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An infrared absorption spectroscopy study of the endohedral water molecule in a solid mixture of H2O@C60 and C60 was carried out at liquid helium temperature. From the evolution of the spectra during the ortho–para conversion process, the spectral lines were identified as para-H2O and ortho-H2O transitions. Eight vibrational transitions with rotational side peaks were observed in the mid-infrared: ω1, ω2, ω3, 2ω1, 2ω2, ω1 + ω3, ω2 + ω3, and 2ω2 + ω3. The vibrational frequencies ω2 and 2ω2 are lower by 1.6% and the rest by 2.4%, as compared to those of free H2O. A model consisting of a rovibrational Hamiltonian with the dipole and quadrupole moments of H2O interacting with the crystal field was used to fit the infrared absorption spectra. The electric quadrupole interaction with the crystal field lifts the degeneracy of the rotational levels. The finite amplitudes of the pure v1 and v2 vibrational transitions are consistent with the interaction of the water molecule dipole moment with a lattice-induced electric field. The permanent dipole moment of encapsulated H2O is found to be 0.50 ± 0.05 D as determined from the far-infrared rotational line intensities. The translational mode of the quantized center-of-mass motion of H2O in the molecular cage of C60 was observed at 110 cm−1 (13.6 meV). [ABSTRACT FROM AUTHOR]

We have measured the temperature dependence of the infrared spectra of a hydrogen molecule trapped inside a C60 cage, H2@C60, in the temperature range from 6 to 300 K and analyzed the excitation spectrum by using a five-dimensional model of a vibrating rotor in a spherical potential. The electric dipole moment is induced by the translational motion of endohedral H2 and gives rise to an infrared absorption process where one translational quantum is created or annihilated, ΔN = ±1. Some fundamental transitions, ΔN = 0, are observed as well. The rotation of endohedral H2 is unhindered but coupled to the translational motion. The isotropic and translation-rotation coupling part of the potential are anharmonic and different in the ground and excited vibrational states of H2. The vibrational frequency and the rotational constant of endohedral H2 are smaller than those of H2 in the gas phase. The assignment of lines to ortho- and para-H2 is confirmed by measuring spectra of a para enriched sample of H2@C60 and is consistent with the earlier interpretation of the low temperature infrared spectra [Mamone et al., J. Chem. Phys. 130, 081103 (2009)]. [ABSTRACT FROM AUTHOR]

We report the observation of quantized translational and rotational motion of molecular hydrogen inside the cages of C60. Narrow infrared absorption lines at the temperature of 6 K correspond to vibrational excitations in combination with translational and rotational excitations and show well-resolved splittings due to the coupling between translational and rotational modes of the endohedral H2 molecule. A theoretical model shows that H2 inside C60 is a three-dimensional quantum rotor moving in a nearly spherical potential. The theory provides both the frequencies and the intensities of the observed infrared transitions. Good agreement with the experimental results is obtained by fitting a small number of empirical parameters to describe the confining potential, as well as the relative concentration of ortho- and para-H2. [ABSTRACT FROM AUTHOR]

The low-temperature structure and dynamics of guest molecules of p-xylene incorporated in the isopropyl-calix[4] arene(2:1) p-xylene complex have been investigated by solid state nuclear magnetic resonance (NMR). Using one-dimensional 1H-decoupled 13C cross-polarization magic-angle-spinning (MAS) NMR and two-dimensional 1H–13C correlation spectroscopy, a full assignment of the 13C and 1H chemical shifts has been made. Using 1H NMR relaxometry, the effects of thermal history on the structure of the system have been investigated. Rapidly cooled samples have 1H spin-lattice relaxation times T1, which at low temperature (T<60 K) are typically two orders of magnitude faster than those observed in annealed samples which have been cooled slowly over many hours. In both forms, the low-temperature relaxation is driven by the dynamics of the weakly hindered methyl rotors of the p-xylene guest. The substantial difference in T1 is attributed in the rapidly cooled sample to disorder in the structure of the complex leading to a wide distribution of correlation times and methyl barrier heights. A comparison of the linewidths and splittings in the high resolution 13C MAS spectra of the two forms provides structural insight into the nature of the disorder. Using 1H field-cycling NMR relaxometry, the methyl dynamics of the p-xylene guest in the annealed sample have been fully characterized. The B-field dependence of the 1H T1 maps out the spectral density from which the correlation times are directly measured. The methyl barrier heights are determined from an analysis of the temperature dependence. [ABSTRACT FROM AUTHOR]

We report a solid-state NMR study of the anisotropic nuclear spin interactions in H2O@C60 at room temperature. We find evidence of significant dipole-dipole interactions between the water protons, and also a proton chemical shift anisotropy (CSA) interaction. The principal axes of these interaction tensors are found to be perpendicular. The magnitude of the CSA is too large to be explained by a model in which the water molecules are partially aligned with respect to an external axis. The evidence indicates that the observed CSA is caused by a distortion of the geometry or electronic structure of the fullerene cages, in response to the presence of the endohedral water. [ABSTRACT FROM AUTHOR]

The quantum dynamics of a hydrogen molecule encapsulated inside the cage of a C60 fullerene molecule is investigated using inelastic neutron scattering (INS). The emphasis is on the temperature dependence of the INS spectra which were recorded using time-of-flight spectrometers. The hydrogen endofullerene system is highly quantum mechanical, exhibiting both translational and rotational quantization. The profound influence of the Pauli exclusion principle is revealed through nuclear spin isomerism. INS is shown to be exceptionally able to drive transitions between ortho-hydrogen and para-hydrogen which are spin-forbidden to photon spectroscopies. Spectra in the temperature range 1.6≤T≤280 K are presented, and examples are given which demonstrate how the temperature dependence of the INS peak amplitudes can provide an effective tool for assigning the transitions. It is also shown in a preliminary investigation how the temperature dependence may conceivably be used to probe crystal field effects and inter-fullerene interactions. [ABSTRACT FROM AUTHOR]

The quantum dynamics of dihydrogen molecules entrapped inside fullerene cages has been investigated using inelastic neutron scattering (INS). For the endofullerene H2@C60 the low-lying energy levels of the manifold of coupled translational and rotational states have been accurately determined by studying INS spectra recorded in the temperature range 1.5 ⩽ T ⩽ 240K. The majority of transitions observed in the INS spectra interconvert the nuclear spin isomers orthohydrogen and parahydrogen. The cage potential has icosahedral symmetry and splittings observed in the INS spectra reveal the coupling of translational and rotational angular momentum of the H2 molecules. The effects of nuclear spin symmetry, isotope mass effects, and cage anisotropy have been further investigated by studying HD@C60 and H2 inside an open cage endofullerene. The momentum transfer κ arising from the neutron scattering event has also been investigated. The κ-dependence spectra reflect the physical dimensions of the dihydrogen molecule and its confinement in its cage. We show how this may be used as a tool for assigning the INS transitions. [ABSTRACT FROM AUTHOR]

Parahydrogen-induced polarization (PHIP) is an emerging technique to enhance the signal of stable isotope metabolic contrast agents for Magnetic Resonance (MR). The objective of this study is to continue establishing 1- 13 C-pyruvate-d 3 , signal-enhanced via PHIP, as a hyperpolarized contrast agent, obtained in seconds, to monitor metabolism in human cancer. Our focus was on human pancreatic and colon tumor xenografts. 1- 13 C-vinylpyruvate-d 6 was hydrogenated using parahydrogen. Thereafter, the polarization of the protons was transferred to 13 C. Following a workup procedure, the free hyperpolarized 1- 13 C-pyruvate-d 3 was obtained in clean aqueous solution. After injection into animals bearing either pancreatic or colon cancer xenografts, slice-selective MR spectra were acquired and analyzed to determine rate constants of metabolic conversion into lactate and alanine. 1- 13 C-pyruvate-d 3 proved to follow the increased metabolic rate to lactate and alanine in the tumor xenografts., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Enhancing magnetic resonance signal via hyperpolarization techniques enables the real-time detection of metabolic transformations even in vivo. The use of para-hydrogen to enhance 13 C-enriched metabolites has opened a rapid pathway for the production of hyperpolarized metabolites, which usually requires specialized equipment. Metabolite precursors that can be hyperpolarized and converted into metabolites at any given field would open up opportunities for many labs to make use of this technology because already existing hardware could be used. We report here on the complete synthesis and hyperpolarization of suitable precursor molecules of the side-arm hydrogenation approach. The better accessibility to such side-arms promises that the para-hydrogen approach can be implemented in every lab with existing two channel NMR spectrometers for 1 H and 13 C independent of the magnetic field., (© 2023 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.)

In recent years, parahydrogen-induced polarization side arm hydrogenation (PHIP-SAH) has been applied to hyperpolarize [1- 13 C]pyruvate and map its metabolic conversion to [1- 13 C]lactate in cancer cells. Developing on our recent MINERVA pulse sequence protocol, in which we have achieved 27% [1- 13 C]pyruvate carbon polarization, we demonstrate the hyperpolarization of [1,2- 13 C]pyruvate (∼7% polarization on each 13 C spin) via PHIP-SAH. By altering a single parameter in the pulse sequence, MINERVA enables the signal enhancement of C1 and/or C2 in [1,2- 13 C]pyruvate with the opposite phase, which allows for the simultaneous monitoring of different chemical reactions with enhanced spectral contrast or for the same reaction via different carbon sites. We first demonstrate the ability to monitor the same enzymatic pyruvate to lactate conversion at 7T in an aqueous solution, in vitro , and in-cell (HeLa cells) via different carbon sites. In a second set of experiments, we use the C1 and C2 carbon positions as spectral probes for simultaneous chemical reactions: the production of acetate, carbon dioxide, bicarbonate, and carbonate by reacting [1,2- 13 C]pyruvate with H 2 O 2 at a high temperature (55 °C). Importantly, we detect and characterize the intermediate 2-hydroperoxy-2-hydroxypropanoate in real time and at high temperature.

The metabolism of malignant cells differs significantly from that of healthy cells and thus, it is possible to perform metabolic imaging to reveal not only the exact location of a tumor, but also intratumoral areas of high metabolic activity. Herein, we demonstrate the feasibility of metabolic tumor imaging using signal-enhanced 1- 13 C-pyruvate-d 3 , which is rapidly enhanced via para-hydrogen, and thus, the signal is amplified by several orders of magnitudes in less than a minute. Using as a model, human melanoma xenografts injected with signal-enhanced 1- 13 C-pyruvate-d3, we show that the conversion of pyruvate into lactate can be monitored along with its kinetics, which could pave the way for rapidly detecting and monitoring changes in tumor metabolism., (© 2022 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

In line with recent paradigm shifts in toxicity testing, in vivo nuclear magnetic resonance (NMR) is a powerful tool for studying the biological impacts and perturbations caused by toxicants in living organisms. However, despite the excellent molecular insights that can be obtained through this technique, in vivo NMR applications are hampered by considerable experimental challenges such as poor line shape and spectral overlap. Here, we demonstrate the application of singlet-filtered NMR to target specific metabolites and facilitate the study of metabolite fluxes in living Daphnia magna , an aquatic keystone species and model organism. Informed by mathematical simulations and experiments on ex vivo organisms, singlet state NMR is used to monitor the flux of metabolites such as d-glucose and serine in living D. magna , during the environmentally relevant processes of anoxic stress and reduced food availability. Overall, singlet state NMR is shown to have significant future potential for studying metabolic processes in vivo ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hyperpolarization methods in magnetic resonance enhance the signals by several orders of magnitude, opening new windows for real-time investigations of dynamic processes in vitro and in vivo. Here, we propose a field-independent para-hydrogen-based pulsed method to produce rapidly hyperpolarized 13 C-labeled substrates. We demonstrate the method by polarizing the carboxylic carbon of the pyruvate moiety in a purposely designed precursor to 24 % at ≈22 mT. Following a fast purification procedure, we measure 8 % polarization on free [1- 13 C]pyruvate in clean water solutions at physiological conditions at 7 T. The enhanced signals allow real-time monitoring of the pyruvate-lactate conversion in cancer cells, demonstrating the potential of the method for biomedical applications in combination with existing or developing magnetic resonance technologies., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Bimodal molecular probes combining nuclear magnetic resonance (NMR) and fluorescence have been widely studied in basic science, as well as clinical research. The investigation of spin phenomena holds promise to broaden the scope of available probes allowing deeper insights into physiological processes. Herein, a class of molecules with a bimodal character with respect to fluorescence and nuclear spin singlet states is introduced. Singlet states are NMR silent but can be probed indirectly. Symmetric, perdeuterated molecules, in which the singlet states can be populated by vanishingly small electron-mediated couplings (below 1 Hz) are reported. The lifetimes of these states are an order of magnitude longer than the longitudinal relaxation times and up to four minutes at 7 T. Moreover, these molecules show either aggregation induced emission (AIE) or aggregation caused quenching (ACQ) with respect to their fluorescence. In the latter case, the existence of excited dimers, which are proposed to use in a switchable manner in combination with the quenching of nuclear spin singlet states, is observed., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Hyperpolarization is a nuclear magnetic resonance (NMR) technique which can be used to significantly enhance the signal in NMR experiments. In recent years, the possibility to enhance the NMR signal of heteronuclei by the use of para -hydrogen induced polarization (PHIP) has gained attention, especially in the area of possible applications in magnetic resonance imaging (MRI). Herein we introduce a way to synthesize a fully deuterated, 15 N labelled amino acid derivative and the possibility to polarize the 15 N by means of hydrogenation with para -hydrogen to a polarization level of 0.18%. The longevity of the polarization with a longitudinal relaxation time of more than a minute can allow for the observation of dynamic processes and metabolic imaging in vivo . In addition, we observe the phenomenon of proton-deuterium exchange with a homogeneous catalyst leading to signal enhanced allyl moeities in the precursor., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Dendrimers are a class of branched, highly symmetric macromolecules that have been shown to be useful for a vast number of different applications. Potential uses as fluorescence sensors, in catalysis and perhaps most importantly in medical applications as drug delivery systems or cytotoxica have been proposed. Herein we report on an exotic behaviour of the nuclear spins in a dendritic macromolecule in the presence of different paramagnetic ions. We show that the stability of the long lived nuclear singlet state, is affected by the presence of Cu(II), whereas other ions did not have any influence at all. This effect could not be observed in the case of a simple tripeptide, in which the nuclear singlet stability was influenced by all investigated paramagnetic ions, a potentially useful effect in the development of Cu(II) selective probes. By adding a fluorescent marker to our molecule we could show that the nuclear singlet multimer (NUSIMER) is taken up by living cells. Furthermore we were able to show that nuclear singlet state NMR can be used to investigate the NUSIMER in the presence of living cells, showing that an application in in vivo NMR can be feasible.

The amyloid cascade hypothesis proposes that amyloid-beta (Aβ) aggregation is the initial triggering event in Alzheimer's disease. Here, we utilize NMR spectroscopy and monitor the structural dynamics of two variants of Aβ, Aβ40 and Aβ42, as a function of temperature. Despite having identical amino acid sequence except for the two additional C-terminal residues, Aβ42 has higher aggregation propensity than Aβ40. As revealed by the NMR data on dynamics, including backbone chemical shifts, intra-methyl cross-correlated relaxation rates and glycine-based singlet-states, the C-terminal region of Aβ, especially the G33-L34-M35 segment, plays a particular role in the early steps of temperature-induced Aβ aggregation. In Aβ42, the distinct dynamical behaviour of C-terminal residues at higher temperatures is accompanied with marked changes in the backbone dynamics of residues V24-K28. The distinctive role of the C-terminal region of Aβ42 in the initiation of aggregation defines a target for the rational design of Aβ42 aggregation inhibitors., (© 2021 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Background: It is almost unknown whether the driving status is associated with HRQOL among individuals in highest age., Aims: Based on a multicenter prospective cohort study, the objective of this study was to examine whether the driving status is associated with health-related quality of life (HRQOL) among the oldest old in Germany., Methods: Cross-sectional data from follow-up wave 9 (n = 544) were derived from the "Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe). Average age was 90.3 years (± 2.7; 86 to 101 years). The current driver status (no; yes) was used in our analysis. The EuroQoL EQ-5D questionnaire was used to assess HRQOL in this study., Results: Regression analysis showed that being a current driver was associated with the absence of problems in 'self-care' [OR 0.41 (95%-CI 0.17 to 0.98)], and 'usual activities' [OR 0.48 (0.26 to 0.90)], whereas it was not significantly associated with problems in 'pain/discomfort' [OR  0.82 (0.47 to 1.45)] and 'anxiety/depression' [OR  0.71 (0.36 to 1.39)]. Being a current driver was marginally significantly associated with the absence of problems in 'mobility' [OR 0.60 (0.34 to 1.06)]. While being a current driver was not associated with the EQ-VAS in the main model, it was positively associated with the driving status (β = 5.00, p < .05) when functional impairment was removed from the main model., Discussion: Our findings provide first evidence for an association between driving status and HRQOL among the oldest old., Conclusions: Future longitudinal studies are required to evaluate a possible causal relationship between driving status and HRQOL in very old individuals., (© 2020. The Author(s).)