Single Stage Tandem Mass Spectrometry Assignment of the C-5 Uronic Acid Stereochemistry in Heparan Sulfate Tetrasaccharides using Electron Detachment Dissociation

The analysis of heparan sulfate (HS) glycosaminoglycans presents many challenges, due to the high degree of structural heterogeneity arising from their non-template biosynthesis. Complete structural elucidation of glycosaminoglycans necessitates the unambiguous assignments of sulfo modifications and the C-5 uronic acid stereochemistry. Efforts to develop tandem mass spectrometric-based methods for the structural analysis of glycosaminoglycans have focused on the assignment of sulfo positions. The present work focuses on the assignment of the C-5 stereochemistry of the uronic acid that lies closest to the reducing end. Prior work with electron-based tandem mass spectrometry methods, specifically electron detachment dissociation (EDD), have shown great promise in providing stereo-specific product ions, such as the B₃ ^´ –CO₂, which has been found to distinguish glucuronic acid (GlcA) from iduronic acid (IdoA) in some HS tetrasaccharides. The previously observed diagnostic ions are generally not observed with 2-O-sulfo uronic acids or for more highly sulfated heparan sulfate tetrasaccharides. A recent study using electron detachment dissociation and principal component analysis revealed a series of ions that correlate with GlcA versus IdoA for a set of 2-O-sulfo HS tetrasaccharide standards. The present work comprehensively investigates the efficacy of these ions for assigning the C-5 stereochemistry of the reducing end uronic acid in 33 HS tetrasaccharides. A diagnostic ratio can be computed from the sum of the ions that correlate to GlcA to those that correlate to IdoA.

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Graphical Abstract ?

     

Determination of the primary structure and carboxyl p<Emphasis Type="Italic">K</Emphasis><Subscript>A</Subscript>s of heparin-derived oligosaccharides by band-selective homonuclear-decoupled two-dimensional <Superscript>1</Superscript>H NMR

Determination of the structure of heparin-derived oligosaccharides by ¹H NMR is challenging because resonances for all but the anomeric protons cover less than 2 ppm. By taking advantage of increased dispersion of resonances for the anomeric H¹ protons at low pD and the superior resolution of band-selective, homonuclear-decoupled (BASHD) two-dimensional ¹H NMR, the primary structure of the heparin-derived octasaccharide ∆UA(2S)-[(1 → 4)-GlcNS(6S)-(1 → 4)-IdoA(2S)-]₃-(1 → 4)-GlcNS(6S) has been determined, where ∆UA(2S) is 2-O-sulfated ∆^4,5-unsaturated uronic acid, GlcNS(6S) is 6-O-sulfated, N-sulfated β-d-glucosamine and IdoA(2S) is 2-O-sulfated α-l-iduronic acid. The spectrum was assigned, and the sites of N- and O-sulfation and the conformation of each uronic acid residue were established, with chemical shift data obtained from BASHD-TOCSY spectra, while the sequence of the monosaccharide residues in the octasaccharide was determined from inter-residue NOEs in BASHD-NOESY spectra. Acid dissociation constants were determined for each carboxylic acid group of the octasaccharide, as well as for related tetra- and hexasaccharides, from chemical shift–pD titration curves. Chemical shift–pD titration curves were obtained for each carboxylic acid group from sub-spectra taken from BASHD-TOCSY spectra that were measured as a function of pD. The pK _As of the carboxylic acid groups of the ∆UA(2S) residues are less than those of the IdoA(2S) residues, and the pK _As of the carboxylic acid groups of the IdoA(2S) residues for a given oligosaccharide are similar in magnitude. Relative acidities of the carboxylic acid groups of each oligosaccharide were calculated from chemical shift data by a pH-independent method.     

A Stable and Recoverable Chiral Ru Lewis Acid: Synthesis,Asymmetric Diels–Alder Catalysis and Structure of the Lewis Acid Methacrolein Complex

Ease of generation , stablity in solution at ambient temperature, high enantioselectivity in Diels–Alder reactions, efficient catalyst recovery, and large rate differences on variation of the anion are all characteristics of the new Ru Lewis acid [CpRu((S,S)-biphop-F)]⁺ (biphop-F=(C₆F₅)₂POCH₂(Ph)CH₂(Ph)OP(C₆F₅)₂). The structure of complex 1 (L=methacrolein, Y=SbF₆) provides evidence for a cooperative binding of the dienophile by both the Lewis acid and the anion.     

Effect of the Substituents of the Neighboring Ring in the Conformational Equilibrium of Iduronate in Heparin‐like Trisaccharides

Based on the structure of the regular heparin, we have prepared a smart library of heparin‐like trisaccharides by incorporating some sulfate groups in the sequence α‐D ‐GlcNS‐ (1‐4)‐α‐L ‐Ido2S‐(1‐4)‐α‐D ‐GlcN. According to the 3D structure of heparin, which features one helix turn every four residues, this fragment corresponds to the minimum binding motif. We have performed a complete NMR study and found that the trisaccharides have a similar 3D structure to regular heparin itself, but their spectral properties are such that allow to extract very detailed information about distances and coupling constants as they are isotropic molecules. The characteristic conformational equilibrium of the central iduronate ring has been analyzed combining NMR and molecular dynamics and the populations of the conformers of the central iduronate ring have been calculated. We have found that in those compounds lacking the sulfate group at position 6 of the reducing end glucosamine, the population of ²S₀ of the central iduronate residue is sensitive to the temperature decreasing to 19 % at 278 K. On the contrary, the trisaccharides with 6‐O‐sulfate in the reducing end glucosamine keep the level of population constant with temperature circa 40 % of ²S₀ similar to that observed at room temperature. Another structural feature that has been revealed through this analysis is the larger flexibility of the L ‐IdoAS‐ D ‐GlcN glycosidic linkage, compared with the D ‐GlcNS‐L ‐IdoA. We propose that this is the point where the heparin chain is bended to form structures far from the regular helix known as kink that have been proposed to play an important role in the specificity of the heparin–protein interaction.     

Synthesis,Antiproliferative Activity and DNA-Binding Properties of Nitrogen and Sulfur Heterocyclic Norcantharidin Acylamide Acid

Three novel norcantharidin acylamide acids (L¹?N‐thiadiazole norcantharidin acylamide acid, C₁₀H₁₁N₃O₄S; L²?N‐thiazole norcantharidin acylamide acid, C₁₁H₁₂N₂O₄S and L³?N‐benzothiazole norcantharidin acylamide acid, C₁₅H₁₄N₂O₄S) were synthesized by the reactions of norcantharidin (NCTD?7‐oxabicyclo[2,2,1]heptane‐2,3‐dicarboxylic acid anhydride, C₈H₈O₄) with 2‐amino‐1,3,4‐thiadiazole (C₂H₃N₃S), 2‐aminothiazole (C₃H₄N₂S) and 2‐aminobenzothiazole (C₇H₆N₂S), respectively. Their structures were characterized by elemental analysis, IR, and NMR. The inhibition rates of L³ was much higher than those of L¹ and L² against human hepatoma cells SMMC7721 cell lines in vitro. The interaction between the compounds and DNA was studied by means of fluorescence quenching studies and viscosity measurements. The emission intensities decreased obviously with increasing concentration of the compounds in the fluorescence quenching experiments. The linear Stern‐Volmer quenching constant K_sq values were 0.62 (L¹), 0.55 (L²) and 1.08 (L³), respectively. The binding abilities followed the trend from high to low were L³, L¹ and L², respectively. The results of viscosity measurements showed that L¹ and L² might bind to DNA via partial intercalation, while L³ bound mainly in intercalation.     

<Superscript>1</Superscript>H NMR signal at 2.10 ppm in the spectrum of KMnO<Subscript>4</Subscript>-bleached heparin sodium: identification of the chemical origin using an NMR-only approach

The recently revised European Pharmacopeia and US Pharmacopeia heparin sodium monographs include nuclear magnetic resonance (NMR) tests on both identity and purity. In KMnO₄-bleached heparin, an unidentified NMR signal is present at 2.10 ppm at a level of 15–20% of the mean of signal height of the major glucosamine (GlcNAc/GlcNS,6S) anomeric proton signal at 5.42 ppm and of the major iduronic acid (IdoA2S) anomeric proton signal at 5.21 ppm. According to the new monographs, no unidentified signals greater than 4% should be detected at that position. Thus, the material did not meet the acceptance criterion. The signal at 2.10 ppm has been present at the same level in all released MSD KMnO₄-bleached heparin sodium batches analyzed over the past 10 years. The signal is a result of the KMnO₄ bleaching. No (oversulfated) chondroitin sulfate or dermatan sulfate was detected in this material. A comprehensive NMR study using long-range heteronuclear 2D techniques identifies this signal at 2.10 ppm as originating from the acetyl methyl group of (6-sulfated) 2-N-acetyl-2-deoxy-glucono-1,5-lactone. This modified monosaccharide is formed by the KMnO₄ oxidation of the reducing end of a terminal N-acetylglucosamine.     

Synthese und Molekülstruktur des heterobimetallischen sulfidoacetato‐verbrückten Zr,Mo‐Komplexes [Cp°2Zr(OOCCH2S‐κ2O,S)(μ‐O‐OOCCH2S‐κ1O, κ2O′, S)(MoCp′2)] (Cp° = C5EtMe4, Cp′ = C5MeH4)

Synthesis and Molecular Structure of the Heterobimetallic Sulfidoacetato‐bridged Zr, Mo Complex [Cp°₂Zr(OOCCH₂S‐κ²O, S)(μ‐O‐OOCCH₂S‐κ¹O, κ²O′, S)(MoCp′₂)] (Cp° = C₅EtMe₄, Cp′ = C₅MeH₄) The reaction of [Cp°₂Zr(OOCCH₂SH‐κ¹O)(OOCCH₂SH‐κ²O, O′)] with [Cp′₂MoH₂] yields the dinuclear Zr^IV/Mo^IV complex [Cp°₂Zr(OOCCH₂S‐κ²O, S)(μ‐O‐OOCCH₂S‐κ¹O, κ²O′, S)(MoCp′₂)] ( 1 ) (Cp° = C₅EtMe₄, Cp′ = C₅MeH₄). For comparison of NMR data, [Cp′₂Mo(OOCCH₂S‐κ²O, S)] ( 2 ) was prepared from [Cp′₂MoH₂] and mercaptoacetic acid. 1 and 2 were characterized spectroscopically (¹H, ¹³C NMR and IR) and a crystal structure determination was carried out on 1 .     

Supramolecular Interaction of Fullerenes with a Curved π‐Surface of a Monomeric Quadruply Ring‐Fused Porphyrin

Molecular binding of fullerenes, C₆₀ and C₇₀, with the Zn^II complex of a monomeric ring‐fused porphyrin derivative ( 2 ‐py) as a host molecule, which has a concave π‐conjugated surface, has been confirmed spectroscopically. The structures of associated complexes composed of fullerenes and 2 ‐py were explicitly established by X‐ray diffraction analysis. The fullerenes in the 2:1 complexes, which consist of two 2 ‐py molecules and one fullerene molecule, are fully covered by the concave surfaces of the two 2 ‐py molecules in the crystal structure. In contrast, in the crystal structure of the 1:1 complex consisting of one 2 ‐py molecule and one C₆₀ molecule, the C₆₀ molecule formed a π–π stacked pair with a C₆₀ molecule in the neighboring complex using a partial surface, which was uncovered by the 2 ‐py molecule. Additionally, the molecular size of fullerene adopted significantly affects the ¹H NMR spectral changes and the redox properties of 2 ‐py upon the molecular binding.     

Synthesis of Thiocyameluric Acid C6N7S3H3, Its Reaction to Alkali Metal Thiocyamelurates and Organic Tris(dithio)cyamelurates

Thiocyameluric acid C₆N₇S₃H₃, the tri-thio analogue of cyameluric acid, is a key compound for the synthesis of new s-heptazine (tri-s-triazine) derivatives. Here, two different routes for the synthesis of thiocyameluric acid and its reaction to tris(aryldithio)- and tris(alkyldithio)cyamelurates C₆N₇(SSR)₃ are reported as well as transformation to alkali metal thiocyamelurates M₃[C₆N₇S₃], M=Na, K. These compounds were characterised by FTIR, Raman, solution ¹³C and ¹H NMR spectroscopies, thermal gravimetric analysis (TGA) and elemental analysis. The three (de)protonation steps of thiocyameluric acid were investigated by acid–base titration followed via UV/Vis absorption spectroscopy. While it was not possible to determine the three pK_a values, it could be postulated that the acid strength probably increases in the following order: cyanuric acid (C₃N₃O₃H₃) < thiocyanuric acid (C₃N₃S₃H₃) < cyameluric acid (C₆N₇O₃H₃) < thiocyameluric acid (C₆N₇S₃H₃). Single crystals of Na₃[C₆N₇S₃]⋅10 H₂O and K₃[C₆N₇S₃]⋅6 H₂O were obtained and the structures analyzed by single crystal X-ray diffraction. Additionally, quantum chemical calculations were performed to get insights into the electronic structure of thiocyameluric acid and to clarify the thiol–thione tautomerism. Based on a comparison of calculated and measured vibrational spectra it can be concluded that thiocyameluric acid and the di- and mono-protonated anions exist in the thione form.     

Gas-phase and solution conformations of the alpha-L-iduronic acid structural unit of heparin

The IdoA2S structural unit of heparin (subunit G) may oscillate among the three conformations (4C1, 1C4, and 2So). Only the twisted boat conformation allowed the biologically active pentasaccharide unit of heparin (DEFGH) to bind to antithrombin. Our work reports, in detail, the results of systematic large-scale theoretical investigations of the three basic conformations (4C1, 1C4, and 2So) of the IdoA2S structural unit of heparin, its anionic forms, and its sodium salt using the B3LYP/6-311++G(d, p) and B3LYP/6-31+G(d) model chemistries. According to our calculations, the most stable structure of these molecules corresponds to the 2So skew-boat conformation. This form is also the most stable in a water solution. The 2So conformation of neutral molecules is not maintained in the anionic species. With anions, both 1C4 and 4C1 conformations are present. The relative stability of individual species of the substituted iduronic acid affects extra stabilization by means of intramolecular hydrogen bonds. The calculated macroscopic pKa of 1,4-DiOMe IdoA2S are as follows: pKa = 0.25 for the terminal C(2)-OSO3H group, pKa = 3.67 for the terminal C(5)-CO2H group, and pKa = 14.00 for the C(3)-OH hydroxyl group. The computed Gibbs interaction energies, DeltaGdegrees , for the reaction 1,4-DiOMe IdoA2S(2-) + 2Na+ <==> 1,4-DiOMe IdoA2SNa2 (4C1, 1C4, and 2So conformations) are negative and span a rather small energy interval (from -1244 to -1290 kJ mol(-1)).     

Structural organization of dithiocarbamate heteropolynuclear gold(III)-cadmium complexes from X-ray crystallography and 113Cd MAS NMR spectroscopy data

We study the interaction of dialkyl substituted and cyclic cadmium dithiocarbamates with [AuCl₄]^? anions in 2M HCl medium. The state of the chemisorbents upon contact with AuCl₃ solutions is controlled by ¹¹³Cd MAS NMR spectroscopy. The result of the heterogeneous reactions involving chemisorption binding of gold(III) from the solutions and partial ion exchange is the formation of heteropolynuclear gold(III)-cadmium complexes. The crystal and molecular structure of the acetone-solvated form of polymeric bis-(N,N-diethyldithiocarbamato-S,S′) gold(III) hexachlorodicadmate is identified by single-crystal XRD. The main structural moieties of the compound are complex [Au{S₂CN(C₂H₅)₂}₂]⁺ cations and [Cd₂Cl₆]^2? anions. The structural self-organization of the complex at the supramolecular level is attributed to the secondary Au…S bonds between neighboring isomeric complex gold(III) cations; the bonding results in the formation of linear polymer ([Au{S₂CN(C₂H₅)₂}₂]⁺) _n chains, with [Cd₂Cl₆]^2? anions alternating to the right and left of the chains.     

First Example of Te-C Bond Cleaved Product in the Reaction of C8 H 8 TeI 2 with Ammonium Pipertidine Dithiocarbamate

Abstract

A series of 1,3-dihydro-2λ⁴-benzotellurole-2,2-diyl di-thiocarbamates C₈H₈TeR₂ and C₈H₈TeIR ( R═ S ₂CNC₅H₁₀, S₂CNHC₆H₅, S₂CNC₄H₈O) have been synthesised by the reactions of C8H8TeI₂ with the corresponding ammonium salts of piperidine-, aniline- and morpholine- dithiocarbamates in 1:1 and 1:2 molar ratio, respectively. They have been characterized by FT-IR and (¹H, ¹³C) NMR spectroscopy. The reaction of C₈H₈TeI₂ with (NH₄S₂CNC₅H₁₀) in 1:2 molar ratio gives C₈H₈Te(S₂CNC₅H₁₀)₂ [IR, (¹H, ¹³C)NMR evidence] and X-ray quality crystals of Te(S₂CNC₅H₁₀)₂ in very low yield, demonstrating the formation of the first Te–C bond-cleaved product.The monomers of Te(S₂CNC₅H₁₀)₂ are connected through intermolecular Te…S secondary bonds and it exists as a dimer in the solid state. These dimers are interconnected through intermolecular S…S secondary bonds to yield 3D-supramolecular network.     

A Disulfide Bridge Allows for Site‐Selective Binding in Liver Bile Acid Binding Protein Thereby Stabilising the Orientation of Key Amino Acid Side Chains

The presence of a disulfide bridge in liver bile acid binding protein (L‐BABP/S‐S) allows for site‐selective binding of two bile acids, glycochenodeoxycholic (GCDA) and glycocholic acid (GCA), differing only in the presence of a hydroxyl group. The protein form devoid of the disulfide bridge (L‐BABP) binds both bile salts without discriminating ability. We investigate the determinants of the molecular recognition process in the formation of the heterotypic L‐BABP/S‐S complex with GCA and GCDA located in the superficial and inner protein sites, respectively. The comparison of the NMR spectroscopy structure of heterotypic holo L‐BABP/S‐S, the first reported for this protein family, with that of the homotypic L‐BABP complex demonstrates that the introduction of a S–S link between adjacent strands changes the conformation of three key residues, which function as hot‐spot mediators of molecular discrimination. The favoured χ₁ rotameric states (t, g⁺ and g^? for E99, Q100 and E109 residues, respectively) allow the onset of an extended intramolecular hydrogen‐bond network and the consequent stabilisation of the side‐chain orientation of a buried histidine, which is capable of anchoring a specific ligand.     

Molecular Recognition of Rosmarinic Acid from Salvia sclareoides Extracts by Acetylcholinesterase: A New Binding Site Detected by NMR Spectroscopy

Acetylcholinesterase (AChE) inhibition is one of the most currently available therapies for the management of Alzheimer’s disease (AD) symptoms. In this context, NMR spectroscopy binding studies were accomplished to explain the inhibition of AChE activity by Salvia sclareoides extracts. HPLC‐MS analyses of the acetone, butanol and water extracts eluted with methanol and acidified water showed that rosmarinic acid is present in all the studied samples and is a major constituent of butanol and water extracts. Moreover, luteolin 4′‐O‐glucoside, luteolin 3′,7‐di‐O‐glucoside and luteolin 7‐O‐(6′′‐O‐acetylglucoside) were identified by MS² and MS³ data acquired during the LC‐MSⁿ runs. Quantification of rosmarinic acid by HPLC with diode‐array detection (DAD) showed that the butanol extract is the richest one in this component (134 μg mg^?1 extract). Saturation transfer difference (STD) NMR spectroscopy binding experiments of S. sclareoides crude extracts in the presence of AChE in buffer solution determined rosmarinic acid as the only explicit binder for AChE. Furthermore, the binding epitope and the AChE‐bound conformation of rosmarinic acid were further elucidated by STD and transferred NOE effect (trNOESY) experiments. As a control, NMR spectroscopy binding experiments were also carried out with pure rosmarinic acid, thus confirming the specific interaction and inhibition of this compound against AChE. The binding site of AChE for rosmarinic acid was also investigated by STD‐based competition binding experiments using Donepezil, a drug currently used to treat AD, as a reference. These competition experiments demonstrated that rosmarinic acid does not compete with Donepezil for the same binding site. A 3D model of the molecular complex has been proposed. Therefore, the combination of the NMR spectroscopy based data with molecular modelling has permitted us to detect a new binding site in AChE, which could be used for future drug development.     

The First Fully Planar C5‐Conformation of Homooligopeptides Prepared from a Chiral α‐Ethylated α,α‐Disubstituted Amino Acid: (S)‐Butylethylglycine (=(2S)‐2‐Amino‐2‐ethylhexanoic Acid)

An optically active α‐ethylated α,α‐disubstituted amino acid, (S)‐butylethylglycine (=(2S)‐2‐amino‐2‐ethylhexanoic acid; (S)‐Beg; (S)‐ 2 ), was prepared starting from butyl ethyl ketone ( 1 ) by the Strecker method and enzymatic kinetic resolution of the racemic amino acid. Homooligopeptides containing (S)‐Beg (up to hexapeptide) were synthesized by conventional solution methods. An ethyl ester was used for the protection at the C‐terminus, and a trifluoroacetyl group was used for the N‐terminus of the peptides. The structures of tri‐ and tetrapeptides 5 and 6 in the solid state were solved by X‐ray crystallographic analysis, and were shown to have a bent planar C₅‐conformation (tripeptide) and a fully planar C₅‐conformation (tetrapeptide) (see Figs. 1 and 2, resp.). The IR and ¹H‐NMR spectra of hexapeptide 8 revealed that the dominant conformation in CDCl₃ solution was also a fully planar C₅‐conformation. These results show for the first time that the preferred conformation of homopeptides containing a chiral α‐ethylated α,α‐disubstituted amino acid is a planar C₅‐conformation.     

Tribenzotriquinacene Receptors for C60 Fullerene Rotors: Towards C3 Symmetrical Chiral Stators for Unidirectionally Operating Nanoratchets

The synthesis of a stereochemically pure concave tribenzotriquinacene receptor ( 7 ) for C₆₀ fullerene, possessing C₃ point group symmetry, by threefold condensation of C₂‐symmetric 1,2‐diketone synthons ( 5 ) and a hexaaminotribenzotriquinacene core ( 6 ) is described. The chiral diketone was synthesized in a five‐step reaction sequence starting from C_2h‐symmetric 2,6‐di‐tert‐butylanthracene. The highly diastereo‐discriminating Diels–Alder reaction of 2,6‐di‐tert‐butylanthracene with fumaric acid di(?)menthyl ester, catalyzed by aluminium chloride, is the relevant stereochemistry introducing step. The structure of the fullerene receptor was verified by ¹H and ¹³C NMR spectroscopy, mass spectrometry and single crystal X‐ray diffraction. VCD and ECD spectra were recorded, which were corroborated by ab initio DFT calculations, establishing the chiral nature of 7 with about 99.7 % ee, based on the ee (99.9 %) of the chiral synthon ( 1 ). The absolute configuration of 7 could thus be established as all‐S [(2S,7S,16S,21S,30S,35S)‐( 7 )]. Spectroscopic titration experiments reveal that the host forms 1:1 complexes with either pure fullerene (C₆₀) or fullerene derivatives, such as rotor 1′‐(4‐nitrophenyl)‐3′‐(4‐N,N‐dimethylaminophenyl)‐pyrazolino[4′,5′:1,2][60]fullerene ( R ). The complex stability constants of the complexes dissolved in CHCl₃/CS₂ (1:1 vol. %) are K([ C₆₀ ? 7 ])=319(±156) M ^?1 and K([ R ? 7 ])=110(±50) M ^?1. With molecular dynamics simulations using a first‐principles parameterized force field the asymmetry of the rotational potential for [ R ? 7 ] was shown, demonstrating the potential suitability of receptor 7 to act as a stator in a unidirectionally operating nanoratchet.     

Über die Umsetzung von P4E3I2 (E = S,Se) mit einigen Carbonsäuren und Dithiocarbonsäuren

On the Reaction of P₄E₃I₂ (E = S, Se) with some Carboxylic Acids and Dithiocarbamic Acids By the reaction of α-P₄E₃I₂ (E = S, Se) with carboxylic acids, dithiobenzoic acid or dithiocarbamic acids in the presence of triethylamin or with (C₆H₅)₃SnR, or of β-P₄E₃I₂ with tin-organic compounds α-P₄E₃(I)R, α(β)-P₄E₃R₂ [R = ? OC(O)C₆H₅, ? OC(O)CH₃, ? SC(S)NC₅H₁₀, ? SC(S)N(C₂H₅)₂], α-P₄S₃(I)SC(S)C₆H₅, α-P₄S₃(SC(S)C₆H₅)₂ and β-P₄E₃(I)R (R = ? OC(O)C₆H₅, ? OC(O)CH₃) were prepared in solution and identified by ³¹P NMR spectroscopy. In addition α-P₄S₃(NC₅H₁₀)(SC(S)NC₅H₁₀) was detected. The β-isomers could be obtained also with lesser yields by the reaction with the dithiocarbamic acids, too. The substitution of the second iodine ligand in β-P₄E₃I₂ resulted mainly in β-P₄S₃(R_exo)₂ and by inversion of the configuration at a phosphorus atom, in β-P₄E₃R_exoR_endo. α-P₄S₃I₂ reacted with methanol in CS₂ to α-P₄S₃(OCH₃)(SC(S)OCH₃) and α-P₄S₃(SC(S)OCH₃)₂. The ³¹P NMR data of the compounds are discussed. The ³¹P NMR spectra of the α(β)-P₄E₃ dithiocarbamates indicate dynamic processes in the solution, e. g. α-P₄S₃(I)(SC(S)NR₂) showed an intramolecular conversion, due to the anisobidentate dithiocarbamate ligand. This behaviour had not previously been noticed for compounds with a P₄S₃-skeleton.     

氯化锌催化下C60与枞酸的反应

拟利用枞酸分子中的非同环共轭二烯在氯化锌作用下异构化成具有同环共轭二烯的海松酸结构, 再与C₆₀进行Diels-Alder加成反应, 预测可以得到Diels-Alder加成产物. C₆₀、枞酸及氯化锌在邻二氯苯溶剂中, 在氮气保护下于175～180 ℃反应8 h, 将反应物洗涤后进行硅胶柱层析分离, 采用FT-IR, ¹³C NMR, ¹H NMR和MALDI-TOF-MS等分析方法对反应主要产物进行结构测定, 却意外发现得到C₆₀与枞酸的加成过程中发生了脱羧脱氢反应且产物含有芳环的化学结构.     

The Tetraphenylester of the μ-Imido-Dithiodiphosphoric Acid and its palladium complex — crystal structures

The preparations of [(C₆H₅O)₂PS]₂NH ( SS ) and its Pd complex [Pd{C₆H₅O₂P(S)NP(S)(OC₆H₅) ₂}₂] ( PDSS ) are described. The compounds were characterized by elemental analysis, NMR, and mass spectra and X-ray structure analysis. The structure of SS contains two independent molecules in an asymmetric unit which are joined into dimers via N …? H …? S hydrogen bonds. SS is a Br?nsted acid And reacts with Pd^II to a neutral chelate complex. The structure of PDSS is composed of isolated molecules with Pd atom in the center of symmetry. The Pd atom is coordinated by 4 S atoms in a distorted square-planar arrangement with average distance Pd? S 2.345(6) Å and an angle S? Pd? S 98.29(4)°.     

Conformational selection of the AGA*IA(M) heparin pentasaccharide when bound to the fibroblast growth factor receptor

The interaction of the synthetic pentasaccharide AGA*IA(M) (GlcNS,6S-GlcA-GlcNS,3S,6S-IdoA2S-GlcNS,6S-Me) with the extracellular Ig2 domain of the fibroblast growth factor receptor (FGFR2) has been studied by NMR and computational methods. Analysis of the heparin pentasaccharide in the free state and in the complex indicates the existence of a conformational selection process. Although an equilibrium exists between the (1)C(4) and (2)S(0) conformers (ratio 60:40) of the 2-O-sulfo-α-L-iduronate ring (IdoA2S) in the free state, FGFR2 selects only the unique twisted-boat (2)S(0) conformation of this IdoA2S residue. In addition, the protein residues involved in the binding with AGA*IA(M) have also been characterized. The NMR results obtained, from both the ligand and protein perspective, were employed to model the bound conformation of the pentasaccharide by a combined docking and molecular dynamic simulation approach.