Comment on "Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape".

In a recent article, Konwar et al. [ Langmuir 2022, 38, 11087-11098.] reported a new relationship between the structure of clusters of superparamagnetic nanoparticles and the proton nuclear magnetic resonance transverse relaxation they induce. In this comment, we would like to express reservations concerning the adequacy of the new relaxation model proposed in this work.

Breaking the ring: 53Cr-NMR on the Cr8Cd molecular nanomagnet.

An accurate experimental characterization of finite antiferromagnetic (AF) spin chains is crucial for controlling and manipulating their magnetic properties and quantum states for potential applications in spintronics or quantum computation. In particular, finite AF chains are expected to show a different magnetic behaviour depending on their length and topology. Molecular AF rings are able to combine the quantum-magnetic behaviour of AF chains with a very remarkable tunability of their topological and geometrical properties. In this work we measure the 53Cr-NMR spectra of the Cr8Cd ring to study the local spin densities on the Cr sites. Cr8Cd can in fact be considered a model system of a finite AF open chain with an even number of spins. The NMR resonant frequencies are in good agreement with the theoretical local spin densities, by assuming a core polarization field A C = -12.7 T µ B -1. Moreover, these NMR results confirm the theoretically predicted non-collinear spin arrangement along the Cr8Cd ring, which is typical of an even-open AF spin chain.

Effect of Spin Clustering on Basic and Relaxometric Properties of Magnetic Nanoparticles.

An increasing awareness about novel medical applications of smaller, inorganic-based nanoparticles, possessing unique properties at the nanoscale, has led to a burst of research activities in the development of "nanoprobes" for diagnostic medicine and agents for novel, externally activated therapies. In this research field magnetic nanoparticles are prominent due to fundamental peculiar properties particularly appealing for their use in materials and biomedical applications. Aiming to study the relationship between the topology of the magnetic nanoparticles and their efficacy as MRI contrast agents (relaxometric properties), we prepared three different stable colloidal suspension (ferrofluid) of magnetic nanobeads (MNBs) constituted by a discrete number of maghemite nanoparticles, arranged in disordered clusters or ordered in a polymeric matrix. An accurate morpho-dimensional and magnetic characterization displays the close correlation between the magnetic fundamental properties and the topology of our spin systems. The NMR relaxometry profiles confirmed the nature of the physical mechanisms inducing the increase of nuclear relaxation rates at low (magnetic anisotropy) and high (Curie relaxation) magnetic fields. Moreover the transverse relaxivity (r2) values for all the MNBs are higher than those of common contrast agents and the differences between the three MNBs are suggested to be due to the spin topology effect.

Local spin dynamics of iron oxide magnetic nanoparticles dispersed in different solvents with variable size and shape: A 1H NMR study.

Colloidal magnetic nanoparticles (MNPs) based on a nearly monodisperse iron oxide core and capped by oleic acid have been used as model systems for investigating the superparamagnetic spin dynamics by means of magnetometry measurements and nuclear magnetic resonance (1H NMR) relaxometry. The key magnetic properties (saturation magnetization, coercive field, and frequency dependent "blocking" temperature) of MNPs with different core size (3.5 nm, 8.5 nm, and 17.5 nm), shape (spherical and cubic), and dispersant (hexane and water-based formulation) have been determined. 1H NMR dispersion profiles obtained by measuring the r1 (longitudinal) and r2 (transverse) nuclear relaxivities in the frequency range 0.01-60 MHz confirmed that in all samples the physical mechanisms that drive the nuclear relaxation are the Néel reversal at low temperature and the Curie relaxation at high frequency. The magnetization reversal time at room temperature extracted from the fitting of NMR data falls in the typical range of superparamagnetic systems (10-9-10-10 s). Furthermore, from the distance of minimum approach we could conclude that water molecules do not arrive in close vicinity of the magnetic core. Our findings contribute to elucidate the local spin dynamics mechanisms in colloidal superparamagnetic nanoparticles which are useful in biomedical application as, e.g., contrast agents for magnetic resonance imaging.

NMR relaxation induced by iron oxide particles: testing theoretical models.

Superparamagnetic iron oxide particles find their main application as contrast agents for cellular and molecular magnetic resonance imaging. The contrast they bring is due to the shortening of the transverse relaxation time T 2 of water protons. In order to understand their influence on proton relaxation, different theoretical relaxation models have been developed, each of them presenting a certain validity domain, which depends on the particle characteristics and proton dynamics. The validation of these models is crucial since they allow for predicting the ideal particle characteristics for obtaining the best contrast but also because the fitting of T 1 experimental data by the theory constitutes an interesting tool for the characterization of the nanoparticles. In this work, T 2 of suspensions of iron oxide particles in different solvents and at different temperatures, corresponding to different proton diffusion properties, were measured and were compared to the three main theoretical models (the motional averaging regime, the static dephasing regime, and the partial refocusing model) with good qualitative agreement. However, a real quantitative agreement was not observed, probably because of the complexity of these nanoparticulate systems. The Roch theory, developed in the motional averaging regime (MAR), was also successfully used to fit T 1 nuclear magnetic relaxation dispersion (NMRD) profiles, even outside the MAR validity range, and provided a good estimate of the particle size. On the other hand, the simultaneous fitting of T 1 and T 2 NMRD profiles by the theory was impossible, and this occurrence constitutes a clear limitation of the Roch model. Finally, the theory was shown to satisfactorily fit the deuterium T 1 NMRD profile of superparamagnetic particle suspensions in heavy water.

Characterization of magnetic nanoparticles from Magnetospirillum Gryphiswaldense as potential theranostics tools.

We investigated the theranostic properties of magnetosomes (MNs) extracted from magnetotactic bacteria, promising for nanomedicine applications. Besides a physico-chemical characterization, their potentiality as mediators for magnetic fluid hyperthermia and contrast agents for magnetic resonance imaging, both in vitro and in vivo, are here singled out. The MNs, constituted by magnetite nanocrystals arranged in chains, show a superparamagnetic behaviour and a clear evidence of Verwey transition, as signature of magnetite presence. The phospholipid membrane provides a good protection against oxidation and the MNs oxidation state is stable over months. Using an alternate magnetic field, the specific absorption rate was measured, resulting among the highest reported in literature. The MRI contrast efficiency was evaluated by means of the acquisition of complete NMRD profiles. The transverse relaxivity resulted as high as the one of a former commercial contrast agent. The MNs were inoculated into an animal model of tumour and their presence was detected by magnetic resonance images two weeks after the injection in the tumour mass.

Non-conventional superconducting fluctuations in Ba(Fe1-xRhx)2As2 iron-based superconductors.

We measured the static uniform spin susceptibility of Ba(Fe(1-x)Rh(x))(2)As(2) iron-based superconductors, over a broad range of doping (0.041 ⩽ x ⩽ 0.094) and magnetic fields. At small fields (H ⩽ 1 kOe) we observed, above the transition temperature Tc, the occurrence of precursor diamagnetism, which is not ascribable to the Ginzburg-Landau theory. On the contrary, our data agree with a phase fluctuation model, which has been used to interpret a similar phenomenology occurring in the high-Tc cuprate superconductors. Additionally, in the presence of strong fields, the unconventional fluctuating diamagnetism is suppressed, whereas Ginzburg-Landau fluctuations are found, in agreement with literature.

Magnetic properties and hyperfine interactions in Cr8, Cr7Cd, and Cr7Ni molecular rings from ¹9F-NMR.

A detailed experimental investigation of the (19)F nuclear magnetic resonance is made on single crystals of the homometallic Cr8 antiferromagnetic molecular ring and heterometallic Cr7Cd and Cr7Ni rings in the low temperature ground state. Since the F(-) ion is located midway between neighboring magnetic metal ions in the ring, the (19)F-NMR spectra yield information about the local electronic spin density and (19)F hyperfine interactions. In Cr8, where the ground state is a singlet with total spin S(T) = 0, the (19)F-NMR spectra at 1.7 K and low external magnetic field display a single narrow line, while when the magnetic field is increased towards the first level crossing field, satellite lines appear in the (19)F-NMR spectrum, indicating a progressive increase in the Boltzmann population of the first excited state S(T) = 1. In the heterometallic rings, Cr7Cd and Cr7Ni, whose ground state is magnetic with S(T) = 3/2 and S(T) = 1/2, respectively, the (19)F-NMR spectrum has a complicated structure which depends on the strength and orientation of the magnetic field, due to both isotropic and anisotropic transferred hyperfine interactions and classical dipolar interactions. From the (19)F-NMR spectra in single crystals we estimated the transferred hyperfine constants for both the F(-)-Ni(2+) and the F(-)-Cd(2+) bonds. The values of the hyperfine constants compare well to the ones known for F(-)-Ni(2+) in KNiF3 and NiF2 and for F(-)-Cr(3+) in K2NaCrF6. The results are discussed in terms of hybridization of the 2s, 2p orbitals of the F(-) ion and the d orbitals of the magnetic ion. Finally, we discuss the implications of our results for the electron-spin decoherence.

Assembly-mediated interplay of dipolar interactions and surface spin disorder in colloidal maghemite nanoclusters.

Controlled assembly of single-crystal, colloidal maghemite nanoparticles is facilitated via a high-temperature polyol-based pathway. Structural characterization shows that size-tunable nanoclusters of 50 and 86 nm diameters (D), with high dispersibility in aqueous media, are composed of ∼13 nm (d) crystallographically oriented nanoparticles. The interaction effects are examined against the increasing volume fraction, φ, of the inorganic magnetic phase that goes from individual colloidal nanoparticles (φ = 0.47) to clusters (φ = 0.72). The frozen-liquid dispersions of the latter exhibit weak ferrimagnetic behaviour at 300 K. Comparative Mössbauer spectroscopic studies imply that intra-cluster interactions come into play. New insight emerges from the clusters' temperature-dependent ac susceptibility that displays two maxima in χ''(T), with strong frequency dispersion. Scaling-law analysis together with the observed memory effects suggests that a superspin-glass state settles-in at TB ∼ 160-200 K, while at lower-temperatures, surface spin-glass freezing is established at Tf ∼ 40-70 K. In such nanoparticle-assembled systems, with increased φ, Monte Carlo simulations corroborate the role of the inter-particle dipolar interactions and that of the constituent nanoparticles' surface spin disorder in the emerging spin-glass dynamics.

NMR-D study of the local spin dynamics and magnetic anisotropy in different nearly monodispersed ferrite nanoparticles.

We present a systematic experimental comparison of the superparamagnetic relaxation time constants obtained by means of dynamic magnetic measurements and (1)H-NMR relaxometry, on ferrite-based nanosystems with different composition, various core sizes and dispersed in different solvents. The application of a heuristic model for the relaxivity allowed a comparison between the reversal time of magnetization as seen by NMR and the results from the AC susceptibility experiments, and an estimation of fundamental microscopic properties. A good agreement between the NMR and AC results was found when fitting the AC data to a Vogel-Fulcher law. Key parameters obtained from the model have been exploited to evaluate the impact of the contribution from magnetic anisotropy to the relaxivity curves and estimate the minimum approach distance of the bulk solvent.

Local spin density in the Cr7Ni antiferromagnetic molecular ring and 53Cr-NMR.

We present (53)Cr-NMR spectra collected at low temperature in a single crystal of the heterometallic antiferromagnetic (AF) ring Cr(7)Ni in the S = 1/2 ground state with the aim of establishing the distribution of the local electronic moment in the ring. Due to the poor S/N we observed only one signal which is ascribed to three almost equivalent (53)Cr nuclei in the ring. The calculated spin density in Cr(7)Ni in the ground state, with the applied magnetic field both parallel and perpendicular to the plane of the ring, turns out to be AF staggered with the greatest component of the local spin for the Cr(3+) ions next to the Ni(2+) ion. The (53)Cr-NMR frequency was found to be in good agreement with the local spin density calculated theoretically by assuming a core polarization field of H(cp) = - 11 T/µ(B) for both orientations, close to the value found previously in Cr(7)Cd. The observed orientation dependence of the local spin moments is well reproduced by the theoretical calculation and evidences the importance of single-ion and dipolar anisotropies.

Atomic force microscopy imaging of lipid rafts of human breast cancer cells.

Several studies suggest that the plasma membrane is composed of micro-domains of saturated lipids that segregate together to form lipid rafts. Lipid rafts have been operationally defined as cholesterol- and sphingolipid-enriched membrane micro-domains resistant to solubilization by non-ionic detergents at low temperatures. Here we report a biophysical approach aimed at investigating lipid rafts of MDA-MB-231 human breast cancer cells by coupling an atomic force microscopy (AFM) study to biochemical assays namely Western blotting and high performance thin layer chromatography. Lipid rafts were purified by ultracentrifugation on discontinuous sucrose gradient using extraction with Triton X-100. Biochemical analyses proved that the fractions isolated at the 5% and 30% sucrose interface (fractions 5 and 6) have a higher content of cholesterol, sphingomyelin and flotillin-1 with respect to the other purified fractions. Tapping mode AFM imaging of fraction 5 showed membrane patches whose height corresponds to the one awaited for a single lipid bilayer as well as the presence of micro-domains with lateral dimensions in the order of a few hundreds of nanometers. In addition, an AFM study using specific antibodies suggests the presence, in these micro-domains, of a characteristic marker of lipid rafts, the protein flotillin-1.

Multifunctional nanoparticles for dual imaging.

For imaging with different modalities, labels, which provide contrast for all modalities, are required. Colloidal nanoparticles composed out of an inorganic core and a polymer shell offer progress in this direction. Both, the core and the polymer shell, can be synthesized to be fluorescent, magnetic, or radioactive. When different cores are combined with different polymer shells, different types of particles for dual imaging can be obtained, as for example, fluorescent cores with radioactive polymer shells. Properties and perspectives of such nanoparticles for multimodal imaging are discussed.

Unconventional nonequilibrium dynamics in Ni10 magnetic molecules: evidence from NMR.

Crystals containing Ni10 magnetic molecules display an unprecedented form of out-of-equilibrium behavior of the bulk magnetization M at temperatures as high as 17 K. We have performed 1H NMR measurements to probe the local Ni magnetic moments and their dynamics. It is apparent that no freezing of the Ni moments occurs, in striking contrast to what is observed in blocked superparamagnetic systems. The average local moments display the same behavior as M, thus unambiguously demonstrating the intrinsic character of the phenomenon. This result supports the hypothesis that the slowing down of M is due to a resonant phonon trapping mechanism which prevents the thermalization of M but not the fast spin flippings of the individual molecular moments. Indeed, the measured nuclear spin-lattice relaxation rate points to fast single-molecule dynamics at low temperature.

Water-soluble rhamnose-coated Fe3O4 nanoparticles.

Water-soluble biocompatible rhamnose-coated Fe(3)O(4) nanoparticles of 4.0 nm are obtained by covalent anchorage of rhamnose on the nanoparticles surface via a phosphate linker. These nanoparticles present superparamagnetic behavior and nuclear relaxivities in the same order of magnitude as Endorem that make them potential magnetic resonance imaging (MRI) contrast agents of a second generation, where the saccharides represent also specific ligands able to target lectins on skin cells.

Synthesis and characterization of polyethylenimine-based iron oxide composites as novel contrast agents for MRI.

OBJECT: Use of polyethylenimines (PEIs) of different molecular weight and selected carboxylated-PEI derivatives (PEI-COOH) in the synthesis and stabilization of iron oxide nanoparticles, to obtain possible multifunctional contrast agents. MATERIALS AND METHODS: Oxidation of Fe(II) at slightly elevated pH and temperature resulted in the formation of highly soluble and stable nanocomposites of iron oxides and polymer. Composites were characterized and studied by atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffractometry, AC and DC magnetometry, NMR relaxometry and magnetic resonance imaging (MRI). RESULTS: From AFM the dimensions of the aggregates were found to be in the ~150-250 nm size region; the mean diameter of the magnetic core of the compounds named PEI-25, PEI-500 and PEI-COOH60 resulted d approximately 20 +/- 5 nm for PEI-25, d approximately 9.5 +/- 1.0 nm for PEI-500 and d approximately 6.8 +/- 1.0 nm for PEI-COOH60. In PEI-COOH60 TEM and X-ray diffractometry revealed small assemblies of mineral magnetic cores with clear indications that the main constituents are maghemite and/or magnetite as confirmed by AC and DC SQUID magnetometry. For PEI-COOH60, the study of NMR-dispersion profiles revealed r (1) and r (2) relaxivities comparable to superparamagnetic iron-oxide commercial compounds in the whole investigated frequency range 7 < or = nu < or = 212 MHz. CONCLUSION: PEI-25 was studied as possible MRI contrast agent (CA) to map the cerebral blood volume (CBV) and cerebral blood flow (CBF) in an animal model obtaining promising results. The reported compounds may be further functionalized to afford novel multifunctional systems for biomedical applications.

Two-step magnetic ordering in quasi-one-dimensional helimagnets: possible experimental validation of villain's conjecture about a chiral spin liquid phase.

Low-temperature specific heat, magnetic susceptibility, and zero-field muon spin resonance (microSR) measurements have been performed in the quasi-one-dimensional molecular helimagnetic compound Gd(hfac)3NITEt. The specific heat presents two anomalies at T(0)=2.19+/-0.02 K and T(N)=1.88+/-0.02 K, which both disappear upon the application of a weak magnetic field. Conversely, magnetic susceptibility and muSR data show the divergence of two-spin correlation functions only at T(N)=1.88+/-0.02 K. These results suggest an experimental validation of Villain's conjecture of a two-step magnetic ordering in quasi-one-dimensional XY helimagnets; i.e., the paramagnetic phase and the helical spin solid phase are separated by a chiral spin liquid phase, where translational invariance is broken without violation of rotational invariance.

Effect of p53 haploinsufficiency on melphalan-induced genotoxic effects in mouse bone marrow and peripheral blood.

Mice heterozygous for a p53 null mutation develop tumours induced by genotoxic carcinogens with a shorter latency than wild type mice and have been proposed as an alternate animal model for carcinogenicity testing. Some literature data suggest that p53+/- mice might also be more sensitive to the short-term effects of genotoxic agents and manifest a haploinsufficiency phenotype that could contribute to the higher tumour susceptibility. We have compared the induction of micronuclei in bone marrow and blood of p53+/- and p53+/+ isogenic mice after treatment with a single or multiple doses of melphalan (MLP), a crosslinking genotoxic carcinogen. We have also characterized the mechanism of micronucleus induction with CREST staining of kinetochore proteins to distinguish between chromosome break- and chromosome loss-induced micronuclei. Significant increases of micronucleated bone marrow polychromatic erythrocytes and blood reticulocytes were induced under all MLP exposure conditions. The frequency of micronucleated blood erythrocytes increased linearly with duration of exposure. Micronuclei were essentially a consequence of chromosome break events. After a single MLP dose, a significant reduction of the frequency of polychromatic erythrocytes in bone marrow of p53+/+ animals suggested the induction of cytotoxicity/cell cycle delay. This effect was not observed in p53+/- mice. We believe this finding to provide some evidence of a haploinsufficiency phenotype in the modulation of cell cycle/apoptotic pathways mediated by the p53 protein. In bone marrow of wild type mice, an increased effect of multiple MLP doses was detected over that of a single administration, whereas, in p53+/- mice, no differential effect was found of different exposure durations. Possibly, the probability of micronucleus formation increased under chronic exposure because of increased cell division in response to peripheral anemia and a reduction of p53 protein level had a small effect on cell cycle modulation and on such indirect mechanism of micronucleus induction. However, pairwise comparisons between the frequencies of cells with micronuclei in wild type and p53+/- mice under all exposure conditions did not show statistically significant differences, suggesting that the observed effects of p53 haploinsufficiency were weak and temporary and a higher/faster induction of irreversible chromosome damage could not account for the increased susceptibility of p53+/- mice to MLP-induced tumours.

Muon spin rotation studies of spin dynamics at avoided level crossings in LiY0.998Ho0.002F4.

We have studied the Ho3+ spin dynamics for LiY0.998Ho0.002F4 via the positive muon (mu+) transverse field depolarization rate lambdaTF as a function of temperature and magnetic field. We find sharp minima in lambdaTF(H) at fields for which the Ho3+ ion system has field-induced (avoided) level crossings. The reduction scales with calculated level repulsions, suggesting that mu+ depolarization by slow fluctuations of nonresonant Ho3+ spin states is partly suppressed when resonant tunneling opens new fluctuation channels at frequencies much greater than the muon precession frequency.

Local spin moment distribution in antiferromagnetic molecular rings probed by NMR.

The NMR spectra of 19F and 53Cr have been obtained at low temperatures in a heterometallic substituted antiferromagnetic (AF) ring Cr7Cd with an S=3/2 ground state and compared with the spectra in a homometallic Cr8 AF ring with an S=0 ground state. From the analysis of the spectra one can derive directly model independent values of the staggered nonuniform distribution of the local moment in the heterometallic ring Cr7Cd. The experimental values are found to be in excellent agreement with the theoretical values calculated on the basis of an effective spin Hamiltonian which includes crystal field effects.