Tetra-kis(tri-ethyl-enediamin-1-ium) dodeca-µ2-chlorido-hexakis(thio-cyanato-κN)hexa-octa-hedro-niobate.

The crystal structure of the cluster complex salt, (C6H13N2)4[Nb6(NCS)6Cl12] or (H-DABCO)4[Nb6Cl12(NCS)6] (DABCO = tri-ethyl-enedi-amine or 1,4-di-aza-bicyclo-[2.2.2]octa-ne), comprises octa-hedral Nb6 cluster cores, which are µ2-coordinated by 12 chloride ligands (bridging the octa-hedral edges, inner ligand sphere). Furthermore, each Nb atom is N-bonded to a terminal thio-cyanate ligand (outer ligand sphere). The discrete clusters carry a charge of -4, which is compensated by four monoprotonated DABCO mol-ecules. These are arranged in rows, which are N-H⋯Cl and N-H⋯N hydrogen bonded to the anions and among each other.

Dipeptide-Derived Alkynes as Potent and Selective Irreversible Inhibitors of Cysteine Cathepsins.

The potential of designing irreversible alkyne-based inhibitors of cysteine cathepsins by isoelectronic replacement in reversibly acting potent peptide nitriles was explored. The synthesis of the dipeptide alkynes was developed with special emphasis on stereochemically homogeneous products obtained in the Gilbert-Seyferth homologation for C≡C bond formation. Twenty-three dipeptide alkynes and 12 analogous nitriles were synthesized and investigated for their inhibition of cathepsins B, L, S, and K. Numerous combinations of residues at positions P1 and P2 as well as terminal acyl groups allowed for the derivation of extensive structure-activity relationships, which were rationalized by computational covalent docking for selected examples. The determined inactivation constants of the alkynes at the target enzymes span a range of >3 orders of magnitude (3-10 133 M-1 s-1). Notably, the selectivity profiles of alkynes do not necessarily reflect those of the nitriles. Inhibitory activity at the cellular level was demonstrated for selected compounds.

Tetra-aqua-dodekakis-µ2-chlorido-di-iodido-octa-hedro-hexa-niobium(12 Nb-Nb) tetra-hydro-furan octa-solvate.

The title compound, [Nb6Cl12I2(H2O)4]·8THF (THF is tetra-hydro-furan, C4H8O), comprises an uncharged niobium cluster unit surrounded by THF solvent mol-ecules. The edges of the {Nb6} octa-hedron are µ 2-coordinated by twelve chlorido ligands. Four in-plane (equatorial plane) aqua ligands and two iodido ligands coordinating above and below the plane are bound at the corners of the {Nb6} atomic octa-hedron. O-H⋯O hydrogen bonds are formed between the aqua ligands and the THF solvent mol-ecules; one THF molecule is disordered over two positions with the major component having a site occupancy of 0.64 (2).

Strong Cluster-Supported Brønsted Acids: Hexanuclear Niobium Cluster Compounds with Protonated Crown Ether Cations: (Crown-H)2[Nb6Cl12iX6a] (X = Cl or Br) and the Intermediate [Nb6Cl16(H2O)2]·4 dioxane.

Six cluster salts which consist of hexanuclear cluster anions [Nb6Cl12iX6a]2- (X = Cl or Br) and protonated crown ether molecules (15-crown-5 (15cr5) and 12-crown-4 (12cr4)) or crown ether-stabilized oxonium cations as well as one compound consisting of neutral cluster units, [Nb6Cl16(H2O)2]·4 dioxane, were synthesized in good to high yields. The single-crystal X-ray structures of six of these compounds were determined. The cation/anion ratios and the bond distances confirm in all cases oxidized cluster cores with 14 cluster-based electrons. The cations of the cluster salts are either sandwich-type dimers of the formula [(15cr5)H]22+ or [(15cr5)(H3O)]22+ with the protons or oxonium ions embedded in between the crown ether rings or monomeric units in the case of [(12cr4)H]+. 1H NMR investigations show that the cluster salts are strong Brønsted acids. The fact that the cluster core of [Nb6Cl16(H2O)2]·4 dioxane is oxidized but still carries water ligands indicates that within the multi-step reaction sequence of the formation of the cluster-supported acids, the oxidation step happens much faster than the ligand exchange steps. Temperature-dependent 2H MAS NMR spectra of deuterium-exchanged [(15cr5)H]2[Nb6Cl18]·2 CHCl3 are indicative of dynamic processes of the hydrogen-bonded protons within the crown ether molecule.

Cluster Compounds with Oxidised, Hexanuclear [Nb6 Cli 12 Ia 6 ]n- Anions (n=2 or 3).

Four mixed-halide cluster salts with chloride-iodide-supported octahedral Nb6 metal atoms cores were prepared and investigated. The cluster anions have the formula [Nb6 Cli 12 Ia 6 ]n- with Cl occupying the inner ligand sites and I the outer one. They are one- or two-electron-oxidized (n=2 or 3) with respect to the starting material cluster. (Ph4 P)+ and (PPN)+ function as counter cations. The X-ray structures reveal a mixed occupation of the outer sites for only one compound, (PPN)3 [Nb6 Cli 12 Ia 5.047(9) Cla 0.953 ]. All four compounds are obtained in high yield. If in the chemical reactions a mixture of acetic anhydride, CH2 Cl2 , and trimethylsilyl iodide is used, the resulting acidic conditions lead to form the two-electron-oxidised species (n=2) with 14 cluster-based electrons (CBEs). If only acetic anhydride is used, the 15 CBE species (n=3) is obtained in high yield. Interesting intermolecular bonding is found in (Ph4 P)2 [Nb6 Cli 12 Ia 6 ] ⋅ 4CH2 Cl2 with I⋅⋅⋅I halogen bonding and π-π bonding interactions between the phenyl rings of the cations in (PPN)3 [Nb6 Cli 12 Ia 5.047(9) Cla 0.953 ]. The solubility of (Ph4 P)2 [Nb6 Cli 12 Ia 6 ] ⋅ 4CH2 Cl2 has been determined qualitatively in a variety of solvents, and good solubility in the aprotic solvents CH3 CN, THF and CH2 Cl2 has been found.

[Nb6Cl14(pyrazine)4], a Versatile Precursor for Ligand-Supported Hexanuclear Niobium Cluster Compounds: Synthesis, Characterization, Follow-Up Reactions, and Intermolecular Interactions.

The compound [Nb6Cl14(pyrazine)4]·2CH2Cl2 (1) was investigated for its suitability as a starting compound for new ligand-supported hexanuclear niobium cluster compounds. The synthesis, stability to air and increased temperature, solubility and usability for subsequent reactions of 1, and purification and separation of the reaction products are discussed. The compounds with cluster units [Nb6Cl14L4], where L = iso-quinoline N-oxides (2), 1,1-dimethylethylenediamines (3), or thiazoles (4), and [Nb6Cl14(PEt3)3.76(Et3PO)0.24][Nb6Cl14(MeCN)4]·4MeCN (5) are presented as follow-up products. The crystal structures of compounds 1-5 are analyzed, and the structures are discussed with respect to their intra- and intermolecular bonding situations and crystal packing. In addition to hydrogen bonds and π-π interactions, the appearance of chalcogen and halogen bonds and lone pair-π interactions between Nb6 cluster units was observed for the first time.

Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core.

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling 99mTc using the fac-[Tc(CO)3]+ core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed. The labeling was accomplished using a tricarbonyl kit and a 99mTc-pertechnetate generator eluate showing 87% radiochemical conversion. The respective rhenium-based, non-radioactive reference compounds were synthesized using (Et4N)2[Re(CO)3Br3] as precursor. All products were analyzed by NMR, MS, and elemental analysis. Additional XRD analyses were performed.

New Low-Melting Triply Charged Homoleptic Cr(III)-Based Ionic Liquids in Comparison to Their Singly Charged Heteroleptic Analogues.

A series of new low-melting triply charged homoleptic Cr(III)-based ionic liquids of the general formula (RMIm)3[Cr(NCS)6] (R = methyl, ethyl, n-butyl, benzyl) is reported. Their syntheses and properties are described in comparison to their singly charged heteroleptic analogues of the general formula (RMIm)[Cr(NCS)4L2] (R = methyl, ethyl, n-butyl, benzyl; L = pyridine, γ-picoline). In total, sixteen new Reineckate related salts with large imidazolium cations are described. Out of these, five compounds were crystallized, and their structures determined by single-crystal X-ray structure analyses. They all consisted of discrete anions and cations with octahedrally coordinated Cr(III) ions. In the structures, various hydrogen contacts interconnect the entities to build up hydrogen bonded networks. Thermal investigations showed relatively low melting points for the homoleptic complexes. The compounds with the [Cr(NCS)6]3- anion melt without decomposition and are stable up to 200 K above their melting points. The complex salts with the [Cr(NCS)4L2]- anion, in contrast, start to decompose and lose L molecules (Pyr or Pic) already at the melting point.

Cluster Salts [Nb6 Cl12 (HIm)6 ]An (with HIm=1H-imidazole and A=Mineral Acid Anion, n=1 or 2) Made in and with Brønsted-basic Ionic Liquids and Liquid Mixtures.

Four new hexanuclear niobium cluster compounds of the general formula [Nb6 Cl12 (HIm)6 ](A)n ⋅ x(solvent molecule) (HIm=1H-imidazole, A=mineral acid anion, Cl- (n=2) (1), (SO4 )2- (n=1) (2), (CrO4 )2- (n=1) (3), and (HAsO4 )2- (n=1) (4)) were prepared. Their synthesis can be done in basic ionic liquids, which form on the addition of a mineral acid, which also delivers the counter anion for the final cluster compound, to an excess of the 1H-imidazole. Some addition of an auxiliary solvent, like methanol, improves the speed of crystallisation. The cluster unit comprises a hexanuclear Nb6 unit of octahedral shape with the edges bridged by Cl atoms and the exo sites being occupied by N-bonded 1H-imidazole ligands. The cluster cation carries sixteen cluster-based electrons. Between the NH groups of the ligands of the cluster unit, the anions and the co-crystallised water (1), or 1H-imidazole and methanol molecules (2, 3, and 4) a network of hydrogen bonds exists.

(S)-Alanine ethyl ester tetra-cyanidoborate, (C5H12NO)[B(CN)4].

The title mol-ecular salt, C5H12NO+·C4BN4 - or (C5H12NO)[B(CN)4], was obtained as single crystals by slow evaporation of a solution of the compound in aceto-nitrile over several weeks. The asymmetric unit contains two (S)-alanine ethyl ester cations and two tetra-cyanidoborate anions, which are linked by N-H⋯N hydrogen bonds. The compound exhibits a relatively low melting point of 110°C and shows a solid-solid phase transition near room temperature (T s-s = 29°C) on the basis of DSC measurements.

1-Butyl-3-methyl-imidazolium tri-bromido-(tri-phenyl-phosphane-κP)nickelate(II) butan-1-ol hemisolvate.

The solvated title salt, (C8H15N2)[NiBr3(P(C6H5)3)]·0.5C4H10O, was obtained in the form of single crystals directly from the reaction mixture. The mol-ecular structure consists of separated 1-butyl-3-methyl-imidazolium cations, tri-bromido-(tri-phenyl-phosphane)nickelate(II) anions and half a solvent mol-ecule of 1-butanol, all connected via multiple hydrogen contacts to form a three-dimensional network. The co-crystallized 1-butanol mol-ecule is disordered and adopts two orientations. The central C-C bonds of both orientations are located on an inversion centre (Wyckoff site 2b of space group P21/n). Thereby, each orientation has again two orientations with the OH group being located either on one or the other side of the C4 alkyl chain. The dried solvent-free compound exhibits a relatively low melting point (m.p. = 412 K).

Hexa-aqua-dodeca-µ2-iodido-octahedro-hexa-tantalum diiodide tetra-hydrate.

In the crystal structure of the cluster salt, [Ta6I12(H2O)6]I2·4H2O, the octa-hedral {Ta6} cluster core is µ2-coordinated by twelve iodido ligands (inner ligand sphere) whereas the six aqua ligands coordinate each at the six outer positions. The discrete, inversion-symmetric cluster complex is double-positively charged, and two iodide anions are present in the crystal structure as counter-ions. In addition, four water mol-ecules are co-crystallized. Hydrogen bonds between the cluster unit, the iodide anions and co-crystallized water mol-ecules stabilize the charge-assisted packing in the crystal structure.

Hexa-aquadodeca-µ2-chlorido-octa-hedro-hexa-niobium diiodide.

The title compound, [Nb6Cl12(H2O)6]I2, consists of the niobium cluster cation [Nb6Cl12(H2O)6]2+ and two non-coordinating, charge-balancing iodide ions. The edges of the Nb6 octa-hedron are bridged by chlorido ligands. Each Nb atom is further coordinated by a water ligand. The cluster cation has a charge of +2, which is balanced by that of two iodide anions.

In the footsteps of August Michaelis: Syntheses and Thermodynamics of Extremely Low-Volatile Ionic Liquids.

A series of nine different known ionic liquids or low melting salts was synthesised and purified. They are composed of the [NTf2 ]- (bis(trifluoromethane)sulfonimide), [OTf]- (trifluoro-methane-sulfonate), or [B(CN)4 ]- (tetracyanidoborate) anion and [Ph4 P]+ (tetraphenylphosphonium), [Ph3 BzP]+ (triphenylbenzyl phosphonium), [n Bu4 P]+ (tetra-n butylphosphonium), [n BuPh3 P]+ (tri-phenyl-n butylphosphonium), [n Bu4 N]+ (tetra-n butylammonium), or the [PPN]+ (bis(triphenylphosphine)iminium) cation. Precise vapour pressure data and enthalpies of vaporisation were measured using the Quartz Crystal Microbalance (QCM) method and evaluated. Structure-property relations are established using the obtained data as well as literature known data of ILs with alkyl-substituted imidazolium cations. It turns out that ILs with the tetracyanidoborate anion have even higher values of the enthalpy of vaporisation than those with the common [NTf2 ]- or [OTf]- anion and therefore are even less volatile.

Synthesis, radiolabelling and initial biological characterisation of 18F-labelled xanthine derivatives for PET imaging of Eph receptors.

Eph receptor tyrosine kinases, particularly EphA2 and EphB4, represent promising candidates for molecular imaging due to their essential role in cancer progression and therapy resistance. Xanthine derivatives were identified to be potent Eph receptor inhibitors with IC50 values in the low nanomolar range (1-40 nm). These compounds occupy the hydrophobic pocket of the ATP-binding site in the kinase domain. Based on lead compound 1, we designed two fluorine-18-labelled receptor tyrosine kinase inhibitors ([18F]2/3) as potential tracers for positron emission tomography (PET). Docking into the ATP-binding site allowed us to find the best position for radiolabelling. The replacement of the methyl group at the uracil residue ([18F]3) rather than the methyl group of the phenoxy moiety ([18F]2) by a fluoropropyl group was predicted to preserve the affinity of the lead compound 1. Herein, we point out a synthesis route to [18F]2 and [18F]3 and the respective tosylate precursors as well as a labelling procedure to insert fluorine-18. After radiolabelling, both radiotracers were obtained in approximately 5% radiochemical yield with high radiochemical purity (>98%) and a molar activity of >10 GBq µmol-1. In line with the docking studies, first cell experiments revealed specific, time-dependent binding and uptake of [18F]3 to EphA2 and EphB4-overexpressing A375 human melanoma cells, whereas [18F]2 did not accumulate at these cells. Since both tracers [18F]3 and [18F]2 are stable in rat blood, the novel radiotracers might be suitable for in vivo molecular imaging of Eph receptors with PET.

Deuteration versus ethylation - strategies to improve the metabolic fate of an 18F-labeled celecoxib derivative.

The inducible isoenzyme cyclooxygenase-2 (COX-2) is closely associated with chemo-/radioresistance and poor prognosis of solid tumors. Therefore, COX-2 represents an attractive target for functional characterization of tumors by positron emission tomography (PET). In this study, the celecoxib derivative 3-([18F]fluoromethyl)-1-[4-(methylsulfonyl)phenyl]-5-(p-tolyl)-1H-pyrazole ([18F]5a) was chosen as a lead compound having a reported high COX-2 inhibitory potency and a potentially low carbonic anhydrase binding tendency. The respective deuterated analog [D2,18F]5a and the fluoroethyl-substituted derivative [18F]5b were selected to study the influence of these modifications with respect to COX inhibition potency in vitro and metabolic stability of the radiolabeled tracers in vivo. COX-2 inhibitory potency was found to be influenced by elongation of the side chain but, as expected, not by deuteration. An automated radiosynthesis comprising 18F-fluorination and purification under comparable conditions provided the radiotracers [18F]5a,b and [D2,18F]5a in good radiochemical yields (RCY) and high radiochemical purity (RCP). Biodistribution and PET studies comparing all three compounds revealed bone accumulation of 18F-activity to be lowest for the ethyl derivative [18F]5b. However, the deuterated analog [D2,18F]5a turned out to be the most stable compound of the three derivatives studied here. Time-dependent degradation of [18F]5a,b and [D2,18F]5a after incubation in murine liver microsomes was in accordance with the data on metabolism in vivo. Furthermore, metabolites were identified based on UPLC-MS/MS.

Bis(1-dodecyl-4-aza-1-azoniabi-cyclo-[2.2.2]octane)tetra-iso-thio-cyanato-cobalt(II).

The title compound, [Co(C18H37N2)2(NCS)4], consists of a cobalt(II) ion positioned on the origin of the triclinic unit cell. It is coordinated by the N atoms of two trans-oriented 1-dodecyl-4-aza-1-azoniabi-cyclo-[2.2.2]octane (DABCO+) cations, which carry n-dodecyl chains at the non-coordinating N atoms. The distorted octa-hedral coordination environment of the CoII ion is completed through four N atoms of iso-thio-cyanate ions, which are arranged within the equatorial plane. Non-classical hydrogen bonding of the types C-H⋯N and C-H⋯S between the filamentous mol-ecules lead to the formation of layers parallel to (001).

Bis(N-adamantyl-N'-ethyl-imidazolium) tetra-bromido-manganate(II).

The title compound, (C15H23N2)2[MnBr4], comprises two N-adamantyl-N'-ethyl-imidazolium cations and one tetra-hedral [MnBr4]2- anion. Next to Coulombic inter-actions, weak hydrogen bonds of the type C-H⋯Br consolidate the crystal packing, building up a three-dimensional network.

Low-Melting Manganese (II)-Based Ionic Liquids: Syntheses, Structures, Properties and Influence of Trace Impurities.

The synthesis of more than 10 new magnetic ionic liquids with [MnX4]2- anions, X = Cl, NCS, NCO, is presented. Detailed structural information through single-crystal X-ray diffraction is given for (DMDIm)[Mn(NCS)4], (BnEt3N)2[Mn(NCS)4], and {(Ph3P)2N}2[Mn(NCO4)]·0.6H2O, respectively. All compounds consist of discrete anions and cations with tetrahedrally coordinated Mn (II) atoms. They show paramagnetic behavior as expected for spin-only systems. Melting points are found for several systems below 100 °C classifying them as ionic liquids. Thermal properties are investigated using differential scanning calorimetry (DSC) measurements. The physicochemical properties of density, dynamic viscosity, electrolytic conductivity, and surface tension were measured temperature-dependent of selected samples. These properties are discussed in comparison to similar Co containing systems. An increasing amount of bromide impurity is found to affect the surface tension only up to 3.3%.

A Hexanuclear Niobium Cluster Compound Crystallizing as Macroscopic Tubes.

Compounds with ordered structures in one or two dimensions are exciting materials and investigated intensively in many different areas of science. Many activities have been put into the preparation of low-dimensional nano-scaled structures and many compounds in this size regime are known. Contrary, the number of known compounds that have low-dimensional macroscopic sized structures that form directly in a chemical reaction is very limited. Here, we present the synthesis of the niobium cluster compound [(Et2 O)2 H]2 [Nb6 Cl18 ], crystals of which grow in form of large hexagonal empty tubes of several centimeter length and diameters in the range of 2 mm. The single-crystal X-ray structure of this compound has been refined. Under warming, the compound readily eliminates diethyl ether molecules and decomposes. From a closer look at the crystallization process a step-by-step scheme of the procedure of the tube growth is proposed. The overall conclusion from this proposal is that a crucial balance between the cluster solution concentration, the crystal growth speed and the ether diffusion speed results in the formation of macroscopic crystal tubes.