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This work is aimed at providing a systematic and comprehensive analysis of the anomeric effect exerted by the isothiocyanato (NCS) group taking the xylopyranose ring as a scaffold because enhanced effects have been detected in that ring-bearing halogen and pseudohalogen substituents. To this end, both α- and β-anomers of tri-O-acetoxypyranosyl-D-xylose have been prepared and thoroughly characterized. The axial preference of the isothiocyanato group reflects a dominant anomeric effect, whose origin could be determined through DFT calculations with identification of the stereoelectronic interactions as revealed by Natural Bond Orbital (NBO) analysis. In this way, this study expands the repertoire of groups biasing the conformation and reactivity of monosaccharides and related heterocycles.

The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol-Tishchenko reaction of N-tert-butyl sulfinimines. One diastereoisomer (from 32 possibilities) predominates, and a series of cyclic and acyclic 3-amino-1,5-diol derivatives are synthesized in good yields (up to 80%) and excellent diastereoselectivities (up to >98:2 dr). Investigations support two reversible aldol steps, and multiple intermediates which are funnelled through a remarkably selective, irreversible, Tishchenko reduction, in a Curtin-Hammett phenomenon. DFT calculations using a disolvated (THF) model reveal the factors controlling stereoselectivity in the final irreversible Tishchenko step.

Protein-carbohydrate interactions are implicated in many biochemical/biological processes that are fundamental to life and to human health. Fluorinated carbohydrate analogues play an important role in the study of these interactions and find application as probes in chemical biology and as drugs/diagnostics in medicine. The availability and/or efficient synthesis of a wide variety of fluorinated carbohydrates is thus of great interest. Here, we report a detailed study on the synthesis of monosaccharides in which the hydroxy groups at their 4- and 6-positions are replaced by all possible mono- and difluorinated motifs. Minimization of protecting group use was a key aim. It was found that introducing electronegative substituents, either as protecting groups or as deoxygenation intermediates, was generally beneficial for increasing deoxyfluorination yields. A detailed structural study of this set of analogues demonstrated that dideoxygenation/fluorination at the 4,6-positions caused very little distortion both in the solid state and in aqueous solution. Unexpected trends in α/β anomeric ratios were identified. Increasing fluorine content always increased the α/β ratio, with very little difference between regio- or stereoisomers, except when 4,6-difluorinated.

An asymmetric synthesis of α-spiro-δ-lactam via organocascade reaction from easily accessible starting materials is reported. The catalytic sequence undergoes enantioselective Michael addition of β-ketoamide to α,β-unsaturated aldehyde catalysed by a secondary amine catalyst, followed by hemiaminal annulation. Optically enantiopure compounds with two contiguous stereogenic centres are obtained in good yields and excellent selectivities (up to >20:1 dr and up to >99% ee).

We report a combined experimental and computational study on the cycloadditions of bicyclic 1,3-thiazolium-4-olates, derived from thiazolidin-2-thiones, with asymmetrically-substituted acetylenes. These results provide further mechanistic insights into the above dipolar cycloadditions and enable an unequivocal characterization by NMR spectroscopy of regiochemical patterns as previous derivatives had substituents at both C-2 (in the dipole) and C-6 (in products). Accordingly, new dihydrothiazolopyrid-2-ones have been obtained from a thioisomunchnone lacking substitution at C-2. With the aim of assessing the steric hindrance as well as the facial stereoselection induced by a bulky group on the Si face (relative to C-7a) of the mesoionic heterocycle, a chiral thioisomunchnone has also been obtained along with the resulting optically active thiazolopyridones. A computational study of these particular cycloadditions, largely based on an NBO analysis, allowed us to evaluate the influence of substituents on intermolecular steric repulsions, charge transfers, as well as solvent effects.

International audience; Fluorinated proline derivatives have found diverse applications in areas ranging from medicinal chemistry over structural biochemistry to organocatalysis. Depending on the stereochemistry of monofluorination at the proline 3- or 4-position, different effects on the conformational properties of proline (ring pucker, cis/ trans isomerization) are introduced. With fluorination at both 3- and 4-positions, matching or mismatching effects can occur depending on the relative stereochemistry. Here we report, in full, the syntheses and conformational properties of three out of the four possible 3,4-difluoro-l-proline diastereoisomers. The yet unreported conformational properties are described for (3 S,4 S)- and (3 R,4 R)-difluoro-l-proline, which are shown to bias ring pucker and cis/ trans ratios on the same order of magnitude as their respective monofluorinated progenitors, although with significantly faster amide cis/ trans isomerization rates. The reported analogues thus expand the scope of available fluorinated proline analogues as tools to tailor proline's distinct conformational and dynamical properties, allowing for the interrogation of its role in, for instance, protein stability or folding.

The palladium(II) chlorostibine complex [PdCl2(SbMe2Cl)2]2 has a dimeric structure in the solid state, stabilized by hyper-coordination at the Lewis amphoteric Sb centers. Reaction with 8 equiv of MeLi forms [Pd4(μ3-SbMe3)4(SbMe3)4], whose structure comprises a tetrahedral Pd(0) core with four terminal SbMe3 ligands and four μ3-SbMe3 ligands, one capping each triangular Pd3 face. Density functional theory calculations, supported by energy decomposition analysis and the natural orbitals for chemical valence scheme, highlight significant donor and acceptor orbital contributions to the bonding between both the terminal and the bridging SbMe3 ligands and the Pd4 core.

The regioselective protection of both methyl galactopyranoside anomers at the 2 and 3-positions as the butane diacetal (BDA) is well known. Here we describe the formation of an unexpected byproduct, which mainly occurs when α-methyl galactopyranoside is reacted with 2,3-butanedione under BF3•OEt2 catalysis. The structure of the byproduct, which did not arise from anomerisation to the β-anomer or from BDA formation at the galactopyranoside 3,4-positions, was elucidated by NMR and X-ray crystallographic analysis, and proved to be the expected BDA protected galactopyranoside, but in which the stereochemistry of both its BDA acetal centres are inverted. Interestingly, the conformation of the resulting six-membered BDA ring was distorted to a skew boat conformation in order to maintain anomeric stabilisation.

We describe the oxidation of flavanones by employing phenyliodonium diacetate to form the flavone (15), isoflavone (8) and 2,3-dihydrobenzofurane (18) in this study. The oxidative method was found to be regioselective and dependent on the substitution pattern present on the two aromatic rings of the starting flavanone. The structures of products obtained were fully characterized by using IR, 1 H and 13 C NMR spectroscopy and Mass spectrometry. X-ray crystallography further confirms the structures of flavones and isoflavone. The density field theory calculations have also been performed to get more insight about the structures, electronic and spectroscopic properties of synthetic flavonoid derivatives. The geometrical parameters such as bond lengths and angels showed a good correlation with the values obtained through X-ray crystallography. Moreover, the theoretically simulated vibrational and UV-vis spectral values are in agreement with the experimental results.

Lead(II) tetrafluoroborate and hexafluorosilicate complexes with 2,2′-bipyridyl, 1,10-phenathroline and 2,2′:6′,2″-terpyridyl have been prepared from the ligand and lead salt in aqueous/MeCN. Crystal structures are reported for [Pb(bipy)2(SiF6)], [Pb(phen)2(SiF6)] and [Pb(bipy)2(BF4)2] which are dinuclear with each lead coordinated “cis” to the two diimines and with the bridging fluoroanions completing eight or nine-coordination. [Pb(phen)2(BF4)2] is eight-coordinate and mononuclear with “cis” diimines and two κ2-BF4− groups. [Pb(phen)2(H2O)2(SiF6)] is also mononuclear with a κ2-SiF62− group and two coordinated water molecules. Reaction of Pb(BF4)2 with 2,2′:6′,2″-terpyridyl gave only [Pb(terpy)3][BF4]2, but Pb(SiF6) produced [Pb(terpy)(H2O)(SiF6)], which is a chain polymer with bridging SiF62− groups and significant π-stacking of the imine rings. The work has identified a number of coordination modes of the SiF62− anion, which has been little used in coordination chemistry but proves to be versatile and also stable (to decomposition/hydrolysis).

[GeCl2(dioxane)] reacts with the neutral aza-macrocyclic ligands L, L = Me3tacn (1,4,7-trimethyl-1,4,7-triazacyclononane), Me4cyclen (1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) or Me4cyclam (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and two mol. equiv. of Me3SiO3SCF3 in thf solution to yield the unusual and hydrolytically very sensitive [Ge(L)][O3SCF3]2 as white solids in moderate yield. Using shorter reaction times [Ge(Me3tacn)]Cl2 and [Ge(Me3tacn)]Cl[O3SCF3] were also isolated; the preparation of [Ge(Me4cyclen)][GeCl3]2 is also described. The structures of the Me3tacn complexes show κ(3)-coordination of the macrocycle, with the anions interacting only weakly to produce very distorted five- or six-coordination at germanium. In contrast, the structure of [Ge(Me4cyclen)][O3SCF3]2 shows no anion interactions, and a distorted square planar geometry at germanium from coordination to the tetra-aza macrocycle. Crystal structures of the Si(iv) complexes, [SiCl3(Me3tacn)]Y (Y = O3SCF3, BAr(F); [B{3,5-(CF3)2C6H3}4]) and [SiHCl2(Me3tacn)][BAr(F)], obtained from reaction of SiCl4 or SiHCl3 with Me3tacn, followed by addition of either Me3SiO3SCF3 or Na[BAr(F)], contain distorted octahedral cations, with facialκ(3)-coordinated Me3tacn. The open-chain triamine, Me2NCH2CH2N(Me)CH2CH2NMe2 (pmdta), forms [SiCl3(pmdta)][BAr(F)] and [SiBr3(pmdta)][BAr(F)] under similar conditions, containing mer-octahedral cations.

A novel pyridyl urea based macrocycle has been synthesised and fully characterised including a single crystal X-ray structure determination. The synthetic approach first involves the reaction of benzyloxycarbonylaminopropyl-3-isocyanate with t-butyl 2-[(2-aminopyridin-3-yl)oxy]acetate resulting in a coupling product. After deprotection of the amine and acid moieties and coupling subsequent coupling in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), a macrocycle is formed. The structures of the compounds were confirmed by mass spectrometry and NMR spectroscopy. The X-ray crystal structure of the macrocycle reveals as expected a non-binding conformation with an intramolecular hydrogen bond between the urea NH and the pyridyl nitrogen.

The syntheses of new o-carboranyldiols bearing aromatic rings bis-[R(hydroxy)methyl]-1,2-dicarba-closo-dodecaborane (R = 2-pyridyl 1a, 3-pyridyl 1b, 4-pyridyl 1c, 2-quinolyl 1d, 4-quinolyl 1e, henyl 1f) are reported. The compounds are obtained as mixtures of meso (syn) and racemic (anti) stereoisomers with a slight diastereomeric excess (syn:anti ratio of 0.7:1) in all cases but in 1b. The cristal structures of the meso compounds syn-1a.2MeOH, syn-1b, syn-1f.0.25H2 O and racemic anti-1a.MeOH, anti-1a.EtOH, and anti-1d.2H2 O are reported. We provide an analysis of these compounds by means of NMR and X-ray crystallography, in the context of crystal engineering and chiral recognition. The results show that the cristal packings for these alcohols are dominated by the supramolecular O-H...N and/or O-H...O hydrogen bonds. Supramolecular analysis of all compounds in this work reveals that homochiral self-assembly, that is, formation of homochiral hydrogen bonded complexes, prevails over heterochiral self-assembly (formation of heterochiral hydrogen bonded complexes). Fil: Di Salvo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: Paterakis, Christos . Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: Ying Tsang, Min . Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: García, Yolanda. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: Viñas, Clara . Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: Teixidor, Francesc . Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: Giner Planas, José . Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Los Materiales de Barcelona; España Fil: Light, Mark E. . University Of Southampton; Reino Unido Fil: Hursthouse, Michael B. . University Of Southampton; Reino Unido Fil: Choquesillo Lazarte, Duane . Consejo Superior de Investigaciones Cientificas; España

The synthesis and characterization of iron and manganese complexes containing the tetrachlorocatecholboryl (BO2C6Cl4) ligand are reported. Crystallographic study of the methylcyclopentadienyl derivative (eta(5)-C5H4Me)Fe(CO)(2)BO2C6Cl4 allows comparison of structure and bonding with related complexes of the type (eta(5)-C5R5)Fe(CO)(2)B(OR)(2) and reveals that the relative orientation of (eta(5)-C5H4Me)Fe(CO)(2) and BO2C6Cl4 moieties is influenced by intramolecular C---H...O hydrogen bonding. Additionally, an alternative route to catecholboryl complexes from dilithiocatechol is reported.

2'-O-(2-Methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine phosphoramidite (MEPU) has been synthesized from d-ribose and 5-iodouracil and incorporated into triplex-forming oligonucleotides (TFOs) by automated solid-phase oligonucleotide synthesis. The TFOs gave very high triplex stability with their target duplexes as measured by ultraviolet/fluorescence melting and DNase I footprinting. The incorporation of MEPU into TFOs renders them resistant to degradation by serum nucleases.

Gated ion transport across biological membranes is an intrinsic process regulated by protein channels. Synthetic anion carriers (anionophores) have potential applications in biological research; however, previously reported examples are mostly nonspecific, capable of mediating both electrogenic and electroneutral (nonelectrogenic) transport processes. Here we show the transmembrane Cl(-) transport studies of synthetic phenylthiosemicarbazones mimicking the function of acid-sensing (proton-gated) ion channels. These anionophores have remarkable pH-switchable transport properties with up to 640-fold increase in transport efficacy on going from pH 7.2 to 4.0. This "gated" process is triggered by protonation of the imino nitrogen and concomitant conformational change of the anion-binding thiourea moiety from anti to syn. By using a combination of two cationophore-coupled transport assays, with either monensin or valinomycin, we have elucidated the fundamental transport mechanism of phenylthiosemicarbazones which is shown to be nonelectrogenic, inseparable H(+)/Cl(-) cotransport. This study demonstrates the first examples of pH-switchable nonelectrogenic anion transporters.

The anion transport and binding properties of a series of bis-amide based compounds have been studied in POPC lipid bilayers. The compounds display evidence of aggregation in solution with single crystal X-ray crystallographic analysis showing hydrogen bonding between the amide substituents of adjacent receptors in the solid state.

Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

Square peg in a round ball: squaramides are shown to be potent transmembrane anion transporters for both chloride and bicarbonate, performing better than the thiourea and urea analogues. Studies into the nature of this transport point to a mobile carrier mechanism, where the squaramide delivers the anion cargo across the lipid bilayer (see scheme, green sphere=anion). These drug-like molecules provide a platform for the development of a new generation of anion-transport systems.

Aminobenzothiazole-functionalised phosphane 1 and its corresponding phosphorus(V) analogues 2-4 were synthesised in high yields. New 1D polymeric salts K[ClC6H3NC(S)NP(E)Ph-2](infinity) (E = O 5; E = S 6) were shown, by using single-crystal X-ray diffraction, to exhibit unique potassium metal ion coordination through either kappa(3)-N2O tridentate (E = O) or kappa(2)-N-2 bridging (E = S) modes. In contrast,kappa(2)-NE chelation (E = S, Se) was observed upon complexation to a range of metal fragments including {Ir(eta(5)-Cp*)Cl} (E = S 8; E = Se 9), {Rh(eta Cp-5*)Cl} (E = S 10; E = Se 11), {Ru(eta(6)-p-MeC(6)H(4)iPr)Cl} (E = S 12), {Ru(eta(6)-C6Me6)Cl} (E = S 13) and {Pt(PMe2Ph)Cl} (E = S 14). All new compounds were characterised by a combination of multinuclear NMR, FTIR and microanalysis. Seven compounds were structurally characterised by using single-crystal X-ray crystallography.

Synthetic prodiginine obatoclax shows promise as a potential anticancer drug. This compound promotes apoptosis of cancer cells, although the mechanism of action is unclear. To date, only the inhibition of BCL-2 proteins has been proposed as a mechanism of action. To gain insight into other possible modes of action, we have studied the anion-binding properties of obatoclax and related analogues in solution, in the solid state, and by means of density functional theory calculations. These compounds are well suited to interact with anions such as chloride and bicarbonate. The anion-transport properties of the compounds synthesized were assayed in model phospholipid liposomes by using a chloride-selective-electrode technique and (13)C NMR spectroscopy. The results demonstrated that these compounds are efficient anion exchangers that promote chloride, bicarbonate, and nitrate transport through lipid bilayers at very low concentrations. In vitro studies on small-cell lung carcinoma cell line GLC4 showed that active ionophores are able to discharge pH gradients in living cells and the cytotoxicity of these compounds correlates well with ionophoric activity.

International audience; The first single-crystal X-ray diffraction study of tetrafluorinated monosaccharide derivatives is presented. Both α- and β-methyl 2,3-dideoxy-2,2,3,3-tetrafluoro-d-galactopyranoside anomers adopt the (4)C(1) conformation. The values for the C1-O1 and C1-O5 bond lengths and the O5-C1-O1-CH(3) dihedral angles are in line with what can be expected from the anomeric and exo-anomeric effects. The chair conformations are slightly distorted, presumably due to repulsion between 1,3-diaxial C-O and C-F bonds. The asymmetric unit of both compounds contains up to three independent molecules, which differ in the conformation of the hydroxymethyl group (including in one case a 'forbidden'gg rotamer). The molecular packing of the β-anomer shows a clear segregation between fluorinated and hydrophilic domains, while for the α-anomer the regions of fluorine segregation are broken by interleafing of OMe groups. There is one close OH⋯F contact, which is likely to arise from the crystal packing. NMR studies show that the two anomers also adopt a (4)C(1) conformation in solution (D(2)O, CDCl(3)).

Schiff bases derived from 2-hydroxy-1-naphthaldehyde, or 1-hydroxy-2-naphthaldehyde, and different saturated N-aminoheterocycles have been prepared. Their structures have been elucidated in both solution and the solid state, including unequivocal X-ray diffraction analyses. Experimental data evidence the presence of imine (or hydrazone) structures as the most stable tautomers, while all attempts to switch to enamine (or enhydrazine) structures based on electronic and steric considerations were unsuccessful. A complete conformational analysis assisted by DFT calculations at B3LYP/6-31G? and M06-2X/6-311++G?? levels has been performed on each series of representative structures.

The reaction of [Ni(pftp)] [pftp = N,N-propane-1,3-diyl-(6-formyl-4-methyliminatothiophenolato)] with hydroxylamine hydrochloride in the presence potassium acetate in MeOH resulted in the formation of the complex [Ni(LH2)] [L = N,N-propane-1,3-diyl-(4-methyl-2-methyliminato-6-methyloxime-thiophenolato)] in good yield. A single crystal X-ray diffraction structural determination showed a mononuclear nickel(II) complex with the new acyclic ligand LH2 that had been functionalised with two oxime groups containing an empty N(oxime)2S2 pocket to which another metal ion could be added. A further reaction of [Ni(LH2)] with NiCl2·6H2O, triethylamine and ammonium hexafluorophosphate in MeOH gave a dark red product that yielded red crystals of [Ni2(LH)]PF6·DMF via slow recrystallisation from a DMF/PriOH solvent mixture. A single crystal X-ray diffraction study of these crystals confirmed the presence of a dinuclear nickel(II) complex linked by a dithiolato-bridge. Both nickel(II) ions exhibited square-planar geometry where the metal centres are coordinated in two distinct cis-S2N(imine)2 and cis-S2N(oxime)2 binding sites provided by the new dicompartmental oxime/thiolate-containing ligand LH

The halostibine complexes [CpFe(CO)2(SbMe2Br)][CF3SO3] and [CpFe(CO)2(SbMe2Br)][BF4] both contain significant interactions between the anion and the formally neutral Sb(III) ligand, which simultaneously displays Lewis acidic and Lewis basic properties. The unexpected secondary product [CpFe(CO)(Me2BrSb-?-Br-SbBrMe2)] is formed in the presence of excess ligand, the strongly associated Br– anion bridging the two Sb donors to form a four-membered FeSb2Br ring.

This paper describes the synthesis and structural elucidation of 1,3-oxazolidines derived from tris(hydroxymethyl)aminomethane (TRIS) and pyridine-based aldehydes. Divergent results were obtained with other formylpyridines, such aspyridoxal, in which intramolecular hydrogen-bonding largely stabilizes the iminic structure. The oxazolidines may undergo ring-opening under acetylating conditions to afford imines through different mechanistic pathways, which have also been evaluated by DFT calculations

A series of oxazolidines derived from tris(hydroxymethyl)aminomethane (TRIS; 1), have been prepared efficiently. Geometries optimized at the B3LYP/6-31G* level of theory, along with the crystal data of compounds 9 and 12 and NOESY correlations, point to a strong endo anomeric effect that anchors a preferential conformation and subsequently dictates the completely regioselective ring-opening of the oxazolidine moiety under acetylating conditions to afford imines instead of N-acetyloxazolidines. This process was monitored by 1H NMR spectroscopy, corroborated by synthesis, and rationalized by the intermediacy of an iminium ion. Oxazolidine–imine equilibria are also described for TRIS and other aminopolyols. The equilibria are shifted to the heterocyclic partner as the number of reactive hydroxy groups increases. The structures of an unprotected imine (31) and a per-O-acetylated derivative (43) have also been established by crystallographic analyses.

The structures of N-benzyl-N'-{6-[(4-carboxylatobenzyl)aminocarbonyl]-2-pyridylmethyl}guanidinium, C(23)H(23)N(5)O(3), (I), and N-[2-(benzylaminocarbonyl)ethyl]-N'-{6-[(4-carboxylatobenzyl)aminocarbonyl]-2-pyridylmethyl}guanidinium monohydrate, C(26)H(28)N(6)O(4).H(2)O, (II), both form three-dimensional supramolecular hydrogen-bonded networks based on a dimeric primary synthon involving carboxylate-guanidinium linkages. The differences in the geometries and hydrogen-bonding connectivities are driven by the additional methylpropionamide group and water of crystallization of (II).

Mesoionic heterocycles derived from 1,3-thiazolium-4-olates (thioisomunchnones) undergo thionation with aryl isothiocyanates to afford the corresponding 4-thiolate derivatives. Here, we document this transformation in detail, giving a crystallographic characterization of the solid-state structures. From the mechanistic viewpoint, the formal thionation process could be consistent with a [2 + 2] reaction of the exocyclic C-O bond of the thioisomunchnone with the C=S double bond of the isothiocyanate moiety, which would be competing with a (3 + 2) process as usual in mesoionic rings. Theoretical computations at the [B3LYP/6-31G(d):PM3] level, in which only bond-forming and bond-breaking reactions and neighboring atoms are treated at the DFT level, do reproduce the experimental results and rule out the expected pathway. Calculations instead suggest the existence of a four-step domino pathway through several polar intermediates that agrees with the electronic nature of the substituents involved. The mechanistic hypothesis has further been corroborated by an experiment with isotopically (13)C-labeled PhNCS that unambiguously shows the way in which the exchange reaction occurs.

Arsenic(III), antimony(III) and bismuth(III) compounds of the type, [M{S2P(OR)2}3] (where M = As, Sb and Bi; R = o-, m-, p-C6H4Me) were obtained by reactions of MCl3 with ammonium salts of the corresponding O,O′-ditolyl dithiophosphate on refluxing in benzene. These compounds were characterized by elemental analysis, IR, 1H NMR and 31P NMR spectroscopy. The single crystal X-ray structures of three representative compounds were determined. [As{S2P(OC6H4Me-m)2}3]·0.5C6H14 crystallizes as triclinic in the space group P 1 ¯ with a = 10.9396(1), b = 14.1891(2), c = 17.5359(2) A, α = 70.731(1), β = 84.734(1), γ = 74.205(1)°, Z = 4, V = 2472.37(5) A3. [Sb{S2P(OC6H4Me-m)2}3] and [Bi{S2P(OC6H4Me-m)2}3] both crystallize as monoclinic in the space group P21 with a = 12.4520(3), b = 22.8760(5), c = 16.2165(4) A, β = 93.022(1)°, Z = 4, V = 4612.9(2) A3 and with a = 12.4903(2), b = 22.9554(4), c = 16.1032(3) A, β = 92.4300(10)°, Z = 4, V = 4612.96(14) A3, respectively. In all three molecules, the central metal atom is surrounded by all six sulfur atoms of the three chelating anisobidentate O,O′-ditolyl dithiophosphate groups in a pseudo trigonally distorted octahedron with a lone pair positioned on one of the triangular octahedral faces. The three metal sulfur bonds adjacent to the lone pair (capped face) are longer than the three furthest from the lone pair (uncapped face). Inter-ligand angles between the longer bonds are greater than those between the shorter bonds.

Bis(O,O'-ditolyl/dibenzyl dithiophosphato)cobalt(II) complexes with pyridine ligands of the type [Co{S2P(OR)(2)}(2)(C5H5N)(2)] (R = o-, m-, p-C6H4Me, CH2Ph) have been synthesized by the reaction of CoCl2(C5H5N)(2) and the corresponding ammonium salt of O,O'-ditolyl/dibenzyl dithiophosphate in methanol. These newly synthesized adducts were characterized by elemental analysis, IR, UV-Vis spectroscopy, magnetic susceptibility measurements and single crystal X-ray diffraction. These structures confirm that in the pyridine complex the geometry around the cobalt metal centre is distorted octahedral, and in the amine complex it is distorted trigonal bipyramidal. (C) 2008 Elsevier Ltd. All rights reserved.

Single crystal X‐ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and solid‐state NMR (SSNMR) techniques are used to analyze the structures of two nonsolvated polymorphs of {4‐(4‐chloro‐3‐fluorophenyl)‐2‐[4‐(methyloxy)phenyl]‐1,3‐thiazol‐5‐yl} acetic acid. These polymorphs are enantiotropically‐related with a thermodynamic transition temperature of 35 ± 3°C. The crystal structure of Form 1, which is thermodynamically more stable at lower temperatures, was determined by SCXRD. The crystal structure of Form 2 was determined using PXRD structure solution methods that were assisted using two types of SSNMR experiments, dipolar connectivity experiments and chemical shift measurements. These experiments determined certain aspects of local conformation and intermolecular packing in Form 2 in comparison to Form 1, and provided qualitative knowledge that assisted in obtaining the best possible powder structure solution from the X‐ray data. NMR chemical shifts for 1 H, 13 C, 15 N, and 19 F nuclei in Forms 1 and 2 are sensitive to hydrogen‐bonding behavior, molecular conformation, and aromatic π‐stacking interactions. Density functional theory (DFT) geometry optimizations were used in tandem with Rietveld refinement and NMR chemical shielding calculations to improve and verify the Form 2 structure. The energy balance of the system and other properties relevant to drug development are predicted and discussed. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4756–4782, 2008

A one-pot procedure for preparing chiral 1,3-oxazolidines derived from N-methyl-d-glucamine and aryl aldehydes is described. It has been carried out by using readily available reagents and operationally simple conditions allowing the preparation of the acyclic C-nucleoside analogs in high yields. The structure of these derivatives has been fully characterized by NMR correlations and single-crystal X-ray diffraction. Some reactions also provide access to the corresponding tetrahydro-1,3-oxazines by an alternative ring closure. Mechanistic considerations account for the observed steric course.

A novel tri-n-butyl(IV) derivative of 2-thiobarbituric acid (HTBA) of formula[(n-Bu)3Sn(TBA)⋅H2O](1) has been synthesized and characterized by elemental analysis and119Sn-NMR and FT-IR spectroscopic techniques. The crystal structure of complex1has been determined by single crystal X-ray diffraction analysis at 120(2) K. The geometry around Sn(IV) is trigonal bipyramidal. Threen-butyl groups and one oxygen atom from a deprotonated 2-thiobarbituric ligand are bonded to the metal center. The geometry is completed with one oxygen from a water molecule. Compound1exhibits potent, in vitro, cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, polycyclic aromatic hydrocarbons (PAH, benzo[a]pyrene) carcinogenesis. In addition, the inhibition caused by1, in the rate of lipoxygenase (LOX) catalyzed oxidation reaction of linoleic acid to hyperoxolinoleic acid, has been also kinetically and theoretically studied. The results are compared to that of cisplatin.

A series of chiral imines derived from 1-amino-1-deoxyalditols such as d-glucamine, a rather unexplored raw material from the chiral pool, have been serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by means of an unexpected acetylation. The structure of these substances is supported by spectroscopic and crystallographic data. The acetylates also trigger a complex dynamic transformation, in which an initially configured trans oxazolidine converts into a more stable cis-configured derivative. Both isomers can also exist as rotational conformers (E,Z) as a consequence of the restricted rotation around the N-acetyl bond. The barriers to rotation have been determined by variable-temperature experiments. Overall, this transformation most likely involves the intermediacy of a chiral iminium ion, which has been documented in the synthesis of nitrogen heterocycles, thus explaining the experimental facts.

Reaction of WX6 (X = Cl or Br) with O(SiMe3)2 in CH2Cl2, followed by addition of MeCN and a further equivalent of O(SiMe3)2 in CH2Cl2 gives [WO2X2(MeCN)2] in situ, which subsequently react with the dithioethers MeS(CH2)2SMe, iPrS(CH2)2SiPr or 1,4-dithiane to afford the first series of WVI thioether complexes, [WO2X2(dithioether)]. The very moisture-sensitive yellow complexes have been characterised by microanalysis, IR, 1H and 13C{1H} NMR spectroscopy, which indicate cis-dioxido and trans-dihalide arrangements in the monomers with two thioether donor atoms completing the very distorted octahedral geometry (confirmed by a crystal structure of [WO2Cl2{iPrS(CH2)2SiPr}]). The strongly polymerised WO2X2 compounds themselves are not useful synthons for the preparation of the WVI thioether complexes and substitution of the dimethoxyethane ligand in [WO2Cl2{MeO(CH2)2OMe}] by dithioethers is also incomplete. Molybdenum(VI) dioxidodichloride thioether complexes of the form [MoO2Cl2(L)] (L = iPrS(CH2)2SiPr, 1,4-dithiane, 2-[15]aneS2O3, 2-[14]aneS4 and 2-[12]aneS4) ([15]aneS2O3 = 1,4-dithia-7,10,13-trioxacyclopentadecane, [14]aneS4 = 1,4,8,11-tetrathiacyclotetradecane, [12]aneS4 = 1,4,7,10-tetrathiacyclododecane) and the unusual dinuclear [Mo2O4Cl4{o-C6H4(CH2SMe)2}2] are obtained by direct treatment of MoO2Cl2 with the appropriate ligand. The [Mo2O4Cl4{o-C6H4(CH2SMe)2}2] adopts an unexpected metallocyclic structure with cis-MoCl2 units and bridging bidentate dithioether (confirmed crystallographically). The structure of a new polymorph of [WO2Cl2{MeO(CH2)2OMe}] is also described.

A new macrocyclic receptor incorporating a thiourea moiety has been synthesised. Crystal structures of the macrocycle showed that the receptor has a rigid backbone but the thiourea moiety can orientate itself to bind to a DMSO solvent molecule. Force-field (MMFFs) calculations were performed to model the macrocycle and its binding properties with respect to N-protected amino acids, which were measured experimentally by NMR titration. Binding free energies were calculated by using the mode integration algorithm (MINTA) or free-energy perturbation (FEP). Excellent qualitative agreement with experiment was obtained. To further exploit the accuracy of the free-energy predictions for this system, the faster free-energy algorithm MINTA was used as a prediction tool to test the binding affinity of the macrocycle towards a series of several other amino acid derivatives, which speeded up considerably the screening process and reduced laboratory costs.

The synthesis of a N-confused calix[4]pyrrole-α-carbaldehyde is reported, together with its Knoevenagel reaction derivatives. The X-ray crystal structure of the aldehyde and two derivatives are reported showing the macrocycles adopting ‘confused 1,3-alternate’ conformations in all cases. The affinity of these macrocycles for a range of anionic guests has been measured in DMSO-d6/0.5% water, and the results compared with the parent N-confused calix[4]pyrrole parent macrocycle. These studies show that the derivatives have a significantly higher affinity for anionic guests than the parent system.

The Group 1 complexes, [M(Me6[18]aneN6)][BAr(F)] (M = Li-Cs; Me6[18]aneN6 = 1,4,7,10,13,16-hexamethyl-1,4,7,10,13,16-hexaazacyclooctadecane; BAr(F) = tetrakis{3,5-bis(trifluoromethyl)-phenyl}borate), are obtained in high yield by reaction of the macrocycle with M[BAr(F)] in anhydrous CH2Cl2 solution, and characterised spectroscopically ((1)H, (13)C{(1)H}, (7)Li, (23)Na, and (133)Cs NMR), by microanalysis and, for M = Li, K, and Rb, by single crystal X-ray analysis. The structures show N6-coordination to the metal ion; the small ionic radius for Li(+) leads to a puckered conformation. In contrast, the K(+) ion fits well into the N6 plane, with the [BAr(F)](-) anions above and below, leading to two K(+) species in the asymmetric unit (a hexagonal planar [K(Me6[18]aneN6)](+) cation and a '[K(Me6[18]aneN6)(κ(1)-BAr(F))2](-) anion', with long axial KF interactions). The Rb(+) ion sits above the N6 plane, with two long axial RbF interactions in one cation and two long, mutually cis RbF interactions in the other. The unusual sandwich cations, [M(Me3tacn)2](+) (M = Na, K; distorted octahedral, N6 donor set) and half-sandwich cations [Li(Me3tacn)(thf)](+) (distorted tetrahedron, N3O donor set), [Li(Me4cyclen)(OH2)](+), and [Na(Me4cyclen)(thf)](+) (both distorted square pyramids with N4O donor sets) were also prepared (Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane, Me4cyclen = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane). Density functional theory (DFT) calculations, using the BP86 and B3LYP functionals, show that the accessibility of the [M(Me3tacn)2](+) sandwich cations depends strongly on the M(+) ionic radius, such that it is sufficiently large to avoid steric clashing between the Me groups of the two rings, and small enough to avoid very acute N-M-N chelate angles. The calculations also show that coordination to the Group 1 cation involves significant donation of electron density from the p-orbitals on the N atoms of the macrocycle, rather than purely electrostatic interactions.

Unprecedented homoleptic octathioether macrocyclic coordination to Na(+) in [Na([24]aneS8)](+) has been achieved by using Na[B{3,5-(CF3)2-C6H3}4] as a source of "naked" Na(+) ions and confirmed crystallographically, with d(Na-S) = 2.9561(15)-3.0524(15) Å. Density functional theory calculations show that there is electron transfer from the S 3p and C 2p valence orbitals of the ligand to the 3s and 3p orbitals of the Na(+) ion upon complexation.

Lithium 2-thienyltellurolate, generated from 2-thienyl lithium, reacts at -78 degrees C in THF with chloroethyl ethyl sulfide to give a (Te, S) ligand 1-ethylthio-2-[2-thienyltelluro]ethane (L) as a red oil. The complexes [PdCl2(L)] (1), [PtCl2(L)] (2), [Ag(L)(2)][ClO4] (3) and [CuBr(L)](2) (4) were synthesized. The complex [HgCl2(L)] on crystallization decomposed giving Th2TeCl2 (5) [where Th = 2-thienyl], which was characterized by X-ray diffraction on its single crystals. The ligand L and complexes 1-4 exhibit proton and carbon-13 NMR spectra, which are characteristic. The coordination through Te in 1-4 is indicated by downfield coordination shifts in the position of the TeCH2 signal of L. Complex I was characterized by X-ray diffraction on its single crystals. The geometry around Pd is square planar. The Pd-Te, Pd-S and Pd-Cl bond lengths are 2.5040(4), 2.273(1) and 2.322(1)/2.380(1) angstrom, respectively. There are intermolecular interactions between Te (coordinated to Pd) and Cl, and sulfur and Cl. The Te-Cl and S-Cl distances, 3.401 and 3.488 A, respectively, are shorter than the sum of the van der Waal's radii (3.81 and 3.55 A, respectively). The Pd-Pd distance between the two molecules is 3.4156(6) A, greater than the sum of van der Waal's radii (3.26 A). The structure of 5 is typical of that of a tellurium(IV) compound (saw-horse type). The two Te-Cl bond lengths are identical, 2.480(1) A. The geometry around Te in 5 can be best described as pseudo tetrahedral (trigonal bipyramidal with a lone pair on one corner of the triangle).

The (P, S) ligand 1-(ethylthio)-2-(diphenylphosphino) ethane (L) is synthesized by reacting Ph2PLi with CH3CH2SCH2CH2Cl. The yield is good (similar to 85%) and the method of preparation is simpler than the liquid ammonia based one reported earlier. Its complexation with Cu(I), Hg(II) and organometallic species of Ru(II) are explored. All the complexes and the ligand exhibit characteristic proton, carbon-13 and phosphorus-31 NMR spectra. The single crystal structure of the Hg(II) complex has been determined. It is found to be a three coordinate complex. The sum of the bond angles at Hg, viz. P(1)-Hg(1)-Br(1), P(1)-Hg(1)-Br(2) and Br(1)-Hg(1)-Br(2), is approximate to 360 degrees. Thus the geometry around Hg can best be described as essentially trigonal planar. The Hg(1)-P(1) bond length is 2.415(1) angstrom and the Hg-Br bond lengths are 2.5152(6) and 2.5952(6) angstrom. There exists a weak secondary interaction between Hg and the S donor site of the ligand [Hg(1)•••S(1) bond distance 3.063(1) A < sum of van der Waal's radii 3.35 A].

A series of eight adducts of the form (RR‘R‘ ‘N)2·Zn(C6F5)2 have been prepared through treatment of the Lewis acid Zn(C6F5)2 with 2 equiv of the corresponding amine (R = tBu or CH2Ph, R‘ = R‘ ‘ = H; R = R‘ = Me or CH2Ph, R‘ ‘ = H; R = Me, R‘ = CH2Ph, R‘ ‘ = H; RR‘ = cyclo-C4H8 or cyclo-C5H10, R‘ ‘ = H; R = R‘ = Me, R‘ ‘ = CH2Ph). The solid-state structures of all eight compounds have been elucidated by single-crystal X-ray diffraction. In each case the geometry about the zinc atom is essentially tetrahedral. However, there is considerable variation in the supramolecular architectures in the solid state. A number of types of noncovalent interactions are observed including phenyl−pentafluorophenyl stacking, X−H···F−C contacts, and offset face-to-face contacts between pentafluorophenyl rings, giving rise to one-, two-, and three-dimensional supramolecular structures. In our examples we find that no one intermolecular interaction predominates.

A mesoionic acyclic C-nucleoside (4), serves as the starting chiron to construct highly functionalized 2-aza-7-thiabicyclo[2.2.1]heptanes and heptenes by means of a [3+2] cycloaddition with acetylenic and olefinic dipolarophiles. Further elimination of either sulfur or hydrogen sulfide leads to acyclic C-nucleosides bearing a heterocyclic moiety of 2-pyridone.

Using a phosphorus based Mannich condensation reaction the new pyridylphosphines {5-Ph2PCH2N(H)}C5H3(1-Cl) and {2-Ph2PCH2N(H)}C5H3(5-Br)N (1-Br) have been synthesised in good yields (60% and 88%, respectively) from Ph2PCH2OH and the appropriate aminopyridine. The ligands 1-Cl and 1-Br display variable coordination modes depending on the choice of late transition-metal complex used. Hence P-monodentate coordination has been observed for the mononuclear complexes AuCl(1-Cl) (2), AuCl(1-Br) (3), RuCl2(p-cymene)(1-Cl) (4), RuCl2(p-cymene)(1-Br) (5), RhCl2(Cp*)(1-Cl) (6), RhCl2(Cp*)(1-Br) (7), IrCl2(Cp*)(1-Cl) (8), IrCl2(Cp*)(1'-Cl) (8'), IrCl2(Cp*)(1-Br) (9), cis-/trans-PdCl2(1-Cl)(2) (10), cis-/trans-PdCl2(1-Br)(2) (11), cis-PtO2(1-Cl)(2) (12) and cis-PtCl2(1-Br)(2) (13). Reaction of Pd(Me)Cl(cod) (cod = cycloocta-1,5-diene) with either 1 equiv. of 1-Br or the known pyridylphosphines 1'-Cl, 1-OH or 1-H gave the P/N-chelate complexes Pd(Me)Cl(1-Br-1-H) (14)-(17). All new compounds have been fully characterised by spectroscopic and analytical methods. Furthermore the structures of 4, 5, 10 and 16 center dot (CH3)(2)SO have been elucidated by single crystal X-ray crystallography. A crystal structure of the dinuclear metallocycle trans, trans-[PdCl2{ mu-P/N-{Ph2PCH2N(H)} C5H4N}(2) center dot CHCl3, 18 center dot CHCl3, has also been determined. Here 1-H bridges, using both P and pyridyl N donors, two dichloropalladium centres affording a 12-membered ring with the PdCl2 units adopting a head-to-tail arrangement.

Reactions of RSnCl3 (R = Et and nBu) with internally functionalized oximes in 1:1 and 1:2 stoichiometric ratios in anhydrous benzene afforded non-ionic fibrous complexes of the general formula RSnCl3 · nHONC(R?)Ar [R = Et and Bu; R? = H, Me n = 1 and 2 (1–8); R? = only Me (9–11); Ar = 2-NC5H4, 2-OC4H3. Except for 1:1 furyl derivative, the value of 119Sn chemical shifts for all these derivatives in the 119Sn NMR spectra suggests hexa-coordination around tin atom. The crystal and molecular structures of one of the adducts nBuSnCl3 · HONC(Me)Py-2 · C6H5Me (2.tol.) and of a trinuclear hydroxo bridged stannoxane {nBuSnCl2(ONC(Me)Py-2)OH}2SnnBuCl · 0.5 HONC(Me)Py-2 (12), obtained on hydrolysis of nBuSnCl3 · 2HONC(Me)Py-2 (6), revealed a distorted octahedral environment around tin with the participation of both nitrogen atoms (ring as well as oxime nitrogen atom of the same ligand moiety) in coordination. In compound (2.tol.), the existence of intramolecular hydrogen bonding between the hydroxyl proton of the ligand moiety and the chlorine atom stabilizes the geometry. Unique asymmetric Sn–O(H)–Sn and Sn–O–N–Sn bridges are present in compound (12), resulting in a linear trinuclear stannoxane framework.

4-MeOC6H4Te-Na+ and Te2- generated in situ by reduction of (4-MeOC6H4Te)(2) and elemental Te, respectively, with sodium borohydride on reaction with 2-[3-(2-chloroethoxy)propyl]-6-methylpyridine in N-2 atmosphere results in 1-(4-methoxyphenyltelluro)-2-[3-(6-methyl-2-pyridyl)propoxy]ethane (L-I) 2-methyl-6-{3-[2-({2-[3-(6-methyl-2-pyridyl)propoxy]ethyl}telluranyl)eth oxy]propyl}pyridine (L 2) as viscous oils. Their proton and carbon-13 NMR spectra are characteristic. The L 2 shows signs of decay within few days. The complexes [PdCl2(L-I)](2) (1), [PtCl2(L-I)](2) (2), [HgBr2(L-I)] (3), [PdCl2(L-2)](2) (6), [PtCl2(L-2)](2) (7) and [(PdCl2)(3)(L-2)(2)](8) have been synthesized and found to give characteristic 1 H and 13 C NMR spectra. The 3 on crystallization from acetone:hexane (2: 1) mixture gives MeOC6H4HgBr (4) and [RTe+-HgBr2]Br- (R = -CH2CH2OCH2CHCH2-(2-(6-CH3-C5H3N))) (5). The crystals of 1, 2 and 4 are subjected to X-ray diffraction and their structures are solved. The I and 2 are 20-membered metallomacrocycles and do not dissociate in solution. The crystals of I and 2 have chloroform and benzene, respectively, in the lattice whereas 4 is a linear ArHgBr type species. The Pd/Pt in 1 and 2 has square planar geometry. The Pd-Te and Pd-N bond lengths in 1 are 2.530(1)/2.5313(9) and 2.097(4) and 2.101(4) angstrom, respectively.

Several unusual complexes of ytterbium(II) stabilised by coordination to mixed O4X2-donor macrocyclic ligands (X = O, NH, S or Se) are described. Distorted 8-coordination is evident from the crystal structure of the neutral [YbI2([18]aneO4Se2)], forming the first reported example of Yb(II)-selenoether coordination.

The existence of a dihydrogen bond (S-H...H-B) and its combination with a C-H...S hydrogen bond in an unusual cooperative effect are demonstrated from a combination of experimental and theoretical methods. This cooperative effect seems to be responsible for self-assembly of mercaptane-metallacarborane complexes such as closo-[3-Ru(eta6-C6H6)-8-HS-1,2-C2B9H10] (1) and closo-[3-Co(eta5-C5H5)-8-HS-1,2-C2B9H10] (3), which present identical supramolecular two-dimensional polymeric networks. The findings, besides documenting structurally the first S-H...(H-B)2 dihydrogen bond and the unconventional cooperative ability of a boron-attached SH group, prove that substituted carboranes have the potential to serve as building blocks for assembling complex structures.