Producing Conventional and Transient Amino(mercapto)methyl Radicals by Addition of Muonium to a Crystalline Thioformamide (Mes*NHCH=S).

Muonium (Mu=µ+e-) is composed of a muon of light isotope of proton (µ+) and electron (e-) and can be used as a light surrogate for a hydrogen atom. In this paper, we investigated addition of muonium to a newly synthesized Mes*-substituted thioformamide (Mes*NHCH=S, Mes*=2,4,6-tBu3C6H2). Transverse-field muon spin rotation (TF-µSR) of a solution sample of the thioformamide confirmed addition of muonium to the sulfur atom leading to the corresponding C-centered radical [Mes*NHC(H)⋅-SMu]. Density functional theory (DFT) calculations assigned a conventional amino(mercapto)methyl radical, in which both nitrogen and carbon were slightly pyramidalized, and the calculated muon hyperfine coupling constant (hfcc) including the muon isotope effect was compatible with the experimentally determined parameter. However, the muon level-crossing resonance (µLCR) spectrum of an anisotropic crystalline sample indicated two paramagnetic species, and the major product showed the considerably larger muon hfcc compared with the conventional structure of the amino(mercapto)methyl radical. The unusual transient muoniated thioformamide with the larger muon hfcc that showed rapid relaxation could be only explained by a transient structure including planarization of the nitrogen and carbon atoms in Mes*NHC(H)⋅-SMu.

Difluoromethylborates and Muonium for the Study of Isonitrile Insertion Affording Phenanthridines via Imidoyl Radicals.

The 6-(difluoromethyl)phenanthridine unit is a highly attractive fluoroalkyl-substituted planar nitrogen heterocycle in pharmaceutical and agrochemical research. In this paper, we report that difluoromethylborates can be used as a source of difluoromethyl radicals for isonitrile insertion, leading to 6-(difluoromethyl)phenanthridines. Tuning the aryl substituents in the difluoromethylborates and oxidizing reagents enabled the synthesis of 6-(difluoromethyl)phenanthridines through the generation of difluoromethyl radical and spontaneous intramolecular cyclization of the CF2H-imidoyl radical intermediates. The presence of difluoromethyl radicals was experimentally confirmed, and the reaction mechanisms including imidoyl radical and prompt cyclization reactions could be supported theoretically. Furthermore, we obtained valuable information about the imidoyl radical intermediate by performing transverse-field muon spin rotation (TF-µSR) measurements of 2-isocyano-4'-methoxy-1,1'-biphenyl and using density functional theory (DFT) calculations to interpret the spectra. Muonium, a simple free radical, preferentially adds to the carbon atom of the isonitrile unit, yielding the corresponding imidoyl radical. The temperature dependence of the muon hyperfine coupling constant and the spin relaxation of the muoniated radical signal are compatible with the intramolecular cyclization of biaryl-substituted imidoyl radicals on the µs time scale.

Bioactivity of the cannabigerol cannabinoid and its analogues - the role of 3-dimensional conformation.

Cannabinoids are naturally occurring bioactive compounds with the potential to help treat chronic illnesses including epilepsy, Parkinson's disease, dementia and multiple sclerosis. Their general structures and efficient syntheses are well documented in the literature, yet their quantitative structure-activity relationships (QSARs), particularly 3-dimensional (3-D) conformation-specific bioactivities, are not fully resolved. Cannabigerol (CBG), an antibacterial precursor molecule for the most abundant phytocannabinoids, was characterised herein using density functional theory (DFT), together with selected analogues, to ascertain the influence of the 3D structure on their activity and stability. Results showed that the CBG family's geranyl chains tend to coil around the central phenol ring while its alkyl side-chains form H-bonds with the para-substituted hydroxyl groups as well as CH⋯π interactions with the aromatic density of the ring itself, among other interactions. Although weakly polar, these interactions are structurally and dynamically influential, effectively 'stapling' the ends of the chains to the central ring structure. Molecular docking of the differing 3-D poses of CBG to cytochrome P450 3A4 resulted in lowered inhibitory action by the coiled conformers, relative to their fully-extended counterparts, helping explain the trends in the inhibition of the metabolic activity of the CYP450 3A4. The approach detailed herein represents an effective method for the characterisation of other bioactive molecules, towards improved understanding of their QSARs and in guiding the rational design and synthesis of related compounds.

Radio-Frequency Manipulation of State Populations in an Entangled Fluorine-Muon-Fluorine System.

Entangled spin states are created by implanting muons into single-crystal LiY_{0.95}Ho_{0.05}F_{4} to form a cluster of correlated, dipole-coupled local magnetic moments. The resulting states have well-defined energy levels allowing experimental manipulation of the state populations by electromagnetic excitation. Experimental control of the evolution of the muon spin polarization is demonstrated through application of continuous, radio-frequency electromagnetic excitation fields. A semiclassical model of quantum, dipole-coupled spins interacting with a classical, oscillating magnetic field accounts for the muon spin evolution. On application of the excitation field, this model shows how changes in the state populations lead to the experimentally observed effects, thus enabling a spectroscopic probe of entangled spin states with muons.

Paramagnetic probes in an organic semiconductor: µSR and DFT calculations of the Mu adducts of Alq3 and 8-hydroxyquinoline.

It has been claimed that longitudinal field muon spin relaxation (LF-µSR) experiments on the organic semiconductor (OSC) tris-(8-hydroxyquinoline)aluminum(III) (Alq3) have measured electron hopping rates of ∼1012s-1, while density functional theory (DFT) calculations suggest that electron hopping between a muoniated radical and a neighboring molecule is energetically unfavorable and that the LF-µSR experiments were probing muoniated radicals with localized spin density. We have performed avoided level crossing muon spin resonance (ALC-µSR) and transverse field muon spin rotation (TF-µSR) measurements on Alq3 and 8-hydroxyquinoline (8hq), which is meant to model the muoniated radicals present in Alq3 when they are not in an OSC. These are supplemented by benchmarked DFT calculations. The ALC-µSR and TF-µSR spectra of 8hq and Alq3 are best explained by Mu adding to all six secondary carbons of the quinolate rings with roughly equal yields and localized spin density. There is no evidence in the TF-µSR spectrum of Alq3 for the formation of radicals with muon hyperfine coupling constants of 23 or 91 MHz as reported earlier by others. Our measurements support the view that there is localized spin density on the molecule to which Mu is covalently bound and the muon is not a passive probe in organic systems as it can be incorporated into radicals that have different electronic structures to the parent compounds. The muoniated radicals in Alq3 are more short-lived than in 8hq, which could be due to interactions with mobile electrons in the OSC, but with electron spin flip rates on the order of ∼107s-1.

A ß-NMR study of the depth, temperature, and molecular-weight dependence of secondary dynamics in polystyrene: Entropy-enthalpy compensation and dynamic gradients near the free surface.

We investigated the depth, temperature, and molecular-weight (MW) dependence of the γ-relaxation in polystyrene glasses using implanted 8Li+ and ß-detected nuclear magnetic resonance. Measurements were performed on thin films with MW ranging from 1.1 to 641 kg/mol. The temperature dependence of the average 8Li spin-lattice relaxation time (T1 avg) was measured near the free surface and in the bulk. Spin-lattice relaxation is caused by phenyl ring flips, which involve transitions between local minima over free-energy barriers with enthalpic and entropic contributions. We used transition state theory to model the temperature dependence of the γ-relaxation, and hence T1 avg. There is no clear correlation of the average entropy of activation (Δ‡S̄) and enthalpy of activation (Δ‡H̄) with MW, but there is a clear correlation between Δ‡S̄ and Δ‡H̄, i.e., entropy-enthalpy compensation. This results in the average Gibbs energy of activation, Δ‡G, being approximately independent of MW. Measurements of the temperature dependence of T1 avg as a function of depth below the free surface indicate the inherent entropic barrier, i.e., the entropy of activation corresponding to Δ‡H̄ = 0, has an exponential dependence on the distance from the free surface before reaching the bulk value. This results in Δ‡G near the free surface being lower than the bulk. Combining these observations results in a model where the average fluctuation rate of the γ-relaxation has a "double-exponential" depth dependence. This model can explain the depth dependence of 1/T1 avg in polystyrene films. The characteristic length of enhanced dynamics is ∼6 nm and approximately independent of MW near room temperature.

Magnesium(II)-ATP Complexes in 1-Ethyl-3-Methylimidazolium Acetate Solutions Characterized by 31 Mg ß-Radiation-Detected NMR Spectroscopy.

The complexation of MgII with adenosine 5'-triphosphate (ATP) is omnipresent in biochemical energy conversion, but is difficult to interrogate directly. Here we use the spin- 1/2 ß-emitter 31 Mg to study MgII -ATP complexation in 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) solutions using ß-radiation-detected nuclear magnetic resonance (ß-NMR). We demonstrate that (nuclear) spin-polarized 31 Mg, following ion-implantation from an accelerator beamline into EMIM-Ac, binds to ATP within its radioactive lifetime before depolarizing. The evolution of the spectra with solute concentration indicates that the implanted 31 Mg initially bind to the solvent acetate anions, whereafter they undergo dynamic exchange and form either a mono- (31 Mg-ATP) or di-nuclear (31 MgMg-ATP) complex. The chemical shift of 31 Mg-ATP is observed up-field of 31 MgMg-ATP, in accord with quantum chemical calculations. These observations constitute a crucial advance towards using ß-NMR to probe chemistry and biochemistry in solution.

Dynamics and local environment of an aromatic counterion bound to di-chain cationic surfactant bilayers studied by avoided level crossing muon spin resonance: evidence for counterion condensation.

Avoided level crossing muon spin resonance (ALC-µSR) has been used to study the reorientational dynamics of muon-spin-labelled 2,4,6-trimethylbenzoate (246TMB-) counterions and their interaction with DODMAC (dioctadecyldimethylammonium chloride) bilayers in the Lα and Lß liquid crystalline states. The muoniated radical anion formed by the addition of muonium to the secondary carbons of the aromatic ring of 246TMB- is used as a local spin probe. The muon and methylene proton hyperfine parameters and the electron spin relaxation rate (λe) of the muoniated spin probe were determined as a function of temperature by modelling the ALC-µSR spectra with Monte Carlo numerical simulations. The observation of a Δ1 resonance indicates that 246TMB- is undergoing anisotropic motion and doesn't reside in the aqueous layer in either the Lα and Lß phases. The lack of an abrupt change in the hyperfine parameters or λe when the system goes from the Lß to the Lα lamellar liquid crystalline phases suggests that 246TMB- is located at the oil-water interface rather than within the bilayer. The hyperfine parameters indicate that 246TMB- is undergoing large amplitude reorientational motion about a preferred orientation resulting from the bilayer's electric field. The interaction between 246TMB- and the bilayer decreases and the amplitude of the wobbling-in-a-cone motion increases with increasing temperature. The temperature dependence of the electron spin relaxation rate indicates the barrier to reorientation is 41.7 kJ mol-1.

Muonium Addition to a peri-Trifluoromethylated 9-Phosphaanthracene Producing a High-Energy Paramagnetic π-Conjugated Fused Heterocycle.

In this communication, we report muon spin rotation/resonance (µSR) studies for understanding radical reactivity of 10-mesityl-1,8-bis(trifluoromethyl)-9-phosphaanthracene. Transverse-field muon spin rotation (TF-µSR) and muon avoided level-crossing resonance (µLCR) measurements successfully visualized a paramagnetic species produced by regioselective addition of muonium (Mu) to the skeletal phosphorus atom. Density functional theory (DFT) calculations for the P-muoniation product suggested two possible isomers. Whereas the most stable isomer including the envelope-type phosphorus heterocycle shows considerably different hyperfine coupling constants (hfcs) from those of the TF-µSR and µLCR, the metastable structure accompanying the almost planar tricyclic π-conjugated skeleton could simulate the experimentally determined hfcs. The metastable planar π-conjugated paramagnetic tricyclic-fused skeleton is promoted by the larger zero-point energy due to the light muon (µ+ ), one ninth of the proton mass.

Measured radiation effects on InGaAsP/InP ring resonators for space applications.

Photonic ring resonators can be considered building blocks of new concept satellite payloads for implementing several functions, such as filtering and sensing. In particular, the use of a high Q-factor ring resonator as sensing element into a Resonant Micro Optic Gyroscope (RMOG), provides a remarkable improvement of the performance with respect to the competitive technologies. To qualify a ring resonator for Space applications, the radiation effects on it in the Space must be carefully evaluated. Here, we investigate the effects of gamma radiation on a high Q InGaAsP/InP ring resonator, for the first time, to our knowledge. The ring resonator under study has a footprint of about 530 mm2 and it is based on a InGaAsP/InP rib waveguide, with a width of 2 µm and a thickness of 0.3 µm, formed on a 0.7 µm thick slab layer on an InP substrate 625 µm thick. For a total dose of about 320 krad Co60 gamma irradiation, a mean variation of about 13% and 4% was measured for Q and extinction ratio (ER), respectively, with respect to the values before irradiation (Q = 1.36 × 106, ER = 6.24 dB). Furthermore, the resonance peak red-shifts with a linear behaviour was observed increasing the total dose of the absorbed radiation, with a maximum resonance detuning of about 810 pm. These non-significant effects of a quite high gamma radiation dose confirm the potential of high-Q InP-based ring resonators into Space systems or subsystems.

Free Radical Reactivity of a Phosphaalkene Explored Through Studies of Radical Isotopologues.

Muonium (Mu), an H atom analogue, is employed to probe the addition of free radicals to the P=C bond of a phosphaalkene. Specifically, two unprecedented muoniated free radicals, MesP. -CMu(Me)2 (1 a, minor product) and MesPMu-C. Me2 (1 b, major product), were detected by muon spin spectroscopy (µSR) when a solution of MesP=CMe2 (1: Mes=2,4,6-trimethylphenyl) was exposed to a beam of positive muons (µ+ ). The µ+ serves as a source of Mu (that is, Mu=µ+ +e- ). To confirm the identity of the major product 1 b, its spectral features were compared to its isotopologue, MesPH-C. (Me)CH2 Mu (2 a). Conveniently, 2 a is the sole product of the reaction of MesPH(CMe=CH2 ) (2) with Mu. For all observed radicals, muon, proton, and phosphorus hyperfine coupling constants were determined by µSR and compared to DFT-calculated values.

Direct measurements of the temperature, depth and processing dependence of phenyl ring dynamics in polystyrene thin films by ß-detected NMR.

There is indirect evidence that the dynamics of a polymer near a free surface are enhanced compared with the bulk but there are few studies of how dynamics varies with depth. ß-Detected nuclear spin relaxation of implanted 8Li+ has been used to directly probe the temperature and depth dependence of the γ-relaxation mode, which is due to phenyl rings undergoing restricted rotation, in thin films of atactic deuterated polystyrene (PS-d8) and determine how the depth dependence of dynamics is affected by sample processing, such as annealing, floating on water and the inclusion of a surfactant, and by the presence of a buried interface. The activation energy for the γ-relaxation process is lower near the free surface. Annealing the PS-d8 films and then immersing in water to mimic the floating procedure used to transfer films had negligible effects on the thickness of the region near the free surface with enhanced mobility. Measurements on a bilayer film indicate enhanced phenyl ring dynamics near the buried interface compared with a single film at the same depth. PS-d8 films annealed with the surfactant sodium dodecyl sulfate (SDS) deposited on the surface show enhanced dynamics in the bulk compared with a pure PS-d8 film and a PS-d8 film where the SDS was washed away. There is less contrast between the surface and bulk in the SDS-treated sample, which could account for the elimination of the Tg confinement effect observed in films containing SDS [Chen and Torkelson, Polymer, 2016, 87, 226].

Observation of a Metastable P-Heterocyclic Radical by Muonium Addition to a 1,3-Diphosphacyclobutane-2,4-diyl.

A 1,3-diphosphacyclobutane-2,4-diyl contains a unique unsaturated cyclic unit, and the presence of radical-type centers have been expected as a source of functionality. This study demonstrates that the P-heterocyclic singlet biradical captures muonium (Mu=[µ+ e- ]), the light isotope of a hydrogen radical, to generate an observable P-heterocyclic paramagnetic species. Investigation of a powder sample of 2,4-bis(2,4,6-tri-t-butylphenyl)-1-t-butyl-3-benzyl-1,3-diphosphacyclobutane-2,4-diyl using muon (avoided) level-crossing resonance (µLCR) spectroscopy revealed that muonium adds to the cyclic P2 C2 unit. The muon hyperfine coupling constant (Aµ ) indicated that the phosphorus atom bearing the t-butyl group trapped muonium to provide a metastable P-heterocyclic radical involving the ylidic MuP(<)=C moiety. The observed regioselective muonium addition correlates the canonical formula of 1,3-diphosphacyclobutane-2,4-diyl.

Partitioning of 2-phenylethanol and limonene cosurfactants in C12E4.

Avoided level-crossing muon spin resonance (ALC-µSR) has been used to study the dynamics and local environment of spin probes formed by muonium (Mu) addition to 2-phenylethanol (PEA) and limonene (1-methyl-4-(1-methylethenyl)-cyclohexene) in an aqueous dispersion of the nonionic surfactant C12E4 (tetra(ethylene glycol) n-dodecyl ether). The spin probes derived from both cosurfactants reside within the micelles in the L1 phase and the bilayers in the Lα phase rather than in the aqueous region. The local polarity measured by the different isomers of the Mu adducts of PEA suggests there is a water gradient within the micelles and bilayers. Slow rotation of the micelles broadened the Δ1 resonances with increasing temperature in the L1 phase while narrower Δ1 resonances were observed in the Lα phase due to the rapid rotation of the spin probes around a preferred axis, which was wobbling within a cone.

ß-NMR measurements of molecular-scale lithium-ion dynamics in poly(ethylene oxide)-lithium-salt thin films.

ß-detected NMR (ß-NMR) has been used to study the molecular-scale dynamics of lithium ions in thin films of poly(ethylene oxide) (PEO) containing either lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) or lithium trifluoroacetate (LiTFA) salts at monomer-to-salt ratios (EO/Li) of 8.3. The results are compared with previous ß-NMR measurements on pure PEO and PEO with lithium triflate (LiOTf) at the same loading [McKenzie et al., J. Am. Chem. Soc. 136, 7833 (2014)]. Activated hopping of 8Li+ was observed in all of the films above ∼250 K, with the hopping parameters strongly correlated with the ionicity of the lithium salt rather than the polymer glass transition temperature. The pre-exponential factor increases exponentially with ionicity, while the activation energy for hopping increases approximately linearly, going from 6.3±0.2 kJ mol-1 in PEO:LiTFA to 17.8±0.2 kJ mol-1 in PEO:LiTFSI. The more rapid increase in the pre-exponential factor outweighs the effect of the larger activation energy and results in 8Li+ hopping being fastest in PEO followed by PEO:LiTFSI, PEO:LiOTf, and PEO:LiTFA.

Enhanced high-frequency molecular dynamics in the near-surface region of polystyrene thin films observed with ß-NMR.

ß-detected nuclear spin relaxation of (8)Li(+) has been used to probe the depth dependence of molecular dynamics in high- and low-molecular-weight deuterated polystyrene. The average nuclear spin-lattice relaxation rate, 1/T(avg)(1), is a measure of the spectral density of the polymer motion at the Larmor frequency (41 MHz at 6.55 T). In both samples, 1/T(avg)(1) is depth independent below ∼200 K but above this temperature it decreases approximately exponentially with distance from the free surface, returning to bulk behavior for depths greater than ∼10 nm. This is direct evidence for a region near the free surface with enhanced molecular dynamics compared with the bulk. The effective thickness of the surface region increases with increasing temperature and is finite even above the glass transition. These results present challenges for the current understanding of dynamics near the surface of polymer glasses.

Rate constants for the slow Mu + propane abstraction reaction at 300 K by diamagnetic RF resonance.

The study of kinetic isotope effects for H-atom abstraction rates by incident H-atoms from the homologous series of lower mass alkanes (CH4, C2H6 and, here, C3H8) provides important tests of reaction rate theory on polyatomic systems. With a mass of only 0.114 amu, the most sensitive test is provided by the rates of the Mu atom. Abstraction of H by Mu can be highly endoergic, due to the large zero-point energy shift in the MuH bond formed, which also gives rise to high activation energies from similar zero-point energy corrections at the transition state. Rates are then far too slow near 300 K to be measured by conventional TF-µSR techniques that follow the disappearance of the spin-polarised Mu atom with time. Reported here is the first measurement of a slow Mu reaction rate in the gas phase by the technique of diamagnetic radio frequency (RF) resonance, where the amplitude of the MuH product formed in the Mu + C3H8 reaction is followed with time. The measured rate constant, kMu = (6.8 ± 0.5) × 10(-16) cm(3) s(-1) at 300 K, is surprisingly only about a factor of three slower than that expected for H + C3H8, indicating a dominant contribution from quantum tunneling in the Mu reaction, consistent with elementary transition state theory calculations of the kMu/kH kinetic isotope effect.

Proton, muon and ¹³C hyperfine coupling constants of C60X and C70X (X = H, Mu).

The reaction of H atoms with fullerene C70 has been investigated by identifying the radical products formed by addition of the atom muonium (Mu) to the fullerene in solution. Four of the five possible radical isomers of C70Mu were detected by avoided level-crossing resonance (µLCR) spectroscopy, using a dilute solution of enriched (13)C70 in decalin. DFT calculations were used to predict muon and (13)C isotropic hyperfine constants as an aid to assigning the observed µLCR signals. Computational methods were benchmarked against previously published experimental data for (13)C60Mu in solution. Analysis of the µLCR spectrum resulted in the first experimental determination of (13)C hyperfine constants in either C70Mu or C70H. The large number of values confirms predictions that the four radical isomers have extended distributions of unpaired electron spin.

ß-NMR measurements of lithium ion transport in thin films of pure and lithium-salt-doped poly(ethylene oxide).

ß-Detected nuclear spin relaxation of (8)Li(+) has been used to study the microscopic diffusion of lithium ions in thin films of poly(ethylene oxide) (PEO), where the implanted lithium ions are present in extremely low concentration, and PEO with 30 wt % LiCF3SO3 over a wide range of temperatures both above and below the glass transition temperature. Recent measurements by Do et al. [Phys. Rev. Lett. 2013, 111, 018301] found that the temperature dependence of the Li(+) conductivity was identical to that of the dielectric α relaxation and was well described by the Vogel-Fulcher-Tammann relation, implying the α relaxation dominates the Li(+) transport process. In contrast, we find the hopping of Li(+) in both samples in the high temperature viscoelastic phase follows an Arrhenius law and depends significantly on the salt content. We propose that the hopping of Li(+) between cages involves motion of the polymer but that it is only for long-range diffusion where the α relaxation plays an important role.

Muon spin spectroscopy of ferrocene: characterization of muoniated ferrocenyl radicals.

Radicals formed by the reaction of muonium (Mu), a light isotope of hydrogen, with ferrocene and ferrocene-d10 have been studied with the avoided level crossing muon spin resonance (ALC-µSR) and longitudinal field muon spin relaxation (LF-µSR) techniques between 10 and 100 K. A single type of radical was observed in each compound and the muon hyperfine coupling constants (hfcc) and the muon spin relaxation rates were measured as a function of temperature. A previous report concerning the observation of Mu adducts of ferrocene (U. A. Jayasooriya et al. Chem. - Eur. J., 2007, 13, 2266-2276) appears to be incorrect. DFT calculations were performed to aid in the assignment of the ALC-µSR spectra. A tentative assignment is that the observed radicals were formed by Mu addition to the exterior of the cyclopentadienyl rings and that the structures are distorted due to interactions with neighbouring molecules. The temperature dependence of the muon hfcc can be explained assuming the population of two levels with different muon hfccs separated by 1.4 ± 0.1 kJ mol(-1). The temperature dependence of the width and amplitude of the Δ1 resonance and the muon spin relaxation rate suggests that the electron spin relaxation rate increase with temperature, but the relaxation mechanism is unknown.