Lanthanides enhance pulmonary absorption of insulin

In an effort to investigate the enhancement effect of lanthanide ions (Ln³⁺) on the absorption of larger molecules from the pulmonary pathway, insulin (mol. wt.=5730) was chosen as a model peptide. The absorption of insulin preadministered or coadministered with Ln³⁺ from the lung was investigated by means of an in situ pulmonary absorption experiment. The enhancement absorption of insulin by Ln³⁺ ions was evaluated by calculating the various bioavailabilities (Fr) of insulin from pulmonary absorption. Moreover, the temporal change of Gd content in serum was also investigated. Results showed that the promoting effect of Ln³⁺ on the bioavailability of insulin is closely related to its species, concentration, and delivery order. The effect of the median Ln³⁺ series was remarkably greater than that of light and heavy Ln³⁺. The anionic form of Gadolinium (Fr=68.4%) seemed to be more effective compared with its cationic form (Fr=59.5%). Coadministration of Gd³⁺ with insulin (Fr=80.1%) was the most effective in increasing insulin absorption from the lung. Gd³⁺ was rapidly absorbed and metabolized to a normal level after 4 h. It was suggested that lanthanides in a very low concentration might become potent absorption enhancers to improve absorption of larger molecules via the pulmonary pathway.     

A new heavy lanthanide-dependent DNAzyme displaying strong metal cooperativity and unrescuable phosphorothioate effect

In vitro selection of RNA-cleaving DNAzymes was performed using three heavy lanthanide ions (Ln³⁺): Ho³⁺, Er³⁺ and Tm³⁺. The resulting sequences were aligned together and about half of the library contained a new family of DNAzyme. These DNAzymes have a simple loop structure, and they are active only with the seven heavy Ln³⁺. Among the tested non-lanthanide ions, only Y³⁺ induced cleavage and even Pb²⁺ failed to cleave, suggesting a very high specificity. A representative DNAzyme, Tm7, has a sigmoidal metal binding curve with a Hill coefficient of 3, indicating that three metal ions are involved in the catalytic step. Its pH-rate profile has a slope of 1, suggesting a single deprotonation step is involved in the rate-limiting step. Tm7 has a cleavage rate of 1.6 min⁻¹ at pH 7.8 with 10 μM Er³⁺. Phosphorothioate substitution at the cleavage junction completely inhibits the activity, which cannot be rescued by Cd²⁺ alone, or by a mixture of Er³⁺ and Cd²⁺, suggesting that two interacting metal ions are involved in direct bonding to both non-bridging oxygen atoms. A new model involving three lanthanide ions is proposed based on this study. A biosensor is engineered using Tm7 to detect Dy³⁺ down to 14 nM.     

Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3-DPG), conformational changes of globin and bidirectional changes of 2,3-DPG-hemoglobin’s oxygen affinity

The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3-DPG-Hb) induced by Ln³⁺ binding were studied by spectroscopic methods. The binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln³⁺ binding causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3-DPG non-specifically. The results using the ultrafiltration method indicate that Ln³⁺ binding sites for Hb can be classified into three categories: i.e. positive cooperative sites (N_I), non-cooperative strong sites (N_S) and non-cooperative weak sites (N_W) with binding constants in decreasing order: K_I>K_S>K_W. The total number of binding sites amounts to about 65 per Hb tetramer. Information on reaction kinetics was obtained from the change of intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation of fluorescence dependent on Ln³⁺ concentration and temperature was observed and can be attributed to the successive conformational changes induced by Ln³⁺ binding. The results also reveal the bidirectional changes of the oxygen affinity of Hb in the dependence on Ln³⁺ concentration. At the range of [Ln³⁺]/[Hb]<2, the marked increase of oxygen affinity (P₅₀ decrease) with the Ln³⁺ concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight rebound of oxygen affinity in higher Ln³⁺ concentration can be interpreted by the transition to the T-state of the Hb tetramer induced by Ln³⁺ binding. This was indicated by the changes in secondary structure characterized by the decrease of α-helix content.     

Influence of rare earth elements (Y,Gd and Lu) on the luminescent properties of green phosphor ZnMoO4:Tb3+

(Zn,Ln_x)MoO₄:Tb³⁺ (Ln = Y³⁺, Gd³⁺ and Lu³⁺) were prepared using the co‐precipitation method. Phase impurity, morphology and composition were investigated by power X‐ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The experimental results show that crystal structure is not destroyed after doping an appropriate amount of Y³⁺, Gd³⁺ and Lu³⁺. EDS analysis reveals that Y, Gd and Lu have been successfully doped into ZnMoO₄. In addition, the morphology of the phosphors is notably improved, exhibiting homogeneous dispersion morphology and irregular shapes of particle size ~ 0.5–1 µm. The luminescent intensity of (Zn,Ln_x)MoO₄:Tb³⁺ (Ln = Y³⁺, Gd³⁺ and Lu³⁺) phosphor is obviously higher than that of ZnMoO₄:Tb³⁺ phosphor. The energy transfer process between trivalent rare earth ions indicates that the inert earth ions can act as an energy bridge from MoO₄^2‐ to Tb³⁺. Copyright © 2013 John Wiley & Sons, Ltd.     

Coordination compounds of divalent lanthanides with crown ethers

New complexes LnI₂·18-crown-6 (Ln-Sm, Tm, Dy, Nd) and LnJ₂·dibenzo-18-crown-6 (Ln-Sm, Tm) were synthesized using the solutions of LnI₂ in THF. The compounds obtained oxidize quickly in air, but are relatively stable in an inert atmosphere. The Tm²⁺ complex is decomposed by light. The compounds obtained are poorly soluble in THF, the Sm²⁺ and Tm²⁺ compounds are soluble in CH₃CN, forming solutions with a period of half oxidation of 170 h and 6 min, respectively. Iodide ions of the complexes can be substituted for Cl^? during treatment of the compounds by solution of LiCl in THF. The reflection spectra of the compounds synthesized are similar to the absorption spectra of Ln²⁺ in THF, although a shift of bands towards the short wave region is observed.The study of the Ln²⁺ oxidation kinetics in H₂O, CH₃CN, THF in the presence of crown ethers has shown that their stability is influenced not only by the type of solvent, relative solubility and stability of complexes Ln²⁺ and Ln³⁺, but also by phenyl groups, and by decreasing stability of Dy²⁺ and Nd²⁺.     

Over 104-fold amplified upconversion luminescence of lanthanide nanocrystals through optical oscillator-like system

Recently, lanthanide (Ln) luminescent nanocrystals have attracted increasing attention in various fields such as biomedical imaging, lasers, and anticounterfeiting. However, due to the forbidden 4f–4f transition of lanthanide ions, the absorption cross-section and luminescence brightness of lanthanide nanocrystals are limited. To address the challenge, we constructed an optical oscillator-like system to repeatedly simulate lanthanide nanocrystals to enhance the absorption efficiency of lanthanide ions on excitation photons. In this optical system, the upconversion luminescence (UCL) of Tm³⁺ emission of ~450 nm excited by a 980 nm laser can be amplified by a factor beyond 10⁴. The corresponding downshifting luminescence of Tm³⁺ at 1460 nm was enhanced by three orders of magnitude. We also demonstrated that the significant luminescence enhancement in the designed optical oscillator-like system was general for various lanthanide nanocrystals including NaYF₄:Yb³⁺/Ln³⁺, NaErF₄@NaYF₄ and NaYF₄:Yb³⁺/Ln³⁺@NaYF₄:Yb³⁺@NaYF₄ (Ln = Er, Tm, Ho) regardless of the wavelengths of excitation sources (808 and 980 nm). The mechanism study revealed that both elevated laser power in the optical system and multiple excitations on lanthanide nanocrystals were the main reason for the luminescence amplification. Our findings may benefit the future development of low-threshold upconversion and downshifting luminescence of lanthanide nanocrystals and expand their applications.     

Evidence for cooperative effects in the binding of polyvalent metal ions to pure phosphatidylcholine bilayer vesicle surfaces

An internal NMR monitor for the study of lanthanide ion (Ln³⁺) binding to phospholipid bilayer membranes has been developed. The dimethylphosphate anion, DMP^?, forms labile complexes with Ln³⁺ in aqueous solution and in solutions also containing bilayer dispersions. The hyperfine shift in the DMP^? resonance induced by Pr³⁺ ions has been used to determine the overall thermodynamic formation constants for the Pr(DMP)²⁺ and Pr(DMP)₂⁺ complexes: 81 (M^?1) and 349 (M^?2) at 52°C; the limiting hyperfine shift (³¹P) at 52°C is 91.5 ppm downfield. These parameters, applied to the observed DMP^? hyperfine shift in the presence of the membrane, establish both the free Pr³⁺ concentration and the amount of Pr³⁺ bound to the phospholipid surface. Extensive data for the binding of Pr³⁺ to the outer surfaces of sonicated vesicles yield a limiting hyperfine shift per Pr³⁺ of 181.6 ppm downfield for the dipalmitoylphosphatidylcholine ³¹P resonance at 52°C, clearly demonstrating that the binding stoichiometry is two DPPCs per Pr³⁺. A Hill analysis indicates that the binding data are more anti-cooperative than a realistic Langmuir isotherm, yet more cooperative than a Stern isotherm incorporating electrostatic considerations at the Debye-Hückel level. Fittings to specific models lead to a cooperative model in which tense (T) sites, with low affinity for Pr³⁺, present in the absence of metal ions, quickly give way to relaxed (R) sites (two DPPCs per site), with much higher affinity for Pr³⁺, as the amount of Pr³⁺ bound to the surface increases. The intrinsic equilibrium constants for the binding of Pr³⁺ to DPPC vesicles are 2 M^?1 and 3 000 M^?1 for the T and R sites, respectively, at 52°C. The distribution coefficient between these sites ([R]/[T]) in the absence of Ln³⁺ is 0.14 at 52°C. We picture the binding site conversion as a head-group conformational change involving mostly the choline moiety. Sketchy results for binding on the inside vesicle surface indicate that the overall affinity for Pr³⁺ is significantly greater and suggest that the site stoichiometry may be different.     

The transport kinetics of lanthanide species in a single erythrocyte probed by confocal laser scanning microscopy

 A novel method has been developed to visualize and follow the temporal course of lanthanide transport across the membrane into a single living erythrocyte. By means of confocal scanning microscopy and the optical section technique, the entry of lanthanide ions was followed by the fluorescence quenching of fluorescein isothiocyanate (FITC)-labeled membrane and cytosol. From the difference of the quenching kinetics of the whole section and the central area, the time for diffusion through the membrane and the diffusion in the extracellular and intracellular media can be deduced. To clarify the mechanism of lanthanide-induced fluorescence quenching of FITC-labeled erythrocytes and to ensure that this reaction can be used in this method, the reaction was investigated by steady-state fluorescence techniques. The results showed that the lanthanides strongly quenched the florescence emitted by FITC covalently bound to membrane proteins and cytosolic proteins. The static quenching mechanism is responsible for the fluorescence quenching of FITC-labeled proteins by Ln species. The quenching mechanism is discussed on the basis of complex formation. The dependence of fluorescence quenching on both ion size and the total orbital angular momentum L supports the complexation mechanism. The transport time across the membrane is strikingly correlated with Ln species and extracellular concentration. For a given concentration, the transport time of [Ln(cit)₂]^3– is much shorter than that of Ln³⁺, since they enter the cells via the anion channel. This is supported by the inhibition effect of 4,4′-diisothiocyanato-2,2′-stilbenendisulfonate on the transport of [Ln(cit)₂]^3–. On the other hand, the transport of free Ln³⁺ might be attributed to the enhanced permeability of erythrocytes owing to Ln³⁺ binding. These findings strongly demonstrate the existence of the non-internalization mechanism of Ln species uptake by erythrocytes. Received: 7 January 1999 / Accepted: 7 May 1999     

The formation pathway of tetramolecular G-quadruplexes

Oligonucleotides containing guanosine stretches associate into tetrameric structures stabilized by monovalent ions. In order to describe the sequence of reactions leading to association of four identical strands, we measured by NMR the formation and dissociation rates of (TGnT)₄ quadruplexes (n = 3–6), their dissociation constants and the reaction orders for quadruplex formation. The quadruplex formation rates increase with the salt concentration but weakly depend on the nature (K⁺, Na⁺ or Li⁺) of the counter ions. The activation energies for quadruplex formation are negative. The quadruplex lifetimes strongly increase with the G-tract length and are much more longer in K⁺ solution than in Na⁺ or Li⁺ solutions. The reaction order for quadruplex formation is 3 in 0.125 M KCl and 4 in LiCl solutions. The kinetics measurements suggest that quadruplex formation proceeds step by step via sequential strand association into duplex and triplex intermediate species. Triplex formation is rate limiting in 0.125 M KCl solution. In LiCl, each step of the association process depends on the strand concentration. Parallel reactions to formation of the fully matched canonical quadruplex may result in kinetically trapped mismatched quadruplexes making the canonical quadruplex practically inaccessible in particular at low temperature in KCl solution.     

Lanthanides: New life metals?

Lanthanides (Ln³⁺) that are Rare Earth Elements, until recently thought to be biologically inert, have recently emerged as essential metals for activity and expression of a special type of methanol dehydrogenase, XoxF. As XoxF enzyme homologs are encoded in a wide variety of microbes, including microbes active in important environmental processes such as methane and methanol metabolism, Ln³⁺ may represent some of the key biogeochemical drivers in cycling of carbon and other elements. However, significant gaps in understanding the role of Ln³⁺ in biological systems remain as the functions of most of the proteins potentially dependent of Ln³⁺ and their roles in specific metabolic networks/respective biogeochemical cycles remain unknown. Moreover, enzymes dependent on Ln³⁺ but not related to XoxF enzymes may exist, and these so far have not been recognized. Through connecting the recently uncovered genetic divergence and phylogenetic distribution of XoxF-like enzymes and through elucidation of their activities, metal and substrate specificities, along with the biological contexts of respective biochemical pathways, most parsimonious scenarios for their evolution could be uncovered. Generation of such data will firmly establish the role of Ln³⁺ in the biochemistry of Life inhabiting this planet.     

31P NMR lineshapes of β-P (ATP) in the presence of mg2+ and ca2+ : estimate of exchange rates

The ³¹ P NMR chemical shift of β-P of adenosine triphosphate (ATP) undergoes a substantial change (2&#x0303;–3 ppm) upon chelation of divalent ions such as Mg²⁺ or Ca²⁺. In the presence of nonsaturating amounts of Mg²⁺ or Ca²⁺, the lineshape of this resonance depends on the characteristic association and dissociation rates of these metal-ATP complexes. A procedure for computer simulation of this lineshape is outlined. A comparison of computer-simulated lineshapes with the experimental lineshapes obtained at 121 MHz was used to determine the following dissociation rate of Mg²⁺ and Ca²⁺ from their ATP complexes at 20°C and pH 8.0: Ca²⁺, > 3 × 10⁵ s^?1 (Hepes buffer); Mg²⁺, 1200 s^-1 (no buffer), 1000 s^-1 (Tris buffer) and 2100 s^?1 (Hepes buffer). The limits of error are ± 10% in these values. For the Mg²⁺ complexes, the rates were determined as a function of temperature to obtain activation energies (with a maximum deviation of 10% in the least-squares fit): 8.1 $\text{Kcal}\text{mole}$ (no buffer and Hepes buffer) and 6.8 $\text{kcal}\text{mole}$ (Tris buffer). Lineshapes of the β-Presonance simulated as a function of Mg²⁺ concentration, using 2100 s^?1 for the dissociation rate, are also presented. The computer simulation of lineshapes offers a reliable and straightforward method for the determination of exchange rates of diamagnetic cations from their ATP complexes, under a variety of sample conditions.     

Modulation of I A Potassium Current in Adrenal Cortical Cells by a Series of Ten Lanthanide Elements

The modulation of I _A K⁺ current by ten trivalent lanthanide (Ln³⁺) cations spanning the series with ionic radii ranging from 0.99 ? to 1.14 ? was characterized by the whole-cell patch clamp technique in bovine adrenal zona fasciculata (AZF) cells. Each of the ten Ln³⁺s reduced I _A amplitude measured at +20 mV in a concentration-dependent manner. Smaller Ln³⁺s were the most potent and half-maximally effective concentrations (EC₅₀s) varied inversely with ionic radius for the larger elements. Estimation of EC₅₀s yielded the following potency sequence: Lu³⁺ (EC₅₀= 3.0 μm) ≈ Yb³⁺ (EC₅₀= 2.7 μm) > Er³⁺ (EC₅₀= 3.7 μm) ≥ Dy³⁺ (EC₅₀= 4.7 μm) > Gd³⁺ (EC₅₀= 6.7 μm) ≈ Sm³⁺ (EC₅₀= 6.9 μm) > Nd³⁺ (EC₅₀= 11.2 μm) > Pr³⁺ (EC₅₀= 22.3 μm) > Ce³⁺ (EC₅₀= 28.0 μm) > La³⁺ (EC₅₀= 33.7 μm). Ln³⁺s altered selected voltage-dependent gating and kinetic parameters of I _A with a potency and order of effectiveness that paralleled the reduction of I _A amplitude. Ln³⁺s markedly slowed activation kinetics and shifted the voltage-dependence of I _A gating such that activation and steady-state inactivation occurred at more depolarized potentials. In contrast, Ln³⁺s did not measurably alter inactivation or deactivation kinetics and only slightly slowed kinetics of inactivated channels returning to the closed state. Replacement of external Ca²⁺ with Mg²⁺ had no effect on the concentration-dependent inhibition of I _A by Ln³⁺s. In contrast to their action on I _A K⁺ current, Ln³⁺s inhibited T-type Ca²⁺ currents in AZF cells without slowing activation kinetics. These results indicate that Ln³⁺ modulate I _A K⁺ channels through binding to a site on I _A channels located within the electric field but which is not specific for Ca²⁺. They are consistent with a model where Ln³⁺ binding to negative charges on the gating apparatus alters the voltage-dependence and kinetics of channel opening. Ln³⁺s modulate transient K⁺ and Ca²⁺ currents by two fundamentally different mechanisms. Received: 21 January 1997/Revised: 3 April 1998     

New pieces to the lanthanide puzzle

Recently, rare‐earth elements lanthanides (Ln³⁺) have emerged as enzyme cofactors of methanol dehydrogenases of the XoxF type. It is now understood that XoxF enzymes can functionally replace the alternative, calcium‐dependent, MxaFI‐type methanol dehydrogenases, when Ln³⁺ are available. These rare‐earth metals are not only essential for XoxF activity, but they also regulate gene expression, in a reverse fashion, activating the expression of XoxF and repressing the expression of MxaFI. This type of regulation has created multiple conundrums, including the details of the solubility, transport, sensing and selection mechanisms for Ln³⁺ by the bacterial cells, as well as the questions relevant to the evolution of the alternative enzymes and their potentially different redox properties. Overall, the newly discovered biological activity of Ln³⁺ presents a big puzzle. Ochsner et al. add several pieces to this puzzle, utilizing a model phyllosphere colonizer Methylobacterium extorquens PA1. They determine that Ln³⁺ sensing by this organism can take place via both XoxF‐dependent and XoxF‐independent mechanisms. They also identify genes for a TonB‐dependent transporter and an ABC‐type transporter and demonstrate that both are essential for Ln³⁺‐dependent methanol metabolism. The puzzle still requires multiple additional pieces for completion, but great strides have been made toward the goal of solving it.     

Surface potential effects on metal ion binding to phosphatidylcholine membranes. 31P NMR study of lanthanide and calcium ion binding to egg-yolk lecithin vesicles

³¹P NMR of phosphatidylcholine (lecithin) from egg-yolk in sonicated vesicles has been measured in the presence of various ions. Addition of Ln³⁺³ or Ca²⁺ shifted the ³¹P resonance of the phosphate groups of the outer surface of the vesicles. These shifts were measured at varied lanthanide or Ca²⁺ concentration at different ionic strengths obtained by addition of NaCl. The shifts induced by Tb³⁺ and Ca²⁺ have been analyzed using the theory of the diffuse double layer. Corrections were introduced for the effect of the ionic strength on the activities of the ions. The binding efficiency is shown to be controlled by the electrostatic potential produced by the bound cations at the membrane surface. This potential is slightly modified due to weak chloride binding. Binding constants have been derived.     

Eu3+-doped LaF3-based inorganic–organic hybrid nanostructured materials for broad-spectrum excitation and strong photoluminescence

Inorganic–organic hybrid nanoparticles formed by lanthanide-doped nanostructures and organic ligands have been intensively studied, which could greatly increase their photoluminescence performance as a result of the energy transfer process from organic ligands to Ln³⁺ ions. However, the photoluminescence intensity and excitation spectral width are still quite limited on coordinating with a single type of organic ligand. In this work, Eu³⁺-doped LaF₃ (LaF₃:Eu³⁺) nanoparticles were prepared using a hydrothermal method, and were then hybridized with benzoic acid and thenoyltrifluoroacetone to form the hybrid nanostructures. After that, the hybrid nanostructures were mixed with 2,2′-azobisisobutyronitrile and methyl methacrylate to prepare the composites. The sample obtained by hybridization and composite doping with 5% Eu³⁺ exhibited the best photoluminescence performance. The excitation peak width and luminescence intensity of the hybrid nanostructures were significantly increased. The excitation spectral width of the inorganic–organic mixed hybrid nanostructures was particularly enhanced, and covered the whole ultraviolet band region of solar light on Earth. The prepared composites exhibited good optical properties.     

Structural analysis and photoluminescence properties of low dimensional lanthanide tetracyanometallates

The synthesis of a number of lanthanide tetracyanometallate (TCM) compounds have been carried out by reaction of Ln³⁺ nitrate salts and potassium tetracyanometallates in solvent systems containing dimethylsulfoxide and water. These reactions result in the isolation of three distinct structure types: (1) monoclinic [Ln(DMSO)₄(H₂O)₃M(CN)₄](M(CN)₄)_0.5·2H₂O (Ln = Eu, Tb and M = Pd, Pt), (2) orthorhombic {La(DMSO)₃(H₂O)₂(NO₃)M(CN)₄}_∞·H₂O (M = Pd, Pt), and (3) orthorhombic {Ln(DMSO)₃(H₂O)(NO₃)M(CN)₄}_∞ (Ln = Tb and M = Pd, Pt; Ln = Er, Yb and M = Pt) in the form of single crystals. Single-crystal X-ray diffraction has been used to investigate their structural features. Structure type 1 is a zero dimensional ionic compound with a M/Ln ratio of 1.5:1. It contains coordinated as well as uncoordinated [M(CN)₄]²⁻ (M = Pd, Pt) anions and features relatively long platinophilic interactions. Structure types 2 and 3 differ quite drastically from structure type 1, but they are very similar to each other. Both of the latter are one-dimensional in nature due to chains containing linkage of Ln³⁺ coordination spheres with trans-bridging [M(CN)₄]²⁻ anions. These coordination polymers both have a M/Ln ratio of 1:1, a lack of platinophilic interactions, and incorporation of a bidentate NO₃⁻ for charge balance. Photoluminescence properties for select Eu³⁺ and Tb³⁺ compounds have been investigated. They show characteristic absorption and emission for the Ln³⁺ ions, but no significant influence of the tetracyanometallate anions.     

Ca(2+) dissociation from the C-terminal EF-hand pair in calmodulin: a steered molecular dynamics study

We used steered molecular dynamics (SMD) to simulate the process of Ca²⁺ dissociation from the EF-hand motifs of the C-terminal lobe of calmodulin. Based on an analysis of the pulling forces, the dissociation sequences and the structural changes, we show that the Ca²⁺-coordinating residues lose their binding to Ca²⁺ in a stepwise fashion. The two Ca²⁺ ions dissociate from the two EF-hands simultaneously, with two distinct groups among the five Ca²⁺-coordinating residues affecting the EF-hand conformational changes differently. These results provide new insights into the effects of Ca²⁺ on calmodulin conformation, from which a novel sequential mechanism of Ca²⁺-calmodulin dissociation is proposed.     

The Effects of Lanthanoid on the Structure–Function of Lactate Dehydrogenase from Mice Heart

The activity of lactate dehydrogenase (LDH, EC1.1.1.27) is often changed upon inflammatory responses in animals. Lanthanoid (Ln) was shown to provoke various inflammatory responses both in rats and mice; however, the molecular mechanism by which Ln³⁺ exert its toxicity has not been completely understood, especially that we know little about the mechanism of the interaction between Ln with 4f electron shell and alternation valence and LDH. In this report, we investigated the mechanisms of LaCl₃, CeCl₃, and NdCl₃ on LDH activity in vivo and in vitro. Our results showed that La³⁺, Ce³⁺, and Nd³⁺ could significantly activate LDH in vivo and in vitro; the order of activation was Ce³⁺?>?Nd³⁺?>?La³⁺?>?control. The affinity of LDH for Ce³⁺ was higher than Nd³⁺ and La³⁺; the saturated binding sites for Ce³⁺ on the LDH protein were 1.2 and for La³⁺ and Nd³⁺ 1.55. Ln³⁺ caused the reduction of exposure degree of cysteine or tryptophan/tyrosine of LDH, the increase of space resistance, and the enhancement of α-helix in secondary structure of LDH, which was greatest in Ce³⁺ treatment, medium in Nd³⁺ treatment, and least in La³⁺ treatment. It implied that the changes of structure–function on LDH caused by Ln³⁺ were closely related to the characteristics of 4f electron shell and alternation valence in Ln.     

Novel gaseous polyatomic binary and ternary lanthanide oxides

A variety of novel gaseous polyatomic binary and ternary oxides were observed at ambient temperature arising from lanthanide (Ln) nitrate Schiff base complexes, simple salts and sesquioxides, in an FAB mass spectrometer. The new binary oxides (as singly positive ions) detected are Ln₂O₃, Ln₃O₃, Ln₃O₄, Ln₄O₄, Ln₄O₅, Ln₄O₆, Ln₅O₆, Ln₅O₇, Ln₅O₈, Ln₆O₈, Ln₆O₉, Ln₇O₁₀, Ln₈O₁₁, Ln₈O₁₂ and Ln₉O₁₃; the ternary gaseous oxides are CeEuO₂, CeEu₂O₃ and Ce₂EuO₄, LaYbO₂, La₂YbO₄ and LaYb₂O₄; NdHoO₃, Nd₂HoO₄, and NdHo₂O₄; YTmO₃; Y_xTm_3−xO₄, x=1−2; Y_xTm_4−xO₆, x=1−3; Y_xTm_5−xO₇, x=1−4; Y_xTm_6−xO₉, x=1−5. Some of these oxides show the lanthanide cations in unusual oxidation states. Gadolinium-gallium ternary oxides, GdGaO₂, GdGaO₃ and Gd₂GaO₄ were also detected. The FAB MS environment is significantly reducing, yielding a homologous series Eu_nO_n where Eu²⁺ is dominant (E°(Eu³⁺/Eu²⁺)=−0.35 V) and no gallium or indium oxides (E°(M³⁺/M°=−0.34 V (In), −0.53 V (Ga)) were formed. The stoichiometry of the polylanthanide ternary oxides formed is determined largely by the chemistry of the major metallic component. The gaseous polyatomic oxides are probably formed through a reductive condensation process involving primary species Ln⁺ and LnO⁺ formed when the rare earth compounds are struck by fast Xe atoms. The demonstrated possibility of double component oxide formation broadens the number and types of gaseous lanthanide oxides which are accessible.     

Membrane perturbations induced by the interactions of zinc ions with band 3 in human erythrocytes

Of group 12 metals, zinc is an essential element to maintain our life, but other metals such as cadmium and mercury are toxic in cellular activities. Interactions of these metals with biomembranes are important to understand their effects on our living cells. Here, we describe the membrane perturbations induced by these metals in human erythrocytes. Of these metals, Zn²⁺ ions only induced the erythrocyte agglutination. Histidine residues in extracellular domains of band 3 participated in Zn²⁺-induced agglutination. Interestingly, it was found that band 3-cytoskeleton interactions play an important role in Zn²⁺-induced agglutination. In contrast with Hg²⁺ and Cd²⁺ ions, Zn²⁺ ions greatly suppressed pressure-induced hemolysis by cell agglutination. Such a suppression was removed upon dissociation of agglutinated erythrocytes by washing, indicating the reversible interactions of Zn²⁺ ions with erythrocyte membranes. Excimer fluorescence of pyrene indicated that spectrin is denatured by a pressure of 200 MPa irrespective of hemolysis suppression. Taken together, these results suggest that the agglutination of erythrocytes due to the interactions of Zn²⁺ ions with band 3 is stable under pressure, but spectrin, cytoskeletal protein, is denatured by pressure