A ferromagnetically coupled copper(II) trinuclear secondary building unit as precursor for the preparation of molecule-based magnets

The compounds 3D-{(Ph₄P)₂[ZnCu₃(Hmesox)₃Cl]·2.5H₂O} (1) and 3D-{(Ph₄P)₂[NiCu₃(Hmesox)₃Cl]·2.5H₂O} (2) have been prepared and their structure and magnetic properties investigated (H₄mesox = mesoxalic acid, 2-dihydroxymalonic acid). The compounds are obtained by means of the same procedure followed to prepare 3D-{(Ph₄P)₂[MnCu₃(Hmesox)₃Cl]·3.5H₂O}and 3D-{(Ph₄P)₂[CoCu₃(Hmesox)₃Cl]}, to which 1 and 2 are isostructural as deducted from the X-ray powder diffraction patterns and IR spectra. During the synthesis the {Cu₃(Hmesox)₃Cl}⁴⁻ unit is generated which acts as ferromagnetically coupled secondary building unit (SBU) to give 3D chiral networks with (10,3)-a topology, the [Zn{Cu₃(C₃HO₆)₃Cl}]²ⁿ⁻ and [Ni{Cu₃(C₃HO₆)₃Cl}]²ⁿ⁻, in 1 and 2, respectively. The tetraphenylphosphonium cations are located in the voids of the 3D anion framework giving a supramolecular 3D cation net with the same (10,3)-a topology as the anion framework and both can be thought of forming interpenetrating supramolecular and covalent (10,3)-a nets. Because of the different nature of the interpenetrated 3D (10,3)-a frameworks a single crystal of 1 and 2 is chiral and enantiopure. The analysis of the magnetic properties in 1 by means of the isotropic spin Hamiltonian, H = −J(S₁S₂ + S₂S₃ + S₁S₃), reveal a ferromagnetic coupling with J = +11.2 cm⁻¹ in the copper(II) trinuclear unit of 1. Compound 2 exhibits long-range magnetic ordering with a T_c of 7.0 K due to a ferrimagnetic coupling between the ferromagnetically coupled copper(II) ions of the trinuclear unit, antiferromagnetically coupled to the Ni(II) ions.     

Raman spectroscopic analysis of the sodium salt of kappa-carrageenan and related compounds in solution

Laser-Raman spectra of Na⁺ kappa-carrageenan, Na⁺ neocarrabiose 4-sulphate, and neocarrabiose in the region 700–1500 cm⁻¹ are reported for solutions in H₂O and D₂O. The C-1-H-1α vibration, coupled with COH related modes, is assigned to a band at 840 cm⁻¹, close to the maximum of the symmetrical COS stretching (∼850 cm⁻¹). The symmetrical SO stretch is proposed to occur near 1040 cm⁻¹ and is probably coupled with COH vibrations which give rise to strong bands in the region 1000–1100 cm⁻¹. The intense band in the region 730–740 cm⁻¹ is ascribed to a complex ring vibration.     

Chain elongation by a seemingly stereospecific cyanohydrin synthesis: the preparation and configurational assignment of 3,7-anhydro-d-threo-l-talo- and -l-galacto-octose

2,6-Anhydro-d-glycero-l-manno-heptose (1) is converted by the cyanohydrin reaction into crystalline d-threo-l-talo-octononitrile (3), which shows mutarotation in water. The equilibrium mixture, as measured by ¹³C-n.m.r. spectroscopy, contains about equal amounts of 3 and its epimer, d-threo-l-galacto-octononitrile. On evaporation of the aqueous mixture, pure, crystalline 3 is again obtained. Labelling experiments in ³H₂O proved that epimerization proceeds through reversible deprotonation. Stabilization of 3 in the solid state is explained by intramolecular hydrogen-bonding. In pyridine, rapid isomerization of 3 occurs. When acetylation of 3 is conducted in this solvent, the yield of 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-talo-octono-nitrile (4) depends strongly on the conditions of acetylation. Acetylation after equilibration produces an equimolar mixture of 4 and its isomer 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-galacto-octononitrile. Structural assignment for both was achieved by 360-Mhz, ¹H- and ¹³C-n.m.r. spectroscopy. Reduction of 4 in pyridine-acetic acid-water in the presence of N,N-diphenylethylenediamine yields a 1:2.36 mixture of 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-talo-octose N,N-diphenylimidazolidine (6) and 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-galacto-octose N,N-diphenylimidazolidine (8). Compounds 6 and 8 could be separated and obtained as crystalline solids, and their structure proved by ¹H- and ¹³C-n.m.r. spectroscopy. Hydrolysis of 6 and 8 gave 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-galacto-octose and -d-threo-l-talo-octose.     

Structural studies of β-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp.

We report structural studies in aqueous solution on backbone cyclic peptides that possess potent antimicrobial activity specifically against Pseudomonas sp. The peptides target the β-barrel outer membrane protein LptD, which plays an essential role in lipopolysaccharide transport to the outer membrane. The peptide L27-11 contains a 12-residue loop (T¹W²L³K⁴K⁵R⁶R⁷W⁸K⁹K¹⁰A¹¹K¹²) linked to a DPro–LPro template. Two related peptides were also studied, one with various Lys to ornithine or diaminobutyric acid substitutions as well as a DLys⁶ (called LB-01), and another containing the same loop sequence, but linked to an LPro–DPro template (called LB-02). NMR studies and MD simulations show that L27-11 and LB-01 adopt β-hairpin structures in solution. In contrast, LB-02 is more flexible and importantly, adopts a wide variety of different backbone conformations, but not β-hairpin conformations. L27-11 and LB-01 show antimicrobial activity in the nanomolar range against Pseudomonas aeruginosa, whereas LB-02 is essentially inactive. Thus the β-hairpin structure of the peptide is important for antimicrobial activity. An alanine scan of L27-11 revealed that tryptophan side chains (W²/W⁸) displayed on opposite faces of the β-hairpin represent key groups contributing to antimicrobial activity.     

The stepwise synthesis of an aldopentaouronic acid derivative related to branched (4-O-methylglucurono)xylans

Benzylation of methyl 2,3-anhydro-4-O-[2-O-benzyl-3,4-di-O-(β-D-xylop yranosyl]-β-D-xylopyranosyl]-β-D-ribopyranoside (1) afforded the crystalline. fully benzylated tetrasaccharide derivative 2. The octa-O-benzyl derivative 3, having only HO-2 unsubstituted, obtained by treatment of 2 with benzyl alcoholate anion in benzyl alcohol, was allowed to react in dichloromethane with methyl 2,3-di-O-benzyl- 1-chloro-1-deoxy-4-O-methy]-α,β-glucopyranuronate in the presence of silver perchlorate and triethylamine to give the branched, 4-O-methyl-α-D-glucuronic acid-containing pentasaccharide derivative 4a as the major product. Subsequent debenzylation afforded the aldopentaouronic acid derivative 5a, which contains all the basic structural features of branched, hardwood (4-O-methylglucurono)xylans. The structure of 5a was confirmed by analysis of its ¹³C-n.m.r. spectrum and the mass-spectral fragmentation pattern of the corresponding fully methylated derivative 6a.     

Structural diversity in thallium chemistry, IV. Further examples of solid state bromothallate(III) derivatives obtained by employing certain classes of alkyl diammonium cations

Six new bromothallate(III)-containing salts with different alkyl diammonium cations have been prepared from bromide containing solutions and studied by single-crystal X-ray crystallographic analyses. The N,N′-diethyl-N,N,N′,N′-tetramethyl-1,2-ethylenediammonium, N-methyl-1,3-propanediammonium, N,N,N′,N′-tetramethyl-1,3-propanediammonium and N,N,N′,N′-tetraethyl-1,2-ethylenediammonium cations yield complexes (I, II, III and IV, respectively) with the [TlBr₅]²⁻ anionic stoichiometry. For I and II, both complexes contain the [TlBr₅]²⁻ anion. In complex II, this appears as a distorted octahedron with one long Tl?Br2′ contact of 3.632(4) Å from an adjacent anion, thus completing the hexacoordination about an otherwise distorted square pyramid. On the other hand, for III and IV, both complexes contain a tetrahedral [TlBr₄]⁻ anion together with an isolated, but hydrogen-bonded, Br⁻ anion. The 1,5-hexanediammonium complex (V) contains tetrahedral [TlBr₄]⁻, slightly distorted octahedral [TlBr₆]³⁻ and Br⁻ anions. The asymmetric unit of the N,N-diethyl-1,3-propanediammonium salt (VI) contains one cation and half of each of a [TlBr₄]⁻ and an axially compressed octahedral [TlBr₆]³⁻ anion. Extensive hydrogen-bonded networks exist in complexes II-VI. NH?Br hydrogen bonds generally have a significant influence on the nature of the anions present in species with the formal [TlBr₅] stoichiometry.     

Functional expression of horsegram (Dolichos biflorus) Bowman–Birk inhibitor and its self-association

Horsegram (Dolichos biflorus), a protein-rich leguminous pulse, native to Southeast Asia and tropical Africa, contains multiple forms of Bowman–Birk inhibitors. The major Bowman–Birk inhibitor from horsegram (HGI-III) was cloned and functionally expressed in Escherichiacoli (rHGI), which moved as a dimer in solution similar to the natural inhibitor. The biochemical characterization of rHGI also points to its close resemblance with HGI-III not only in its structure but also in its inhibitory characteristics. To explore the electrostatic interactions involved in the dimerization, a site-directed mutagenesis approach was used. The role of reactive site residue K²⁴ and the C-terminal Asp in the structure and stability of the dimer was accomplished by mutating K²⁴ and D^75/76. The mutants produced in this study confirm that the self-association of HGI-III is indeed due to the electrostatic interaction between K²⁴ of one monomer and D^75/76 of the second monomer, in agreement with our previous data. The functional expression of a Bowman–Birk inhibitor minus a fusion tag serves as a platform to study the structural and functional effects of the special pattern of seven conserved disulphide bridges.     

Two new pH-controlled metal-organic frameworks based on polynuclear secondary building units with conformation-flexible cyclohexane-1,2,4,5-tetracarboxylate ligand

By regulating the pH values, two new zinc(II) coordination polymers, formulated as [Zn₄(μ₇-CTA^I)(μ₃-OH)(μ₂-OH)₃(H₂O)₂]_n·2n(H₂O) (1), [Zn₂(μ₇-CTA^II)(H₂O)₃]_n (2) have been prepared by a flexible ligand, cyclohexane-1,2,4,5-tetracarboxylic acid (H₄CTA) under hydrothermal conditions. Complex 1 exhibits a two-dimensional binodal (3,6)-connected topological network containing rare octanuclear zinc(II) clusters as the secondary building units (SBU1). Complex 2 displays a three-dimensional binodal (4,8)-connected topological network containing unusual Zn₄(COO)₆ secondary building units (SBU2). And importantly, the conformation of H₄CTA in 1 exhibits (a,e,e,a) fashion and transforms to thermodynamically more stable conformation (e,a,e,e) type in 2 by pH-controlled. In addition, both of the complexes show strong photoluminescence at room temperature, and may be good candidates for potential luminescence materials.     

Isolation and partial characterization of a covalent intermediate between α-chymotrypsin and o-hydroxy-α-toluenesulfonic acid sultone

Reaction of α-chymotrypsin with o-[³⁵S]hydroxy-α-toluenesulfonic acid sultone (I) at pH 7 produces an intermediate which substantially decomposes over a period of 24 hr at pH 3 as determined by gel chromatography. Isolation of the intermediate at pH 3 followed by denaturation in urea, reduction of disulfide bonds, and SDS-urea gel electrophoresis resulted in separation of the three peptides which compose the enzyme. Radioactivity (³⁵S) was associated with the peptide which contains serine 195 and not with the peptide containing histidine 57. These results indicate that a covalent linkage is established between sultone I and α-chymotrypsin, presumably at serine 195.     

The copper-molybdenum antagonism in ruminants. III. Reaction of copper(II) with tetrathiomolybdate(VI)

The stoichiometry of the reaction between Cu(II) and MoS₄²⁻ in neutral aqueous solution was observed to proceed with a 1.5:1 Cu:Mo ratio. The reaction results in the reduction of Cu(II) and the quantitative formation of an insoluble solid. The results contrast with an earlier report of a 1:1 stoichiometric ratio, this latter ratio was, however, observed with Cu^II(albumin) as reactant, in this case no precipitate was observed. The insoluble products were examined by a number of spectroscopic techniques and by X-ray power diffraction and elemental analysis. Two products were identified. Solid A is isostructural with the known (NH₄)Cu^IMoV^VIS₄, i.e. has the composition M^ICuMoS₄, M^I= NH₄⁺, Na⁺ or Et₄N⁺. Solid B has the approximate composition CuMoS₄O_x, x=2−3 and contains Cu(I) and Mo(V) centres. Formation of compound B therefore involves an unusual internal two-electron redox process. The reaction and products are of particular biological significance.     

Enzyme inhibitor modeling with TpZn complexes of functional hydroxamates and oximates

Salicylhydroxamic acid reacts with the enzyme model Tp^Ph,MeZn-OH to form the O,O-chelating hydroxamate complex 1. The hydrogen bonding capacity of zinc enzyme bound hydroxamates is reproduced by cocrystallization of two molecules if 1 with two molecules of methanol and by cocrystallization of one molecule of Tp^Ph,MeZn-acetohydroxamate with one molecule of 3-phenyl-5-methylpyrazole. The complex formed from Tp^Ph,MeZn-OH and N-tosylproline hydroxamic acid, according to its spectra, contains the hydroxamate as an N,N-chelating ligand. In contrast, the oximate derived from pyruvic aldehyde does not act as a chelating ligand, but is monodentate via the oximate oxygen.     

Photoluminescent metal(II)-organic complexes with two distinct atropisomeric units from axially prochiral ligands through C-H?O hydrogen bonds (M = zinc, cobalt, nickel)

By taking advantage of rich-electron modification of pyridine-3,5-dicarboxylates, three photoluminescent isostructural metal-organic complexes, namely, [M(Hsmpdc)₂(H₂O)₄] · 6H₂O (smpdc = 2,6-dimethyl-4-(thiophen-2-yl)pyridine-3,5-dicarboxylate, M = Zn (1), Co (2) and Ni (3)), were synthesized and characterized by single crystal X-ray analyses. There are interesting hydrogen-bonded M²⁺(H₂O)₈ ionic clusters in the structures of title compounds. And of the most interesting is that S- and R-atropisomeric units are constructed from axially prochiral organic ligands through C-H?O hydrogen bonds. Strong photoluminescent emission at 543 nm with obvious red shift might make compound 1 a potentially photoactive solid-state material for its thermal and chemical stability.     

Design of a new fluorescent probe: Pyrrole/imidazole hairpin polyamides with pyrene conjugation at their γ-turn

Fluorophores that are conjugated with N-methylpyrrole-N-methylimidazole (Py–Im) polyamides postulates versatile applications in biological and physicochemical studies. Here, we show the design and synthesis of new types of pyrene-conjugated hairpin Py–Im polyamides (1–5). We evaluated the steady state fluorescence of the synthesized conjugates (1–5) in the presence and absence of oligodeoxynucleotides 5′-CGTATGGACTCGG-3′ (ODN 1) and 5′-CCGAGTCCATACG-3′ (ODN 2) and observed a distinct increase in emission at 386 nm with conjugates 4 and 5. Notably, conjugate 5 that contains a β-alanine linker had a stronger binding affinity (K_D = 1.73 × 10^?8 M) than that of conjugate 4 (K_D = 1.74 × 10^?6 M). Our data suggests that Py–Im polyamides containing pyrene fluorophore with a β-alanine linker at the γ-turn NH₂ position can be developed as the competent fluorescent DNA-binding probes.     

Synthesis of heterodinuclear FeRu(CO)6(R-DAB(6e))(R-DABRNC(H)C(H)NR) Part XV. Comparison of the reactivities of heterodinuclear FeRu(CO)6(R-DAB(6e)) and homodinuclear analogues M2(CO)6(R-DAB(6e)) (M = Fe,Ru). Single-crystal x-ray structures of FeRu(CO)6(i-Pr-DAB(6e)) and FeRu(CO)5(i-Pr-DAB(4e))(C3H4)

The reactions of Fe(CO)₃(R-DAB; R¹, H(4e)) (1a: R = i-Pr, R¹ = H; 1b: R = t-Bu, R¹ = H; 1c: R = c-Hex, R¹ = H; 1e: R = p-Tol, R¹ = H; 1f: R = i-Pr, R¹ = Me) with Ru₃(CO)₁₂ and of Ru(CO)₃(R-DAB; R¹, H(4e)) (2a: R = i-Pr, R¹ = H; 2d: R = CH(i-Pr)₂, R¹ = H) with Fe₂(CO)₉ in refluxing heptane both afforded FeRu(CO)₆(R-DAB; R¹, H(6e)) (3) in yields between 50 and 65%.The coordination mode of the ligand has been studied by a single crystal X-ray structure determination of FeRu(CO)₆(i-Pr-DAB(6e)) (3a). Crystals of 3a are monoclinic, space group P2₁/a, with four molecules in a unit cell of dimensions: a = 22.436(3), b = 8.136(3), c = 10.266(1) Å and β = 99.57(1)°. The structure was refined to R = 0.049 and R_w = 0.052 using 3045 reflections above the 2.5σ(I) level. The molecule contains an FeRu bond of 2.6602(9) Å, three terminally bonded carbonyls to Fe, three terminally bonded carbonyls to Ru and bridging 6e donating i-Pr-DAB ligand. The i-Pr-DAB ligand is coordinated to Ru via N(1) and N(2) occupying an apical and equatorial site respectively (RuN(1) = 2.138(4) RuN(2) = 2.102(3) Å). The C(2)N(2) moiety of the ligand is η²-coordinated to Fe with C(2) in an apical and N(2) in an equatorial site (FeC(2) = 2.070(5) and FeN(2) = 1.942(3) Å).The ¹H and ¹³C NMR data indicate that in all FeRu(CO)₆(R-DAB(6e)) complexes (3a to 3f) exclusively η²-CN coordination to the Fe atom and not to the Ru atom is present irrespective of whether 3 was prepared by reaction of Fe(CO)₃(R-DAB(4e)) (1) with Ru₃(CO)₁₂ or by reaction of Ru(CO)₃(R-DAB(4e)) (2) with Fe₂(CO)₉. In the case of FeRu(CO)₆(i-Pr-DAB; Me, H(6e)) (3f) the NMR data show that only the complex with the C(Me)N moiety of the ligand σ-N coordinated to the Ru atom and the C(H)N moiety η²-coordinated to the Fe atom was formed. Variable temperature NMR experiments up to 140 °C showed that the α-diimine ligand in 3a is stereochemically rigid bonded.FeRu(CO)₆(R-DAB(6e)) (3a and 3e) reacted with allene to give FeRu(CO)₅(R-DAB(4e))(C₃H₄) (4a and 4e). A single crystal X-ray structure determination of FeRu(CO)₅(i-Pr-DAB(4e))(C₃H₄) (4a) was performed. Crystals of 4a are triclinic, space group P1, with two molecules in a unit cell of dimensions: a = 9.7882(7), b = 12.2609(9), c = 8.3343(7) Å, α = 99.77(1)°, β = 91.47(1)° and γ = 86.00(1)°. The structure was refined to R = 0.028 and R_w = 0.043 using 4598 reflections above the 2σ(I) level. The molecule contains an FeRu bond of 2.7405(7) Å and three terminally bonded carbonyls to iron. Two carbonyls are terminally bonded to the Ru atom together with a chelating 4e donating i-Pr-DAB ligand [RuN = 2.110(1) (mean)]. The allene ligand is coordinated in an η³-allylic fashion to the Fe atom while the central carbon of the allene moiety is σ-bonded to the Ru atom (FeC(14) = 2.166(3), FeC(15) = 1.970(2), FeC(16) = 2.127(3) and RuC(15) = 2.075(2) Å). The ¹H and ¹³C NMR data show that in solution the coordination modes of the R-DAB and the allene ligands are the same as in the solid state.Thermolysis reactions of 3a with R-DAB or carbodiimides gave decomposition and did not afford C(imine)C(reactant) coupling products. Thermolysis reactions of 3a with M₃(CO)₁₂ (M = Ru, Os) and Me₃NO gave decomposition. When the reaction of 3a with Me₃NO was performed in the presence of dimethylacetylenedicarboxylate (DMADC) the known complex FeRu(CO)₄(i-Pr-DAB(8e))(DMADC) (5a) was formed in low yield. In 5a the R-DAB ligand is in the 8e coordination mode with both the imine bonds η²-coordinated to iron. The acetylene ligand is coordinated in a bridging fashion, parallel with the FeRu bond.     

Binuclear manganese(III) complexes of an unsymmetric pyrazolate-based compartmental ligand with hard donor set

The synthesis, crystal structure and magnetic properties of manganese(III) binuclear complexes [Mn^III₂(L-3Н)₂(CH₃ОH)₄]·2CH₃ОH (1) and [Mn^III₂(L-3Н)₂(Py)₄]·2Py (2) (L = 3-[(1E)-N-hydroxyethanimidoyl]-4-methyl-1H-pyrazole-5-carboxylic acid) are reported. The ligand contains two distinct donor compartments formed by the pyrazolate-N and the oxime or the carboxylic groups. The complexes were characterized by X-ray single crystal diffraction, revealing that both 1 and 2 consist of dinuclear units in which the two metal ions are linked by double pyrazolate bridges with a planar {Mn₂N₄} core. Cryomagnetic measurements show antiferromagnetic interaction with g = 1.99, J = −3.6 cm⁻¹, Θ = −2.02 K for 1 and g = 2.00, J = −3.7 cm⁻¹, Θ = 1.43 K for 2.     

Synthesis, characterization, crystal structures and magnetic properties of dissymmetrical double schiff base heterotrinuclear complexes: [CuL(H2O)CoCuL] · H2O · CH3OH and [(CuL)2Ni] · 2H2O

A dissymmetrical double Schiff base Cu(II) mononuclear complex: CuHL (1) (where H₃L is N-3-carboxylsalicylidene-N^′-salicylaldehyde-1,2-diaminoethane) and two trinuclear complexes: [CuL(H₂O)CoCuL] · H₂O · CH₃OH (2) and [(CuL)₂Ni] · 2H₂O (3) have been synthesized and characterized by means of elemental analyses, IR and electronic spectra. The crystal structures of two heterotrinucler complexes were determined by X-ray analysis. Each dissymmetrical cell unit of the complex 2 contains two heterotrinucler neutral molecules. In each neutral molecule, the central Co²⁺ ion is located at the site of O₆ with a distorted octahedral geometry and one terminal Cu²⁺ ion at the four-coordination site of N₂O₂, but the other one at the square-pyramidal environment of N₂O₃. Each dissymmetrical unit of the complex 3 contains a heterotrinucler neutral molecule, whose structure is similar to that of 2 except two terminal Cu²⁺ ions both at the inner site of N₂O₂. The magnetic properties of two heterotrinucler complexes have been determined in the temperature range of 5-300 K, which indicate that the interaction between the central Co²⁺ ion or Ni²⁺ ion and the outer Cu²⁺ ions is antiferromagnetic. The exchange integrals are equal to −26.2 cm⁻¹ for 2 and −50.6 cm⁻¹ for 3.     

The hydrogen bonding effect on the halobismuthate(III) geometry: thermal,spectroscopic and structural properties of halobismuthate complexes of 4,6-dimethylpyrimidine-2(1H)-thione

Reactions involving Bi(III) halides and 4,6- dimethylpyrimidine-2(1H)-thione (L) in HX solution result in the formation of [HL]₃[BiX₆]·2H₂O (X=C1, Br) and [HL]₃[Bi₂I₉]. These compounds together with the organic molecule in the form of the hydrochloride, (HLCl) were characterized by means of spectroscopic and thermogravimetric measurements. For HLCl·H₂O (1) and [HL]₃[BiCl₆]·2H₂O (2), X-ray structures were determined. In 1, which crystallizes in the space group Pca2₁, with four molecules in the cell, the structure consists of roughly planar protonated organic molecules stacked along the [100] axis and built up by hydrogen bonds involving chlorine atoms and water molecules. For 2, the space group is P2₁/n, Z=4, the structure contains [BiCl₆]³⁻ anions, protonated organic molecules stacked along the [010] axis and water molecules which form strong hydrogen bonds with the [BiCl₆]³⁻ anions. The final R indices are 0.0320 and 0.0465 for 1 and 2, respectively.     

Design,synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor

Twenty eight new aryloxybenzene analogues were synthesized and their in vitro binding potencies toward S1PR2 were determined using a [³²P]S1P competitive binding assay. Out of these new analogues, three compounds, 28c (IC₅₀ = 29.9 ± 3.9 nM), 28e (IC₅₀ = 14.6 ± 1.5 nM), and 28g (IC₅₀ = 38.5 ± 6.3 nM) exhibited high binding potency toward S1PR2 and high selectivity over the other four receptor subtypes (S1PR1, 3, 4, and 5; IC₅₀ > 1000 nM). Each of the three potent compounds 28c, 28e, and 28g contains a fluorine atom that will allow to develop F-18 labeled PET radiotracers for imaging S1PR2.     

Synthesis and spectroscopic properties of CpRuCl(R-DAB(4e)) and CpRuCo(CO)3(R-DAB(6e)). Part XVII. X-ray structure determination of CpRuCo(CO)3(t-Bu-DAB(6e))

CpRuCl(PPh₃)₂ reacted with excess R-DAB in refluxing toluene to give CpRuCl(R-DAB(4e)) (1a: R = i-Pr; 1b: R = t-Bu; 1c: R = neo-Pent; 1d: R =p-Tol). ¹H NMR and ¹³C NMR spectroscopic data indicated that in these complexes the R-DAB ligand is bonded in a chelating 4e coordination mode.Reaction of 1a and 1b with one equivalent of [Co(CO)₄]⁻ afforded CpRuCo(CO)₃(R-DAB(6e)) (2a: R = i-Pr; 2b: R = t-Bu). The structure of 2b was determined by a single crystal X-ray structure determination. Crystals of 2b are monoclinic, space group P2₁/n, with four molecules in a unit cell of dimensions: a = 16.812(4), b = 12.233(3), c = 9.938(3) Å and β = 105.47(3)°. The structure was solved via the heavy atom method and refined to R = 0.060 and R_w = 0.065 for the 3706 observed reflections. The molecule contains a RuCo bond of 2.660(3) Å and a cyclopentadienyl group that is η⁵-coordinated to ruthenium [RuC(cyclopentadienyl) = 2.208(3) Å (mean)]. Two carbonyls are terminally coordinated to cobalt (CoC(1) = 1.746(7) and CoC(2) = 1.715(6) Å) while the third is slightly asymmetrically bridging the RuCo bond (RuC(3) = 2.025(6) and CoC(3) = 1.912(6) Å). The RuC(3)O(3) and CoC(3)O(3) angles are 138.4(5)° and 136.5(5)°, respectively. The t-Bu-DAB ligand is in the bridging 6e coordination mode: σ-N coordinated to Ru (RuN(2) = 2.125(4) Å), μ₂-N′ bridging the RuCo bond and η²-CN coordinated to Co (RuN(1) = 2.113(5), CoN(1) = 1.941(4) and CoC(4) = 2.084(5) Å). The η²-CN′ bonded imine group has a bond length of 1.394(7) Å indicating substantial π-backbonding from Co into the anti-bonding orbital of this CN bond.¹H NMR spectroscopy indicated that 2a and 2b are fluxional on the NMR time scale. The fluxionality of 6e bonded R-DAB ligands is rarely observed and may be explained by the reversible interchange of the σ-N and η²-CN′ coordinated imine parts of the R-DAB ligand.     

New tirucallane triterpenoids from Picrasma quassioides with their potential antiproliferative activities on hepatoma cells

Seven new tirucallane-type triterpenoids (1–7), kumuquassin A-G, along with 20 known analogues (8–27) were isolated from the stems of Picrasma quassioides. The structures and the absolute configurations of new compounds were elucidated by spectroscopic data, electronic circular dichroism (ECD) spectroscopic analyses and quantum ECD calculations. Notably, kumuquassin A (1) contains a rare Δ^{17, 20} double bond, kumuquassin B (2) is the first example of tirucallane triterpenoid possessing a 5/3 biheterocyclic ring system at the side chain. All the compounds were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B, and several compounds exhibited promising activity. The most potential compound 3 was selected for cell cycle analysis, which showed that 3 could cause an accumulation of HepG2 cells at subG1 peak. Annexin V-FITC/PI staining further confirmed that compound 3 caused death of hepatoma cells through apoptosis induction.