Michael addition of indoles to β-nitrostyrenes catalyzed by HY zeolite under solvent-free conditions

Michael addition of indoles to β-nitrostyrenes is reported using HY zeolite as catalyst under mild reaction conditions. This methodology allows the synthesis of various indole derivatives in good to high yields at 50 °C under solvent-free conditions. The short reaction time and achieving high yield of the desired products are the main advantages of the present work. The catalyst can be easily recovered and reused for six successive runs without considerable changes in yields. This Michael addition catalyzed by HY zeolite is operationally simple and can be considered as a greener protocol as it avoids the use of corrosive acids and toxic reagents.     

Highly Selective “Turn‐On” Fluorescent and Colorimetric Sensing of Fluoride Ion Using 2‐(2‐Hydroxyphenyl)‐2,3‐dihydroquinolin‐4(1 H)‐one based on Excited‐State Proton Transfer

A simple, highly selective and sensitive colorimetric system for the detection of fluoride ion in an aqueous medium has been developed using 2‐(2‐hydroxyphenyl)‐2,3‐dihydroquinolin‐4(1 H)‐one. This system allows selective “turn‐on” fluorescence detection of fluoride ion, which is found to be dependent upon guest basicity. An excited‐state proton transfer is proposed to be the signaling mechanism, which is rationalized by DFT and TD‐DFT calculations. The present sensor can also be applied to detect fluoride levels in real water samples.     

In vivo EPR imaging of the distribution and metabolism of nitroxide radicals in human skin

While altered cellular free radical and redox metabolism are critical factors in many human diseases, it has not been previously possible to both measure and image these processes in humans. The development and application of electron paramagnetic resonance instrumentation capable of in vivo spectroscopy and imaging of free radicals in human skin are reported. The instrumentation uses a specially designed topical resonator and a 2.2-GHz microwave bridge. Noninvasive measurements of the distribution and metabolism of the topically applied nitroxide, (15)N-perdeuterated tempone (100 mM), in forearm skin were performed. A single broad peak due to the concentrated label at the skin surface was initially observed, followed by a sharp doublet from the diluted label that permeated the skin. The penetration of the label into the skin and its metabolic clearance were modeled using kinetic equations. It was observed that the penetration process from the skin surface into the dermis and subcutaneous regions, as well as its clearance from these regions, could be described by single exponential functions. Phantom imaging experiments using the nitroxide showed that a spatial resolution of up to 50 microm could be achieved. The skin imaging measurements showed two bands in the distribution of the label along the skin depth. The first band appeared in the outer 400 microm of the skin, the epidermis region, whereas the second band was centered at a depth of 1000 microm in the subcutaneous region with a thickness about 400 microm. These two bands decayed and merged into a single band with time. The results are important in the understanding of the permeability and metabolism of free radicals in human skin.     

Application of magnetic field over-modulation for improved EPR linewidth measurements using probes with Lorentzian lineshape

Magnetic field modulation in CW electron paramagnetic resonance (EPR) is used for signal detection. However, it can also distort signal lineshape. In experiments where the linewidth information is of particular importance, small modulation amplitude is usually used to limit the lineshape distortion. The use of small modulation amplitude, however, results in low signal-to-noise ratio and therefore affects the precision of linewidth measurements. Recently, a new spectral simulation model has been developed enabling accurate fitting of modulation-broadened EPR spectra in liquids. Since the use of large modulation amplitude (over-modulation) can significantly enhance the EPR signal, the precision of linewidth measurements is therefore greatly improved. We investigated the over-modulation technique in EPR oximetry experiments using the oxygen-sensing probe lithium octa-n-butoxy-substitued naphthalocyanine (LiNc-BuO). Modulation amplitudes 2-18 times the intrinsic linewidth of the probe were applied to increase the spectral signal-to-noise ratio. The intrinsic linewidth of the probe at different oxygen concentrations was accurately extracted through curve fitting from the enhanced spectra. Thus, we demonstrated that the over-modulation model is also applicable to particulate oxygen-sensing probes such as LiNc-BuO and that the lineshape broadening induced by oxygen is separable from that induced by over-modulation. Therefore, the over-modulation technique can be used to enhance sensitivity and improve linewidth measurements for EPR oximetry with particulate oxygen-sensing probes with Lorentzian lineshape. It should be particularly useful for in vivo oxygen measurements, in which direct linewidth measurements may not be feasible due to inadequate signal-to-noise ratio.     

EPR oximetry in three spatial dimensions using sparse spin distribution

A method is presented to use continuous wave electron paramagnetic resonance imaging for rapid measurement of oxygen partial pressure in three spatial dimensions. A particulate paramagnetic probe is employed to create a sparse distribution of spins in a volume of interest. Information encoding location and spectral linewidth is collected by varying the spatial orientation and strength of an applied magnetic gradient field. Data processing exploits the spatial sparseness of spins to detect voxels with nonzero spin and to estimate the spectral linewidth for those voxels. The parsimonious representation of spin locations and linewidths permits an order of magnitude reduction in data acquisition time, compared to four-dimensional tomographic reconstruction using traditional spectral-spatial imaging. The proposed oximetry method is experimentally demonstrated for a lithium octa-n-butoxy naphthalocyanine (LiNc–BuO) probe using an L-band EPR spectrometer.     

Development of a resonator with automatic tuning and coupling capability to minimize sample motion noise for in vivo EPR spectroscopy

EPR spectroscopy has been applied to measure free radicals in vivo; however, respiratory, cardiac, and other movements of living animals are a major source of noise and spectral distortion. Sample motions result in changes in resonator frequency, Q, and coupling. These instabilities limit the applications that can be performed and the quality of data that can be obtained. Therefore, it is of great importance to develop resonators with automatic tuning and automatic coupling capability. We report the development of automatic tuning and automatic coupling provisions for a 750-MHz transversely oriented electric field reentrant resonator using two electronically tunable high Q hyperabrupt varactor diodes and feedback loops. In both moving phantoms and living mice, these automatic coupling control and automatic tuning control provisions resulted in an 8- to 10-fold increase in signal-to-noise ratio.     

Fast EPR imaging at 300 MHz using spinning magnetic field gradients

Electron paramagnetic resonance imaging (EPRI) technology has rapidly progressed in the last decade enabling many important applications in the fields of biology and medicine. At frequencies of 300-1200 MHz a range of in vivo applications have been performed. However, the requisite imaging time duration to acquire a given number of projections, limits the use of this technique in many in vivo applications where relatively rapid kinetics occur. Therefore, there has been a great need to develop approaches to accelerate EPRI data acquisition. We report the development of a fast low-frequency EPRI technique using spinning magnetic field gradients (SMFG). Utilizing a 300 MHz CW (continuous wave) EPRI system, SMFG enabled over 10-fold accelerated acquisition of image projections. 2D images with over 200 projections could be acquired in less than 3s and with 20s acquisitions good image quality was obtained on large aqueous free radical samples. This technique should be particularly useful for in vivo studies of free radicals and their metabolism.     

Structural Insights into Hysteretic Spin-Crossover in a Set of Iron(II)-2,6-bis(1H-Pyrazol-1-yl)Pyridine) Complexes

Bistable spin-crossover (SCO) complexes that undergo abrupt and hysteretic (ΔT_1/2) spin-state switching are desirable for molecule-based switching and memory applications. In this study, we report on structural facets governing hysteretic SCO in a set of iron(II)-2,6-bis(1H-pyrazol-1-yl)pyridine) (bpp) complexes – [Fe(bpp−COOEt)₂](X)₂ ⋅ CH₃NO₂ (X=ClO₄, 1 ; X=BF₄, 2 ). Stable spin-state switching – T_1/2=288 K; ΔT_1/2=62 K – is observed for 1 , whereas 2 undergoes above-room-temperature lattice-solvent content-dependent SCO – T_1/2=331 K; ΔT_1/2=43 K. Variable-temperature single-crystal X-ray diffraction studies of the complexes revealed pronounced molecular reorganizations – from the Jahn-Teller-distorted HS state to the less distorted LS state – and conformation switching of the ethyl group of the COOEt substituent upon SCO. Consequently, we propose that the large structural reorganizations rendered SCO hysteretic in 1 and 2 . Such insights shedding light on the molecular origin of thermal hysteresis might enable the design of technologically relevant molecule-based switching and memory elements.     

A parametric approach to spectral-spatial EPR imaging

Continuous wave electron paramagnetic resonance imaging for in vivo mapping of spin distribution and spectral shape requires rapid data acquisition. A spectral-spatial imaging technique is presented that provides an order of magnitude reduction in acquisition time, compared to iterative tomographic reprojection. The proposed approach assumes that spectral shapes in the sample are well-approximated by members from a parametric family of functions. A model is developed for the spectra measured with magnetic field modulation. Parameters defining the spin distribution and spectral shapes are then determined directly from the measurements using maximum a posteriori probability estimation. The approach does not suffer approximation error from limited sweep width of the main magnetic field and explicitly incorporates the variability in signal-to-noise ratio versus strength of magnetic field gradient. The processing technique is experimentally demonstrated on a one-dimensional phantom containing a nitroxide spin label with constant g-factor. Using an L-band EPR spectrometer, spectral shapes and spin distribution are accurately recovered from two projections and a spectral window which is comparable to the maximum linewidth of the sample.