Liane Hilfert

Decrease of Droplet Size of the Reverse Microemulsion 1-Butyl-3-methylimidazolium Tetrafluoroborate/Triton X-100/Cyclohexane by Addition of Water

In the present contribution, results concerning the role of small amounts of water in the 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4)-in-cyclohexane ionic liquid (IL) reverse microemulsions are reported. Dynamic light scattering (DLS) revealed that the size of microemulsion droplets decreased remarkably with increasing water content although water is often used as a polar component to swell reverse microemulsions. It was thus deduced that the number of microemulsion droplets was increased which was confirmed by conductivity measurements. The states of dissolved water were investigated by Fourier transform IR (FTIR) spectroscopic analysis showing that water molecules mainly act as bound water. 1H NMR along with two-dimensional rotating frame nuclear Overhauser effect (NOE) experiments (ROESY) further revealed that water molecules were mainly located in the periphery of the polar core of the microemulsion droplets and behave like a chock being inserted in the palisade layer of the droplet. This increased the curvature of the surfactant film at the IL/cyclohexane interface and thus led to the decrease of the microemulsion droplet size. The order of surfactant molecules arranged in the interface film was increased and thus induced a loss of entropy. Isothermal titration calorimetry (ITC) indicated that an enthalpy increase compensates for the loss of entropy during the process of microstructural transition.

Metabolic progression markers of neurodegeneration in the transgenic G93A-SOD1 mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. Visualizing corresponding metabolic changes in the brain of patients with ALS with proton magnetic resonance spectroscopy (1H‐MRS) may provide surrogate markers for an early disease detection, for monitoring the progression and for evaluating a treatment response. The primary objective of our study was to evaluate whether modifications in MR metabolite levels occur before clinical disease onset, and whether these changes are directly linked to a distinct spatial progression pattern in the CNS. Therefore, age‐dependent alterations in the cerebral and spinal metabolic profile in the mouse model of ALS overexpressing the mutated human G93A‐superoxide dismutase 1 (G93A‐SOD1) were determined by high‐resolution MRS of tissue extracts at 14.1 Tesla. Both non‐transgenic mice (control mice) and transgenic mice overexpressing the non‐mutated human SOD1 (tg‐SOD1) served as controls. In the spinal cord of G93A‐SOD1 mice significantly decreased levels of N‐acetyl aspartate were already detected 34 days postpartum, i.e. about 60 days before the average disease onset caused by motor neuron decline. In addition, glutamine and γ‐aminobutyric acid concentrations were significantly diminished at Day 75, which is still in the presymptomatic phase of the disease. These metabolic changes were further progressive in the course of the disease and started to involve the brainstem at Day 75. Overall, high‐resolution 1H‐MRS allows a sensitive spatial and temporal metabolite profiling in the presymptomatic phase of ALS even before significant neuronal cell loss occurs.

Exocyclic push–pull conjugated compounds. Part 3. An experimental NMR and theoretical MO ab initio study of the structure, the electronic properties and barriers to rotation about the exocyclic partial double bond in 2-exo-methylene- and 2-cyanoimino-quinazolines and -benzodiazepines

Abstract The structure of a number of 2-exo-methylene substituted quinazolines and benzodiazepines, respectively, 1, 3a,b, 4 ( X=–CN, –COOEt ) and their 2-cyanoimino substituted analogues 2, 3c,d ( X=–CN, –SO 2 C 6 H 4 –Me (p) was completely assigned by the whole arsenal of 1D and 2D NMR spectroscopic methods. The E/Z isomerism at the exo-cyclic double bond was determined by both NMR spectroscopy and confirmed by ab initio quantum chemical calculations; the Z isomer is the preferred one, its amount proved dependent on steric hindrance. Due to the push–pull effect in this part of the molecules the restricted rotation about the partial C2,C11 and C2,N11 double bonds, could also be studied and the barrier to rotation measured by dynamic NMR spectroscopy. The free energies of activation of this dynamic process proved very similar along the compounds studied but being dependent on the polarity of the solvent. Quantum chemical calculations at the ab initio level were employed to prove the stereochemistry at the exo-cyclic partial double bonds of 1–4, to calculate the barriers to rotation but also to discuss in detail both the ground and the transition state of the latter dynamic process in order to better understand electronic, inter- and intramolecular effects on the barrier to rotation which could be determined experimentally. In the cyanoimino substituted compounds 2, 3c,d, the MO ab initio calculations evidence the isomer interconversion to be better described by the internal rotation process than by the lateral shift mechanism.

Nanodroplet Cluster Formation in Ionic Liquid Microemulsions

A common ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF(4)), is used as polar solvent to induce the formation of a reverse bmimBF(4)-in-toluene IL microemulsion with the aid of the nonionic surfactant Triton X-100. The swelling process of the microemulsion droplets by increasing bmimBF(4) content is detected by dynamic light scattering (DLS), conductivity, UV/Vis spectroscopy, and freeze-fracture transmission electron microscopy (FF-TEM). The results show that the microemulsion droplets initially formed are enlarged by the addition of bmimBF(4). However, successive addition of bmimBF(4) lead to the appearance of large-sized microemulsion droplet clusters (200-400 nm). NMR spectroscopic analysis reveal that the special structures and properties of bmimBF(4) and Triton X-100 together with the polar nature of toluene contribute to the formation of such self-assemblies. These unique self-assembled structures of IL-based microemulsion droplet clusters may have some unusual and unique properties with a number of interesting possibilities for potential applications.

One ligand fits all: lanthanide and actinide sandwich complexes comprising the 1,4-bis(trimethylsilyl)cyclooctatetraenyl (=COT′′) ligand

The series of anionic lanthanide(III) sandwich complexes of the type [Ln(COT′′)2]− (COT′′ = 1,4-bis(trimethylsilyl)cyclooctatetraenyl dianion) has been largely extended by the synthesis of eight new derivatives ranging from lanthanum to lutetium. The new compounds [Li(DME)3][Ln(COT′′)2] (Ln = Y (1), La (2), Pr (3), Gd (4), Tm (6), Lu (8)) and [Li(THF)4][Ln(COT′′)2] (Ln = Ho (5), Tm (7)) were prepared in good yields following a straightforward synthetic protocol which involves the treatment of LnCl3 with 2 equiv. of in situ-prepared Li2COT′′ in either DME (=1,2-dimethoxyethane) or THF. The neutral actinide sandwich complexes An(COT′′)2 (An = Th (9), U (10)) and An(COT′′′)2 (COT′′′ = 1,3,6-tris(trimethylsilyl)cyclooctatetraenyl dianion; An = Th (11), U (12)) were synthesized in a similar manner, starting from ThCl4 or UCl4, respectively. The COT′′ ligand imparts excellent solubility even in low-polar solvents as well as excellent crystallinity to all new compounds studied. All twelve new f-element sandwich complexes have been structurally authenticated by single-crystal X-ray diffraction. All are nearly perfect sandwich complexes with little deviation from the coplanar arrangement of the substituted COT′′ rings. Surprisingly, all six [Li(DME)3][Ln(COT′′)2] complexes covering the entire range of Ln3+ ionic radii from La3+ to Lu3+ are isostructural (space group P). Compound 10 is the first uranocene derivative for which 13C NMR data are reported.

Investigation of the “bent sandwich-like” divalent lanthanide hydro-tris(pyrazolyl)borates Ln(TpiPr2)2 (Ln = Sm, Eu, Tm, Yb)

The series of homoleptic lanthanide(II) “bent sandwich-like” hydro-tris(pyrazolyl)borate complexes Ln(TpiPr2)2 (Ln = Sm (1), Eu (2), Tm (3), Yb (4); TpiPr2 = hydro-tris(3,5-diisopropylpyrazolyl)borate) has been completed by the synthesis of the hitherto unknown europium and ytterbium derivatives 2 and 4. Both compounds were prepared in high yields by treatment of LnI2(THF)2 (Ln = Eu, Yb) with 2 equiv. of KTpiPr2 in a THF solution. Although the molecules are sterically highly congested, an X-ray diffraction study of bright red 4 revealed a similar bent B–Yb–B arrangement (151.1° and 153.9°, two independent molecules) as in the previously investigated Sm(II) and Tm(II) complexes 1 and 3. An initial reactivity study showed a very different behavior with acetonitrile. While 2 and 4 proved to be unreactive toward acetonitrile, the more strongly reducing Sm(II) complex 1 yielded two new products. The major product was the dark green-black acetonitrile solvate SmII(TpiPr2)2·CH3CN (5), while the second product, the colorless (TpiPr2)SmIII(3,5-iPr2pz)2(NCCH3) (6) with two 3,5-diisopropyl-pyrazolate ligands, resulted from oxidation of samarium to the trivalent state and degradation of a TpiPr2 ligand. Disappointingly, from the most reducing Tm(II) complex 3 only the ligand fragmentation product pyrazabole, [HB(3,5-iPr2pz)2]2 (7), could be isolated and the fate of the Tm containing by-product(s) remains unknown. The new compounds 4–6 were structurally authenticated through single-crystal X-ray diffraction. The europium compound 2 shows an extremely bright yellow emission in solution, which can be observed also at daylight excitation, as well as in the solid state. The high intensity is even remarkable when compared to other Eu(II) containing materials. The photoluminescence was investigated with the conclusion that the rigidity of this complex is responsible for these outstanding luminescence properties.

Accurate quantification of water–macromolecule exchange induced frequency shift: Effects of reference substance

Water–macromolecule exchange induces a bulk water frequency shift contributing to the contrast in phase imaging. For separating the effects of the water–macromolecule exchange and the macromolecule susceptibility, appropriate internal or external references are needed. In this study, two internal reference compounds, 2,2,3,3‐tetradeuterio‐3‐trimethylsilyl‐propionate (TMSP) and 1,4‐dioxane, were used to study the macromolecule‐dependent water frequency shift in a bovine serum albumin (BSA)–water system in detail. For TMSP, the water–macromolecule exchange shift depended on both the BSA and the reference concentration and stabilized to a value of 0.025 ppm/mM (298 K, TMSP concentrations > 30 mM). For dioxane, the dependency of the water–macromolecule exchange shift on the BSA concentration is independent of dioxane at low concentrations. The resulting shift was smaller (0.009 ppm/mM) when compared with using higher TMSP concentrations as reference. This discrepancy might be due to additional dioxane–water interactions. Measurements with an external chloroform reference in a coaxial geometry showed a shift of −0.013 ppm/mM resulting from the opposing effects of macromolecules in water exchange‐induced shift and diamagnetic susceptibility shift. All these effects should be considered in the interpretation of tissue phase contrast. From the experimental data, the equilibrium binding constant between BSA and TMSP has been quantified to be Kd = 1.3 ± 0.4, and the estimated number of interaction sites for BSA is 12.7 ± 2.6. Magn Reson Med, 2013.

1H, 13C and 15N NMR study and molecular modelling of 2,3-di-substituted quinoxalines with sterically hindered aromatic and heteroaromatic substituents

Abstract The 1 H, 13 C and 15 N chemical shifts of a series of 2,3-di-substituted quinoxaline derivatives, substituted with heteroaromatic moieties in position 2, were measured and discussed with respect to π-electron distribution and stereodynamic behavior. The preferred conformations were calculated by semi-empirical (PM3 hamiltonian) and ab initio (HF/6–31G∗) calculations and compared with the experimental results. The observed NMR parameters are related to the calculated torsional twists. Steric interactions between the substituents in both the 3- and 3′-positions are the major cause for the non-planarity of the investigated compounds.

Synthesis and catalytic activity of homoleptic lanthanide-tris(cyclopropylethinyl)amidinates

Reactions of anhydrous lanthanide trichlorides, LnCl3 (Ln = Nd, Sm, Ho), with 3 equiv. of lithium-cyclopropylethinylamidinates, Li[c-C3H5–CC–C(NR)2] (1a: R = cyclohexyl (Cy), 1b: R = iPr), afforded the new homoleptic lanthanide(III) tris(cyclopropylethinylamidinate) complexes [c-C3H5–CC–C(NCy)2]3Sm (2a) and [c-C3H5–CC–C(NiPr)2]3Ln (Ln = Nd (2b), Sm (2c), Ho (2d)) as air- and moisture-sensitive crystalline solids in moderate to good isolated yields (45–79%). The formation of unsolvated, homoleptic Ln(III) tris(cyclopropylethinylamidinate) was confirmed by an X-ray diffraction study of the holmium derivative [c-C3H5–CC–C(NiPr)2]3Ho (2d). EI mass spectra of the new rare-earth metal amidinates indicated a significant volatility. An initial catalysis study revealed that these complexes catalyze the addition of terminal alkynes to carbodiimides to give propiolamidines of the type R–CC–C(NR′)(NHR′). The molecular structure of N,N′-dicyclohexyl-phenylpropiolamidine, Ph–CC–C(NCy)(NHCy) (4), was also determined by X-ray diffraction.

A Synthetic Route to Quaternary Pyridinium Salt-Functionalized Silsesquioxanes

A synthetic route to potentially biocidal silsesquioxanes functionalized by quaternary pyridinium functionalities has been developed. N-Alkylation reactions of the precursor compounds 4-(2-(trimethoxysilyl)ethyl)-pyridine (5) and 4-(2-trichloro-silylethyl)pyridine (6) with iodomethane, n-hexylbromide, and n-hexadecylbromide cleanly afforded the corresponding N-alkylpyridinium salts (7–10). The synthesis of a 4-(2-ethyl)pyridine POSS derivative (2) was achieved by capping of the silsesquioxane trisilanol Cy7Si7O9(OH)3 (1) via two different preparative routes. Attempts to use compound 2 as precursor for quaternary pyridinium salt-functionalized POSS derivatives were met with only partial success. Only the reaction with iodomethane cleanly afforded the new N-methylpyridinium salt 12 in high yield, whereas n-hexylbromide and n-hexadecylbromide failed to react with 2 even under forcing conditions.