Magic Angle Spinning Solid-State 13C Photochemically Induced Dynamic Nuclear Polarization by a Synthetic Donor-Chromophore-Acceptor System at 9.4 T.

Solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) is a nuclear magnetic resonance spectroscopy technique in which nuclear spin hyperpolarization is generated upon optical irradiation of an appropriate donor-acceptor system. Until now, solid-state photo-CIDNP at high magnetic fields has been observed only in photosynthetic reaction centers and flavoproteins. In the present work, we show that the effect is not limited to such biomolecular samples, and solid-state 13C photo-CIDNP can be observed at 9.4 T under magic angle spinning using a frozen solution of a synthetic molecular system dissolved in an organic solvent. Signal enhancements for the source molecule larger than a factor of 2300 are obtained. In addition, we show that bulk 13C hyperpolarization of the solvent can be generated via spontaneous 13C-13C spin diffusion at natural abundance.

Probing Homogeneous Catalysts and Precatalysts in Solution by Exchange-Mediated Overhauser Dynamic Nuclear Polarization NMR.

Triphenylphosphine (PPh3) is a ubiquitous ligand in organometallic chemistry that has been shown to give enhanced 31P NMR signals at high magnetic field via a scalar-dominated Overhauser effect dynamic nuclear polarization (OE DNP). However, PPh3 can only be polarized via DNP in the free form, while the coordinated form is DNP-inactive. Here, we demonstrate the possibility of enhancing the 31P NMR signals of coordinated PPh3 in metal complexes in solution at room temperature by combining Overhauser effect DNP and chemical exchange between the free and coordinated PPh3 forms. With this method, we successfully obtain 31P DNP enhancements of up to 2 orders of magnitude for the PPh3 ligands in Rh(I), Ru(II), Pd(II), and Pt(II) complexes, and we show that the DNP enhancements can be used to determine the activation energy of the ligand exchange reaction.

Molecular Mechanisms Underlying Detection Sensitivity in Nanoparticle-Assisted NMR Chemosensing.

Nanoparticle-assisted nuclear magnetic resonance (NMR) chemosensing exploits monolayer-protected nanoparticles as supramolecular hosts to detect small molecules in complex mixtures via nuclear Overhauser effect experiments with detection limits down to the micromolar range. Still, the structure-sensitivity relationships at the basis of such detection limits are little understood. In this work, we integrate NMR spectroscopy and atomistic molecular dynamics simulations to examine the covariates that affect the sensitivity of different NMR chemosensing experiments [saturation transfer difference (STD), water STD, and high-power water-mediated STD]. Our results show that the intensity of the observed signals correlates with the number and duration of the spin-spin interactions between the analytes and the nanoparticles and/or between the analytes and the nanoparticles' solvation molecules. In turn, these parameters depend on the location and dynamics of each analyte inside the monolayer. This insight will eventually facilitate the tailoring of experimental and computational setups to the analyte's chemistry, making NMR chemosensing an even more effective technique in practical use.

Optically Enhanced Solid-State 1H NMR Spectroscopy.

Low sensitivity is the primary limitation to extending nuclear magnetic resonance (NMR) techniques to more advanced chemical and structural studies. Photochemically induced dynamic nuclear polarization (photo-CIDNP) is an NMR hyperpolarization technique where light is used to excite a suitable donor-acceptor system, creating a spin-correlated radical pair whose evolution drives nuclear hyperpolarization. Systems that exhibit photo-CIDNP in solids are not common, and this effect has, up to now, only been observed for 13C and 15N nuclei. However, the low gyromagnetic ratio and natural abundance of these nuclei trap the local hyperpolarization in the vicinity of the chromophore and limit the utility for bulk hyperpolarization. Here, we report the first example of optically enhanced solid-state 1H NMR spectroscopy in the high-field regime. This is achieved via photo-CIDNP of a donor-chromophore-acceptor molecule in a frozen solution at 0.3 T and 85 K, where spontaneous spin diffusion among the abundant strongly coupled 1H nuclei relays polarization through the whole sample, yielding a 16-fold bulk 1H signal enhancement under continuous laser irradiation at 450 nm. These findings enable a new strategy for hyperpolarized NMR beyond the current limits of conventional microwave-driven DNP.

Deuterated TEKPol Biradicals and the Spin-Diffusion Barrier in MAS DNP.

The sensitivity of NMR spectroscopy is considerably enhanced by dynamic nuclear polarization (DNP). In DNP polarization is transferred from unpaired electrons of a polarizing agent to nearby proton spins. In solids, this transfer is followed by the transport of hyperpolarization to the bulk via 1 H-1 H spin diffusion. The efficiency of these steps is critical to obtain high sensitivity gains, but the pathways for polarization transfer in the region near the unpaired electron spins are unclear. Here we report a series of seven deuterated and one fluorinated TEKPol biradicals to probe the effect of deprotonation on MAS DNP at 9.4 T. The experimental results are interpreted with numerical simulations, and our findings support that strong hyperfine couplings to nearby protons determine high transfer rates across the spin diffusion barrier to achieve short build-up times and high enhancements. Specifically, 1 H DNP build-up times increase substantially with TEKPol isotopologues that have fewer hydrogen atoms in the phenyl rings, suggesting that these protons play a crucial role transferring the polarization to the bulk. Based on this new understanding, we have designed a new biradical, NaphPol, which yields significantly increased NMR sensitivity, making it the best performing DNP polarizing agent in organic solvents to date.

Uniform water-mediated saturation transfer: A sensitivity-improved alternative to WaterLOGSY.

In the study of small molecule ligands and candidate macromolecular targets, water spins in long-lived association with macromolecules (proteins or nanoparticles) constitute a remarkable source of magnetization that can be exploited to reveal ligand-target binding. In this work we show how the selective saturation of water spins complemented with adiabatic off-resonance spin-locks can remove the NOE contribution of bulk water in the final difference spectrum, leading to uniformly enhanced signals that reveal weak ligand-target interactions.

Hybrid nanoreceptors for high sensitivity detection of small molecules by NMR chemosensing.

"Nanoparticle-assisted NMR chemosensing" combines magnetization transfer NMR techniques with the recognition abilities of gold nanoparticles (AuNPs) to isolate the NMR spectrum of relevant organic species in mixtures. The efficiency of the magnetization transfer is crucial to set the detection limit of the technique. To this aim, a second generation of nanoreceptors obtained by the self-organization of 2 nm AuNPs onto the surface of bigger silica nanoparticles shows better magnetization transfer performances, allowing the detection of analytes in water down to 10 µM concentration using standard instrumentation.

Chromatographic NMR spectroscopy: the effect of hollow silica microspheres on magnetic field inhomogeneities and resonance lineshapes.

Micrometric hollow silica spheres can effectively reduce magnetic field inhomogeneities when employed as a stationary phase in the context of NMR chromatography. We here provide a description of the NMR line broadening phenomenon for physically representative collections of hollow spheres with different geometries and filling factors. Our results highlight how, within the explored conditions, a proper modelling of the line broadening phenomenon should consider the enhanced relaxation of the spins during their diffusion across the spherical shells, and possibly other slow motional effects.

Nanoparticle-assisted NMR spectroscopy: A chemosensing perspective.

Sensing methodologies for the detection of target compounds in mixtures are important in many different contexts, ranging from medical diagnosis to environmental analysis and quality assessment. Ideally, such detection methods should allow for both identification and quantification of the targets, minimizing the possibility of false positives. With very few exceptions, most of the available sensing techniques rely on the selective interaction of the analyte with some detector, which in turn produces a signal as a result of the interaction. This approach hence provides indirect information on the targets, whose identity is generally ensured by comparison with known standards, if available, or by the selectivity of the sensor system itself. Pursuing a different approach, NMR chemosensing aims at generating signals directly from the analytes, in the form of a (complete) NMR spectrum. In this way, not only are the targets unequivocally identified, but it also becomes possible to identify and assign the structures of unknown species. In this review we show how relaxation- and diffusion-based NMR techniques, assisted by appropriate nanoparticles, can be used to edit the 1H NMR spectrum of a mixture and extract the signals of specific target compounds. Monolayer-protected nanoparticles, in particular those made from gold, are well suited to this task because they provide a versatile, protein-size support to build or incorporate supramolecular receptors. Remarkably, the self-organized and multifunctional nature of the nanoparticle coating allows exploitation of different kinds of non-covalent interactions, to provide tailored binding sites for virtually any class of molecules. From the NMR standpoint, the reduced translational and rotational diffusion rates of bulky nanoparticles offer a way to manipulate the states of the monolayer spins and build a reservoir of magnetization that can be selectively transferred to the interacting analytes. In addition, the low correlation time and the enhanced rigidity of the coating molecules (due to their grafting and crowding on the particle surface) promote efficient spin diffusion, useful in saturation transfer experiments. The optimized combination of NMR experiments and nanoreceptors can ultimately allow the detection of relevant analytes in the micromolar concentration range, paving the way to applications in the diagnostic field and beyond.

Dynamic Origin of Chirality Transfer between Chiral Surface and Achiral Ligand in Au38 Clusters.

The transfer of chirality between nanomolecules is at the core of several applications in chiral technology such as sensing and catalysis. However, the origin of this phenomenon and how exactly nanoscale objects transfer chirality to molecules in their vicinity remain largely obscure. Here, we show that the transfer of chirality for the intrinsically chiral gold cluster Au38(SR)24 is site dependent; that is, it differs depending on the ligand-binding sites. This is closely related to the dynamic nature of the ligands on the cluster surface. Using a combination of NMR techniques and molecular dynamics simulations, we could assign the four symmetry-unique ligands on the cluster. The study reveals largely different conformational dynamics of the bound ligands, explaining the diverse diastereotopicities observed for the CH2 protons of the ligands. Although chirality is a structural property, our study reveals the importance of dynamics for the transfer of chirality.

Molecular-Dynamics-Simulation-Directed Rational Design of Nanoreceptors with Targeted Affinity.

Here, we demonstrate the possibility of rationally designing nanoparticle receptors with targeted affinity and selectivity for specific small molecules. We used atomistic molecular-dynamics (MD) simulations to gradually mutate and optimize the chemical structure of the molecules forming the coating monolayer of gold nanoparticles (1.7 nm gold-core size). The MD-directed design resulted in nanoreceptors with a 10-fold improvement in affinity for the target analyte (salicylate) and a 100-fold decrease of the detection limit by NMR-chemosensing from the millimolar to the micromolar range. We could define the exact binding mode, which features prolonged contacts and deep penetration of the guest into the monolayer, as well as a distinct shape of the effective binding pockets characterized by exposed interacting points.

Nanoparticle-Assisted NMR Spectroscopy: Enhanced Detection of Analytes by Water-Mediated Saturation Transfer.

Nanoparticle-assisted "NMR chemosensing" is an experimental protocol that exploits the selective recognition abilities of nanoparticle receptors to detect and identify small molecules in complex mixtures by nuclear Overhauser effect magnetization transfer. Although the intrinsic sensitivity of the first reported protocols was modest, we have now found that water spins in long-lived association at the nanoparticle monolayer constitute an alternative source of magnetization that can deliver a remarkable boost of sensitivity, especially when combined with saturation transfer experiments. The approach is general and can be applied to analyte-nanoreceptor systems of different compositions. In this work, we provide an account of the new method and we propose a generalized procedure based on a joint water-nanoparticle saturation to further upgrade the sensitivity, which ultimately endows selective analyte detection down to the micromolar range on standard instrumentation.

1 H NMR Chemosensing of Potassium Ions Enabled by Guest-Induced Selectivity Switch of a Gold Nanoparticle/Crown Ether Nanoreceptor.

Invited for this month's cover is the group of Prof. Fabrizio Mancin from the University of Padova, Italy. The cover picture shows an 18-crown-6-functionalized gold nanoparticle that switches its molecular recognition preference from organic cations to organic anions in the presence of potassium ions, thus allowing 1 H NMR sensing of potassium. Read the full text of the article at 10.1002/cplu.201900028.

1 H NMR Chemosensing of Potassium Ions Enabled by Guest-Induced Selectivity Switch of a Gold Nanoparticle/Crown Ether Nanoreceptor.

A sensing protocol to detect potassium ions in water by 1 H NMR spectroscopy is described. The method exploits the K+ -modulated affinity of 18-crown-6 functionalized gold nanoparticles towards organic ions, combined with NOE magnetization transfer. Binding of K+ to the crown ether moieties switches the nanoreceptor preference (and its ability to transfer magnetization) from organic cations (tyramine) to organic anions (phloretate). In this way, a ratiometric NMR signal is produced with a detection limit of 0.6 mM. Detection can be performed in 20 min with standard instruments and with little interference from other alkali and alkaline earth metal ions present in the sample.

Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition.

The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which could explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs.