylene/vinylacetate) containing 3 mol % vinylacetate is linked to increased mobility in the amorphous phase, as identified by line‐narrowing of ¹H wideline nuclear magnetic resonance (NMR) spectra and by reduced cross‐polarization efficiency in ¹³C NMR. Other morphological parameters, such as crystallinity, measured as 30 to 35% by differential scanning calorimetry (DSC) and NMR, are hardly changed by annealing. Small‐angle X‐ray scattering and NMR studies, using spin diffusion as well as T_1ρ and T₁ relaxation, detected only a small increase in crystallite thickness. The annealing‐induced enhancement in segmental mobility in the amorphous regions corresponds to a temperature shift of about 10 K, from which an increase of the motional rate by a factor of 2 is estimated, and which can account for the enhancement in the permeability. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 2774–2780, 2001     

Generation and detection of the radical cation and the dication derived from 4,9‐diethyl[1,4]dihydrodithiino[5,6‐f]benzotrithiole and its 5‐oxide

4,9‐Diethyl[1,4]dihydrodithiino[5,6‐f]benzotrithiole (DTBT) gave a radical cation, DTBT(•+), and a dication, DTBT(2+), on treatment with a single‐electron oxidizing reagent. Both compounds showed an ESR signal, whereas the dication, generated by this procedure, was silent for ¹H NMR. Hydrolysis of DTBT(2+) gave DTBT 1‐oxide (DTBT 1‐O) and 2‐oxide (DTBT 2‐O) together with DTBT and a mixture of several dioxides. A singlet‐state dication, DTBT(2+)‐S, which was generated upon treatment of DTBT 5‐oxide (DTBT 5‐O) with concentrated D₂SO₄, was detected by ¹H and ¹³C NMR. After 20 h, the NMR signals disappeared while the solution was active for ESR. The results suggest that (i) a species generated from DTBT by oxidation with the single‐electron oxidizing reagent is a triplet‐state dication, DTBT(2+)‐T, and (ii) DTBT(2+)‐S, initially generated, gradually isomerizes to DTBT(2+)‐T in the solution, and DTBT(2+)‐T forms a partial spin pair. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:394–401, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20445     

New Experimental Insight into the Nature of Metal−Metal Bonds in Digallium Compounds: J Coupling between Quadrupolar Nuclei

Multiple bonding between atoms is of ongoing fundamental and applied interest. Here, we report a multinuclear (¹H, ¹³C, and ⁷¹Ga) solid‐state magnetic resonance spectroscopic study of digallium compounds which have been proposed, albeit somewhat controversially, to contain single, double, and triple Ga?Ga bonds. Of particular relevance to the nature of these bonds, we have carried out two‐dimensional ⁷¹Ga J/D‐resolved NMR experiments which provide a direct measurement of J(⁷¹Ga,⁷¹Ga) spin–spin coupling constants across the gallium?gallium bonds. When placed in the context of clear‐cut experimental data for analogous singly, doubly, and triply bonded carbon spin pairs or boron spin pairs, the ⁷¹Ga NMR data clearly support the notion of a different bonding paradigm in the gallium systems. Our findings are consistent with an increasing role across the purported gallane–gallene–gallyne series for classical and/or slipped π‐type bonding orbitals.     

Solid‐state 11B and 13C NMR,IR, and X‐ray crystallographic characterization of selected arylboronic acids and their catechol cyclic esters

Nine arylboronic acids, seven arylboronic catechol cyclic esters, and two trimeric arylboronic anhydrides (boroxines) are investigated using ¹¹B solid‐state NMR spectroscopy at three different magnetic field strengths (9.4, 11.7, and 21.1 T). Through the analysis of spectra of static and magic‐angle spinning samples, the ¹¹B electric field gradient and chemical shift tensors are determined. The effects of relaxation anisotropy and nutation field strength on the ¹¹B NMR line shapes are investigated. Infrared spectroscopy was also used to help identify peaks in the NMR spectra as being due to the anhydride form in some of the arylboronic acid samples. Seven new X‐ray crystallographic structures are reported. Calculations of the ¹¹B NMR parameters are performed using cluster model and periodic gauge‐including projector‐augmented wave (GIPAW) density functional theory (DFT) approaches, and the results are compared with the experimental values. Carbon‐13 solid‐state NMR experiments and spectral simulations are applied to determine the chemical shifts of the ipso carbons of the samples. One bond indirect ¹³C‐¹¹B spin‐spin (J) coupling constants are also measured experimentally and compared with calculated values. The ¹¹B/¹⁰B isotope effect on the ¹³C chemical shift of the ipso carbons of arylboronic acids and their catechol esters, as well as residual dipolar coupling, is discussed. Overall, this combined X‐ray, NMR, IR, and computational study provides valuable new insights into the relationship between NMR parameters and the structure of boronic acids and esters. Copyright © 2012 John Wiley & Sons, Ltd.     

Spin Crossover and Valence Tautomerism in Neutral Homoleptic Iron Complexes of Bis(pyridylimino)isoindolines

Homoleptic iron complexes of six bis(pyridylimino)isoindoline (bpi) ligands with different substituents (H, Me, Et, tBu, OMe, NMe₂) at the 4‐positions of the pyridine moieties have been prepared and studied with regard to temperature‐dependent spin and redox states by a combination of ⁵⁷Fe Mössbauer spectroscopy, SQUID magnetometry, single‐crystal X‐ray diffraction analysis, X‐band EPR, and ¹H NMR spectroscopy. While the H‐, methyl‐, and ethyl‐substituted complexes remain in a pure high‐spin state irrespective of the temperature, the 4‐tert‐butyl‐substituted derivative shows spin‐crossover behavior. The methoxy‐ and dimethylamino‐substituted compounds were found to easily undergo oxidation. In the crystalline state, valence tautomeric behavior was observed for the methoxy derivative as a thermally activated charge‐transfer transition, accompanied by a spin crossover above 200 K. The valence tautomerism leads to a chelate with one of the bpi ligands as a dianion radical L^2?. and with an effective spin of S=2.     

Stacking Structure of Confined 1‐Butanol in SBA‐15 Investigated by Solid‐State NMR Spectroscopy

Understanding the complex thermodynamic behavior of confined amphiphilic molecules in biological or mesoporous hosts requires detailed knowledge of the stacking structures. Here, we present detailed solid‐state NMR spectroscopic investigations on 1‐butanol molecules confined in the hydrophilic mesoporous SBA‐15 host. A range of NMR spectroscopic measurements comprising of ¹H spin–lattice (T₁), spin–spin (T₂) relaxation, ¹³C cross‐polarization (CP), and ¹H,¹H two‐dimensional nuclear Overhauser enhancement spectroscopy (¹H,¹H 2D NOESY) with the magic angle spinning (MAS) technique as well as static wide‐line ²H NMR spectra have been used to investigate the dynamics and to observe the stacking structure of confined 1‐butanol in SBA‐15. The results suggest that not only the molecular reorientation but also the exchange motions of confined molecules of 1‐butanol are extremely restricted in the confined space of the SBA‐15 pores. The dynamics of the confined molecules of 1‐butanol imply that the ¹H,¹H 2D NOESY should be an appropriate technique to observe the stacking structure of confined amphiphilc molecules. This study is the first to observe that a significant part of confined 1‐butanol molecules are orientated as tilted bilayered structures on the surface of the host SBA‐15 pores in a time‐average state by solid‐state NMR spectroscopy with the ¹H,¹H 2D NOESY technique.     

Application of HSQC in the delineation of NMR signals of E and Z isomers of octadecyl p‐coumarates

Octadecyl p‐coumarates undergo E–Z isomerization in daylight. Although ¹H NMR, ¹³C NMR and ¹H–¹H COSY gave indications about this isomerization, the overlapping of some signals in the ¹H NMR of aromatic region prevented the delineation of signals of the individual isomers. However, heteronuclear spin quantum coupling correlation (HSQC) with the unique feature of two sets of nearby δ_C–δ_H correlations gave conclusive evidence for this isomerization and helped in the delineation of ¹H NMR and ¹³C NMR signals of E‐octadecyl p‐coumarate and Z‐octadecyl p‐coumarate. Copyright © 2012 John Wiley & Sons, Ltd.     

Heterocyclic analogs of xanthiones: 5,6‐fused 3‐methyl‐1‐phenylpyrano[2,3‐c]pyrazol‐4(1H) thiones—synthesis and NMR (1H, 13C, 15N) data

Various [5,6]pyrano[2,3‐c]pyrazol‐4(1H)‐thiones were synthesized in high yields by treatment of the corresponding [5,6]pyrano[2,3‐c]pyrazol‐4(1H)‐ones with Lawesson's reagent. Detailed NMR spectroscopic studies were undertaken of the title compounds. Complete and unambiguous assignment of chemical shifts (¹H, ¹³C, ¹⁵N) and coupling constants (¹H,¹H; ¹³C,¹H) was achieved by the combined application of various one‐ and two‐dimensional (1D and 2D) NMR spectroscopic techniques. Unequivocal mapping of most ¹³C,¹H spin coupling constants is accomplished by 2D (δ, J) long‐range INEPT spectra with selective excitation. Copyright © 2010 John Wiley & Sons, Ltd.     

Metallobiliverdin Radicals—DFT Studies

Several aspects of the molecular and electronic structure of biliverdin derivatives have been studied using density functional theory (DFT). The calculations have been performed for complexes of trianion (BvO₂)^3? and dianion [BvO(OH)]^2?, derived from two tautomeric forms of biliverdin, BvO₂H₃ and [BvO(OH)]H₂, with redox innocent metal ions: lithium(I ), zinc(II ), and gallium(III ). One‐electron‐oxidized and ‐reduced forms of each complex (cation and anion radicals) have been also considered. The molecular structures of all species investigated are characterized by a helical arrangement of tetrapyrrolic ligands with the metal ion lying in the plane formed by the two central pyrrole rings. The spin density distribution in four types of metallobiliverdin radicals—[(BvO₂^.)Mⁿ⁺]^n‐2, [{BvO(OH)^.}Mⁿ⁺]^n‐1 (cation radicals), [(BvO2^.)Mⁿ⁺]^n‐4, [{BvO(OH)^.}Mⁿ⁺]^n‐3 (anion radicals)—has been investigated. In general, the absolute values of spin density on meso carbon atoms were larger than for the β‐carbon atoms. Sign alteration of spin density has been found for meso positions, and also for the β‐carbon atoms of at least two pyrrole rings. The calculated spin density maps accounted for the essential NMR spectroscopic features of iron biliverdin derivatives, including the considerable isotropic shifts detected for the meso resonances and shift alteration at the meso and β‐positions.     

Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic investigations

NMR spectroscopic studies are undertaken with derivatives of 2‐pyrazinecarboxylic acid. Complete and unambiguous assignment of chemical shifts (¹H, ¹³C, ¹⁵N) and coupling constants (¹H,¹H; ¹³C,¹H; ¹⁵N,¹H) is achieved by combined application of various 1D and 2D NMR spectroscopic techniques. Unequivocal mapping of ¹³C,¹H spin coupling constants is accomplished by 2D (δ,J) long‐range INEPT spectra with selective excitation. Phenomena such as the tautomerism of 3‐hydroxy‐2‐pyrazinecarboxylic acid are discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

Structural determination of ε‐lactams by 1H and 13C NMR

The thermodynamic products (ε‐lactams) of the degradation of ten different spirocyclic oxaziridines were analyzed by ¹H and ¹³C NMR spectroscopy. The preferred conformations were determined by examining the homonuclear spin–spin coupling constant and the chemical shift effects of the N‐substituent and the alkyl group of the aliphatic ring on ¹H and ¹³C NMR spectra. Copyright © 2009 John Wiley & Sons, Ltd.     

Coexistence of Two Thermally Induced Intramolecular Electron Transfer Processes in a Series of Metal Complexes [M(Cat‐N‐BQ)(Cat‐N‐SQ)]/[M(Cat‐N‐BQ)2] (M=Co,Fe, and Ni) bearing Non‐Innocent Catechol‐Based Ligands: A Combined Experimental and Theoretical Study

The different thermally induced intermolecular electron transfer (IET) processes that can take place in the series of complexes [M(Cat‐N‐BQ)(Cat‐N‐SQ)]/[M(Cat‐N‐BQ)₂], for which M=Co ( 2 ), Fe ( 3 ) and Ni( 4 ), and Cat‐N‐BQ and Cat‐N‐SQ denote the mononegative (Cat‐N‐BQ^?) or dinegative (Cat‐N‐SQ^2?) radical forms of the tridentate Schiff‐base ligand 3,5‐di‐tert‐butyl‐1,2‐quinone‐1‐(2‐hydroxy‐3,5‐di‐tert‐butylphenyl)imine, have been studied by variable‐temperature UV/Vis and NMR spectroscopies. Depending on the metal ion, rather different behaviors are observed. Complex 2 has been found to be one of the few examples so far reported to exhibit the coexistence of two thermally induced electron transfer processes, ligand‐to‐metal (IET^LM) and ligand‐to‐ligand (IET^LL). IET^LL was only found to take place in complex 3 , and no IET was observed for complex 4 . Such experimental studies have been combined with ab initio wavefunction‐based CASSCF/CASPT2 calculations. Such a strategy allows one to solicit selectively the speculated orbitals and to access the ground states and excited‐spin states, as well as charge‐transfer states giving additional information on the different IET processes.