The conformation of the idopyranose ring revisited: How subtle O-substituent induced changes can be deduced from vicinal 1H-NMR coupling constants.

The idopyranose ring plays a pivotal role in the conformational, dynamical, and intermolecular binding aspects of glycosaminoglycans like heparin and dermatan sulfate and it was early on assigned a role in the Sugar Code governing biological recognition processes. There is consensus that next to the two canonical 1C4 and 4C1 chair conformations, the conformational space accessible to the idopyranose ring entails a 2SO skew-boat conformation, but the equilibrium between these three ring puckers has evaded satisfactory quantification. In this study a meta-analysis of X-ray solid-state data and vicinal NMR coupling constants is presented, based on the Truncated Fourier Puckering (TFP) formalism and the generalized Karplus (CAGPLUS) equation. This approach yields a model-free, granular and consistent reckoning of 159 idopyranose solution puckering equilibria studied by NMR and allows us to reproduce the involved 636 NMR vicinal couplings with an overall residual RMS(Jobs-Jcalc) of 0.184 Hz. Our analyses show that for all ring systems examined, the idopyranosyl chair conformations take up the same ring pucker irrespective of the ring substituent pattern or a vast variety in experimental conditions. Instead, it is the (skew-)boat conformation that adapts to the substitution pattern of the idopyranose ring or a specific sulfation pattern of neighboring saccharides. All idopyranose rings are involved in conformational equilibria that subsume the aforementioned conformers which turn out to differ only a few kJ/mole in conformational energy. Thus, the plasticity and flexibility of idopyranose remains intact under practically all circumstances and, as the glycosidic linkages in heparin are considered to be relatively stiff, the iduronic moiety functions as the linchpin of heparin flexibility thereby being rather a "space(r)" than a "letter" in the alleged Sugar Code alphabet.

Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis.

Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra®. The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming both structure and absolute configuration. The iduronic acid adopts a somewhat distorted chair conformation. Due to the presence of many sulfur atoms in the highly sulfated pentasaccharide, anomalous dispersion could be applied to determine the absolute configuration. A comparison with the conformation of Fondaparinux in solution, as well as complexed with proteins is presented. The content of the solution reference standard was determined by quantitative NMR using an internal standard both in 1999 and in 2016. A comparison of the results allows the conclusion that this method shows remarkable precision over time, instrumentation and analysts.

Mono(NCN-pincer palladium)-metalloporphyrin catalysts: evidence for supramolecular bimetallic catalysis.

The synthesis and catalytic properties of ditopic mono-pincer-mono-porphyrin complexes were investigated. The statistical Adler condensation reaction of 3,5-bis(methoxymethyl)-4-bromo-benzaldehyde, p-tolylaldehyde, and pyrrole, furnished an AB(3)-type tetraphenylporphyrin, containing three meso-p-tolyl groups and one meso-3,5-bis(methoxymethyl)-4-bromophenyl group. This material was converted into the ditopic ligand [2H(Br)], which comprises one porphyrin site and an NCN-pincer type ligand moiety. In order to metalate this compound in a stepwise, site-selective manner, two distinct synthetic routes were followed. Route A relies on the introduction of a metal in the porphyrin cavity followed by pincer metalation and a reversal of this order is employed for route B. For the hetero-bimetallic pincer-porphyrin target compounds, route A invariably proved to be the highest yielding alternative, giving pincer-porphyrin hybrids of general formula [M(1)(M(2)X)] (M(1) = 2H, Mg, Co, Ni, Zn; M(2) = Pd, Br; X = Cl, Br). (195)Pt NMR spectroscopy revealed that the porphyrin metal has a modest influence on the electron density on the NCN-pincer Pt site. When the analogous cationic Pd complexes were used as Lewis acid catalysts for the double Michael addition between methyl vinyl ketone and ethyl alpha-cyanoacetate, it was noted that the catalytic activity did not depend on the central metal for M(1) = 2H, Ni, and Zn. However, when Mg occupied the porphyrin cavity, the rate of the reaction increased by a factor of six. Although a rate enhancement was observed when catalysis was conducted with a mixture of the two constituents of [Mg(PdOH(2))]BF(4) (i.e. MgTTP and [PdOH(2)(NCN)]BF(4)) this could not fully account for the rate enhancement. We believe that the rationale for this behaviour is dual, consisting of "cooperative dual catalysis" and supramolecular aggregation of two or more catalyst-substrate complexes.

Mono- and dinuclear platinum(II) compounds with 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. Structure, cytotoxic activity and reaction with 5'-GMP.

Mono- and dinuclear platinum(II) coordination compounds of formula cis-[PtCl(2)(NH(3))(dmtp)], 1, cis-[PtCl(2)(dmtp)(2)], 2 and {H(+)[C(28)H(32)Cl(2)N(16)Pt(2)](2+)(NO(3))(3)(H(2)O)(6)}, 3, in which dmtp is 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine have been synthesized and characterized by infrared and by (1)H, (13)C, (195)Pt NMR spectroscopy. The coordination units of the cationic species of formula [Pt(2)(mu-dmtp)(2)Cl(2)(dmtp)(2)](2+) are built up by two platinum atoms in a square-planar environment. Two sites are occupied by two 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) bridging ligands which are linked to both metal atoms through their nitrogen atoms in positions 3 and 4. The other two positions are occupied by one monodentate 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) molecule and a coordinated chloride. This compound is the first in which the same triazolopyrimidine ligand (dmtp) coordinates to a metal ion in two different ways, i.e. bridging bidentate and non-bridging monodentate. In addition, the interaction of compounds 1 and 2 with 5'-GMP was investigated in solution by (1)H NMR spectroscopy. The cytotoxicity of all the new platinum(II) compounds were studied by using two different cell lines: T47D (breast cancer) and HCV29T (bladder cancer).

Synthesis, crystal structure, studies in solution and cytotoxicity of two new fluorescent platinum(II) compounds containing anthracene derivatives as a carrier ligand.

Two new cytotoxic fluorescent platinum(II) compounds, cis-[Pt(A9opy)Cl2] (1) and cis-[Pt(A9pyp)(DMSO)Cl2] (2),have been designed, synthesized, and characterized by IR, 1H NMR, and 195Pt NMR spectroscopy; electrospray ionization mass spectrometry (ESI-MS); and single-crystal X-ray diffraction. The carrier ligands selected for thesynthesis of these fluorescent platinum(II) compounds are E-2-[1-(9-anthryl)-3-oxo-3-prop-2-enylpyridine] (abbreviatedas A9opy) and E-1-(9-anthryl)-3-(2-pyridyl)-2-propenone (abbreviated as A9pyp). The compound cis-[Pt(A9opy)Cl2](1) comprises a peculiar cis-platinum(II) organometallic compound, in which the platinum(II) ion is bound to the photoisomerizable carbon-carbon double bond of the carrier ligand. The effects of the metal-ion coordination on the photoisomerization of the carbon-carbon double bond of the ligand have been studied. In contrast, the carrier ligand A9pyp used for the synthesis of the cis-[Pt(A9pyp)(DMSO)Cl2] compound (2) does not undergo such anisomerization process and remains in the E conformation, while coordinated to the platinum(II) ion through the nitrogen of the pyridine ring. In addition to the synthesis and characterization, solution studies of both compounds have also been performed in detail, including NMR and ESI-MS spectroscopy. Moreover, a high degree of cytotoxicactivity of compound 1 was found, as compared to cisplatin and its corresponding platinum-free molecule, in a series of human tumor cell lines. Compound 2 was also found to be highly active against these cell lines but appeared less active compared to the platinum-free molecule.

Counterion effect on the spin-transition properties of the cation [Fe(btzx)3]2+ (btzx=m-Xylylenebis(tetrazole)).

The influence of the counteranion on the structure and the spin-transition properties of original 1D bis(tetrazole) Fe(II) systems, namely [Fe(btzx)(3)]X(2) (X=PF(6) (-) (1), CF(3)SO(3) (-) (2) and ClO(4) (-) (3); btzx=m-xylylenebis(tetrazole)) is studied. The X-ray crystal structures of compounds 1 and 2 are described in detail. These structures present a solvent molecule encapsulated within pockets formed by btzx ligands along the 1D coordination chains. Compound 2 is shown to be the first structurally characterised alternating HS-LS 1D spin-transition system (HS=high spin, LS=low spin). The magnetic susceptibility measurements of all three compounds are compared. The degree of completion and the transition temperature are both drastically influenced by the counterion used, while surprisingly, the cooperative nature of the transition is not affected by the choice of counterion. Compounds 1 and 2 are further studied by Mössbauer spectroscopy and their distinct LIESST properties are compared.

Efficient near-UV photosensitization of the Tb(III) green luminescence by use of 2-hydroxyisophthalate ligands.

The first examples of lanthanide complexes with a 2-hydroxyisophthalate ligand are reported; the blue-emitting ligand acts as a very efficient sensitizer of the Tb(III) green emissions and does so in the near-UV region.

(S)-6-Methyl-∊-caprolactone.

The chiral title compound, C(7)H(12)O(2), a lactone derivative, features a seven-membered ring that adopts a chair conformation. The crystal structure is stabilized by weak C-H⋯O inter-actions occurring in the (100) plane. The absolute configuration was assigned on the basis of the enantioselective synthesis.

Ureidobenzotriazine multiple H-bonding arrays: the importance of geometrical details on the stability of H-bonds.

A 3-ureidobenzo-1,2,4-triazine 1-N-oxide (1) was synthesized successfully. The derivative displays an acceptor-donor-acceptor-acceptor (ADAA) hydrogen-bonding motif in CDCl(3) and DMSO-d(6) solution as well as in the solid state. Although moderately strong association of 1 was observed with DAD motifs, nonspecific binding is observed with ureidopyridines featuring a complementary DADD array. Density functional calculations of conformations 1a and 1b together with two complexes revealed the clearly nonplanar geometry of the multiply hydrogen-bonded complex, in which some bonds are significantly longer (3.2 A) than is optimal for H-bonds. As a result, only very small free energies of association were calculated, in line with the experimentally observed absence of specific assembly of the components.

[Fe(mu-btzmp)2(btzmp)2](ClO4)2: a doubly-bridged 1D spin-transition bistetrazole-based polymer showing thermal hysteresis behaviour.

The reaction of btzmp (1,2-bis(tetrazol-1-yl)-2-methylpropane) with Fe(ClO4)2 generates a 1D polymeric species, [Fe(mu-btzmp)2(btzmp)2](ClO4)2, showing a steep spin transition (T(1/2) / =136 K and T(1/2) / =133 K) with a 3 K thermal hysteresis. The crystal structure at 100 and 200 K reveals that, in contrast to other bistetrazole based spin-transition systems such as [Fe(endi)3](BF4)2 and [Fe(btzp)3](ClO4)2, the present compound has only two ligands bridging the metallic centres, while the other two coordination positions are occupied by two mono-coordinated (non-bridging) btzmp ligands. This peculiarity confers an unprecedented crystal packing in the series of 1D bistetrazole based polymers. The change in spin state is accompanied by an order/disorder transition of the ClO4* counterion. A careful examination of the structural changes occurring upon the spin transition indicates that this order/disorder is most likely affected by the modification of the [tetrazole-centroid]-ND-Fe angle (which is typical of bistetrazole spin-transition materials). Apart from X-ray analysis, also magnetic susceptibility, Mössbauer and UV-vis spectroscopies have been used to characterise the HS and the LS states of [Fe(mu-btzmp)2(btzmp)2](ClO4)2.

Hexanuclear [Ni6L12] metallacrown framework consisting of NiS4 square-planar and NiS5 square-pyramidal building blocks.

The hexanuclear [Ni(6)L(12)] (2) wheel-type cluster adopts an unusual structural motif whereby four NiS(4) square-planar and two NiS(5) square-pyramidal units are conjoined by edge sharing; the NiS(5) units resemble the Ni centre of the inactive state in the [NiFe] hydrogenase.

The synthesis, chemical and biological properties of dichlorido(azpy)gold(III) chloride (azpy=2-(phenylazo)pyridine) and the gold-induced conversion of the azpy ligand to the chloride of the novel tricyclic pyrido[2,1-c][1,2,4]benzotriazin-11-ium cation.

A new Au(III) coordination compound with the ligand 2-(phenylazo)pyridine has been synthesized and fully characterized by means of elemental analysis, IR, UV-visible, conductivity measurements, NMR, electrospray ionization (ESI-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). The chemical stability of the cation in this compound, [Au(azpy)Cl(2)](+) (abbreviated: Au-azpy), was analyzed by means of several physicochemical methods. While stable in the solid state, stability studies performed with the gold compound in solution showed an unexpected and unprecedented reactivity. A cationic organic derivative of 2-(phenylazo)pyridine, (abbreviated: pyrium), was produced from the solution and has been isolated as its chloride salt and characterized by crystal structure determination, elemental analysis, NMR, ESI-MS and conductivity studies in solution. This cyclization reaction is reported for the first time in the case of gold coordination compounds. The Au adduct and the pyrium cation were investigated as potential cytotoxic and anticancer agents, and both show moderate to high cytotoxic properties in cisplatin-sensitive and cisplatin-resistant ovarian carcinoma cell lines, A2780; and cisplatin-sensitive and cisplatin-resistant murine lymphocytic leukemia cell lines, L1210. Significant anticancer activity against the cisplatin resistant cell lines was found for the pyrium salt, ruling out the occurrence of cross resistance phenomena.

Structural elucidation of dendritic host-guest complexes by X-ray crystallography and molecular dynamics simulations.

The multiple monovalent binding of adamantyl-urea poly(propyleneimine) dendrimers with carboxylic acid-urea guests was investigated using molecular dynamics simulations and X-ray crystallography to better understand the structure and behavior of the dynamic multivalent complex in solution. The results from the two methods are consistent and suggest a preferred molecular picture of this complicated aggregate of multiple components. The guest molecules can bind to the dendrimer in a variety of ways although most involve hydrogen-bonding interactions between urea groups of the dendrimer with urea and/or carboxylic acid groups of the guest. In addition, acid-base interactions between the carboxylic acid of the guest and the tertiary amine in the interior of the dendritic host are present. Our proposed structure gives important information about the predominant dynamic interactions between the host and guest and illustrates how they fit together and interact with each other.

A new, easily recyclable arylating agent based on a diphosphino-digold(I) complex.

The synthesis of two organogold(I) complexes, [(Au(NCN))2(dppbp)] (6) and [(Au(Phebox))2(dppbp)] (9), and their application in subsequent transmetalating reactions are described. A trinuclear organogold(I) complex, [(AuCl)3(tdpppb)] (4) is also reported, which exhibits a surprisingly high solubility in dichloromethane. It was found that 6 and 9 can cleanly transfer the anionic NCN-([C(6)H(3)(CH(2)NMe(2))2-2,6]-) or Phebox-([2,6-bis(oxazolinyl)phenyl]-) moiety to Ti(IV) and Pd(II) centers, respectively. The coproduct [(AuCl)2(dppbp)] (3, dppbp is [4-Ph(2)PC(6)H(4)]2 (1)) formed during this transmetalation reaction, precipitates almost quantitatively from the reaction mixture (toluene) and can thus be separated by simple filtration. In comparison, [AuCl(PPh3)], formed as the coproduct in the transmetalation reaction of [Au(NCN)(PPh3)] with metal salts, has a higher solubility in apolar solvents and thus is more difficult to separate from the resultant organometallic complex. Digold complex 6 has been characterized by NMR spectroscopy and crystallographic analyses. These analyses show that the two gold units are essentially independent. The formation of a dimetallic transmetalating agent based on gold(I) had no effect on its transmetalating properties.

Study on the isomerism in meso-amavadin and an amavadin analogue.

An X-ray crystallographic study of 'meso-amavadin' revealed that in the crystal the negatively charged anionic species of the title compound join into infinite hydrogen-bonded chains, counterbalanced by cationic hydronium species. Along with water of crystallization a three-dimensional hydrogen-bonded network is formed. Based on NMR- and X-ray data of amavadin and 'meso-amavadin', a model was developed that accounts for the structure of amavadin-type complexes, i.e. vanadium(IV) non-oxo complexes that contain two ligands with a tridentate N-hydroxyiminodiacetate backbone. The model describes the different arrangements of the two ligands around the vanadium and it accounts for eventual symmetry in the complex. The model was used for the interpretation of NMR-data of an amavadin analogue with a benzyl group at the ligand backbone.

Novel linear transition metal clusters of a heptadentate bis-beta-diketone ligand.

The synthesis and the structure of the new potentially heptadentate ligand 1,3-bis-(3-oxo-3-(2-hydroxyphenyl)-propionyl)-2-methoxybenzene (H5L) is described. The reaction in pyridine or DMF of this ligand with various M(AcO)2 salts (M = NiII, CoII, MnII) leads to very different products depending on the metal. Thus, the dinuclear complexes [M2(H3L)2(py)4] (M = NiII, 1; CoII, 2) or the linear zigzag tetranuclear clusters [Mn4(H2L)2(AcO)2(py)5] (3) and [Mn4(H2L)2(AcO)2(dmf)4] (4) have been synthesized and characterized crystallographically. Slow oxidation of complex 3 leads to the formation of the novel mixed-valence linear complex [Mn3(HL)2(py)6] (5), displaying an unprecedented asymmetric MnIIIMnIIIMnII topology. The coordination geometry of complexes 1 to 5 has been analyzed and discussed by means of continuous shape measures. Magnetic measurements of 3 and 5 demonstrate that the metals within these complexes weakly interact magnetically with coupling constants of J1 = -1.13 cm-1 and J2 = -0.43 cm-1 (S = 0) for complex 3 and J1 = -5.4 cm-1 and J2 = -0.4 cm-1 (S = 5/2) for complex 5 (using the H = -Sigma2JijSiSj convention). These results are consistent with X-band EPR measurements on these compounds.

Platinum-catalyzed hydroformylation of terminal and internal octenes.

A brief historic overview of Pt/Sn-catalyzed hydroformylation as well as recent advances in the hydroformylation of internal alkenes is provided. This serves as background for the results obtained with the [Pt(Sixantphos)Cl(2)] system, for which the molecular structure and the spectroscopic data are described. Insitu UV/Vis-spectroscopic studies have revealed rapid formation of the corresponding Pt-stannate complex upon reaction with SnCl(2), whereas high-pressure insitu IR-spectroscopy showed formation of a Pt-CO species and a short-lived Pt-H species under syngas, as well as rapid evolution of aldehyde product upon addition of 1-octene to the preformed catalyst in the IR autoclave. The hydroformylation of 1-octene and the i-octenes has been performed. For the internal alkenes, selective tandem isomerization/hydroformylation towards n-nonanal is observed with this catalyst system.

(4aS,5R,7R,8S,8aR)-8-(1,3-Dioxolan-2-yl)-7,8-dimethyl-5-(1-methyl-ethen-yl)perhydro-naphthalen-2-one.

In the chiral title compound, C(18)H(28)O(3), the two six-membered rings of the perhydronaphthalenone adopt a rigid chair-chair conformation and the five-membered dioxolanyl ring adopts an envelope conformation. The crystal structure is stabilized only by weak inter-actions.

Bis[bis(2-pyridylcarbonyl)aminato]iron(III) perchlorate acetonitrile disolvate.

The title compound, [Fe(C12H8N3O2)2]ClO4.2C2H3N, contains Fe(III) in a distorted octahedral coordination environment, with the Fe-N(pyridine) bonds significantly longer than the Fe-N(amine) bonds. The crystal packing involves a bifurcated C-H...(O,O) contact that is also found in all other [M(C12H8N3O2)2] complexes reported previously.