Hyperpolarized Water to Study Protein-Ligand Interactions

The affinity between a chosen target protein and small molecules is a key aspect of drug discovery. Screening by popular NMR methods such as Water-LOGSY suffers from low sensitivity and from false positives caused by aggregated or denatured proteins. This work demonstrates that the sensitivity of Water-LOGSY can be greatly boosted by injecting hyperpolarized water into solutions of proteins and ligands. Ligand binding can be detected in a few seconds, whereas about 30 min is usually required without hyperpolarization. Hyperpolarized water also enhances proton signals of proteins at concentrations below 20 M so that one can verify in a few seconds whether the proteins remain intact or have been denatured

Rapid porosity and permeability changes of calcareous sandstone due to CO₂-enriched brine injection

Reservoir injectivity and storage capacity are the main constraints for geologic CO2 sequestration, subject to safety and economic considerations. Brine acidification following CO2 dissolution leads to fluid-rock interactions that alter porosity and permeability, thereby affecting reservoir storage capacity and injectivity. Thus, we determined how efficiently CO2-enriched brines could dissolve calcite in sandstone cores and how this affects the petrophysical properties. During computerized tomography monitored flow-through reactor experiments, calcite dissolved at a rate largely determined by the rate of acid supply, even at high flow velocities which would be typical near an injection well. The porosity increase was accompanied by a significant increase in rock permeability, larger than that predicted using classical porosity-permeability models. This chemically driven petrophysical change might be optimized using injection parameters to maximize injectivity and storage

The Preparation of Hyperpolarized Water and its Use to Enhance "waterLOGSY" Drug Screening

Amongst several NMR techniques for Fragment Based Drug Discovery, water LOGSY consists in observing signals arising after magnetization transfer from water to ligand by the nuclear Overhauser effect. Nonetheless, due to the intrinsic low sensitivity of NMR, decent signals only come as the reward of lengthy experiments with large amounts of analytes. As the ligand concentrations usually exceed that of the protein by orders of magnitude, the detection of strong binders becomes impossible by Water LOGSY. We propose the use of hyperpolarized water prepared by Dissolution Dynamic Nuclear Polarization to enhance signals in Water LOGSY. Both experimental time and amounts of protein and/or ligand can be dramatically reduced, which should enable unambiguous detection of both weak and strong binders

Boosting Dissolution-Dynamic Nuclear Polarization by Multiple-Step Dipolar Order Mediated 1H->13C Cross-Polarization

Dissolution-dynamic nuclear polarization can be boosted by employing multiplecontact cross-polarization techniques to transfer polarization from 1H to 13C spins. The method is efficient and significantly reduces polarization build-up times, however, it involves high-power radiofrequency pulses in a superfluid helium environment which limit its implementation and applicability and prevent a significant scaling-up of the sample size. We propose to overcome this limitation by a stepwise transfer of polarization using a lowenergy and low-peak power radiofrequency pulse sequence where the 1H®13C polarization transfer is mediated by a dipolar spin order reservoir. An experimental demonstration is presented for [1-13C]sodium acetate. A solid-state 13C polarization of ~43.5% was achieved using this method with a build-up time constant of ~5.1 minutes, leading to a ~28.5% 13C polarization in the liquidstate after sample dissolution. The low-power multiple-step polarization transfer efficiency with respect to the most advanced and highest-power multiple-contact cross-polarization approach was found to be ~0.69.</p

Hyperpolarized NMR Metabolomics at Natural 13 C Abundance

Real-time diffusion NMR analysis of mixturessummitPersistent and Transportable Hyperpolarization for Magnetic ResonanceHYPROTIN 80193