Solid‐state NMR characterizations on phase structures and molecular dynamics of poly(ethylene‐co‐vinyl acetate)

Solid‐state nuclear magnetic resonance spectroscopy and relaxation measurements, together with DSC, have been used to elucidate the structures and molecular dynamics in poly(ethylene‐co‐vinyl acetate) (EVA). It has been found that besides immobile orthorhombic and monoclinic crystalline phases, the third mobile crystalline phase (possibly the phase) of a considerable amount (36% of total crystalline phases) appears in the EVA samples, which forms during room‐temperature aging as a result of the secondary crystallization and melts at temperature somewhat higher than room temperature. Such a mobile crystalline phase has not only the well‐defined chemical shift of its own, but also has different molecular mobility from the orthorhombic phase. The mobile crystalline phase is characterized by the rapid relaxation of the longitudinal magnetization, which is caused by conventional spin‐lattice relaxation, while the slow relaxation of the longitudinal magnetization occurring in the orthorhombic phase is originated from the chain diffusion. In addition, the amorphous phase also contains two components: an interfacial amorphous phase and a melt‐like amorphous phase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2864–2879, 2006     

A Nuclear Singlet Lifetime of More than One Hour in Room‐Temperature Solution

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are supremely important techniques with numerous applications in almost all branches of science. However, until recently, NMR methodology was limited by the time constant T₁ for the decay of nuclear spin magnetization through contact with the thermal molecular environment. Long‐lived states, which are correlated quantum states of multiple nuclei, have decay time constants that may exceed T₁ by large factors. Here we demonstrate a nuclear long‐lived state comprising two ¹³C nuclei with a lifetime exceeding one hour in room‐temperature solution, which is around 50 times longer than T₁. This behavior is well‐predicted by a combination of quantum theory, molecular dynamics, and quantum chemistry. Such ultra‐long‐lived states are expected to be useful for the transport and application of nuclear hyperpolarization, which leads to NMR and MRI signals enhanced by up to five orders of magnitude.     

Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long‐Lived SABRE‐Induced Hyperpolarization

Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, ¹⁵N₂‐diazirine can be hyperpolarized by the SABRE‐SHEATH method, sustaining both singlet and magnetization states, thus offering a path to long‐lived polarization storage. Herein, we show the generality of this approach by illustrating that the diazirine tag alone is sufficient for achieving excellent signal enhancements with long‐lasting polarization. Our investigations reveal the critical role of Lewis basic additives, including water, on achieving SABRE‐promoted hyperpolarization. The application of this strategy to a ¹⁵N₂‐diazirine‐containing choline derivative demonstrates the potential of ¹⁵N₂‐diazirines as molecular imaging tags for biomedical applications.     

Hydrophilic,Upconverting, Multicolor,Lanthanide‐Doped NaGdF4 Nanocrystals as Potential Multifunctional Bioprobes

Monodisperse water‐soluble hexagonal phase Ln³⁺‐doped NaGdF₄ upconverting nanocrystals (UCNCs) have been successfully fabricated by means of a fast, facile, and environmentally friendly microwave‐assisted route with polyethylenimine as the surfactant. Fine‐tuning of the UC emission from visible to near‐IR and finally to white light has been achieved. Furthermore, studies of the magnetic resonance imaging as well as the magnetization (magnetization–magnetic field curves) and the targeted recognition properties of FA‐coupled amine‐functionalized NaGdF₄@SiO₂ UCNCs indicate that the obtained NaGdF₄ UCNCs can be potential candidates for dual‐mode optical/magnetic bioapplications.     

Gas sorption environments in poly(2,6‐dimethyl‐1,4‐phenylene oxide) by xenon‐129 nuclear magnetic resonance: Effects of processing

One‐ and two‐dimensional xenon‐129 nuclear magnetic resonance (¹²⁹Xe NMR) experiments were performed on a series of poly(2,6‐dimethyl‐1,4‐phenylene oxide) (PXE) samples to characterize the sorption environments and the relative mobility of xenon in the samples. Samples of PXE in sealed NMR tubes pressurized with xenon were studied as a function of temperature, pressure, and processing. In a dense cast film of PXE, the shift relative to the free gas resonance is smaller than that observed for typical glassy polymers, indicating a higher free volume environment. Solubility rises rapidly as temperature decreases. The lower shift and rapid increase in solubility with decreasing temperature are consistent with a relatively high free volume environment for gas sorption. If PXE is antiplasticized, the shift is slightly larger, the increase in signal intensity with decreasing temperature is smaller, and the line widths are greater. This sample is a better packed glass with less free volume and slower diffusion. Samples of PXE produced by rapid precipitation have broad lines and even lower shifts corresponding to a wide distribution of higher free volume environments. The appearance of two lines at low temperatures is consistent with the presence of a bimodal distribution of environments similar to what has been observed with positron annihilation lifetime spectroscopy. The resonance closest to the free gas resonance is associated with very large free volume elements relative to those of traditional glassy polymers. In two‐dimensional experiments, there is a rapid exchange of xenon by diffusion between the two environments, indicating the close spatial proximity of the environments. Two‐dimensional experiments and one‐dimensional progressive saturation experiments reflect a rapid exchange of xenon between the sorbed state and the free gas resonance for the precipitated samples. At low temperatures, the high field peak exchanges more rapidly with the free gas. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1965–1974, 2002     

Non‐classical Design of High‐Efficiency Sensitizers for Dye‐Sensitized Solar Cells

The dye regeneration step in a dye‐sensitized solar cell (DSSC) affects significantly the device efficiency. To be able to predict the dye regeneration efficiency by the electrolyte this paper provides a facile way to design high‐efficiency sensitizers for DSSC. This paper proposes, for the first time, a simple and ingenious way to identify the dye regeneration sites and their relative efficiencies when a specific electrolyte is used. Two steps are proposed to identify the dye regeneration sites and their relative regeneration efficiencies: (1) drawing all the resonance structures of the oxidized dye to determine the regeneration sites, and (2) choosing the most favored site for dye regeneration as the chemically softest (when the redox couple used is soft I⁻/I₃⁻ pair) and the least spatially hindered site. The regeneration sites identified by the resonance structures are consistent with the β‐LUSO (β lowest unoccupied spin orbital) distribution, which is generally used for identifying the dye regeneration sites, calculated with DT‐DFT theory. The relative dye regeneration efficiency and photovoltaic performance of both ruthenium and metal‐free organic dyes predicted by the method reported here are supported by experimental data and the proposed dye regeneration mechanism. Several types of dye molecules are used to demonstrate the correctness of this new tool. This non‐classical tool, which uses the well‐known chemical knowledge of the resonance structure and hard–soft acid–base principle, without any computer calculation or physicochemical measurement, provides a very simple and powerful tool to quickly conceive high‐efficiency sensitizers for DSSCs.     

Observation of Noise‐Triggered Chaotic Emissions in an NMR‐Maser

We report a new phenomenon observed when the magnetization of dissolved hyperpolarized ¹²⁹Xe is intense and opposite to the Boltzmann magnetization. Without radio‐frequency (rf) excitation, the system spontaneously emits a series of rf bursts characterized by very narrow bandwidths (0.03 Hz at 138 MHz). This chaotic NMR‐maser illustrates the increase in the complexity of spin dynamics at high magnetization levels by unveiling an inhomogeneous spatial organization of the xenon magnetization and an apparent dependence of the xenon transverse relaxation time on its polarization and/or on time.     

1H‐19F REDOR‐filtered NMR spin diffusion measurements of domain size in heterogeneous polymers

Solid state NMR spectroscopy is inherently sensitive to chemical structure and composition and thus makes an ideal method to probe the heterogeneity of multicomponent polymers. Specifically, NMR spin diffusion experiments can be used to extract reliable information about spatial domain sizes on multiple length scales, provided that magnetization selection of one domain can be achieved. In this paper, we demonstrate the preferential filtering of protons in fluorinated domains during NMR spin diffusion experiments using ¹H‐¹⁹F heteronuclear dipolar dephasing based on rotational echo double resonance (REDOR) MAS NMR techniques. Three pulse sequence variations are demonstrated based on the different nuclei detected: direct ¹H detection, plus both ¹H?¹³C cross polarization and ¹H?¹⁹F cross polarization detection schemes. This ¹H‐¹⁹F REDOR‐filtered spin diffusion method was used to measure fluorinated domain sizes for a complex polymer blend. The efficacy of the REDOR‐based spin filter does not rely on spin relaxation behavior or chemical shift differences and thus is applicable for performing NMR spin diffusion experiments in samples where traditional magnetization filters may prove unsuccessful. This REDOR‐filtered NMR spin diffusion method can also be extended to other samples where a heteronuclear spin pair exists that is unique to the domain of interest.     

Long‐Lived 1H Nuclear Spin Singlet in Dimethyl Maleate Revealed by Addition of Thiols

Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) have become important techniques in many research areas. One major limitation is the relatively low sensitivity of these methods, which recently has been addressed by hyperpolarization. However, once hyperpolarization is imparted on a molecule, the magnetization typically decays within relatively short times. Singlet states are well isolated from the environment, such that they acquire long lifetimes. We describe herein a model reaction for read‐out of a hyperpolarized long‐lived state in dimethyl maleate using thiol conjugate addition. This type of reaction could lend itself to monitoring oxidative stress or hypoxia by sensitive detection of thiols. Similar reactions could be used in biosensors or assays that exploit molecular switching. Singlet lifetimes of about 4.7 min for ¹H spins in [D₄]MeOH are seen in this system.     

Synthesis and Antiproliferative Activity of 6‐Ferrocenyl‐3‐Substituted 7H‐1,2,4‐Triazolo[3, 4‐b]‐1,3,4‐Thiadiazines

Five new 6‐ferrocenyl‐3‐substituted 7H‐1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazines ( 3a‐e ) have been synthesized and characterized on the basis of elemental analyses and spectral data. The antiproliferative activities were examined in two human cell lines (BJ and HT 1080) with the acid phosphatase assay. The results showed that all compounds could reduce cell viability. The significant difference between the two cell lines was that fibrosarcoma HT 1080 cells could indeed be more susceptible to the compounds than the normal fibroblast BJ cells.     

One‐Dimensional Spin Chains from CuII Ions and 2,5‐Bis(pyrazol‐1‐yl)‐1,4‐dihydroxybenzene

The purple colored coordination polymer [1 Cu]_n was obtained from 2,5‐bis(pyrazol‐1‐yl)‐1,4‐dihydroxybenzene and CuBr₂ in aqueous ammonia. The crystal structure of [1 Cu]_n was determined from high resolution X‐ray powder diffraction data using the method of simulated annealing. In the solid state, [1 Cu]_n features largely independent linear chains, all of them being oriented parallel to the c‐axis of the crystal. The Cu ions are coordinated in a square‐planar fashion by two nitrogen atoms and two anionic oxygen donors. Magnetic susceptibility and magnetization measurements indicate the Cu ions in [1 Cu]_n to be antiferromagnetically coupled with a coupling constant of about 20 K.     

Free‐Radical Termination Kinetics Studied Using a Novel SP‐PLP‐ESR Technique

Summary: A novel method for measuring termination rate coefficients, k_t, in free‐radical polymerization is presented. A single laser pulse is used to instantaneously produce photoinitiator‐derived radicals. During subsequent polymerization, radical concentration is monitored by time‐resolved electron spin resonance (ESR) spectroscopy. The size of the free radicals, which exhibits a narrow distribution increases linearly with time t, which allows the chain‐length dependence of k_t to be deduced. The method will be illustrated using dodecyl methacrylate polymerization as an example.

Two straight lines provide a very satisfactory representation of the chain‐length dependence of k_t over the entire chain‐length region (c_R = radical concentration).     

The Synthesis and Biological Evaluation of N‐Substituted 1H‐Benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines

The synthesis of 1H‐benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines has been developed. Synthesized bisheteroaryls contain two privileged medicinal scaffolds, aminopyrazole and benzimidazole, with two diversity positions at N1 of benzimidazole and C3 of pyrazole, respectively. The three‐step synthesis includes the Mitsunobu N‐alkylation of benzimidazole and subsequent one‐pot formation of aminopyrazole involving substitution of methylthio groups with amine and hydrazine followed with final ring closure. Inhibitory activity toward cyclin‐dependent kinase 2/cyclin E and cytotoxicity against two cancer cell lines were evaluated for all novel pyrazoles. Two compounds showed modest cyclin‐dependent kinase inhibition activity and cytotoxicity against cancer cell lines K562 and MCF7.     

Synthesis of Bis‐acridine Derivatives Exhibiting Anticancer and Anti‐inflammatory Activity

A series of bis‐acridine derivatives 3a – j and 5a – j have been synthesized by condensation of 9‐chloro‐2,4‐(un)substituted acridines (1a – e) and 9‐isothiocyanato‐2,4‐(un)substituted acridines (4a – e) with diamine 2a and 2b , respectively. These bis‐acridines were evaluated in vitro for activity against a panel of human cancer cell lines of lung (NCI H‐522), ovary (PA1), breast (T47D), colon (HCT‐15), and liver (HepG2). Several bis‐acridines were found to possess good anticancer activity against various cancer cell lines. Of these, compound 3h exhibited good anticancer activity against all cancer cell lines tested except liver (HepG2) cell line. In addition to this, these compounds were screened for anti‐inflammatory activity at a dose of 50 mg/kg p.o. Compound 3g exhibited 41% anti‐inflammatory activity, which is better than most commonly used standard drug ibuprofen, which showed 39% anti‐inflammatory (at 50 mg/kg p. o.) activity.     

Broadband excitation pulses for high‐field solid‐state nuclear magnetic resonance spectroscopy

In nuclear magnetic resonance spectroscopy, experimental limits due to the radiofrequency transmitter and/or coil means that conventional radiofrequency pulses (“hard pulses”) are sometimes not sufficiently powerful to excite magnetization uniformly over a desired range of frequencies. Effects due to nonuniform excitation are most frequently encountered at high magnetic fields for nuclei with a large range of chemical shifts. Using optimal control theory, we have designed broadband excitation pulses that are suitable for solid‐state samples under magic‐angle‐spinning conditions. These pulses are easy to implement, robust to spinning frequency variations, and radiofrequency inhomogeneities, and only four times as long as a corresponding hard pulse. The utility of these pulses for uniformly exciting ¹³C nuclei is demonstrated on a 900 MHz (21.1 T) spectrometer. Copyright © 2012 John Wiley & Sons, Ltd.     

NMR analysis of 6‐(2′,3′‐dihydro‐1′H‐inden‐1′‐yl)‐1H‐indene

¹H, ¹³C and two‐dimensional NMR analyses were applied to determine the NMR parameters of 6‐(2′,3′‐dihydro‐1′H‐inden‐1′‐yl)‐1H‐indene. The measurements were accomplished with 0.5 mg of the substance, this quantity being sufficient to determine the chemical shifts of all the H and C atoms, and also the appropriate coupling constants and to give the complete NMR resonance assignments of the molecule. The predicted patterns of the four different H atoms of the methylene groups of the indane structural element coincided completely with the complex patterns in the NMR spectra. Copyright © 2002 John Wiley & Sons, Ltd.     

An approach to estimate the energy and strength of the intramolecular hydrogen bond in different conformers of 4‐methylamino‐3‐penten‐2‐one

The molecular structure and intramolecular hydrogen bond energy of 32 conformers of 4‐methylamino‐3‐penten‐2‐one were investigated at MP2 and B3LYP levels of theory using the standard 6–31G** basis set and AIM analyses. Furthermore, calculations for all the possible conformations of 4‐methylamino‐3‐penten‐2‐one in water solution were also carried out at B3LYP/6–31G** level of theory. The calculated geometrical parameters and conformational analyses in gas phase and water solution show that the ketoamine conformers of this compound are more stable than the other conformers (i.e., enolimine and ketoimine). This stability is mainly due to the formation of a strong N? H···O intramolecular hydrogen bond, which is assisted by π‐electrons resonance. Hydrogen bond energies for all conformers of 4‐methylamino‐3‐penten‐2‐one were obtained from the related rotamers method. The nature of intramolecular hydrogen bond existing within 4‐methylamino‐3‐penten‐2‐one has been investigated by means of the Bader theory of atoms in molecules, which is based on topological properties of the electron density. The results of these calculations support the results which obtained by related rotamers method. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Sorption and diffusion of methanol and water in PVDF‐g‐PSSA and Nafion® 117 polymer electrolyte membranes

Sorption and diffusion properties of poly(vinylidene fluoride)‐graft‐poly(styrene sulfonic acid) (PVDF‐g‐PSSA) and Nafion® 117 polymer electrolyte membranes were studied in water/methanol mixtures. The two types of membranes were found to have different sorption properties. The Nafion 117 membrane was found to have a maximum in‐solvent uptake around 0.4 to 0.6 mole fraction of methanol, while the PVDF‐g‐PSSA membranes took up less solvent with increasing methanol concentration. The proton NMR spectra were recorded for membranes immersed in deuterated water/methanol mixtures. The spectra showed that the hydroxyl protons inside the membrane exhibit resonance lines different from the resonance lines of hydroxyl protons in the external solvent. The spectral features of the lines of these internal hydroxyl groups in the membranes were different in the Nafion membrane compared with the PVDF‐g‐PSSA membranes. Diffusion measurements with the pulsed field gradient NMR (PFG‐NMR) method showed that the diffusion coefficient of the internal hydroxyl groups in the solvent immersed Nafion membrane mirrors the changes in the diffusion coefficients of hydroxyl and methyl protons in the external solvent. For the PVDF‐g‐PSSA membranes, a decrease in the diffusion coefficient of the internal hydroxyl protons was seen with increasing methanol concentration. These results indicate that the morphology and chemical structure of the membranes have an effect on their solvent sorption and diffusion characteristics. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 3277–3284, 2000     

A Platinum(II) Phenylphenanthroimidazole with an Extended Side‐Chain Exhibits Slow Dissociation from a c‐Kit G‐Quadruplex Motif

A series of three platinum(II) phenanthroimidazoles each containing a protonable side‐chain appended from the phenyl moiety through copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) were evaluated for their capacities to bind to human telomere, c‐Myc, and c‐Kit derived G‐quadruplexes. The side‐chain has been optimized to enable a multivalent binding mode to G‐quadruplex motifs, which would potentially result in selective targeting. Molecular modeling, high‐throughput fluorescence intercalator displacement (HT‐FID) assays, and surface plasmon resonance (SPR) studies demonstrate that complex 2 exhibits significantly slower dissociation rates compared to platinum phenanthroimidazoles without side‐chains and other reported G‐quadruplex binders. Complex 2 showed little cytotoxicity in HeLa and A172 cancer cell lines, consistent with the fact that it does not follow a telomere‐targeting pathway. Preliminary mRNA analysis shows that 2 specifically interacts with the ckit promoter region. Overall, this study validates 2 as a useful molecular probe for c‐Kit related cancer pathways.     

A pH‐Responsive MRI Agent that Can Be Activated Beyond the Tissue Magnetization Transfer Window

A terbium‐based complex that displays a water exchange CEST resonance well outside the normal magnetization transfer (MT) frequency range of tissues provides a direct readout of pH values by MRI. Deprotonation of the phenolic proton in this complex results in a frequency shift of 56 ppm in a bound water molecule exchange peak between pH 5 and 8. This allows direct imaging of pH without prior knowledge of the agent concentration and with essentially no interference from the tissue MT signal.