Probing Alzheimer's pathology: Exploring the next generation of FDDNP analogues for amyloid ß detection.

Fluorescent probes are a powerful tool for imaging amyloid ß (Aß) plaques, the hallmark of Alzheimer's disease (AD). Herein, we report the synthesis and comprehensive characterization of 21 novel probes as well as their optical properties and binding affinities to Aß fibrils. One of these dyes, 1Ae, exhibited several improvements over FDDNP, an established biomarker for Aß- and Tau-aggregates. First, 1Ae had large Stokes shifts (138-213 nm) in various solvents, thereby reducing self-absorption. With a high quantum yield ratio (φ(dichloromethane/methanol) = 104), 1Ae also ensures minimal background emission in aqueous environments and high sensitivity. In addition, compound 1Ae exhibited low micromolar binding affinity to Aß fibrils in vitro (Kd = 1.603 µM), while increasing fluorescence emission (106-fold) compared to emission in buffer alone. Importantly, the selective binding of 1Ae to Aß1-42 fibrils was confirmed by an in cellulo assay, supported by ex vivo fluorescence microscopy of 1Ae on postmortem AD brain sections, allowing unequivocal identification of Aß plaques. The intermolecular interactions of fluorophores with Aß were elucidated by docking studies and molecular dynamics simulations. Density functional theory calculations revealed the unique photophysics of these rod-shaped fluorophores, with a twisted intramolecular charge transfer (TICT) excited state. These results provide valuable insights into the future application of such probes as potential diagnostic tools for AD in vitro and ex vivo such as determination of Aß1-42 in cerebrospinal fluid or blood.

Towards structurally versatile mesoionic N-heterocyclic olefin ligands and their coordination to palladium, gold, and boron hydride.

We have developed an efficient and versatile approach for the synthesis of a family of 1,2,3-triazole-based mesoionic N-heterocyclic olefin (mNHO) ligands and investigated their coordination to palladium, gold, and boron hydride experimentally and computationally. We reacted mNHOs obtained through deprotonation of the corresponding methylated and ethylated 1,3,4-triaryl-1,2,3-triazolium salts with [Pd(allyl)Cl]2 to give the corresponding [Pd(η3-allyl)Cl(mNHO)] coordination complexes. 13C NMR data revealed the strong σ-donor character of the mNHO ligands, consistent with the calculated bond orders and atom-condensed charges. Furthermore, we also synthesized [AuCl(mNHO)] and a BH3-mNHO adduct by reacting the triazolium salts with AuCl(SMe2) and BH3·THF, respectively. The BH3-mNHO adduct was tested in the reduction of select aldehydes and ketones to alcohols.

3-Nitro-benzo-nitrile.

The crystal structure of 3-nitrobenzonitrile, C7H4N2O2, was elucidated by low-temperature single-crystal X-ray diffraction. The compound crystallizes in the Sohncke space group P21 and features two mol-ecules in the unit cell. Aromatic π-π stacking leads to stacks of mol-ecules in the [100] direction. The absolute structure was established from anomalous dispersion.

Bis-(di-meth-oxy-ethane-1κ2O,O')penta-kis-(1,1,1,3,3,3-hexa-fluoro-propan-2-olato)-2κ3O,3κ2O-µ-hy-droxido-1:3κ2O-µ3-oxido-1:2:3κ3O-magnesiumdialuminium.

Partial hydrolysis of a sample of [Mg(dme)3][Al(hfip)4]2 crystals led to the formation of the title complex, [Mg(dme)2{HOAl(hfip)2OAl(hfip)3}] (dme = di-meth-oxy-ethane and hfipH = hexa-fluoro-iso-propanol) or [Mg(C4H10O2)2O(OH)Al2(C3HF6O)5]. The magnesium cation exhibits a distorted octa-hedral coordination with two bidentate di-meth-oxy-ethane mol-ecules and a dinuclear aluminate anion, coordinated to Mg2+ via oxido and hydroxido units. The anion is an oxido-bridged species, [HOAl(hfip)2(µ-O)Al(hfip)3]2-, with one Al3+ cation tetra-hedrally coordinated by an oxido (O2-) anion, a hydroxido anion, and two hfip groups, whereas the second Al3+ cation is coordinated by the oxido anion and three hfip groups.

Tri-methyl-phosphine oxide dihydrate.

The title hydrate, Me3PO·2H2O, crystallizes in the ortho-rhom-bic space group Pbca with eight formula units per unit cell. The extended structure displays O-H⋯O hydrogen bonding, with Me3PO mol-ecules as acceptors and water mol-ecules acting as donors and acceptors of hydrogen bonds, forming hydrogen-bonded layers, which propagate in the ac plane.

Hydrogen-Bonding Ability of Noyori-Ikariya Catalysts Enables Stereoselective Access to CF3-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution.

Stereopure CF3-substituted syn-1,2-diols were prepared via the reductive dynamic kinetic resolution of the corresponding racemic α-hydroxyketones in HCO2H/Et3N. (Het)aryl, benzyl, vinyl, and alkyl ketones are tolerated, delivering products with ≥95% ee and ≥87:13 syn/anti. This methodology offers rapid access to stereopure bioactive molecules. Furthermore, DFT calculations for three types of Noyori-Ikariya ruthenium catalysts were performed to show their general ability of directing stereoselectivity via the hydrogen bond acceptor SO2 region and CH/π interactions.

(1S,2S)-2-[(S)-2,2,2-Tri-fluoro-1-hy-droxy-eth-yl]-1-tetra-lol.

The crystal structure of the title enanti-opure tetralol derivative {systematic name: (1S,2S)-2-[(S)-2,2,2-tri-fluoro-1-hy-droxy-eth-yl]-1,2,3,4-tetra-hydro-naph-thalen-1-ol}, C12H13F3O2, synthesized by asymmetric transfer hydrogenation, was elucidated by low-temperature single-crystal X-ray diffraction. The enanti-opure compound crystallizes in the Sohncke space group P212121 with one mol-ecule in the asymmetric unit and features intra-molecular as well as inter-molecular O-H⋯O hydrogen bonding. The absolute configuration was established from anomalous dispersion effects.

Aqua-tri-fluorido-boron-1,3-dioxolan-2-one (1/2).

The crystal structure of the co-crystal of aqua-tri-fluorido-boron with two ethyl-ene carbonate (systematic name: 1,3-dioxolan-2-one) mol-ecules, BF3H2O·2OC(OCH2)2, was determined by low-temperature single-crystal X-ray diffraction. The co-crystal crystallizes in the ortho-rhom-bic space group P212121 with four formula units per unit cell. The asymmetric unit consists of an aqua-tri-fluorido-boron mol-ecule and two ethyl-ene carbonate mol-ecules, connected by O-H⋯O=C hydrogen bonds. This crystal structure is an inter-esting example of a superacidic BF3H2O species co-crystallized with an organic carbonate.

(S)-2-[(S)-2,2,2-Tri-fluoro-1-hy-droxy-eth-yl]-1-tetra-lone.

The crystal structure of the title compound, C12H11F3O2, was elucidated by low-temperature single-crystal X-ray diffraction. The enanti-opure compound crystallizes in the Sohncke space group P21 and features one mol-ecule in the asymmetric unit. The structure displays inter-molecular O-H⋯O hydrogen bonding, which links the mol-ecules into infinite chains propagating parallel to [010]. The absolute configuration was established from anomalous dispersion.

Crystal structure reinvestigation of silver(I) fluoride, AgF.

A crystal structure reinvestigation of AgF based on a low-temperature high-resolution single-crystal X-ray diffraction data is reported. Silver(I) fluoride crystallizes in the rock salt structure type (Fm m) with a unit-cell parameter of 4.92171 (14) Šat 100 K, resulting in an Ag-F bond length of 2.46085 (7) Å.

Crystal structure of CaSiF6·2H2O(mP2) and reevaluation of the SiIV-F bond-valence parameter R0.

The structure of a second polymorph of CaSiF6·2H2O [calcium hexafluorido-silicate dihydrate; space group P2/c (No. 13), Pearson symbol mP2] was elucidated by single-crystal X-ray diffraction. It arose as an unexpected product when soda-lime glass was attacked by HF. Its crystal structure consists of infinite ∞ 2[Ca(H2O)2/1(SiF6)4/4] layers oriented parallel to the bc-crystallographic plane, a unique motif among structurally characterized hydrated hexa-fluorido-silicates. The crystal structure also exhibits inter- and intra-layer hydrogen bonds, with the inter-layer O-H⋯O hydrogen bonds involving a disordered hydrogen atom. The large deviation between the calculated bond-valence sum for Si and the expected value prompted a redetermination of the empirical SiIV-F bond-valence parameter R 0. Based on a data set of 42 high-quality crystal structures containing 49 independent SiIV coordination environments, a revised value of 1.534 Šwas derived for R 0.

Catalytic Stereoconvergent Synthesis of Homochiral ß-CF3, ß-SCF3, and ß-OCF3 Benzylic Alcohols.

We describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral ß-CF3, ß-SCF3, and ß-OCF3 benzylic alcohols. The approach is based on dynamic kinetic resolution (DKR) with Noyori-Ikariya asymmetric transfer hydrogenation leading to simultaneous construction of two contiguous stereogenic centers with up to 99.9% ee, up to 99.9:0.1 dr, and up to 99% isolated yield. The origin of the stereoselectivity and racemization mechanism of DKR is rationalized by density functional theory calculations. Applicability of the previously inaccessible chiral fluorinated alcohols obtained by this method in two directions is further demonstrated: As building blocks for pharmaceuticals, illustrated by the synthesis of heat shock protein 90 inhibitor with in vitro anticancer activity, and in particular, needle-shaped crystals of representative stereopure products that exhibit either elastic or plastic flexibility, which opens the door to functional materials based on mechanically responsive chiral molecular crystals.

On the Practical Applications of the Magnesium Fluorinated Alkoxyaluminate Electrolyte in Mg Battery Cells.

High-performance electrolytes are at the heart of magnesium battery development. Long-term stability along with the low potential difference between plating and stripping processes are needed to consider them for next-generation battery devices. Within this work, we perform an in-depth characterization of the novel Mg[Al(hfip)4]2 salt in different glyme-based electrolytes. Specific importance is given to the influence of water content and the role of additives in the electrolyte. Mg[Al(hfip)4]2-based electrolytes exemplify high tolerance to water presence and the beneficial effect of additives under aggravated cycling conditions. Finally, electrolyte compatibility is tested with three different types of Mg cathodes, spanning different types of electrochemical mechanisms (Chevrel phase, organic cathode, sulfur). Benchmarking with an electrolyte containing a state-of-the-art Mg[B(hfip)4]2 salt exemplifies an improved performance of electrolytes comprising the Mg[Al(hfip)4]2 salt and establishes Mg[Al(hfip)4]2 as a new standard salt for the future Mg battery research.

Nitro-sonium tetra-fluorido-borate, NOBF4.

The crystal structure of oxido-nitro-gen(1+) tetra-fluorido-borate (nitro-sonium tetra-fluorido-borate), NO+BF4 -, was refined on the basis of single-crystal X-ray diffraction data at 150 K. The compound crystallizes in the baryte structure type with ortho-rhom-bic Pnma symmetry. The crystal structure exhibits cationic disorder with equal occupation of N and O atoms at the same site.

Mixed Noble-Gas Compounds of Krypton(II) and Xenon(VI); [F5 Xe(FKrF)AsF6 ] and [F5 Xe(FKrF)2 AsF6 ].

The coordination chemistry of KrF2 has been limited in contrast with that of XeF2 , which exhibits a far richer coordination chemistry with main-group and transition-metal cations. In the present work, reactions of [XeF5 ][AsF6 ] with KrF2 in anhydrous HF solvent afforded [F5 Xe(FKrF)AsF6 ] and [F5 Xe(FKrF)2 AsF6 ], the first mixed krypton/xenon compounds. X-ray crystal structures and Raman spectra show the KrF2 ligands and [AsF6 ]- anions are F-coordinated to the xenon atoms of the [XeF5 ]+ cations. Quantum-chemical calculations are consistent with essentially noncovalent ligand-xenon bonds that may be described in terms of σ-hole bonding. These complexes significantly extend the XeF2 -KrF2 analogy and the limited chemistry of krypton by introducing a new class of coordination compound in which KrF2 functions as a ligand that coordinates to xenon(VI). The HF solvates, [F5 Xe(FH)AsF6 ] and [F5 Xe(FH)SbF6 ], are also characterized in this study and they provide rare examples of HF coordinated to xenon(VI).

trans-Diastereoselective Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of α-Acetamido Benzocyclic Ketones via Dynamic Kinetic Resolution.

A highly efficient enantio- and diastereoselective catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution (DKR-ATH) of α,ß-dehydro-α-acetamido and α-acetamido benzocyclic ketones to ent- trans-ß-amido alcohols is disclosed employing a new ansa-Ru(II) complex of an enantiomerically pure syn- N, N-ligand, i.e. ent- syn-ULTAM-(CH2)3Ph. DFT calculations of the transition state structures revealed an atypical two-pronged substrate attractive stabilization engaging the commonly encountered CH/π electrostatic interaction and a new additional O═S═O···HNAc H-bond hence favoring the trans-configured products.

Manifestations of Weak O-H···F Hydrogen Bonding in M(H2O) n(B12F12) Salt Hydrates: Unusually Sharp Fourier Transform Infrared ν(OH) Bands and Latent Porosity (M = Mg-Ba, Co, Ni, Zn).

Eight M(H2O) n(Z) salt hydrates were characterized by single-crystal X-ray diffraction (Z2- = B12F122-): M = Ca, Sr, n = 7; M = Mg, Co, Ni, Zn, n = 6; M = Ba, n = 4, 5. Weak O-H···F hydrogen bonding between the M(H2O) n2+ cations and Z2- resulted in room-temperature Fourier transform infrared (FTIR) spectra having sharp ν(OH) bands, with full widths at half max of 10-30 cm-1, which are much more narrow than ν(OH) bands in room temperature FTIR spectra of most salt hydrates. Clearly resolved νasym(OH/OD) and νsym(OH/OD) bands with Δν(OH) as small as 17 cm-1 and Δν(OD) as small as 11 cm-1 were observed (Δν(OX) = νasym(OX) - νsym(OX)). The isomorphic hexahydrates ( R3̅) have two fac-(H2O)3 sets of H2O ligands and nearly octahedral coordination spheres. They exhibited four resolvable ν(OH) bands, one νasym(OH)/νsym(OH) pair for H2O ligands with longer O(H)···F distances and one νasym(OH)/νsym(OH) pair for H2O ligands with shorter O(H)···F distances. The ν(OH) bands for the three H2O molecules with shorter, slightly stronger O(H)···F hydrogen bonds were broader, more intense, and red-shifted by ca. 25 cm-1 relative to the bands for the three other H2O molecules, the first time that such small differences in relatively weak O(H)···F hydrogen bonds in the same crystalline hexahydrate have resulted in observable IR spectroscopic differences at room temperature. For the first time room temperature ν(OH) values for salt hexahydrates showed the monotonic progression Mg2+ > Co2+ > Ni2+ > Zn2+, essentially the same progression as the p Ka values for these metal ions in aqueous solution. A further manifestation of the weak O-H···F hydrogen bonding in these hydrates is the latent porosity exhibited by Ba(H2O)5,8(Z), Sr(H2O) n,m(Z), and Ca(H2O)4,6(Z). Finally, the H2O/D2O exchange reaction Co(D2O)6(Z) → Co(H2O)6(Z) was ca. 50% complete in 1 h at 50 °C in N2/17 Torr H2O( g).

Fluorinated reduced graphene oxide as a protective layer on the metallic lithium for application in the high energy batteries.

Metallic lithium is considered to be one of the most promising anode materials since it offers high volumetric and gravimetric energy densities when combined with high-voltage or high-capacity cathodes. However, the main impediment to the practical applications of metallic lithium is its unstable solid electrolyte interface (SEI), which results in constant lithium consumption for the formation of fresh SEI, together with lithium dendritic growth during electrochemical cycling. Here we present the electrochemical performance of a fluorinated reduced graphene oxide interlayer (FGI) on the metallic lithium surface, tested in lithium symmetrical cells and in combination with two different cathode materials. The FGI on the metallic lithium exhibit two roles, firstly it acts as a Li-ion conductive layer and electronic insulator and secondly, it effectively suppresses the formation of high surface area lithium (HSAL). An enhanced electrochemical performance of the full cell battery system with two different types of cathodes was shown in the carbonate or in the ether based electrolytes. The presented results indicate a potential application in future secondary Li-metal batteries.

Latent Porosity in Alkali-Metal M2B12F12 Salts: Structures and Rapid Room-Temperature Hydration/Dehydration Cycles.

Structures of the alkali-metal hydrates Li2(H2O)4Z, LiK(H2O)4Z, Na2(H2O)3Z, and Rb2(H2O)2Z, unit cell parameters for Rb2Z and Rb2(H2O)2Z, and the density functional theory (DFT)-optimized structures of K2Z, K2(H2O)2Z, Rb2Z, Rb2(H2O)2Z, Cs2Z, and Cs2(H2O)Z are reported (Z2- = B12F122-) and compared with previously reported X-ray structures of Na2(H2O)0,4Z, K2(H2O)0,2,4Z, and Cs2(H2O)Z. Unusually rapid room-temperature hydration/dehydration cycles of several M2Z/M2(H2O)nZ salt hydrate pairs, which were studied by isothermal gravimetry, are also reported. Finely ground samples of K2Z, Rb2Z, and Cs2Z, which are not microporous, exhibited latent porosity by undergoing hydration at 24-25 °C in the presence of 18 Torr of H2O(g) to K2(H2O)2Z, Rb2(H2O)2Z, and Cs2(H2O)Z in 18, 40, and 16 min, respectively. These hydrates were dehydrated at 24-25 °C in dry N2 to the original anhydrous M2Z compounds in 61, 25, and 76 min, respectively (the exact times varied from sample to sample depending on the particle size). The hydrate Na2(H2O)2Z also exhibited latent porosity by undergoing multiple 90 min cycles of hydration to Na2(H2O)3Z and dehydration back to Na2(H2O)2Z at 23 °C. For the K2Z, Rb2Z, and Cs2Z transformations, the maximum rate of hydration (rhmax) decreased, and the absolute value of the maximum rate of dehydration (rdmax) increased, as T increased. For K2Z ↔ K2(H2O)2Z hydration/dehydration cycles with the same sample, the ratio rhmax/rdmax decreased 26 times over 8.6 °C, from 3.7 at 23.4 °C to 0.14 at 32.0 °C. For Rb2Z ↔ Rb2(H2O)2Z cycles, rhmax/rdmax decreased from 0.88 at 23 °C to 0.23 at 27 °C. For Cs2Z ↔ Cs2(H2O)Z cycles, rhmax/rdmax decreased 20 times over 8 °C, from 6.7 at 24 °C to 0.34 at 32 °C. In addition, the reversible substitution of D2O for H2O in fully hydrated Rb2(H2O)2Z in the presence of N2/16 Torr of D2O(g) was complete in only 60 min at 23 °C.

Coordination of KrF2 to a Naked Metal Cation, Mg2.

Examples of coordination compounds in which KrF2 functions as a ligand are very rare. In contrast, XeF2 provides a rich coordination chemistry with a variety of main-group and transition metal cations. The reactions of Mg(AsF6 )2 and KrF2 in HF or BrF5 solvent have afforded [Mg(KrF2 )4 (AsF6 )2 ] and [Mg(KrF2 )4 (AsF6 )2 ]⋅2 BrF5 , respectively, the first examples of a metal cation ligated by KrF2 . Their X-ray crystal structures and Raman spectra show that the KrF2 ligands and [AsF6 ]- anions are F-coordinated to a naked Mg2+ cation. Quantum-chemical calculations are consistent with essentially non-covalent ligand-metal bonding. These compounds significantly extend the XeF2 -KrF2 analogy and the limited chemistry of krypton by introducing a new class of coordination compound in which KrF2 functions as a ligand towards a naked metal cation.