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The tricyclic BCD substructure of the marine natural product nakadomarin A has been synthesised. The strategy utilised a key carbon-carbon bond-forming reaction between a furan and an N -acyliminium ion derived from a secondary thiolactam. In addition, a novel three-component coupling reaction between a thioamide, an allylic bromide and an isocyanate, leading to the establishment of two new stereogenic centres, is reported. Two key steps in a projected total synthesis of nakadomarin A have been realised by using the unique chemistry of thioamides. Formation of the carbocyclic B ring can be effected by nucleophilic attack of a furan on a thiolactam-derived iminium ion, and the key quaternary centre can be established by a novel three-component coupling reaction.

Background: 4-substituted methylidene oxindoles are pharmacologically important. Detailed analysis and comparison of all the interactions present in crystal structures is necessary to understand how these structures arise. The XPac procedure allows comparison of complete crystal structures of related families of compounds to identify assemblies that are mainly the result of close-packing as well as networks of directed interactions., Results: Five 4-substituted methylidene oxindoles have been synthesized by the Knoevenagel condensation of oxindole with para-substituted aromatic aldehydes and were characterized in the solid state by x-ray crystallography. Hence, the structures of (3E)-3-(4-Bromobenzylidene)-1,3-dihydro-2H-indol-2-one, 3a, (3E)-3-(4-Chlorobenzylidene)-1,3-dihydro-2H-indol-2-one, 3b, (3E)-3-(4-Methoxybenzylidene)-1,3-dihydro-2H-indol-2-one, 3c, (3E)-3-(4-Methylbenzylidene)-1,3-dihydro-2H-indol-2-one, 3d and (3E)-3-(4-Nitrobenzylidene)-1,3-dihydro-2H-indol-2-one, 3e, were elucidated using single crystal X-ray crystallography., Conclusions: A hydrogen bonded dimer molecular assembly or supramolecular construct was identified in all the crystal structures examined along with a further four 1D supramolecular constructs which were common to at least two of the family of structures studied. The 1D supramolecular constructs indicate that once the obvious strong interaction is satisfied to form hydrogen bonded dimer it is the conventionally weaker interactions, such as steric bulk and edge-to-face interactions which compete to influence the final structure formation.

In order to exploit the vast body of currently inaccessible chemical information held in Electronic Laboratory Notebooks (ELNs) it is necessary not only to make it available but also to develop protocols for discovery, access and ultimately automatic processing. An aim of the Dial-a-Molecule Grand Challenge Network is to be able to draw on the body of accumulated chemical knowledge in order to predict or optimize the outcome of reactions. Accordingly the Network drew up a working group comprising informaticians, software developers and stakeholders from industry and academia to develop protocols and mechanisms to access and process ELN records. The work presented here constitutes the first stage of this process by proposing a tiered metadata system of knowledge, information and processing where each in turn addresses a) discovery, indexing and citation b) context and access to additional information and c) content access and manipulation. A compact set of metadata terms, called the elnItemManifest, has been derived and caters for the knowledge layer of this model. The elnItemManifest has been encoded as an XML schema and some use cases are presented to demonstrate the potential of this approach.

The complete mol-ecule of the title compound, C32H28N2, is generated by crystallographic inversion symmetry. The dihedral angles between the central aromatic ring and the pendant adjacent rings are 61.37 (16) and 74.20 (14)°. The N-H group does not participate in hydrogen bonds and there are no aromatic π-π stacking inter-actions in the crystal.

Triphenylene twins are intriguing structures, and those bridged through their 3,6-positions by dipyrromethene units give a new class of macrocycles that can be viewed as rigid, expanded porphyrin derivatives in which coplanarity is enforced in a formally antiaromatic π system. Somewhat surprisingly, however, macrocyclization leads to significant overall stabilization of the dipyrromethene chromophores.

Convenient syntheses of mono- and bis-imidazolium 1,3,5-triazine derivatives bearing piperidine and morpholine substituents are reported. In situ deprotonation of the mono-imidazolium salts and reaction with Ag2O or Au(tht)Cl (tht = tetrahydrothiophene) precursors affords the corresponding Ag(NHC)Cl and Au(NHC)Cl carbene complexes. In the presence of Ag(I) or Au(I) salts the bis-imidazolium pincers eliminate the imidazolium group to afford -OMe or -NMe2 substituted triazines depending on the solvent used. In solution, the Ag(I) and Au(I) complexes show a barrier to rotation about the Ctriazine-Namine bonds, with calculated ΔG(≠) barriers in the region of 70 kJ mol(-1). Single crystal X-ray structures of several of the proligands and their corresponding Ag(I) and Au(I) complexes were obtained. These universally reveal an extended, rigidly planar π-conjugated network between the triazine core, imidazolium/imidazolylidene substituents and exocyclic amine functions, to which the origin of the rotational barrier observed in solution is attributed. Only very weak Ntriazine-metal interactions are observed in the solid state, as indicated by small deviations of the CNHC-Ag-Cl bond angles from 180° and also supported by DFT calculations on the Ag(NHC)Cl complex (NHC = 4,6-dipiperidinyl-2-methylimidazolylidene triazine). Preliminary antimicrobial susceptibility studies against five microorganisms (methicillin resistant Staphylococcus aureus NCTC 13277, S. aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, Proteus mirabilis NCTC 11938 and Candida albicans ATCC 90028) show that the above triazine-based Ag-NHC complexes are active antimicrobial and antifungal agents.

In the title compound, C26H26ClN3O2·C3H7OH, the benzimid-azole ring system is essentially planar [maximum deviation = -0.018 (2) Å] and its mean plane is oriented with respect to the two benzene rings at dihedral angles of 4.51 (6) and 56.16 (6)°, and the dihedral angle between the two benzene rings is 59.11 (7)°. The morpholine ring displays a chair conformation. The propan-2-ol solvent mol-ecule links with the benzimidazole ring via an O-H⋯N hydrogen bond. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into inversion dimers with an R 2 (2)(28) motif. π-π stacking occurs between the parallel chloro-benzene rings [centroid-centroid distance = 3.792 (1) Å]. Weak C-H⋯π inter-actions and short Cl⋯Cl [3.2037 (10) Å] contacts are also observed.

A series of glutarimide derivatives which has two carbonyl coordination sites for intramolecular pentacoordination at silicon with a X(1+n)SiC(3-n)O moiety have been synthesised and characterized. The substituent (leaving group) effects on the Si-O bond exchange between the two coordination sites (resembling a pendulum) have been studied by comparison of the differently substituted (X = F, Cl, OTf, Br and I) structures. The activation parameters for the Si-O bond exchange process were measured by NMR and separately computed and are consistent with the strength of Si-O bond coordination and the nature of the leaving group, X. The temperature-dependent (29)Si NMR spectroscopy is supported by X-ray crystallography and shows that the tetrahedral reactant is converted into pentacoordinate intermediates by intramolecular O-Si association followed by reversion to a tetrahedral geometry by Si-X dissociation. The two association/dissociation patterns offer a model for nucleophilic substitution at a silicon atom. A continuum of structures on the S(N)2 reaction profile from the glutarimide derivatives correlates reasonably well with the structural data obtained from derivatives of lactams, diketopiperazines and quinolones.

A glucoside and cellobioside of glycolamide were synthesised and the crystal chemistry of these compounds investigated. The amidoglucoside crystallised in the P2(1) space group. The primary amide group participates in C(7) and C(17) chains also involving the pyranose oxygen and hydroxyl groups. The amidocellobioside crystallised as a methanol solvate in the P2(1) space group. The amide N-H groups donate hydrogen bonds to oxygen atoms on the cellobiose units, while intramolecular hydrogen bonds give rise to S(7) and S(9) motifs in addition to a R3(3) (9) motif. A tetra-O-acetylglucoside derivative of thioglycolamide and its sulfoxide derivative were synthesised to examine the effect of protecting the glucopyranose hydroxyl groups. The thioglycolamido derivative, which crystallised in the P2(1)2(1)2(1) space group, featured amide N-H groups donating to the glucopyranose oxygen and an acetyloxy group. The sulfoxy derivative crystallised in the P2(1) space group and featured the primary amide groups forming R2(3)(8) motifs generating a 2(1) ladder., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Three new fumaramide-derived [3]rotaxanes have been synthesized, with the aim of macrocycle linking to form a molecular box. In one case, a nine-component templated [3]rotaxane synthesis was accomplished in 40% yield. Rotaxane reduction resulted in an unexpectedly facile de-slipping process.

The asymmetric unit of the title compound, C(15)H(12)N(2)O, contains two independent mol-ecules with different conformations, the phenyl ring and indazole mean plane in the two mol-ecules forming dihedral angles of 50.82 (5) and 89.29 (6)°. In the crystal, weak C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π inter-actions consolidate the packing.

In the title compound, C26H27N3O2, the morpholine ring adopts a chair conformation. The benzene and phenyl rings are inclined to the benzimidazole mean plane by 7.28 (6) and 61.45 (4)°, respectively. In the crystal, pairs of weak C-H⋯O hydrogen bonds link the mol-ecules into inversion dimers. These dimers are further connected via weak C-H⋯N hydrogen bonds. A weak C-H⋯π inter-action is also observed.

Synthesis of the title compounds has been achieved through refinement of a recently reported synthetic protocol whereby varying equivalents of MeMgBr are reacted with 1,4-dioctylphthalonitrile to produce mixtures favoring specific hybrid structures. The initially formed magnesium-metalated compounds are obtained as pure materials and include, for the first time, both isomers (cis and trans) of tetrabenzodiazaporphyrin. The compounds were demetalated to the metal-free analogues, which were then converted into the copper-metalated derivatives. The X-ray structure of the copper tetrabenzotriazaporphyrin derivative is reported. The metal-free and copper-metalated macrocycles exhibit columnar mesophase behavior, and it is found that the mesophase stability is unexpectedly reduced in the diazaporphyrin derivatives compared to the rest of the series. The results of time-dependent density functional theory calculations for the copper complexes are compared to the observed optical properties. Michl's perimeter model was used as a conceptual framework for analyzing the magnetic circular dichroism spectral data, which predicted and accounted for trends in the observed experimental spectra.

The first molecular capsule based on an [Ir(ppy)(2)](+) unit (ppy = 2-phenylatopyridine) has been prepared. Following the development of a method to resolve rac-[(Ir(ppy)(2)Cl)(2)] into its enantiopure forms, homochiral Ir(6)L(4) octahedra where obtained with the tritopic 1,3,5-tricyanobenzene. Solution studies and X-ray diffraction show that these capsules encapsulate four of the six associated counteranions and that these can be exchanged for other anionic guests. Initial photophysical studies have shown that an ensemble of weakly coordinating ligands can lead to luminescence not present in comparable mononuclear systems.

The iridium(III) cyclometalation of alkylated pyrene-benzimidazole ligands proceeds in an unprecedented manner. The resultant complexes display remarkably enhanced photooxidation capabilities using 1,5-dihydroxynaphthalene as a substrate.

The butyl and isopropyl derivatives (4I, 5Br) of chiral pool derived bis-imidazolium dehydrohexitol salts have been prepared. The ditopic N-heterocyclic carbenes 4 and 5 form dinuclear Ag(I) and Pt(II) complexes. All compounds were fully characterised by multinuclear NMR spectroscopy. The bis-imidazolium salt 4I and platinum complexes cis-[Pt(2)(μ-2)(dmso)(2)Cl(4)] and cis-[Pt(2)(μ-4)(dmso)(2)Cl(4)] were characterised by X-ray crystallography. In the case of the Pt(II) complexes, the carbene ring is positioned in a sterically preferred orientation, approximately perpendicular to the platinum coordination plane. The (1)H, (13)C, (15)N and (195)Pt NMR spectra of the platinum complexes show the presence of rotamers due to hindered rotation about the carbene-metal bond.

The X-ray crystal structures of salts and zwitterionic Knoevenagel products from 1-dimethylamino-naphthalene-8-carbaldehyde show long N-C bonds between peri-groups which provide models for incomplete nucleophilic attack on a protonated carbonyl group and electron-deficient alkenes respectively. For the salts the N-C bonds lie in the range 1.625-1.638 Å with C-OH bonds intermediate in length between single and double bonds, while for the zwitterions the N-C bonds lie in the range 1.612-1.660 Å. The structural assignment of the former is supported by solid state (13)C and (15)N NMR studies on doubly isotopically-labelled material. Several zwitterions were converted to naphtha[1,8-bc]azepines by a mechanism involving the tertiary amino effect.

Treatment of Me(2)S·B(C(6)F(5))(n) H(3-n) (n=1 or 2) with ammonia yields the corresponding adducts. H(3)N·B(C(6)F(5))H(2) dimerises in the solid state through N-H···H-B dihydrogen interactions. The adducts can be deprotonated to give lithium amidoboranes Li[NH(2)B(C(6)F(5))(n)H(3-n)]. Reaction of the n=2 reagent with [Cp(2)ZrCl(2)] leads to disubstitution, but [Cp(2)Zr{NH(2)B(C(6)F(5))(2)H}(2)] is in equilibrium with the product of β-hydride elimination [Cp(2)Zr(H){NH(2)B(C(6)F(5))(2)H}], which proves to be the major isolated solid. The analogous reaction with [Cp(2)HfCl(2)] gives a mixture of [Cp(2)Hf{NH(2)B(C(6)F(5))(2)H}(2)] and the N-H activation product [Cp(2)Hf{NHB(C(6)F(5 )(2)H}]. [Cp(2)Zr{NH(2)B(C(6)F(5))(2)H}(2)]·PhMe and [Cp(2)Hf{NH(2)B(C(6)F(5))(2)H}(2)]·4(thf) exhibit β-B-agostic chelate bonding of one of the two amidoborane ligands in the solid state. The agostic hydride is invariably coordinated to the outside of the metallocene wedge. Exceptionally, [Cp(2)Hf{NH(2)B(C(6)F(5))(2)H}(2)]⋅PhMe has a structure in which the two amidoborane ligands adopt an intermediate coordination mode, in which neither is definitively agostic. [Cp(2)Hf{NHB(C(6)F(5))(2)H}] has a formally dianionic imidoborane ligand chelating through an agostic interaction, but the bond-length distribution suggests a contribution from a zwitterionic amidoborane resonance structure. Treatment of the zwitterions [Cp(2)MMe(μ-Me)B(C(6)F(5))(3)] (M=Zr, Hf) with Li[NH(2)B(C(6)F(5))(n)H(3-n)] (n=2) results in [Cp(2) MMe{NH(2)B(C(6)F(5))(2)H}] complexes, for which the spectroscopic data, particularly (1)J(B,H), again suggest β-B-agostic interactions. The reactions proceed similarly for the structurally encumbered [Cp''(2)ZrMe(μ-Me)B(C(6)F(5))(3)] precursor (Cp''=1,3-C(5)H(3)(SiMe(3))(2) , n=1 or 2) to give [Cp''(2)ZrMe{NH(2)B(C(6)F(5))(n)H(3-n)}], both of which have been structurally characterised and show chelating, agostic amidoborane coordination. In contrast, the analogous hafnium chemistry leads to the recovery of [Cp''(2)HfMe(2)] and the formation of Li[HB(C(6)F(5))(3)] through hydride abstraction., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The 6-azabicyclo[3.2.1]octane ring system, prevalent in a range of biologically active molecules, is prepared through a novel semipinacol rearrangement utilizing a cyclic phosphorane or sulfite intermediate. The rearrangement proceeds with exclusive N-acyl group migration of a β-lactam ring and results in carbonyl functionality at the 7- and bridging 8-position of the bicycle. Precursor ring-fused β-lactam diols are prepared through a sequence of 4-exo trig carbamoyl radical cyclization, regioselective dithiocarbamate group elimination, and dihydroxylation.

Reaction of lanthanide nitrates with (t)Bu(3)PO (=L) lead to the isolation of complexes Ln(NO(3))(3)L(2)·H(2)O·nEtOH (Ln = La (1), Nd(2)), Ln(NO(3))(3)L(2) ·nEtOH (Sm(3), Eu(4)), and Ln(NO(3))(3)L(2) (Dy(5), Er(6), Lu(7)). These have been characterized by elemental analysis, infrared and NMR((1)H, (13)C and (31)P) spectroscopy and single-crystal X-ray diffraction. The structures show L to be positioned on opposite sides of the metal with the nitrates forming an equatorial band. When Ln = Dy, Er, and Lu two distinct molecules are present in the unit cell. A major isomer (70%) has a (P)O-Ln-O(P) angle of less than 180° with one of the nitrate ligands twisted out of the plane of the other nitrates while the lower abundance isomer is more symmetric with the (P)O-Ln-O(P) angle of 180° and the nitrate ligands coplanar giving a hexagonal bipyramidal geometry. These isomers cannot be observed by variable temperature solution (31)P NMR measurements but are clearly seen in the solid-state NMR spectrum of the Lu complex. Variable temperature solid-state NMR indicates that the isomers do not interconvert at temperatures up to 100 °C. Attempts to prepare cationic species [Ln(NO(3))(2)L(3)](+)[PF(6)](-) have not been totally successful and led to the isolation of crystals of Lu(NO(3))(3)L(2) and Tb(NO(3))(3)L(2).CH(3)CN (8).

A range of fluoride-encapsulated octasilsesquioxane cage compounds have been prepared using the TBAF route. Our studies suggest that whilst it is relatively straightforward to prepare fluoride-encapsulated octasilsesquioxane cage compounds with adjacent sp(2) carbons, leading to a range of aryl and vinyl substituted compounds, the corresponding sp(3) carbon derivatives are more capricious, requiring an electron withdrawing group that can stabilize the cage whilst not acting as a leaving group. Analysis by X-ray crystallography and solution (19)F/(29)Si NMR spectroscopy of R(8)T(8)@F(-) reveal very similar environments for the encapsulated fluoride octasilsesquioxane cages. Migration of a fluoride ion from inside the cage to outside the cage without breaking the T(8) framework and the possibility of encapsulating other anions within silsesquioxane cages have been also investigated.

The human branched-chain aminotransferase (hBCAT) isoenzymes are CXXC motif redox sensitive homodimers central to glutamate metabolism in the central nervous system. These proteins respond differently to oxidation by H(2)O(2), NO, and S-glutathionylation, suggesting that the redox potential is distinct between isoenzymes. Using various reduced to oxidized glutathione ratios (GSH:GSSG) to alter the redox environment, we demonstrate that hBCATc (cytosolic) has an overall redox potential that is 30 mV lower than hBCATm (mitochondrial). Furthermore, the CXXC motif of hBCATc was estimated to be 80 mV lower, suggesting that hBCATm is more oxidizing in nature. Western blot analysis revealed close correlations between hBCAT S-glutathionylation and the redox status of the assay environment, offering the hBCAT isoenzymes as novel biomarkers for cytosolic and mitochondrial oxidative stress.

In the title compound, C(19)H(15)Cl(2)N(3)O(2), the benzotriazole ring system is approximately planar [maximum deviation = 0.018 (2) Å] and its mean plane is oriented at dihedral angles of 30.70 (5) and 87.38 (4)°, respectively, to the furan and benzene rings while the dihedral angle between furan and benzene rings is 74.46 (6)°. In the crystal, weak C-H⋯N hydrogen bonds link the mol-ecules into chains along the b axis. π-π stacking inter-actions between the parallel dichloro-benzene rings of adjacent mol-ecules [centroid-centroid distance = 3.6847 (9) Å] and weak C-H⋯π inter-actions are also observed.

In the title compound, C(12)H(11)N(3)O(2), the benzotriazole ring system is approximately planar [maximum deviation = 0.008 (1) Å] and its mean plane is oriented at a dihedral angle of 24.05 (4)° with respect to the furan ring. In the crystal, O-H⋯N hydrogen bonds link the mol-ecules into chains along the ac diagonal. π-π stacking between the furan rings, between the triazole and benzene rings, and between the benzene rings [centroid-centroid distances = 3.724 (1), 3.786 (1) and 3.8623 (9) Å] are also observed.

The nonmetal cation polyborate salt of stoichiometry [H(2)en](2)[B(11)O(18)(OH)]·7H(2)O is obtained from the reaction of 1,2-diaminoethane and boric acid (1:5 ratio) in H(2)O/MeOH. An X-ray crystallographic study of the product reveals that the polyborate moiety is composed of two isolated hydrated polyborate anions: [B(4)O(5)(OH)(4)](2-) and [B(7)O(9)(OH)(5)](2-). The structure is templated by the cations with the anions forming a supramolecular H-bonded network, augmented by additional H-bonds involving the waters of crystallization and the cations.

In the title mol-ecule, C(21)H(17)Cl(2)N(3)O, the benzotriazole ring is oriented at dihedral angles of 48.72 (6) and 62.94 (5)°, respectively, to the phenyl and benzene rings and the dihedral angle between the phenyl and benzene rings is 88.95 (6)°. In the crystal, weak C-H⋯N hydrogen bonds link the mol-ecules into chains. π-π contacts between the triazole and benzene rings [centroid-centroid distance = 3.678 (1) Å] and a weak C-H⋯π inter-action are also observed.

In the title compound, C(8)H(9)N(4)S(-)·C(2)H(3)O(2) (-), the cation is essentially planar (r.m.s deviation = 0.037 Å) with the guanidine unit bent out of the plane of the fused-ring system by 4.6 (3)°. In the asymmetric unit, the cations and anions are linked into R(2) (2)(8) motifs. In the crystal, further N-H⋯O and N-H⋯N hydrogen bonds link the components into a two-dimensional network.

The structure of 2-(2-pyridylimino)-2H-1,2,4-thiadiazolo[2,3-a]pyridine (NSN) indicates that the molecule has a planar geometry with a linear N···S···N linkage, creating a tetracyclic structure of the formal C(2v) symmetry. To clarify the nature of the NSN σ(3c-4e) bonding, together with the related NSeN and NTeN, the dynamic and static behaviors are investigated by applying atoms-in-molecules (AIM) dual functional analysis to both the fully optimized and perturbed structures. The structures were optimized computationally, retaining C(2v) symmetry. All bond critical points are detected as expected and exhibited on both sides of the N···Z···N moiety which supports the formation of NZN σ(3c-4e). It is confirmed that N···S···N is of the covalent nature close to Me(2)S(+)-∗-Cl or Me(2)Se(+)-∗-Br, whereas N···Se···N and N···Te···N have the (regular) CS nature close to the CT adducts of Me(2)S(-∗-Cl)(2) (TBP) and Me(2)Se-∗-Br(2) (MC), respectively. An experimental high-resolution charge density determination has been performed on NSN, which thoroughly supports the theoretical results. Very similar results are obtained in the analogous pyrimidyl derivatives for N···S···N, N···Se···N, and N···Te···N. AIM dual functional analysis, as validated by experimental high-resolution charge densities, is thus confirmed to be an excellent method to elucidate the nature of these interactions.

Nine-membered 1,4,7-triphospha- and triarsamacrocycles with unsaturated benzo-backbones have been prepared using the [Cp(R)Fe](+) unit as a template. The cyclisation involves the attack of a coordinated phosphide (or arsenide) nucleophile at an activated, electrophilic ortho-fluorophenyl substituent on a neighbouring pnictide donor. The macrocycle assembly is of the 2 + 1 type where two new chelate rings are formed from appropriately derivatised bidentate and monodentate phosphines/arsines. Both [(η(5)-C(5)H(5))Fe](+) and [(η(5)-C(5)Me(5))Fe](+) may be employed for the cyclisation with higher yields generally being observed with the unsubstituted Cp. All new compounds have been characterised by spectroscopic and analytical methods including the single-crystal X-ray structure determination of [(η(5)-C(5)H(5))Fe(tribenzo-9aneP(3)-Ph,Ph(F)(2))](+), 3a, and [(η(5)-C(5)H(5))Fe(tribenzo-9aneAs(3)-Ph,Ph(F)(2))](+), 5, as the tetraphenylborate salts. The crystal structures are isomorphous and show the unique conformation of these new macrocycles with a 'cup shaped' cavity formed by the rigid benzo-backbones. The 9aneAs(3) derivative is the first example of a nine-membered triarsamacrocycle.

The asymmetric unit of the title compound, C(21)H(17)Cl(2)N(3)O, contains two crystallographically independent mol-ecules with similar conformations. The benzotriazole ring is oriented at dihedral angles of 30.61 (5) and 43.36 (5)°, respectively, to the phenyl and dichloro-phenyl rings in one mol-ecule, and 32.25 (5) and 41.04 (5)° in the other. The dihedral angles between the phenyl and dichloro-phenyl rings are 66.38 (7) and 66.14 (6)° in the two mol-ecules. An intra-molecular O-H⋯N hydrogen bond links the benzotriazole ring and phenyl-propanol unit in each mol-ecule. In the crystal, weak inter-molecular C-H⋯N hydrogen bonds link the mol-ecules into chains along the a axis. π-π stacking between the dichloro-phenyl rings [centroid-centroid distances = 3.809 (1) and 3.735 (1) Å] may further stabilize the crystal structure.

4,5-Dihydroimidazolium ylides formed by conjugate addition-proton transfer from dihydroimidazoles and doubly-activated electron-deficient alkenes afford 2:1 cycloadducts in a one-pot process wherein the alkene also acts as a dipolarophile.

Indolin-2-one (oxindole), (I), undergoes a Knoevenagel condensation with ferrocene-1,1'-dicarbaldehyde, (II), to afford the title complex 3,3'-[(E,E)-ferrocene-1,1'-diyldimethylidyne]diindolin-2-one dichloromethane disolvate, [Fe(C(28)H(20)N(2)O(2))]·2CH(2)Cl(2), (IV). The structure of (IV) contains two ferrocene complex molecules in the asymmetric unit and displays, as expected, intermolecular hydrogen bonding (N-H···O=C) between the indolin-2-one units. Intermolecular π-π stacking interactions are also observed., (© 2011 International Union of Crystallography)

In the title compound, C(14)H(12)N(2)O(2), the asymmetric unit comprises one half-mol-ecule with an inversion center between the pyridine rings. The rings are trans coplanar with the acetyl groups deviating slightly from the mean planes, making a dihedral angle of 4.63 (4)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds, forming a supra-molecular sheet parallel to (100).

(E)- and (Z)-3-Ferrocenylmethylidene-1,3-dihydro-2H-indol-2-ones 1 have been structurally modified in order to explore SAR against a range of kinases. Of note is the submicromolar to low micromolar inhibition of DYRK3 and 4 by a number of complexes. Screening using Xenopus embryos showed some of the compounds to have potent antiangiogenisis activity.

Cyclotriphosphazene derivatives containing a P-NHR group in the side-chain react in the presence of a strong base to form stable intermolecular bridged products. Reaction of sodium hydride with mono-spiro cyclophosphazene derivatives having a P-NH group, N(3)P(3)Cl(4)[O(CH(2))(3)NH], (1a) or N(3)P(3)Cl(4)[CH(3)N(CH(2))(3)NH], (1b) leads to formation of bis-cyclophosphazenes bridged with an eight-membered cyclophosphazene ring in an ansa arrangement (2a, 2b) whereas reaction of sodium hydride with mono-amino cyclophosphazene derivatives [N(3)P(3)Cl(5)(NHR), R = n-hexyl, 3a; i-Pr, 3b; Ph, 3c] give bis-cyclophosphazenes bridged with a four-membered cyclophosphazane ring in a spiro arrangement (4a-c). In the latter reaction P-O-P bridged compounds (5a-c) were also obtained as a result of hydrolysis reactions associated with the amount of moisture in the solvent tetrahydrofuran. In addition, it was found that reaction of a mixture of cyclotriphosphazene with either mono spiro compound, (1a) or (1b), in the presence of sodium hydride lead to formation of the first examples of asymmetrically-bridged cyclophosphazenes (6a-b).

Nucleophilic substitution reactions of N(3)P(3)Cl(4)[NH(CH(2))(3)NMe] (1) and N(3)P(3)Cl(4)[NH(CH(2))(3)O] (2) with mono-functional alcohols (methanol, 2,2,2-trifluoroethanol, phenol) and a secondary amine (pyrrolidine) were used to investigate the relationship between the incoming nucleophile and the proportions of products with substituents that are cis or trans to the spiro NH moiety. The reaction products were characterized by elemental analysis, mass spectrometry, (1)H and (31)P NMR spectroscopy and the configurational isomers by X-ray crystallography. Six products have been characterised with the substituent cis to the spiro NH group for the alcohol (methanol, phenol) and pyrrolidine derivatives of both compounds 1 and 2, compared to just one derivative with the substituent trans to the spiro NH group, that for the pyrrolidine derivative of compound 2. For each reaction the relative proportions of cis and trans isomers were determined by (31)P NMR measurements of the reaction mixtures. It was found that the reactions of compound 1 with all three alcohols and of compound 2 with methanol lead to exclusive formation of isomers with the substituent cis to the NH moiety, whereas all other reactions lead to mixtures of cis and trans isomers in different ratios under standard reaction conditions. However, when crown ether is included in the reaction medium for the reactions of compound 2 with both 2,2,2-trifluoroethanol and phenol, it is found that only cis isomers are formed. All these results are rationalised in terms of the competition between at least two effects; the cis-directing effect by hydrogen bonding of the incoming nucleophile to the spiro N-H group already present on the cyclophophazene ring and the cis-directing effect of the sodium cation coordinating to the oxygen lone pairs of the P-O moiety of the spiro ring.

N(1)-Hydroxy-N(8)-ferrocenyloctanediamide, JAHA (7), an organometallic analogue of SAHA containing a ferrocenyl group as a phenyl bioisostere, displays nanomolar inhibition of class I HDACs, excellent selectivity over class IIa HDACs, and anticancer action in intact cells (IC(50) = 2.4 μM, MCF7 cell line). Molecular docking studies of 7 in HDAC8 (a,b) suggested that the ferrocenyl moiety in 7 can overlap with the aryl cap of SAHA and should display similar HDAC inhibition, which was borne out in an in vitro assay (IC(50) values against HDAC8 (μM, SD in parentheses): SAHA, 1.41 (0.15); 7, 1.36 (0.16). Thereafter, a small library of related JAHA analogues has been synthesized, and preliminary SAR studies are presented. IC(50) values as low as 90 pM toward HDAC6 (class IIb) have been determined, highlighting the excellent potential of JAHAs as bioinorganic probes.

Upregulation of the immunosuppressive cell surface glycoprotein, CD200, is a common feature of acute myeloid leukemia (AML) and is associated with poor patient outcome. We investigated whether CD200 overexpression on AML cells could specifically compromise patient natural killer (NK) cell anti-tumor responses. We found that CD200(hi) patients showed a 50% reduction in the frequency of activated NK cells (CD56(dim)CD16(+)) compared with CD200(lo) patients. Additionally, NK receptor expression (NKp44 and NKp46) on these cells was also significantly downregulated in CD200(hi) patients. To assess whether NK cell activity was directly influenced by CD200 expression, we examined the effect of ectopic expression of CD200. These assays revealed that both NK cell cytolytic activity and interferon-γ response were significantly reduced toward CD200(+) leukemic targets and that these targets showed increased survival compared with CD200(-) cells. Similarly, NK cells isolated from AML patients were less functionally active toward CD200(hi) autologous blasts from both cytolytic and immunoregulatory perspectives. Finally, blocking CD200 alone was sufficient to recover a significant proportion of NK cell cytolytic activity. Together, these findings provide the first evidence that CD200 has a direct and significant suppressive influence on NK cell activity in AML patients and may contribute to the increased relapse rate in CD200(+) patients.

A library of 1,4-benzodiazepines has been synthesized and evaluated against Trypanosoma brucei, a causative parasite of Human African trypanosomiasis. Benzodiazepines possessing a P2- transporter motif were found to have MIC values as low as 0.78 μM., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Topoisomerase II is essential for the maintenance of DNA integrity and the survival of proliferating cells. Topoisomerase II poisons, including etoposide and doxorubicin, inhibit enzyme-mediated DNA ligation causing the accumulation of double-stranded breaks and have been front-line drugs for the treatment of leukemia for many years. Voreloxin is a first-in-class anti-cancer quinolone derivative that intercalates DNA and inhibits topoisomerase II. The efficacy and mechanisms of action of voreloxin in acute myeloid leukaemia were addressed in this study., Design and Methods: Primary acute myeloid leukemia blasts (n = 88) and myeloid cell lines were used in vitro to study voreloxin through viability assays to assess cell killing and synergy with other drugs. Apoptosis and cell cycling were assessed by flow cytometry. DNA relaxation assays were utilized to determine that voreloxin was active on topoisomerase II., Results: The mean lethal dose 50% (LD(50)) (± standard deviation) of voreloxin for primary acute myeloid leukemia blasts was 2.30 μM (± 1.87). Synergy experiments between voreloxin and cytarabine identified synergism in 22 of 25 primary acute myeloid leukemia samples tested, with a mean combination index of 0.79. Apoptosis was shown to increase in a dose-dependent manner. Furthermore, voreloxin was active in the p53-null K562 cell line suggesting that the action of voreloxin is not affected by p53 status. The action of voreloxin on topoisomerase II was confirmed using a DNA relaxation assay., Conclusions: Voreloxin may provide an interesting addition to the cache of drugs available for the treatment of acute myeloid leukemia, a disease with a poor long-term survival. In addition to its potent action as a single agent in dividing cells, the synergy we demonstrated between voreloxin and cytarabine recommends further investigation of this topoisomerase II inhibitor.

A series of arylboronates has been synthesized from the reaction of 2-(2-, (3-, or (4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1{1-3} respectively with a range of N-, S-, and O-nucleophiles, using microwave-mediated chemistry. For the synthesis of N- and S-substituted boronates, a supported base, PS-NMM, was employed, and many reactions were complete within 15 min. With O-nucleophiles, a mixture of tetrabutylammonium bromide, potassium carbonate, and sodium hydroxide was employed. The resulting aminomethyl, mercaptomethyl, or alkoxy-/phenoxymethyl-arylboronates were subjected to microwave-mediated Suzuki Miyaura coupling reactions to afford a range of biaryls in moderate to good yields. The X-ray structures of five boronates were determined.

The extent to which deuterium can act as a protecting group to prevent unwanted 1,5-hydrogen atom transfer to aryl and vinyl radical intermediates was examined in the context of the generation of α-aminoalkyl radicals in a pyrrolidine ring. Intra- and intermolecular radical trapping following hydrogen atom transfer provides an illustration of the use of the primary kinetic isotope effect in directing the outcome of synthetic C-C bond-forming processes.

We present a series of compounds by exploiting the unusual 1,4-aryl shift observed for electron-rich 1,3-dithiole-2-thione and tetrathiafulvalene (TTF) derivatives in the presence of perchloric acid. The mechanistic features of this rearrangement are discussed since this synthetic strategy provides an alternative route for the synthesis and functionalisation of sulfur rich compounds including redox active compounds of TTFs, and a Ni dithiolene.

The first molecular material with the coexistence of ferromagnetism, metal-like conductivity, and chirality has been prepared using an organic/inorganic approach. In this case, a two-dimensional packing of chiral organic radical cations (responsible for both the electrical conductivity and optical activity) was assembled with a layered bimetallic oxalate-based anionic network (responsible for the magnetic properties). Shubnikov-de Haas oscillations confirmed the presence of a Fermi surface even when the transport properties suggested "insulating"-type behavior at very low temperatures.

The asymmetric unit of the title compound, C(21)H(18)ClN(3)O, contains two crystallographically independent mol-ecules which differ slightly in the orientations of chloro-benz-yloxy units. In one of the mol-ecules, the phenyl and chloro-phenyl rings are oriented at dihedral angles of 38.09 (6) and 42.15 (6)°, respectively, with respect to the benzotriazole ring [43.23 (6) and 29.80 (6)° in the other mol-ecule]. The dihedral angle between the phenyl and chloro-phenyl rings is 77.63 (6)° in one of the mol-ecules and 72.97 (6)° in the other. The crystal structure is stabilized by weak C-H⋯π inter-actions.