In a previous publication, we described the use of biradicals, in that case two TEMPO molecules tethered by an ethylene glycol chain of variable length, as polarizing agents for microwave driven dynamic nuclear polarization (DNP) experiments. The use of biradicals in place of monomeric paramagnetic centers such as TEMPO yields enhancements that are a factor of approximately 4 larger (epsilon approximately 175 at 5 T and 90 K) and concurrently the concentration of the polarizing agent is a factor of 4 smaller (10 mM electron spins), reducing the residual electron nuclear dipole broadening. In this paper we describe the synthesis and characterization by EPR and DNP/NMR of an improved polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL). Under the same experimental conditions and using 2.5 mm magic angle rotors, this new biradical yields larger enhancements (epsilon approximately 290) at lower concentrations (6 mM electron spins) and has the additional important property that it is compatible with experiments in aqueous media, including salt solutions commonly used in the study of proteins and nucleic acids.

Theoretical calculations predict that by coupling an exothermic chemical reaction with a nanotube or nanowire possessing a high axial thermal conductivity, a self-propagating reactive wave can be driven along its length. Herein, such waves are realized using a 7-nm cyclotrimethylene trinitramine annular shell around a multiwalled carbon nanotube and are amplified by more than 10(4) times the bulk value, propagating faster than 2 m s(-1), with an effective thermal conductivity of 1.28+/-0.2 kW m(-1) K(-1) at 2,860 K. This wave produces a concomitant electrical pulse of disproportionately high specific power, as large as 7 kW kg(-1), which we identify as a thermopower wave. Thermally excited carriers flow in the direction of the propagating reaction with a specific power that scales inversely with system size. The reaction also evolves an anisotropic pressure wave of high total impulse per mass (300 N s kg(-1)). Such waves of high power density may find uses as unique energy sources.

To date, the cross effect (CE) and thermal mixing (TM) mechanisms have consistently provided the largest enhancements in dynamic nuclear polarization (DNP) experiments performed at high magnetic fields. Both involve a three-spin electron-electron-nucleus process whose efficiency depends primarily on two electron-electron interactions--the interelectron distance R and the correct electron paramagnetic resonance (EPR) frequency separation that matches the nuclear Larmor frequency, /omega(e2)-omega(e1)/ = omega(n). Biradicals, for example, two 2,2,6,6-tetramethyl-piperidine-1-oxyls (TEMPOs) tethered with a molecular linker, can in principle constrain both the distance and relative g-tensor orientation between two unpaired electrons, allowing these two spectral parameters to be optimized for the CE and TM. To verify this hypothesis, we synthesized a series of biradicals--bis-TEMPO tethered by n ethylene glycol units (a.k.a. BTnE)--that show an increasing DNP enhancement with a decreasing tether length. Specifically at 90 K and 5 T, the enhancement grew from approximately 40 observed with 10 mM monomeric TEMPO, where the average R approximately 56 A corresponding to electron-electron dipolar coupling constant omega(d)2 pi = 0.3 MHz, to approximately 175 with 5 mM BT2E (10 mM electrons) which has R approximately 13 A with omega(d)2 pi = 24 MHz. In addition, we compared these DNP enhancements with those from three biradicals having shorter and more rigid tethers-bis-TEMPO tethered by oxalyl amide, bis-TEMPO tethered by the urea structure, and 1-(TEMPO-4-oxyl)-3-(TEMPO-4-amino)-propan-2-ol (TOTAPOL) TOTAPOL is of particular interest since it is soluble in aqueous media and compatible with DNP experiments on biological systems such as membrane and amyloid proteins. The interelectron distances and relative g-tensor orientations of all of these biradicals were characterized with an analysis of their 9 and 140 GHz continuous-wave EPR lineshapes. The results show that the largest DNP enhancements are observed with BT2E and TOTAPOL that have shorter tethers and the two TEMPO moieties are oriented so as to satisfy the matching condition for the CE.

A major challenge in the synthesis of nanotube or nanowire sensors is to impart selective analyte binding through means other than covalent linkages, which compromise electronic and optical properties. We synthesized a 3,4-diaminophenyl-functionalized dextran (DAP-dex) wrapping for single-walled carbon nanotubes (SWNTs) that imparts rapid and selective fluorescence detection of nitric oxide (NO), a messenger for biological signalling. The near-infrared (nIR) fluorescence of SWNT(DAP-dex) is immediately and directly bleached by NO, but not by other reactive nitrogen and oxygen species. This bleaching is reversible and shown to be caused by electron transfer from the top of the valence band of the SWNT to the lowest unoccupied molecular orbital of NO. The resulting optical sensor is capable of real-time and spatially resolved detection of NO produced by stimulating NO synthase in macrophage cells. We also demonstrate the potential of the optical sensor for in vivo detection of NO in a mouse model.

Electrically conductive hyaluronic acid (HA) hydrogels incorporated with single-walled carbon nanotubes (CNTs) and/or polypyrrole (PPy) were developed to promote differentiation of human neural stem/progenitor cells (hNSPCs). The CNT and PPy nanocomposites, which do not easily disperse in aqueous phases, dispersed well and were efficiently incorporated into catechol-functionalized HA (HA-CA) hydrogels by the oxidative catechol chemistry used for hydrogel cross-linking. The prepared electroconductive HA hydrogels provided dynamic, electrically conductive three-dimensional (3D) extracellular matrix environments that were biocompatible with hNSPCs. The HA-CA hydrogels containing CNT and/or PPy significantly promoted neuronal differentiation of human fetal neural stem cells (hfNSCs) and human induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) with improved electrophysiological functionality when compared to differentiation of these cells in a bare HA-CA hydrogel without electroconductive motifs. Calcium channel expression was upregulated, depolarization was activated, and intracellular calcium influx was increased in hNSPCs that were differentiated in 3D electroconductive HA-CA hydrogels; these data suggest a potential mechanism for stem cell neurogenesis. Overall, our bioinspired, electroconductive HA hydrogels provide a promising cell-culture platform and tissue-engineering scaffold to improve neuronal regeneration.