It is shown that surface NMR spectra can be greatly enhanced using dynamic nuclear polarization. Polarization is transferred from the protons of the solvent to the rare nuclei (here carbon-13 at natural isotopic abundance) at the surface, yielding at least a 50-fold signal enhancement for surface species covalently incorporated into a silica framework.

We demonstrate fast characterization of the distribution of surface bonding modes and interactions in a series of functionalized materials via surface-enhanced nuclear magnetic resonance spectroscopy using dynamic nuclear polarization (DNP). Surface-enhanced silicon-29 DNP NMR spectra were obtained by using incipient wetness impregnation of the sample with a solution containing a polarizing radical (TOTAPOL). We identify and compare the bonding topology of functional groups in materials obtained via a sol-gel process and in materials prepared by post-grafting reactions. Furthermore, the remarkable gain in time provided by surface-enhanced silicon-29 DNP NMR spectroscopy (typically on the order of a factor 400) allows the facile acquisition of two-dimensional correlation spectra.

The surface of γ-alumina nanoparticles can be characterized by dynamic nuclear polarization (DNP) surface-enhanced NMR of (27)Al. DNP is combined with cross-polarization and MQ-MAS to determine local symmetries of (27)Al sites at the surface.

SummaryTherapeutic targeting of tumor angiogenesis with VEGF inhibitors results in demonstrable, but transitory efficacy in certain human tumors and mouse models of cancer, limited by unconventional forms of adaptive/evasive resistance. In one such mouse model, potent angiogenesis inhibitors elicit compartmental reorganization of cancer cells around remaining blood vessels. The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1α-dependent fashion, indicative of glycolysis. Tumor cells proximal to blood vessels instead express the lactate transporter MCT1, and p-S6, the latter reflecting mTOR signaling. Normoxic cancer cells import and metabolize lactate, resulting in upregulation of mTOR signaling via glutamine metabolism enhanced by lactate catabolism. Thus, metabolic symbiosis is established in the face of angiogenesis inhibition, whereby hypoxic cancer cells import glucose and export lactate, while normoxic cells import and catabolize lactate. mTOR signaling inhibition disrupts this metabolic symbiosis, associated with upregulation of the glucose transporter GLUT2.

Hyperpolarization is generated by dissolution dynamic nuclear polarization (d-DNP) using a polymer-based polarizing agent dubbed FLAP (filterable labeled agents for polarization). It consists of a thermo-responsive poly(N-isopropylacrylamide), also known as pNiPAM-COOH, labeled with nitroxide radicals. The polymer powder is impregnated with an arbitrary solution of interest and frozen as is. Dissolution is followed by a simple filtration, leading to hyperpolarized solutions free from any contaminants. We demonstrated the use of FLAP to hyperpolarize partially deuterated water up to P((1) H)=6 % with a long relaxation T1 >36 s characteristic of high purity. Water hyperpolarization can be transferred to drugs, metabolites, or proteins that are waiting in an NMR spectrometer, either by exchange of labile protons or through intermolecular Overhauser effects. We also show that FLAPs are suitable polarizing agents for (13) C-labeled metabolites such as pyruvate, acetate, and alanine.

Theory of long-lived nuclear spin states in methyl groups and quantum-rotor induced polarisation

Dynamic nuclear polarization (DNP) [1] combined with magic angle spinning (MAS) [2] can-under favorable conditions-enhance the nuclear spin polarization, that is, the difference between the populations of the Zeeman levels j ai and j bi of a spin I = 1 = 2 by up to two orders of magnitude (e DNP 10 2 ) with respect to the Boltzmann distribution at thermal equilibrium at ca. 100 K, while accelerating relaxation and hence reducing recovery delays by more than an order of magnitude (k = R DNP / R 1 = T 1 /t DNP > 10), thus providing a means of shortening measurement times by up to five orders of magnitude. Where suitable solvents can be found, typical enhancements for 13

Dynamic nuclear polarization (DNP) can enhance the nuclear polarization, that is the difference between the populations of the Zeeman levels j ai and j bi of spin I = 1/2, by up to four orders of magnitude with respect to their Boltzmann distribution at room temperature.[1] This enhancement arises from thermal mixing, which is brought about by microwave saturation of the EPR transitions of stable radicals that are mixed with the sample under investigation before freezing. In dissolution DNP, the sample is usually polarized at low temperatures and moderate magnetic fields (T = 1.2 K and B 0 = 3.35 or 5 T in our laboratory), [2] rapidly dissolved, [3] and heated to ambient temperature by a burst of water vapor.To minimize losses of nuclear spin polarization, the transfer from the polarizer to the NMR spectrometer or MRI magnet, including the settling of mechanical vibrations and convection currents, and, if required, the infusion into living organisms, must be completed within an interval T < T 1 . In our laboratory, the interval T has recently been lowered to 4.5 s. The radicals in the hyperpolarized solution lead to an increase of the longitudinal relaxation rate R 1 = 1/T 1 of the solute, thus limiting the timescales of the dynamic processes that can be monitored with hyperpolarized nuclei. A concomitant enhancement of the transverse relaxation rates R 2 = 1/T 2 leads to undesirable line-broadening. The relaxation rates R LLS = 1/T LLS of the populations of long-lived states (LLS) [4] and the decay rates R LLC = 1/T LLC of long-lived coherences (LLC) [5] are even more sensitive to the presence of free radicals than populations of eigenstates and single-quantum coherences. Free radicals can be toxic, and hyperpolarized solutions should not be infused into living organisms unless the radicals are removed.Herein, we demonstrate how N-oxide radicals that are widely used for DNP, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), can be reduced by scavengers like sodium ascorbate (vitamin C) during the dissolution process into 2,2,6,6-tetramethylpiperidine-1,4-diol (TEMPOL-H; Scheme 1), thus extending transverse and longitudinal relaxation times of solutes and slowing down the decay of their polarization during and after transfer. Scavenging free radicals with ascorbate merely leaves ascorbyl radicals, which rapidly disproportionate, [6] in contrast to scavenging with thiol-based (DTT) or phenolic (Vitamin E) antioxidants, so that no paramagnetic species are present in the sample after dissolution and reduction.Scheme 1. The reduction of TEMPOL by sodium ascorbate, leading to the formation of a delocalized sodium ascorbyl radical and diamagnetic TEMPOL-H.