Electrophilic S‐Trifluoromethylation of Cysteine Side Chains in α‐ and β‐Peptides: Isolation of Trifluoro‐methylated Sandostatin® (Octreotide) Derivatives

The new electrophilic trifluoromethylating 1‐(trifluoromethyl)‐benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF₃ groups to the S‐atom of cysteine side chains of α‐ and β‐peptides (up to 13‐residues‐long; products 7 – 14 ). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2‐position). The products are purified by chromatography, and identified by ¹H‐, ¹³C‐, and ¹⁹F‐NMR spectroscopy, by CD spectroscopy, and by high‐resolution mass spectrometry. The CF₃ groups, thus introduced, may be replaced by H (Na/NH₃), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin‐labelling, imaging, PET) are discussed.     

Structural and variable-temperature NMR studies of 9-diisopropylphosphanylanthracenes and 9,10-bis(diisopropylphosphanyl)anthracenes and their oxidation products

The diisopropylphosphanyl-substituted anthracenes i-Pr2P(C14H9) (1a), i-Pr2P(C14H8)Br (2a), and (i-Pr2P)2(C14H8) (3a) and some of their oxidation products were prepared from 9-bromoanthracene and 9,10-dibromoanthracene, respectively. Low-temperature (1)H NMR spectra of the 9-monophosphanyl-substituted anthracenes 1a and 2a are in accordance with a staggered conformer, while above room temperature dynamic processes occur. The low-temperature NMR spectrum of the 9,10-diphosphanylanthracene 3a indicates the presence of two different rotational isomers. The rotational barrier for 1a was determined from variable-temperature (1)H NMR spectra to be 56 kJ mol(-1) (DeltaG(298K)). The crystal structure determinations show the solid-state conformers to be consistent with the prevailing conformer at low temperature.     

Spectroscopic characterization of molybdenum dinitrogen complexes containing a combination of di- and triphosphine coligands: 31P NMR analysis of five-spin systems

The three molybdenum-N2 complexes [Mo(N2)(dpepp)(depe)] (1), [Mo(N2)(dpepp)(dppe)] (2), and [Mo(N2)(dpepp)(1,2-dppp)] (3), all of which contain a combination of a bi- and a tridentate phosphine ligand, were prepared and investigated by vibrational and (31)P NMR spectroscopy. As a tridentate ligand bis(2-diphenylphosphinoethyl)phenylphosphine (dpepp) has been employed. The three different bidentate ligands are 1,2-bis(diethylphosphino)ethane (depe), 1,2-bis(diphenylphosphino)ethane (dppe), and R-(+)-1,2-bis(diphenylphosphino)propane (1,2-dppp). N-N as well as metal-N vibrations of 1-3 are identified and interpreted in terms of the geometric and electronic structures of the complexes. (31)P NMR spectra are recorded and fully analyzed. Moreover, correlation spectroscopy (COSY)-45 measurements are performed to determine the relative signs of coupling constants. Special attention is directed to a detection of different isomers and their (31)P NMR, as well as vibrational spectroscopic properties. The implications of the results for the area of synthetic nitrogen fixation with phosphine complexes are discussed.     

How important are temperature effects for cluster polarizabilities?

State-of-the-art first-principle all-electron density functional theory calculations on small sodium clusters are performed to study the temperature dependency of their polarizabilities. For this purpose Born-Oppenheimer molecular dynamics simulations with more than 100,000 time steps (>200 ps) are recorded employing gradient corrected functionals in combination with a double-zeta valence polarization basis set. For each cluster 18 trajectories between 50 and 900 K are collected. The cluster polarizabilities are then calculated along these trajectories employing a triple-zeta valence polarization basis set augmented with field-induced polarization functions. The analysis of these calculations shows that the temperature dependency of the sodium cluster polarizabilities varies strongly with cluster size. For several clusters characteristic changes in the polarizability per atom as a function of temperature are observed. It is shown that the inclusion of finite temperature effects resolves the long-standing mismatch between calculated and measured sodium cluster polarizabilities.     

Nucleophilic substitution of nitro groups by [F]fluoride in methoxy-substituted ortho-nitrobenzaldehydes—A systematic study

As model reactions for the introduction of [¹⁸F]fluorine into aromatic amino acids, the replacement of NO₂ by [¹⁸F]fluoride ion in mono- to tetra-methoxy-substituted ortho-nitrobenzaldehydes was systematically investigated. Unexpectedly, the highly methoxylated precursors 2,3,4-trimethoxy-6-nitrobenzaldehyde and 2,3,4,5-tetramethoxy-6-nitrobenzaldehyde showed high maximum radiochemical yields (82% and 48% respectively). When the electrophilicity of the leaving group substituted carbon atom is expressed by its ¹³C NMR chemical shift a good correlation with the reaction rate at the beginning of the reaction (first min) was found (R² = 0.89), whereas the maximum radiochemical yields correlated much poorer with this electrophilicity parameter. This may be caused by side reactions becoming influencial in the further reaction course. As possible side reactions the demethylation of methoxy groups and intramolecular redox reactions could be detected by HPLC/MS.     

Petrographic, chemical and microprobe analysis of an oxidized iron nodule from Dahr Safra, NW Syria: Is it an iron ore, or a meteorite called shale-ball?

The iron nodule DS-S revealed the concentrations of Ni, Co, Ga, Ge, As, Sb, P, S, many trace and rare earth elements, Fe (> 93 wt.%), and 2 wt.% silicates. The plotting of Ga, Ge, Cr, Cu, As, Au, W, and Ir-concentrations vs. Ni/Co in the classes (groups) IIAB, IIIAB, IVA, ungrouped (ung), NBS 809B steel (st), and DS-S, confirmed the meteoritic origin for DS-S. Magnetite-hematite resulted from oxidation during the melting/solidification process of the original meteorite across the atmosphere. The silicates suggested the presence of Ca-rich plagioclase, and traces of opx, cpx, and/or olivine which explained the low concentrations of Ni-Co. The plotting of Ga/Ge vs. Ni/Co; Ni/Co, Ga vs. P; and Ni/Co, Ga/Ge vs. As revealed the affinity of the DS-S nodule with the ungrouped Bellsbank trio. The compositional homogeneity in the DS-S nodule was probably due to O-fugacity. The conformable REE-graphs, for chondrite and DS-S, and the presence of silicates with the same phases suggested a mesosideritic origin for DS-S.     

Encapsulation of cyanometalates by a tris-macrocyclic ligand tricopper(II) complex: syntheses, structural variation, and magnetic exchange coupling pathways

The reaction of [M(CN)(6)](3-) (M = Cr(3+), Mn(3+), Fe(3+), Co(3+)) and [M(CN)(8)](4-/3-) (M = Mo(4+/5+), W(4+/5+)) with the trinuclear copper(II) complex of 1,3,5-triazine-2,4,6-triyltris[3-(1,3,5,8,12-pentaazacyclotetradecane)] ([Cu(3)(L)](6+)) leads to partially encapsulated cyanometalates. With hexacyanometalate(III) complexes, [Cu(3)(L)](6+) forms the isostructural host-guest complexes [[[Cu(3)(L)(OH(2))(2)][M(CN)(6)](2)][M(CN)(6)]][M(CN)(6)]30 H(2)O with one bridging, two partially encapsulated, and one isolated [M(CN)(6)](3-) unit. The octacyanometalates of Mo(4+/5+) and W(4+/5+) are encapsulated by two tris-macrocyclic host units. Due to the stability of the +IV oxidation state of Mo and W, only assemblies with [M(CN)(8)](4-) were obtained. The Mo(4+) and W(4+) complexes were crystallized in two different structural forms: [[Cu(3)(L)(OH(2))](2)[Mo(CN)(8)]](NO(3))(8)15 H(2)O with a structural motif that involves isolated spherical [[Cu(3)(L)(OH(2))](2)[M(CN)(8)]](8+) ions and a "string-of-pearls" type of structure [[[Cu(3)(L)](2)[M(CN)(8)]][M(CN)(8)]](NO(3))(4) 20 H(2)O, with [M(CN)(8)](4-) ions that bridge the encapsulated octacyanometalates in a two-dimensional network. The magnetic exchange coupling between the various paramagnetic centers is characterized by temperature-dependent magnetic susceptibility and field-dependent magnetization data. Exchange between the CuCu pairs in the [Cu(3)(L)](6+) "ligand" is weakly antiferromagnetic. Ferromagnetic interactions are observed in the cyanometalate assemblies with Cr(3+), exchange coupling of Mn(3+) and Fe(3+) is very small, and the octacoordinate Mo(4+) and W(4+) systems have a closed-shell ground state.     

Three-dimensional molecular mapping of a multiple emulsion by means of CARS microscopy

Multiple emulsions consisting of water droplets dispersed in an oil phase containing emulsifier which is emulsified in an outer water phase (W/O/W) are of great interest in pharmacology for developing new drugs, in the nutrition sciences for designing functional food, and in biology as model systems for cell organelles such as liposomes. In the food industry multiple emulsions with high sugar content in the aqueous phase can be used for the production of sweets, because the high sugar content prevents deterioration. However, for these emulsions the refractive indexes of oil and aqueous phase are very similar. This seriously impedes the analysis of these emulsions, e.g., for process monitoring, because microscopic techniques based on transmission or reflection do not provide sufficient contrast. We have characterized the inner dispersed phase of concentrated W/O/W emulsions with the same refractive index of the three phases by micro Raman spectroscopy and investigated the composition and molecular distribution in water-oil-water emulsions by means of three-dimensional laser scanning CARS (coherent anti-Stokes Raman scattering) microscopy. CARS microscopy has been used to study water droplets dispersed in oil droplets at different Raman resonances to visualize different molecular species. Water droplets with a diameter of about 700 nm could clearly be visualized. The advantages of CARS microscopy for studying this particular system are emphasized by comparing this microscopic technique with conventional confocal reflection and transmission microscopies.     

Nitrogen‐Rich Compounds of the Lanthanoids: The 5,5′‐Azobis[1H‐tetrazol‐1‐ides] of some Yttric Earths (Tb,Dy, Ho,Er, Tm,Yb, and Lu)

A set of N‐rich salts, 3 – 9 , of the heavy lanthanoids (terbium, 3 ; dysprosium, 4 ; holmium 5 ; erbium, 6 ; thulium, 7 ; ytterbium, 8 ; lutetium, 9 ) based on the energetic 5,5′‐azobis[1H‐tetrazole] (H₂ZT) was synthesized and characterized by elemental analysis, vibrational (IR and Raman) spectroscopy, and X‐ray structure determination. The synthesis of the lanthanoid salts 3 – 9 was performed by crystallization from concentrated aqueous solutions of disodium 5,5′‐azobis[1H‐tetrazol‐1‐ide] dihydrate (Na₂ZT?2 H₂O; 1 ) and the respective Ln(NO₃)₃?5 H₂O and yielded large rhombic crystals of the type [Ln(H₂O)₈]₂(ZT)₃?6 H₂O in ca. 70% of the theoretical yield. The compounds 3 – 9 are isostructural (triclinic space group P ) to the previously published yttrium salt 2 ; they show, however, a clear lanthanoid contraction of several crystallographic parameters, e.g., the cell volume or the Ln? O bond lengths of the Ln³⁺ ions and the coordinating H₂O molecules. The lanthanoid contraction influences the strengths of the H‐bonds, which can be observed as a red shift by 4 cm^?1 in the characteristic IR band, in particular from 3595 cm^?1 ( 3 ) to 3599 cm^?1 ( 9 ). In good agreement with previous works, 2 – 9 are purely salt‐like compounds without a coordinative bond between the tetrazolide anion and the Ln³⁺ cation.     

Tuning of inter- versus intrachain magnetic interactions in cyano-bridged Ni(II)/M(III) (M = Cr, Fe, Co) chain complexes

The reaction of [M(CN)6]3- (M = Cr3+, Fe3+, Co3+) with the nickel(II) complex of 2,4-diamino-1,3,5-triazin-6-yl-{3-(1,3,5,8,12-pentaazacyclotetradecane)} ([NiL]2+) in excess of ANO3 or ACl (A = Li+, Na+, K+, Rb+, Cs+, NH4+) leads to the cyano-bridged dinuclear assemblies A{[NiL][M(CN)6]}.xH2O (x = 2-5). X-ray structures of Li{[NiL][Cr(CN)6]}.5H2O, NH4{[NiL][Cr(CN)6]}.3.5H2O, K{[NiL][Cr(CN)6]}.4H2O, K{[NiL][Fe(CN)6]}.4H2O, Rb{[NiL][Fe(CN)6]}.3.5H2O, and Cs{[NiL][Fe(CN)6]}.3.5H2O, as well as the powder diffractometry of the entire Fe(III) series, are reported. The magnetic properties of the assemblies are dependent on the monocation A and discussed in detail. New efficient pathways for ferromagnetic exchange between Ni(II) and Fe(III) or Cr(III) are demonstrated. Field dependencies of the magnetization for the Fe(III) samples at low temperature and low magnetic field indicate a weak interchain antiferromagnetic coupling, which is switched to ferromagnetic coupling at increasing magnetic field (metamagnetic behavior). The interchain magnetic coupling can be tuned by the size of the A cations.