MALDI imaging mass spectrometry of lipids by adding lithium salts to the matrix solution

Mass spectrometry imaging of lipids using MALDI–TOF/TOF mass spectrometers is of growing interest for chemical mapping of organic compounds at the surface of tissue sections. Many efforts have been devoted to the best matrix choice and deposition technique. Nevertheless, the identification of lipid species desorbed from tissue sections remains problematic. It is now well-known that protonated, sodium- and potassium-cationized lipids are detected from biological samples, thus complicating the data analysis. A new sample preparation method is proposed, involving the use of lithium salts in the matrix solution in order to simplify the mass spectra with only lithium-cationized molecules instead of a mixture of various cationized species. Five different lithium salts were tested. Among them, lithium trifluoroacetate and lithium iodide merged the different lipid adducts into one single lithium-cationized species. An optimized sample preparation protocol demonstrated that the lithium trifluoroacetate salt slightly increased desorption of phosphatidylcholines. Mass spectrometry images acquired on rat brain tissue sections by adding lithium trifluoroacetate showed the best results in terms of image contrast. Moreover, more structurally relevant fragments were generated by tandem mass spectrometry when analyzing lithium-cationized species.     

Structural study and physical properties of a new phosphate KCuFe(PO4)2

Single crystals of a new phosphate KCuFe(PO₄)₂ have been prepared by the flux method and its structural and physical properties have been investigated. This compound crystallizes in the monoclinic system with the space group P2₁/n and its parameters are: a=7.958(3) Å, b=9.931(2) Å, c=9.039(2) Å, β=115.59(3)° and Z=4. Its structure consists of FeO₆ octahedra sharing corners with Cu₂O₈ units of edge-sharing CuO₅ polyhedra to form undulating chains extending infinitely along the b-axis. These chains are connected by the phosphate tetrahedra giving rise to a 3D framework with six-sided tunnels parallel to the [101] direction, where the K⁺ ions are located. The Mössbauer spectroscopy results confirm the exclusive presence of octahedral Fe³⁺ ions. The magnetic measurements show the compound to be antiferromagnetic with C_m=5.71 emu K/mol and θ=−156.5 K. The derived experimental effective moment μ_ex=6.76μ_B is somewhat higher than the theoretical one of μ_th=6.16μ_B, calculated taking only into account the spin contribution for Fe³⁺ and Cu²⁺ cations. Electrical measurements allow us to obtain the activation energy (1.22 eV) and the conductivity measurements suggest that the charge carriers through the structure are the potassium cations.     

How does internal motion influence the relaxation of the water protons in Ln(III)DOTA-like complexes?

Taking advantage of the Curie contribution to the relaxation of the protons in the Tb(III) complex, and the quadrupolar relaxation of the 17O and 2H nuclei on the Eu(III) complex, the effect of the internal motion of the water molecule bound to [Ln(DOTAM)(H2O)]3+ complexes was quantified. The determination of the quadrupolar coupling constant of the bound water oxygen chi(Omicron)(1 + eta(Omicron)2/3)1/2 = 5.2 +/- 0.5 MHz allows a new analysis of the 17O and 1H NMR data of the [Gd(DOTA)(H2O)]- complex with different rotational correlation times for the Gd(III)-O(water) and Gd(III)-H(water) vectors. The ratio of the rotational correlation times for the Ln(III)-H(water) vector and the overall rotational correlation time is calculated tau(RH)/tau(RO) = 0.65 +/- 0.2. This could have negative consequences on the water proton relaxivity, which we discuss in particular for macromolecular systems. It appears that the final effect is actually attenuated and should be around 10% for such large systems undergoing local motion of the chelating groups.     

Characterization of multimetallic grid-type complexes by electrospray mass spectrometry

The self-assembly of the terdentate ligands 1a-h, based on terpyridine-like binding sites, with octahedrally coordinated metal ions, such as Fe(II), Co(II), Cu(II), Zn(II), Cd(II), Hg(II) and Pb(II), leads to the formation of the supramolecular grid-type complexes 2a-c(M(II)), 3d-g(M(II)) and 4h(M(II)). The structures and compositions of these coordination complexes in solution were deduced from electrospray mass spectrometry (ESMS) measurements. The results agree with the data available from x-ray radiocrystallography in the solid state and/or NMR spectroscopy in solution. ESMS may be applied in cases where other methods are difficult to use or inconclusive. This study stresses the power of ESMS in supramolecular chemistry.     

Adsorption of barium and calcium chloride onto negatively charged alpha-Fe(2)O(3) particles

Adsorption of cations (Na(+), Ca(2+), Ba(2+)) onto negatively charged (pH 10.4) hematite (alpha-Fe(2)O(3)) particles has been studied. The oxide material was carefully prepared in order to obtain monodisperse suspensions of well-crystallized, quasi-spherical particles (50 nm in diameter). The isoelectric point (IEP) is located at pH 8.5. Adsorption of barium ions onto oxide particles was carried out and the electrophoretic mobility was measured throughout the adsorption experiment. Comparison with calcium adsorption at full coverage reveals a higher uptake of Ba(2+). In both cases it shows also that chloride ions coadsorb with M(2) ions. Simultaneous uptake of the positive and negative ions explains why the electrophoretic mobility does not reverse to cationic migration. A theoretical study of the surface speciation has been carried out, using the MuSiC model. It reveals the presence of negative as well as positive sites on both sides of the point of zero charge (PZC) of the hematite particles, which may explain the coadsorption of Ba(2+) and Cl(-) at pH 10.4. The effective charge of the oxide particles, calculated from the electrophoretic mobility, is in very good agreement with the results found with the MuSiC modelization and the chloride/barium adsorption ratio. It also verifies the theory of ionic condensation. Calorimetric measurements gave a negative heat for the overall reaction occurring when Ba(2+)/Cl(-) ions adsorb onto hematite. Despite the fact that anions (Cl(-) and OH(-)) adsorption onto mineral oxides is an exothermic phenomenon, it is likely that barium and calcium adsorption is endothermic, denoting the formation of an inner-sphere complex as reported in the literature.     

Spin densities in a ferromagnetic bimetallic chain compound: polarized neutron diffraction and DFT calculations

The spin population distribution in the ferromagnetically coupled hetero-bimetallic chain compound [MnNi(NO(2))(4)(en)(2)] (en = 1,2-ethanediamine) has been investigated by means of polarized neutron diffraction experiments, and the results compared with those from theoretical estimates obtained via calculations based on density functional theory on dinuclear molecular models of the chain. The spin distributions obtained from experiment and from theory are consistent and reflect a larger spin delocalization from the Ni atom due to the more covalent character of the Ni-N bonds compared to the Mn-O ones. Also a nearly isotropic spin distribution is observed for the more ionic d(5) Mn(2+) ion and a clearly anisotropic distribution for the d(8) Ni(2+) ion. The use of dinuclear molecular models for the calculation of the exchange coupling constant between Ni and Mn provide upper and lower limits (+17.6 and -4.2 cm(-)(1)) for the experimentally determined value (+1.3 cm(-)(1)), depending on how the missing part of the chain is simulated, but yield essentially the same spin distribution. The Mn(II)-Ni(II) weak ferromagnetic coupling in the chain is interpreted in a spin delocalization mechanism as resulting from the weakness of the overlap between the magnetic orbitals centered on nickel and those centered on manganese which are only weakly delocalized on the ligands.     

Super/subcritical fluid chromatography chiral separations with macrocyclic glycopeptide stationary phases

The chiral recognition capabilities of three macrocyclic glycopeptide chiral selectors, namely teicoplanin (Chirobiotic T), its aglycone (Chirobiotic TAG) and ristocetin (Chirobiotic R), were evaluated with supercritical and subcritical fluid mobile phases. A set of 111 chiral compounds including heterocycles, analgesics (nonsteroidal antiinflamatory compounds), beta-blockers, sulfoxides, N-protected amino acids and native amino acids was separated on the three chiral stationary phases (CSPs). All separations were done with an outlet pressure regulated at 100 bar, 31 degrees C and at 4 ml/min. Various amounts of methanol ranging from 7 to 67% (v/v) were added to the carbon dioxide along with small amounts (0.1 to 0.5%, v/v) of triethylamine and/or trifluoroacetic acid. The Chirobiotic TAG CSP was the most effective closely followed by the Chirobiotic T column. Both columns were able to separate, partially or fully, 92% of the enantiomers of the compound set. The ristocetin chiral selector could partially or baseline resolve only 60% of the enantiomers tested. All separations were done in less than 15 min and 70% were done in less than 4 min. The speed of the separations is the main advantage of the use of SFC compared to normal-phase HPLC. In addition, SFC is advantageous for preparative separations with easy solute recovery and solvent disposal.     

Design and synthesis of novel spirocyclopropyl cyclohexane-1,3-diones and -1,3,5-triones for their incorporation into potent HPPD inhibitors

We report the design and the efficient synthesis of novel spirocyclopropyl cyclohexane-1,3-dione and -1,3,5-trione units to be incorporated into potent HPPD inhibitors. New routes involving original combinations of synthetic equivalents of α-cyclopropyl ketone-α-anion and α-cyclopropyl ester-β-cation are described.     

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

Access to N-protected or N-free imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives as potential antiviral compounds was achieved in good yields from N-protected 7-amino-8-halo-2-methylimidazo[1,2-a]pyridines by catalytic coupling of terminal acetylenes under mild conditions using [PdCl₂(PPh₃)₂] or [Cu(Phen)(PPh₃)₂]NO₃.     

A dinuclear manganese(II) complex with the [Mn(2)(mu-O(2)CCH(3))(3)](+) core: synthesis, structure, characterization, electroinduced transformation, and catalase-like activity

Reactions of Mn(II)(PF(6))(2) and Mn(II)(O(2)CCH(3))(2).4H(2)O with the tridentate facially capping ligand N,N-bis(2-pyridylmethyl)ethylamine (bpea) in ethanol solutions afforded the mononuclear [Mn(II)(bpea)](PF(6))(2) (1) and the new binuclear [Mn(2)(II,II)(mu-O(2)CCH(3))(3)(bpea)(2)](PF(6)) (2) manganese(II) compounds, respectively. Both 1 and 2 were characterized by X-ray crystallographic studies. Complex 1 crystallizes in the monoclinic system, space group P2(1)/n, with a = 11.9288(7) A, b = 22.5424(13) A, c =13.0773(7) A, alpha = 90 degrees, beta = 100.5780(10 degrees ), gamma = 90 degrees, and Z = 4. Crystals of complex 2 are orthorhombic, space group C222(1), with a = 12.5686(16) A, b = 14.4059(16) A, c = 22.515(3) A, alpha = 90 degrees, beta = 90 degrees, gamma = 90 degrees, and Z = 4. The three acetates bridge the two Mn(II) centers in a mu(1,3) syn-syn mode, with a Mn-Mn separation of 3.915 A. A detailed study of the electrochemical behavior of 1 and 2 in CH(3)CN medium has been made. Successive controlled potential oxidations at 0.6 and 0.9 V vs Ag/Ag(+) for a 10 mM solution of 2 allowed the selective and nearly quantitative formation of [Mn(III)(2)(mu-O)(mu-O(2)CCH(3))(2)(bpea)(2)](2+) (3) and [Mn(IV)(2)(mu-O)(2)(mu-O(2)CCH(3))(bpea)(2)](3+) (4), respectively. These results have shown that each substitution of an acetate group by an oxo group is induced by a two-electron oxidation of the corresponding dimanganese complexes. Similar transformations have been obtained if 2 is formed in situ either by direct mixing of Mn(2+) cations, bpea ligand, and CH(3)COO(-) anions with a 1:1:3 stoichiometry or by mixing of 1 and CH(3)COO(-) with a 1:1.5 stoichiometry. Associated electrochemical back-transformations were investigated. 2, 3, and the dimanganese [Mn(III)Mn(IV)(mu-O)(2)(mu-O(2)CCH(3))(bpea)(2)](2+) analogue (5) were also studied for their ability to disproportionate hydrogen peroxide. 2 is far more active compared to 3 and 5. The EPR monitoring of the catalase-like activity has shown that the same species are present in the reaction mixture albeit in slightly different proportions. 2 operates probably along a mechanism different from that of 3 and 5, and the formation of 3 competes with the disproportionation reaction catalyzed by 2. Indeed a solution of 2 exhibits the same activity as 3 for the disproportionation reaction of a second batch of H(2)O(2) indicating that 3 is formed in the course of the reaction.