Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles.

Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of 111In-radiolabelled gold nanoparticles (AuNPs; 10-15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.

Improved procedures for production and purification of 135La from enriched [135Ba]BaCO3 on a 16.5 MeV cyclotron.

Lanthanum-135 (135La) is a favorable Auger electron emitter with a high Auger electron yield and low gamma emission, making it promising for Auger electron radiotherapy. However, successful application requires reliable and scalable 135La production. Up to now, metallic natural barium (natBa) is a commonly used target material, but this material is sensitive to moisture and oxidation. BaCO3 has also been tested, due to its higher chemical stability. However, BaCO3 has poor thermal conductivity, limiting the applicable current and making high yield production challenging. In this study, we pressed a mixture of enriched [135Ba]BaCO3 and fine aluminum (Al) powder to provide a stable target with improved thermal conductivity compared to pure BaCO3. After 4 h of irradiation with a 16.5 MeV proton beam at 20 µA current, 1.62 ± 0.18 GBq was produced from a 200 mg [135Ba]BaCO3:Al (1:2, w/w) target. This corresponded to a saturation yield of 11.91 ± 1.31 GBq (or 596 ± 66 MBq/µA). A purification procedure involving initial precipitation, followed by a single composite column containing a layer of TK200 resin and a second layer of branched DGA resin was developed, with 97.1 ± 3.6 % decay corrected 135La recovery. [135La]LaCl3 was obtained in an effective molar activity of 79.6 ± 25.3 MBq/nmol (DOTA titration), 104.0 ± 40.4 MBq/nmol (DTPA titration) and 186.5 ± 83.8 MBq/nmol (CHX-A″-DTPA titration), and a radionuclidic purity (RNP) of >99.9 % at end of purification, hereby demonstrating a purity suitable for radiopharmaceutical use.

Anion and solvent controlled growth of crystalline and amorphous zinc(ii) coordination polymers and a molecular complex.

Controlled bottom-up synthesis of amorphous coordination polymers with tailored metal coordination is a research field in its infancy. In this study, synthesis control was achieved to selectively prepare one-dimensional (1D) crystalline and amorphous zinc(ii)-based coordination polymers and a dimeric molecular compound, all with similar coordination geometry as evidenced by X-ray diffraction and total scattering studies. The compounds were obtained by bottom up self-assembly of Zn(ii) with terephthalate (tph2-) as linker and the enantiopure chelating ligand S-(1,2)-bis(1H-benzimidazol-2-yl)ethanol (L). The solvent and the coordination ability of the precursor zinc salt anion control the crystalline products formed by slow diffusion at room temperature: perchlorate allows isolation of the phase pure crystalline 1D polymer {[Zn(tph)(L)]·H2O·3DMF}n (1·H2O·3DMF, DMF = N,N-dimethylformamide). In contrast, zinc chloride leads to the formation of either a mixture of polymeric 1·H2O·3DMF and a dimeric molecular species [Zn2Cl2(tph)(L)2]·4DMF (2·4DMF), or to the phase pure dimer 2·4DMF, depending on the Zn(ii) : tphH2 stoichiometry. A modified synthesis using zinc nitrate and fast precipitation by base addition results in an amorphous analogue of the 1D polymer (3). Chains of 1·H2O·3DMF pack into a non-porous crystalline material with a surface area of just 6 m2 g-1, while the outer surface area of amorphous polymer 3 is a factor of eight larger. Hence, the amorphous compound provides larger metal site accessibility for potential surface chemical reactions, while maintaining the coordination geometry of the metal sites. The temperature response of crystalline polymer 1·H2O·3DMF was studied using multi-temperature single crystal X-ray diffraction (100-300 K). The a = b axes display normal positive thermal expansion, while the c axis remains constant with increasing temperature due to partial relaxation of the terephthalate linkers and slightly changed geometry within the individual polymer chains.

Cubes on a string: a series of linear coordination polymers with cubane-like nodes and dicarboxylate linkers.

A series of semicrystalline and amorphous one-dimensional (1D) polymeric chains consisting of cubane-like CoII4L4 units (L = S-1,2-bis(benzimidazol-2-yl)ethanol) and dicarboxylates were synthesized and characterized by single crystal diffraction and X-ray total scattering. The polycationic chains are composed of [Co4L4(dicarboxylate)]2+ monomeric units, while one molecular dicarboxylate counterion is balancing the charge of each monomer. The linear compound series has five members, and the crystal structures were solved for [Co4L4(tph)](tph) and [Co4L4(ndc)](ndc), where tph = terephthalate and ndc = 2,6-naphthalenedicarboxylate. Partly crystalline compounds were produced by slow assembly at elevated temperature (over days), while the amorphous compounds were formed by fast precipitation (within minutes). Pair distribution function (PDF) analysis based on X-ray total scattering data reveals the presence of the cubane-like entity in both the amorphous and semicrystalline samples. While the powders are non-porous, precipitation is a fast and versatile method to produce compounds with cubane-like centres with moderate surface areas of 17-49 m2 g-1 allowing for surface chemical reactions. The powders have a high concentration of Lewis base sites as verified by their selective adsorption of CO2 over N2. The use of an amorphous cubane-like polymer for the electrocatalytic oxygen evolution reaction was demonstrated.

Copper-promoted methylene C-H oxidation to a ketone derivative by O2.

The methylene group of the ligand 1,2-di(pyridin-2-yl)-ethanone oxime (dpeo) is slowly oxygenated by the O2 in air under ambient conditions when [Cu(dpeo)2](ClO4)2 is dissolved in ethanol or acetonitrile. An initial transient ketone product, 2-(hydroxyimino)-1,2-di(pyridine-2-yl)ethanone, (hidpe) was characterized in the heteroleptic copper(ii) complex [Cu(bpca)(hidpe)](ClO4). The co-ligand in this complex, N-(2'-pyridylcarbonyl)pyridine-2-carboximidate (bpca-), is derived from a copper-promoted Beckmann rearrangement of hidpe. In the presence of bromide only [Cu(bpca)Br] is isolated. When significant water is present in reaction mixtures copper complexes of dpeo, hidpe and bpca- are not recovered and [Cu(pic)2H2O] is isolated. This occurs since two equivalents of picolinate are ultimately generated from one equivalent of oxidized and hydrolysed dpeo. The copper-dependent O2 activation and consequent stoichiometric dpeo C-H oxidation is reminiscent of the previously observed catalysis of dpeo oxidation by Mn(ii) [C. Deville, S. K. Padamati, J. Sundberg, V. McKee, W. R. Browne, C. J. McKenzie, Angew. Chem., Int. Ed., 2016, 55, 545-549]. By contrast dpeo oxidation is not observed during complexation reactions with other late transition metal(ii) ions (M = Fe, Co, Ni, Zn) under aerobic conditions. In these cases bis and tris complexes of bidentate dpeo are isolated in good yields. It is interesting to note that dpeo is not oxidised by H2O2 in the absence of Cu or Mn, suggesting that metal-based oxidants capable of C-H activation are produced from the dpeo-Cu/Mn systems and specifically O2. The metastable copper complexes [Cu(dpeo)2](ClO4)2 and [Cu(bpca)(hidpe)](ClO4), along with [NiX2(dpeo)2] (X = Cl, Br), [Ni(dpeo)3](ClO4)2, [Co(dpeo)3](ClO4)3 and the mixed valence complex [FeIIIFe(dpeo-H)3(dpeo)3](PF6)4, have been structurally characterized.

O2 Activation and Double C-H Oxidation by a Mononuclear Manganese(II) Complex.

A Mn(II) complex, [Mn(dpeo)2](2+) (dpeo=1,2-di(pyridin-2-yl)ethanone oxime), activates O2, with ensuing stepwise oxidation of the methylene group in the ligands providing an alkoxide and ultimately a ketone group. X-ray crystal-structure analysis of an intermediate homoleptic alkoxide Mn(III) complex shows tridentate binding of the ligand via the two pyridyl groups and the newly installed alkoxide moiety, with the oxime group no longer coordinated. The structure of a Mn(II) complex of the final ketone ligand, cis-[MnBr2(hidpe)2] (hidpe=2-(hydroxyimino)-1,2-di(pyridine-2-yl)ethanone) shows that bidentate oxime/pyridine coordination has been resumed. H2(18)O and (18)O2 labeling experiments suggest that the inserted O atoms originate from two different O2 molecules. The progress of the oxygenation was monitored through changes in the resonance-enhanced Raman bands of the oxime unit.

Helicity inversion and redox chemistry of chiral manganese(II) cubanes.

The chiral ligand S-1,2-bis(1H-benzimidazol-2-yl)ethanol, 1, reacts with manganese(II) salts to form cubanes which readily undergo oxidation reactions leading either to a tetranuclear manganese(II,III) mixed valence complex 4 or to a tetranuclear complex of ligand 5 where the secondary alcohol has been oxidised to an enolate. N-methylation of ligand 1 slows the oxidation reaction and stable manganese(II) cubanes may be isolated. The fully methylated ligand 2 gives a cubane of opposite helicity to that found previously for 1 with cobalt. The inversion may be explained by conformational analysis. Cyclic voltammetry suggests that the manganese cubanes reported here are insufficiently robust to store oxidising equivalents as in the oxygen evolving system of photosystem II.

The coordination chemistry of tartronic acid with copper: magnetic studies of a quasi-equilateral tricopper triangle.

The coordination chemistry of tartronic acid, , with copper(ii) has been investigated. Structures of two complexes are reported containing respectively the complex [Cu(-2H)2Cl](3-) where acts as a bidentate ligand through carboxylates, and [Cu3(-3H)3](3-) where the alcohol function is deprotonated to bridge two coppers in a triangular trinuclear complex. The latter species undergoes facile oxidation leading to carbon-carbon bond formation. The magnetic and EPR properties of the trinuclear complex have been studied in detail.

Enantioselective synthesis of tetranuclear quadruple helicates.

Quadruple helical structures are assembled around a tetranuclear cubane structure using four chiral tridentate ligands and two ligands coordinating diagonally across a face. Stereoselectivity in the complex formation is observed.

Variability of the colloidal molybdate reactive phosphorous concentrations in freshwaters.

Colloidal-size particles play an important, yet not very well understood, role in the speciation of phosphate in freshwaters. This study assesses the size distribution of molybdate reactive phosphorous in various 1.2 microm-filtered freshwaters using cross-flow filtration. Concurrently, colloid size was determined by a single particle counter technique, and mineralogical composition by a combination of transmission electronic microscopy coupled with energy dispersive spectroscopy and selected area electron diffraction. The percentage of colloidal molybdate reactive phosphorous varied a great deal in the samples studied: it ranged from 26% down to only 3%. A direct comparison of the percentages of colloidal-P can be misleading. The simultaneous determination of the amount, size distribution and mineralogical composition of the colloids present in the water bodies proved to be essential for interpreting the results. The causes of the observed variation were numerous and were site-dependent.