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Clinical Scenario: Exercise in the heat can lead to performance decrements and increase the risk of heat illness. Heat acclimation refers to the systematic and gradual increase in exercise in a controlled, laboratory environment. Increased duration and intensity of exercise in the heat positively affects physiological responses, such as higher sweat rate, plasma volume expansion, decreased heart rate, and lower internal body temperature. Many heat acclimation studies have examined the hydration status of the subjects exercising in the heat. Some of the physiological responses that are desired to elicit heat acclimation (ie, higher heart rate and internal body temperature) are exacerbated in a dehydrated state. Thus, euhydration (optimal hydration) and dehydration trials during heat acclimation induction have been conducted to determine if there are additional benefits to dehydrated exercise trials on physiological adaptations. However, there is still much debate over hydration status and its effect on heat acclimation. Clinical Question: Does dehydration affect the adaptations of plasma volume, heart rate, internal body temperature, skin temperature, and sweat rate during the induction phase of heat acclimation? Summary of Findings: There were no observed differences in plasma volume, internal body temperature, and skin temperature following heat acclimation in this critically appraised topic. One study found an increase in sweat rate and another study indicated greater changes in heart rate following heat acclimation with dehydration. Aside from these findings, all 4 trials did not observe statistically significant differences in euhydrated and dehydrated heat acclimation trials. Clinical Bottom Line: There is minimal evidence to suggest that hydration status affects heat acclimation induction. In the studies that met the inclusion criteria, there were no differences in plasma volume concentrations, internal body temperature, and skin temperature. Strength of Recommendation: Based on the Oxford Centre for Evidence-Based Medicine Scale, Level 2 evidence exists.

Introduction/Background* No biomarkers have been established yet to predict response to anti-angiogenic treatment. To test whether the Xerna™ TME Panel, a novel biomarker, is predictive of anti-angiogenic treatment outcome, an exploratory, retrospective analysis of the Phase 1b study of navicixizumab in combination with paclitaxel in platinum resistant ovarian cancer was performed. Navicixizumab is a bispecific anti-angiogenic antibody to vascular endothelial growth factor (VEGF) and delta-like ligand 4. The Xerna™ TME Panel evaluates RNA gene expression data of ~100 genes defining the immune and angiogenic biologies that dominate the tumor microenvironment (TME). This novel diagnostic employs a machine learning model to classify a patient’s TME along immune and angiogenic axes, resulting in classification into one of four TME subtypes—Angiogenic (A), Immune Suppressed (IS), Immune Active (IA) and Immune Desert (ID). We hypothesized that patient TME subtypes classified with angiogenic dominant biology (A/IS) are more likely to benefit from treatment with navicixizimab relative to those in the biomarker negative subgroup (IA/ID). Methodology The Phase 1b study of navicixizumab (3 mg/kg or 4 mg/k, IV, q2w) in combination with paclitaxel (80 mg/m2 IV on D0, D7, and D14 of 28-day cycle) was an open-label, non-randomized study that included 44 patients with platinum-resistant, grade 2/3 ovarian cancer. Patients received a median of 4 prior treatments (63% prior bevacizumab, 45% prior PARP). Pre-treatment tumor tissue was analyzed retrospectively using the Xerna™ TME Panel. Result(s)* The objective response rate per RECIST 1.1 was 43.2% in the overall patient population (n=44). Responses were durable (median 6 months [95% CI, 5.4 months, not estimable]). Pre-treatment tumor tissue was available for 33 patients. In the B-positive subgroup (A/IS, n=13), 62% of patients had an objective response, compared to 25%, in the B-negative subgroup (IA/ID, n=20). PFS was 9.2 months in the B-positive subgroup vs. 3.9 months in the B-negative subgroup, HR = 0.43 [95% CI 0.188 to 0.999]). Conclusion* Navicixizumab plus paclitaxel demonstrated promising clinical activity in this heavily pretreated patient population. The Xerna™ TME Panel may identify patients more likely to benefit from treatment with navicixizumab and should be prospectively evaluated in a future study.

The title compound, diethyl (6-methyl-2-pyridyl)aminoethylenemalonate (1), crystallises in the monoclinic space group P21/c (No. 14). The unit cell parameters are a = 10.5657(7) A, b = 9.1784(5) A, c = 14.5681(7) A, β = 101.636(6)°, Z′ = 1 and Z = 4 at 150 K. The extended structure forms approximately orthogonal columns of stacked molecules. All bond lengths and angles are unremarkable. No disorder, twinning or co-crystallised solvent is present in the structure. An intramolecular hydrogen bond exists between the enamine nitrogen and carbonyl oxygen. Hirshfeld surface analysis reveals a short contact between a carbonyl oxygen and neighbouring aryl hydrogen, as well as a carbonyl–carbonyl interaction. The X-ray structure of diethyl (6-methyl-2-pyridyl)aminoethylenemalonate (1), an intermediate in the synthesis of ethyl nalidixate, is reported, and Hirshfeld surface analysis employed to identify intermolecular interactions within the structure.

We present the syntheses, structures, magnetic data and theoretical analyses for two families of heptanuclear clusters, wherein two staggered dysprosium(III) triangles are linked by various M(III) d‐/p‐block ions. The families differ in the counter‐anion and are of formulae [DyIII6MIII(OH)8(o‐tol)12(MeOH)5(NO3)]∙4MeOH and [DyIII6MIII(OH)8(o‐tol)12(MeOH)6]Cl·6MeOH (M = Cr, Mn, Fe, Co, Al; o‐tol = o‐toluate). We find that variation of the central metal ion M is crucial in tuning the toroidal moments on the triangular units, with diamagnetic M linking ions enhancing the ferrotoroidic coupling. By detailed simulation and analysis of various magnetic measurements, including sub‐kelvin microSquid hysteresis loops, we identified the specific signature of the M linking ions’ modulation of toroidal properties, including the mechanism whereby anisotropic, paramagnetic M ions lead to hysteresis profiles with larger remnant magnetisations and broader coercive fields.

Fluoropyridyl glycosides, synthesized from the corresponding glycosyl bromides, are shown to be excellent donors in glycosylation reactions. Both armed and disarmed donors were prepared and reacted smoothly with a series of glycosyl acceptors. Coupling proceeded in high yields, with activation of the donor achieved using a range of promoters, and also displayed unusually high selectivity. In addition these novel systems offer the potential for introducing a series of glycosyl donors with ‘tunable reactivity’.

The pentamethylcyclopentadienyl (Cp*) antimony(III) cations [Cp*2Sb][B(C6F5)4], [Cp2*Sb][OTf], [Cp*SbCl][B(C6F5)4] and [Cp*Sb][OTf]2 have been isolated and structurally characterised. [Cp*SbCl]+ forms dimers in the solid state via an intermolecular Sb–Cl interaction. Initial screening shows that [Cp*SbCl][B(C6F5)4] is significantly Lewis acidic and can catalyse the dimerisation of 1,1-diphenylethylene; [Cp2*Sb][B(C6F5)4] exhibits negligible Lewis acidity. Highly unstable [Cp*SbF][B(C6F5)4] could not be isolated, but stabilisation with the IMes ligand allowed isolation of [Cp*SbF(IMes)][B(C6F5)4]. Fluorodechlorination of CH2Cl2 and PhCCl3 was observed in the presence of crude [Cp*SbF][B(C6F5)4] in solution. A computational mechanistic investigation suggests that the latter proceeds via a carbocation intermediate.

Methylsulfonylmethane (MSM) is a naturally occurring organosulfur antioxidant. Based on its small size and unique physicochemical properties, MSM exhibits broad tissue distribution and pleiotropic effects. Animal toxicity studies suggest MSM is safe and nontoxic. Though the antioxidant mechanism is presently unclear, MSM has demonstrated the ability to protect against the activities of superoxide dismutase, catalase, and myeloperoxidase while also altering glutathione levels in numerous tissues. Through the modulation of antioxidant enzyme activities and redox hub cycling, MSM impacts cellular and tissue redox status, which can metabolically reprogram cells through redox-sensitive transcription factors. Alternatively, MSM may also affect membrane properties, specifically of mitochondria, thereby affecting reactive oxygen species production. By altering antioxidant potentials in various tissues including the brain, MSM may demonstrate unique immune modulatory properties that could prove useful to various pathological states.

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.

Methylsulfonylmethane (MSM) is a naturally occurring organosulfur compound that has gained popularity as a dietary supplement and is used for a variety of purposes, including as an antiinflammatory agent. Multiple in vitro, animal, and human studies support its use as a safe and effective agent in the treatment of inflammatory conditions, including arthritis. As a GRAS substance, MSM is well tolerated at oral dosages of 2–4 g daily, with few observed side effects. This chapter provides an overview of MSM, with specific attention paid to the role of this dietary supplement in the treatment of inflammatory conditions.

Five complexes of the general formula PdCl2(SbMe2Cl)n (n = 1-5) have been synthesised by combining [PdCl2(MeCN)2] and SbMe2Cl in different molar ratios in toluene. Their solid-state structures have been determined by X-ray crystallography. The complexes display considerable structural diversity: [Pd4Cl8(SbMe2Cl)4] (1, n = 1) is a chloride bridged tetramer, [Pd2Cl4(SbMe2Cl)4] (2, n = 2) is a dimer, [PdCl(SbMe2Cl)2(SbMe2Cl2)] (3, n = 3) is a supramolecular polymer, [Pd2(SbMe2Cl)8]Cl4¬ (4, n = 4) is a loosely associated dimer and [Pd(SbMe2Cl)5]Cl2 (5, n = 5) is a monomer with square pyramidal PdSb5 coordination geometry. Each structure contains secondary interactions between coordinated Sb centres and chloride ligands or anions, resulting in five-coordinate Sb in all cases with a range of Sb∙∙∙Cl bond lengths. The electronic structures of these complexes have been investigated using DFT methods including NBO and Pipek-Mezey localised orbital methods in order to interrogate both the Sb-Pd and secondary Sb∙∙∙Cl bonding.

International audience; Objectives: To inform health-technology assessments of new adjuvant treatments, we describe treatment patterns in patients with complete resection of stage IB-IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United Kingdom (UK).Materials and methods: Data were collected via medical record abstraction. Patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized descriptively.Results: Among the 831 patients studied, 239 (29%) had stage IB disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and 248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402 patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant therapy increased with increasing stage of disease. Cisplatin/vinorelbine and carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens. Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3-not estimable); the 25th percentile was 13.2 months (95% CI, 11.0-15.3). 204 patients (24%) died during the follow-up period. The median overall survival was not reached, the 25th percentile was 31.2 months (95% CI 26.8-36.0 months). 272 patients (33%) had disease recurrence during the follow-up period. For 86 of those patients, the first recurrence was local or regional with no distant metastasis and 14 had further progression to metastatic disease during the follow-up time. For the other 186 patients, the first recurrence involved distant metastases. A total of 200 patients had metastatic disease at any time during study follow-up.Conclusions: Less than half the patients with stage IB-IIIA NSCLC in this observational study received adjuvant systemic therapy. A high rate of first recurrence with distant metastatic disease was observed, emphasising the need for more effective systemic adjuvant therapies in this population.

Background Little is known about which materials and techniques general dentists (GDs) use during endodontic procedures. The objectives were to quantify GDs’ use of specific endodontic tools, quantify inappropriate use, and ascertain whether inappropriate use is associated with GDs’ practice characteristics. Methods GDs in The National Dental Practice-Based Research Network reported in a questionnaire materials and techniques they use during endodontic procedures. Results Among eligible GDs, 1,490 (87%) participated. Most (93%; n = 1,383) used sodium hypochlorite to irrigate. The most commonly used sealers were zinc oxide eugenol (43%) and resin (40%), followed by calcium hydroxide (26%). Most (62%; n = 920) used a compaction obturation technique; 36% (n = 534) used a carrier-based method. Most (96%; n = 1,423) used gutta-percha as a filler; 5% used paste fillers. Few used irrigants (n = 46), techniques (n = 49), or fillers (n = 10) that investigators classified as inappropriate. Conclusions GDs use a broad range of endodontic techniques and materials, often adapting to newer technologies as they become available. Few GDs use tools that the investigators classified as inappropriate. Practical Implications GDs use many types of endodontic techniques and materials, but only a small percentage of them are inappropriate.

Magnesium reduction of MCl5 (M = Nb or Ta) in the presence of R2S (R = Me or nBu) affords the complexes [M2Cl4(R2S)2(?-Cl)2(?-R2S)]. The X-ray structures of those complexes where M = Nb or Ta, R = nBu2S, and of a new polymorph of [Ta2Cl4(Me2S)2(?-Cl)2(?-Me2S)], show that they have confacial bi-octahedral structures with Mdouble bond; length as m-dashM double bonds. The reactions of [Nb2Cl4(R2S)2(?-Cl)2(?-R2S)] with MeSCH2CH2SMe, MeSeCH2CH2SeMe or MeSeCH2CH2CH2SeMe produce the edge-linked dimers [Nb2Cl4(MeSCH2CH2SMe)2(?-Cl)2] and [Nb2Cl4{MeSe(CH2)nSeMe}2(?-Cl)2], all with Mdouble bond; length as m-dashM double bonds (M26+). The tantalum diselenoether complex, [Ta2Cl4(MeSeCH2CH2SeMe)2(?-Cl)2], is similar. Two “dimer of dimers”, [{Nb2Cl4(?-Cl)2(?-Me2S)}2(?-MeSeCH2CH2CH2SeMe)2] and [{Ta2Cl4(?-Cl)2(?-Me2S)}2(?-nBuSeCH2CH2CH2SenBu)2], containing confacial bi-octahedra linked by diselenoether bridges, were obtained as minor by-products and were identified via their X-ray crystal structures. Under similar conditions the xylyl-linked diselenoether, o-C6H4(CH2SeMe)2, gave a complex mixture of products, including [Ta2Cl4{o-C6H4(CH2SeMe)2}2(?-Se)2]. The complexes were characterised by microanalysis, IR and UV–visible spectroscopy. X-ray crystal structures are reported for [Nb2Cl6(nBu2S)3], [Ta2Cl6(nBu2S)3], [Ta2Cl8(Me2S)2], [Ta2Cl6(Me2S)3], [Ta2Cl4{o-C6H4(CH2SeMe)2}2(Se)2], [{Ta2Cl6(Me2S)(nBuSeCH2CH2CH2SenBu)}2] and [Ta2Cl4(Me2S)4(S)2].

This article reviews work up until mid-2014 on the synthesis and properties of transition metal complexes containing the heavier Group 15 Sb(III) and Bi(III) ligands, of general formula ER3 (E = Sb or Bi; R = alkyl, aryl etc, and may include a pendant donor group such as amine or ether) and ER(3-n)Xn (E = Sb or Bi; R is an organic substituent such as alkyl, aryl, etc.; X is an electronegative substituent such as halide; n = 0-3) in which these ligands function as a donor to a transition metal fragment, while simultaneously participating as an acceptor to another electronegative group such as an anionic or metal-coordinated halide, or an amine, ether, etc., leading to Sb/Bi centres bearing more than eight valence electrons ('hypervalent'). The Lewis acid properties of the halostibines and halobismuthines, ER(3-n)Xn, are also reviewed.

A series of cold cathode field emission points to be used for electron impact ionization of background gas in Penning trap mass spectrometry applications have been fabricated by electrochemically etching tungsten rod in a NaOH solution. A new variation of the drop-off etching method that can produce tips with tip radii down to 10 nm is described. We present the results of studies in which the parameters used in the etching process were varied, and the geometry and operation of the resulting tips was investigated by imaging them with a scanning electron microscope and by operating them in field emission mode. Finally, the use of these tips in a Penning trap mass spectrometry application is described.

The principal dietary sources of sulfur, the amino acids methionine and cysteine, may not always be consumed in adequate amounts to meet sulfur requirements. The naturally occurring organosulfur compound, methylsulfonylmethane (MSM), is available as a dietary supplement and has been associated with multiple health benefits. Absorption of MSM by the small intestine and accumulation of the associated sulfur moiety in selected tissues with chronic (8 days) administration were evaluated using juvenile male mice. Intestinal absorption was not saturated at 50 mmol, appeared passive and carrier-independent, with a high capacity (at least 2 g/d-mouse). The 35S associated with MSM did not increase in serum or tissue homogenates between days 2 and 8, indicating a stable equilibrium between intake and elimination was established. In contrast, proteins isolated from the preparations using gel electrophoresis revealed increasing incorporation of 35S in the protein fraction of serum, cellular elements of blood, liver, and small intestine but not skeletal muscle. The potential contributions of protein synthesis using labeled sulfur amino acids synthesized by the gut bacteria and posttranslational sulfation of proteins by incorporation of the labeled sulfate of MSM in 3′-phosphoadenosine 5′-phosphosulfate (PAPS) and subsequent transfer by sulfotransferases are discussed.

A cyclam (1,4,8,11-tetraazacyclotetradecane)-based macrocycle bearing two benzyl and two 2-hydroxy-3,5-di-tert-butylbenzyl pendent arms was synthesized and characterized using spectroscopic techniques and single crystal X-ray diffraction. The macrocycle crystallizes in the triclinic space group P-1, with the asymmetric unit containing one-half of the molecule. The structure is stabilized by hydrogen-bonding which exists between the phenolic protons and the nitrogen atoms of the macrocyclic ring. The presence of this hydrogen bonding is observed in the 1H-NMR due to the deshielded nature of the phenolic OH peak (δ 9.99). Cyclic voltammetry of the ligand revealed a single quasi-reversible peak at −0.58 V (Epc = −0.48 V and Epa = −0.68 V), which is due to the electrochemical oxidation of the phenol to the phenoxyl radical.

Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.

A series of pentavalent niobium and tantalum halide complexes with thio-, seleno- and telluro-ether ligands, [MCl5(EnBu2)] (M = Nb, Ta; E = S, Se, Te), [TaX5(TeMe2)] (X = Cl, Br, F) and the dinuclear [(MCl5)2{o-C6H4(CH2SEt)2}] (M = Nb, Ta), has been prepared and characterised by IR, 1H, 13C{1H}, 77Se, 93Nb and 125Te NMR spectroscopy, as appropriate, and microanalyses. Confirmation of the tantalum(V)–telluroether coordination follows from the crystal structure of [TaCl5(TeMe2)], which represents the highest oxidation state transition metal complex with telluroether coordination structurally authenticated. The Ta(V) monotelluroether complexes are much more stable than the Nb(V) analogues. In the presence of TaCl5 the ditelluroether, CH2(CH2TetBu)2, is decomposed; one of the products is the dealkylated [tBuTe(CH2)3Te][TaCl6], whose structure was determined crystallographically. Crystal structures of [(MCl5)2{o-C6H4(CH2SEt)2}] (M = Nb, Ta) show ligand-bridged species. The complexes bearing β-hydrogen atoms on the terminal alkyl substituents have also been investigated as single source reagents for the deposition of ME2 thin films via low pressure chemical vapour deposition. While the tantalum complexes proved to be unsuitable, the [NbCl5(SnBu2)] and [NbCl5(SenBu2)] deposit NbS2 and NbSe2 as hexagonal platelets onto SiO2 substrates at 750 °C and 650 °C, respectively. Grazing incidence and in-plane X-ray diffraction confirm both materials adopt the 3R-polytype (R3mh), and the sulfide shows preferred orientation with the crystallites aligned predominantly with the c axis perpendicular to the substrate. Scanning electron microscopy and Raman spectra are consistent with the X-ray data.

Background Chimeric antigen receptor (CAR) T cell therapy is FDA-approved for the treatment of refractory or multiple-relapsed CD19+ B-NHL. Despite its ability to induce rapid and durable responses, it carries the risk of significant toxicities including cytokine release syndrome (CRS) and reversible encephalopathy. There have been reports of bone marrow failure after engineered-T cell receptor cellular immunotherapy, however, no such reports exist for CAR-T cells. Here, we report persistent cytopenias after T cell therapy (PCTT) following axicabtagene ciloleucel (axi-cel) infusion. Methods A retrospective analysis of all patients who were treated with commercial axi-cel at the University of Miami/Sylvester Cancer Center was conducted through 10/12/18. PCTT was defined as patients who were alive at 30 days after axi-cel infusion and did not have ANC>500cells/mL without growth factor support. Results Fifteen patients with CD19+ relapse or refractory B-NHL were identified who received commercial axi-cel, but of those 15 patients, 13 were evaluable (one died from cerebral edema on day +7 and the other has not reached the day +30 benchmark yet). Six of the 13 evaluable patients (46%) fulfilled the criterion for PCTT. None of the 6 patients recovered ANC by day +42. Platelets of 50,000/mL or less on the first day of lymphodepleting chemotherapy was found to be a significant predictor for PCTT (p=0.01) in 5 of 6 PCTT patients. We did not find any other predictive associations with factors such as bulky disease, CRP, ferritin, LDH, ANC, or hemoglobin. It was observed that 4 of 6 (66.7%) patients with PCTT developed CRS of at least grade 2 the day after CAR-T infusion requiring tocilizumab infusion as opposed to only 1 of 7 (14.3%) who did not develop PCTT. Conclusions Low platelet count at the first day of lymphodepleting chemotherapy may be an indicator of low stem cell reserve and a predictor for PCTT after axi-cel. In addition, early onset of at least grade 2 CRS may contribute to PCTT after axi-cel. Notably, 5 of 6 patients who went on to develop PCTT would have been excluded from participation in the ZUMA-1 registration trial.

The neutral, distorted octahedral complex [TiCl4(Se n Bu2)2] (1), prepared from the reaction of TiCl4 with the neutral Se n Bu2 in a 1:2 ratio and characterized by IR and multinuclear (1H, 13C{1H}, 77Se{1H}) NMR spectroscopy and microanalysis, serves as an efficient single-source precursor for low-pressure chemical vapor deposition (LPCVD) of titanium diselenide, TiSe2, films onto SiO2 and TiN substrates. X-ray diffraction patterns on the deposited films are consistent with single-phase, hexagonal 1T-TiSe2 (P3m1), with evidence of some preferred orientation of the crystallites in thicker films. The composition and structural morphology was confirmed by scanning electron microscopy (SEM), energy dispersive X-ray, and Raman spectroscopy. SEM imaging shows hexagonal plate crystallites growing perpendicular to the substrate, but these tend to align parallel to the surface when the quantity of reagent is reduced. The resistivity of the crystalline TiSe2 films is 3.36 ± 0.05 × 10-3 Ω·cm with a carrier density of 1 × 1022 cm-3. Very highly selective film growth from the reagent was observed onto photolithographically patterned substrates, with film growth strongly preferred onto the conducting TiN surfaces of SiO2/TiN patterned substrates. TiSe2 is selectively deposited within the smallest 2 μm diameter TiN holes of the patterned TiN/SiO2 substrates. The variation in crystallite size with different diameter holes is determined by microfocus X-ray diffraction and SEM, revealing that the dimensions increase with the hole size, but that the thickness of the crystals stops increasing above ∼20 μm hole size, whereas their lengths/widths continue to increase.

The tripodal tristibine N(CH2-2-C6H4SbMe2)3 (L) has been prepared in high yield and characterized by 1H and 13C{1H} NMR spectroscopy and elemental analysis. A range of reactions with transition-met...

While most high and medium oxidation state (O.S. ≥ 3) metal and non-metal fluorides and oxide fluorides are strong Lewis acids, exploration of their coordination chemistry with neutral ligands has been limited and mostly non-systematic. This is despite the very different properties conferred on the acceptor centre by the small electronegative fluoride ligands compared to the heavier halides. This article sets out these key differences, discusses possible synthetic routes, the key characterisation techniques, and appropriate bonding models. Current knowledge of the coordination chemistry of d, f and p-block fluorides and oxide fluorides with neutral ligands (with donor atoms drawn from Groups 15 and 16 and including N-heterocyclic carbenes) is then presented and discussed, and the differences in properties compared to complexes containing the heavier halides are illustrated. The emphasis is on work published post 1990, but earlier work is also included as essential background and where no more recent information exists. Attention is drawn to unexplored areas meriting investigation and to possible applications of these complexes.

The crystal structure of 2,4-di-tert-butyl-6-hy­droxy­methyl­phenol is presented., The title compound, C15H24O2, is an example of a phenol-based pendant-arm precursor. In the mol­ecule, the phenol hy­droxy group participates in an intra­molecular O—H⋯O hydrogen bond with the pendant alcohol group, forming an S(6) ring. This ring adopts a half-chair conformation. In the crystal, O—H⋯O hydrogen bonds connect mol­ecules related by the 31 screw axes, forming chains along the c axis. The C—C—O angles for the hy­droxy groups are different as a result of the type of hybridization for the C atoms that are involved in these angles. The C—C—O angle for the phenol hy­droxy group is 119.21 (13)°, while the angle within the pendant alcohol is 111.99 (13)°. The bond length involving the phenolic oxygen is 1.3820 (19) Å, which contrasts with that of the alcoholic oxygen which is 1.447 (2) Å. The former is conjugated with the aromatic ring and so leads to the observed shorter bond length.

The reactions of NbCl4 with diphosphine ligands o-C6H4(PMe2)2, Me2PCH2CH2PMe2 or Et2PCH2CH2PEt2 in a 1 : 2 molar ratio in MeCN solution produced eight-coordinate [NbCl4(diphosphine)2]. [NbBr4(diphosphine)2] (diphosphine = o-C6H4(PMe2)2 or Me2PCH2CH2PMe2) were made similarly from NbBr4. X-ray crystal structures show that [NbCl4{o-C6H4(PMe2)2}2] has a dodecahedral geometry, but the complexes with dimethylene-backboned diphosphines are distorted square antiprisms. The Nb-P distances andP-Nb-P angles are very similar in the two types, but Nb-Cl distances are ∼0.1 Å longer in the square antiprismatic complexes. These paramagnetic (d(1)) complexes were also characterised by microanalysis, magnetic measurements, IR and UV-visible spectroscopy. Using a 1 : 1 molar ratio of NbCl4 : diphosphine (diphosphine = Me2PCH2CH2PMe2, Et2PCH2CH2PEt2, Cy2PCH2CH2PCy2 and Ph2PCH2CH2CH2PPh2) afforded [NbCl4(diphosphine)], and [NbBr4(Me2PCH2CH2PMe2)] was obtained similarly. These 1 : 1 complexes are unstable in solution, preventing X-ray crystallographic study, but based upon their diamagnetism, IR, UV-visible and (31)P{(1)H} NMR spectra, they are formulated as halide-bridged dimers [(diphosphine)X2Nb(μ-X)4NbX2(diphosphine)], with single Nb-Nb bonds and chelating diphosphines. The Nb(iv) complexes are prone to hydrolysis and oxidation in solution and the structures of the Nb(v) complexes [NbBr4(Me2PCH2CH2PMe2)2][NbOBr4(MeCN)] with a dodecahedral cation, and [{NbOCl3{Et2P(CH2)2PEt2}}2{μ-Et2P(CH2)2PEt2}] which contains seven-coordinate Nb(v) centres with a symmetrical diphosphine bridge, are reported. The structure of niobium tetrabromide, conveniently made from NbCl4 and BBr3, is a chain polymer with edge-linked NbBr6 octahedra and alternating long and short Nb-Nb distances, the latter ascribed to Nb-Nb bonds.

Alkylhalostibines have been shown to behave either as Lewis acids toward appropriate neutral ligands or as Lewis bases to low-valent metal fragments. The boundaries of their Lewis acid and Lewis base behavior have been determined, and the structural and spectroscopic consequences of the different behaviors probed. [SbMeX2(L–L)] (L–L = 2,2′-bipyridyl, 1,10-phenanthroline) and [SbMeX2(L)2] (L = OPMe3, OPPh3) are five-coordinate, distorted square-pyramidal monomers with the Me group axial, with the bond distances little affected by coordination. Significant changes in the bonding within the group 6 carbonyl complexes [M(CO)5(L′)] are evident, with L′→M σ-donation decreasing across the series L′ = SbMe3 → SbMe2Br → SbMeBr2, and an increase in M→L′ π-acceptance within the same series. Intermolecular interactions are a major feature within these systems, ranging from weak, MCO···Sb interactions in [M(CO)5(SbMe2Br)] and [M(CO)5(SbMeBr2)] to remarkably strong O···Sb hypervalent bonds in [Mn(CO)5(SbMe2Br)][CF3SO3]...

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.

© 2020 by the authors. We report the synthesis, structural and magnetic characterization of five mononuclear DyIII ion complexes using triphenylphosphine oxide as a monodentate ligand. They have formulae [DyIII(OPPh3)3(NO3)3] (1), [DyIII(OPPh3)4(NO3)2](NO3) (2), [DyIII(OPPh3)3Cl3] (3), [DyIII(OPPh3)4Cl2]Cl (4) and [DyIII(OPPh3)4Cl2](FeCl4) (5). These complexes are characterized using single crystal X-ray diffraction, which revealed that each complex has a unique coordination environment around the DyIII ion, which results in varying dynamic magnetic behavior. Ab initio calculations are performed to rationalize the observed magnetic behavior and to understand the effect that the ligand and coordination geometry around the DyIII ion has on the single-molecule magnet (SMM) behavior. In recent years, seven coordinate DyIII complexes possessing pseudo ~D5h symmetry are found to yield attractive blocking temperatures for the development of new SMM complexes. However, here we show that the strength of the donor ligand plays a critical role in determining the effective energy barrier and is not simply dependent on the geometry and the symmetry around the DyIII ion. Seven coordinate molecules possessing pseudo D5h symmetry with strong equatorial ligation and weak axial ligation are found to be inferior, exhibiting no SMM characteristics under zero-field conditions. Thus, this comprehensive study offers insight on improving the blocking temperature of mononuclear SMMs.

A quantitative study has been made of the oxidation of various coals by sulphuric acid–water mixtures. Two coals of different particle sizes showed identical oxidation rates. A mechanism of the oxidation reaction is suggested.

The murine polyomavirus (Py) enters mouse fibroblasts and kidney epithelial cells via an endocytic pathway that is caveola-independent (as well as clathrin-independent). In contrast, uptake of simian virus 40 into the same cells is dependent on caveola. Following the initial uptake of Py, both microtubules and microfilaments play roles in trafficking of the virus to the nucleus. Colcemid, which disrupts microtubules, inhibits the ability of Py to reach the nucleus and replicate. Paclitaxel, which stabilizes microtubules and prevents microtubule turnover, has no effect, indicating that intact but not dynamic microtubules are required for Py infectivity. Compounds that disrupt actin filaments enhance Py uptake while stabilization of actin filaments impedes Py infection. Virus particles are seen in association with actin in cells treated with microfilament-disrupting or filament-stabilizing agents at levels comparable to those in untreated cells, suggesting that a dynamic state of the microfilament system is important for Py infectivity.

Background and Aims: Prebiotic inulin-type fructans are widely consumed in the diet and may have contrasting effects in Crohn’s disease by stimulating gut microbiota and/or by generating functional gastrointestinal symptoms. The aim of this study was to measure fructan and oligofructose intakes in patients with active and inactive Crohn’s disease compared with healthy controls. Methods: Patients with active Crohn’s disease ( n = 98), inactive Crohn’s ( n = 99) and healthy controls ( n = 106) were recruited to a case–control study. Dietary intake of inulin-type fructans was measured using a specific food frequency questionnaire and was compared between the three groups and between patients with different disease phenotypes (Montreal classification). Associations between intakes and disease activity (Harvey–Bradshaw Index, HBI) were also undertaken. Results: Patients with active Crohn’s disease had lower fructan intakes (median 2.9 g/d, interquartile range [IQR] 1.8) than those with inactive Crohn’s (3.6 g/d, 2.1, p = 0.036) or controls (3.9 g/d, 2.1, p = 0.003) and lower oligofructose intakes (2.8 g/d, 1.8) than those with inactive Crohn’s (3.5 g/d, 2.2, p = 0.048) or controls (3.8 g/d, 2.1, p = 0.003). There were no differences in intakes related to disease site or behaviour. There were negative correlations between HBI well-being score and fructan intake ( ρ = –0.154, p = 0.03) and oligofructose intake ( ρ = –0.156, p = 0.028) and for the HBI abdominal pain score and fructan ( ρ = –0.164, p = 0.021) and oligofructose intake ( ρ = –0.157, p = 0.027). Conclusions: Patients with active Crohn’s disease consume lower quantities of fructans and oligofructose than their inactive counterparts and healthy controls. The impact of lower intakes of prebiotic fructans on gut microbiota is unknown and warrants further research.

Introduction: Methylsulfonylmethane (MSM) is a commonly used dietary supplement for the alleviation of joint and muscle pain. It is known primarily for its anti-inflammatory and antioxidant properties. While it is believed to have excellent bioavailability, little is known about its serum concentrations following chronic ingestion. Methods: 20 healthy men were supplemented with 3 grams of MSM daily for four weeks. Blood was collected at baseline and after two and four weeks of supplementation. Serum was analyzed for MSM concentration using Nuclear Magnetic Resonance (NMR) spectroscopy. Results: All baseline samples but one (0.028 mM) was below the limit of quantification for the NMR assay (0.002 mM). Serum MSM values increased across time (p 0.05). A total of 13 of the 20 men demonstrated higher serum MSM values at week 4 as compared to week 2. and eight of these men demonstrated an increase at week 4 of at least 25% above what was observed at week 2. Conclusions: Serum MSM concentrations increase following oral MSM supplementation, in somewhat of a timedependent manner in selected subjects. The pattern of increase varies somewhat from subject to subject, although all individuals experience an increase of approximately 1-3 mM after 2-4 weeks of supplementation.

The title compounds, [1,2-bis­(isopropyl­sulfan­yl)ethane-2κ2S,S′]octa­chlorido-1κ5Cl,2κ3Cl-μ-oxido-ditantalum(V), [Ta2Cl8O(C8H18S2)], (I), and μ-dimethyl­diselane-κ2Se:Se′-μ-oxido-bis­[tetra­chloridotantalum(V)], [Ta2Cl8O(C2H6Se2)], (II), contain six-coordinate TaV centres linked by a nonlinear oxide bridge. Compound (I) contains one TaV centre bonded to a chelating dithio­ether and three terminal chloride ligands, with the second TaV centre bonded to five terminal chloride ligands. In (II), two tetra­chloridotantalum(V) residues are bridged by the diselenide, giving a puckered five-membered Ta/O/Ta/Se/Se ring. The Ta—O distances in the bridges are short in both compounds, indicating that significant multiple-bond character is retained despite the deviation from linearity, and the bond lengths reveal a clear trans influence order of O > Cl > S > Se on the hard TaV centre. The structures are compared with the [Ta2Cl10O]2− anion, which contains a linear oxide bridge.

High quality, nanostructured Bi2Te3,with an unprecedented degree of positional and orientational control of the material form on the nanoscale, is readily obtained by low pressure chemical vapour deposition using a new molecular precursor. This system offers a convenient method that delivers key structural requirements necessary to improve the thermoelectric efficiency of Bi2Te3 and to develop the nascent field of topological insulators.Thermoelectric

Small DNA tumor viruses such as simian virus 40 (SV40) and polyomavirus (Py) take advantage of host cell proteins to transcribe and replicate their DNA. Interactions between the viral T antigens and host proteins result in cell transformation and tumor induction. Large T antigen of SV40 interacts with p53, pRb/p107/p130 family members, and the cyclic AMP-responsive element-binding protein (CREB)-binding protein (CBP)/p300. Py large T antigen is known to interact only with pRb and p300 among these proteins. Here we report that Py large T binds to CBP in vivo and in vitro. In co-transfection assays, Py large T inhibits the co-activation functions of CBP/p300 in CREB-mediated transactivation but not in NF-kappa B-mediated transactivation. p53 appears not to be involved in the functions of CREB-mediated transactivation and is not essential for large T:CBP interaction. Mutations introduced into a region of Py large T with homology to adenovirus E1A and SV40 large T prevent binding to the co-activators. These mutant large T antigens fail to inhibit CREB-mediated transactivation. The CBP/p300-binding Py mutants are able to transform established rat embryo fibroblasts but are restricted in their ability to induce tumors in the newborn mouse, indicating that interaction of large T with the co-activators may be essential for virus replication and spread in the intact host.

Infection of mouse fibroblasts by wild-type polyomavirus results in increased phosphorylation of ribosomal protein S6 (D.A. Talmage, J. Blenis, and T.L. Benjamin, Mol. Cell. Biol. 8:2309-2315, 1988). Here we identify pp70 S6 kinase (pp70S6K) as a target for signal transduction events leading from polyomavirus middle tumor antigen (mT). Two partially transforming virus mutants altered in different mT signalling pathways have been studied to elucidate the pathway leading to S6 phosphorylation. An upstream role for mT-phosphatidylinositol 3-kinase (PI3K) complexes in pp70S6K activation is implicated by the failure of 315YF, a mutant unable to promote PI3K binding, to elicit a response. This conclusion is supported by studies using wortmannin, a known inhibitor of PI3K. In contrast, stable interaction of mT with Shc, a protein thought to be involved upstream of Ras, is dispensable for pp70S6K activation. 250YS, a mutant mT which retains a binding site for PI3K but lacks one for Shc, stimulates pp70S6K to wild-type levels. Mutants 315YF and 250YS induce partial transformation of rats fibroblasts with distinct phenotypes, as judged from morphological and growth criteria. Neither mutant induces growth in soft agar, indicating that an increase in S6 phosphorylation, while necessary for cell cycle progression in normal mitogenesis, is not sufficient for anchorage-independent cell growth. In the polyomavirus systems, the latter requires integration of signals from mT involving both Shc and PI3K.

The key features of arsines, stibines and bismuthines as ligands towards transition metal and main group metal/metalloids are described. Following a brief review of the development of the chemistry, the main synthetic routes to the ligands are described and the advantages and limitations of the various approaches outlined. Current views of the nature of the metal-ligand bonding are evaluated, and the main coordination modes of the ligands described with illustrative examples.

The main synthetic routes to phosphine and arsine macrocycles are described. These include high dilution and template directed routes, and the advantages and disadvantages of these methods are discussed. Syntheses are also described for a selection of mixed donor macrocycles containing P or As donors.

[MF(4)(dmso)(2)] (M = Zr or Hf) and [MF(4)(dmf)(2)], prepared by dissolving MF(4)·nH(2)O in the appropriate solvent, have been used as synthons for a range of complexes of these otherwise intractable tetrafluorides. These reagents react with OPR(3) (R = Me or Ph) or OAsPh(3) (L) in anhydrous CH(2)Cl(2) to form six-coordinate [MF(4)L(2)] which exist as a mixture of cis (predominant form) and trans isomers in CH(2)Cl(2) solution but which crystallise as trans (OPPh(3), OAsPh(3)) or cis (OPMe(3)) forms. Cis-[ZrF(4)(OAsPh(3))(2)] crystals were obtained from MeCN. Cis-[MF(4)(pyNO)(2)] and eight-coordinate (distorted dodecahedral) [MF(4)(L-L)(2)] (L-L = 2,2'-bipy, or 1,10-phen), and [MF(4)(Me(4)-cyclam)] were also obtained. Attempts to prepare complexes with the N-heterocyclic carbene, 1,3-(2,6-di-isopropylphenyl)imidazol-2-ylidene (IDiPP) or alkyl diphosphines were unsuccessful. Crystal structures are reported for trans-[ZrF(4)(OPPh(3))(2)], cis- and trans-[ZrF(4)(OAsPh(3))(2)], cis-[HfF(4)(OPMe(3))(2)], [ZrF(4)(2,2'-bipy)(2)], cis-[HfF(4)(dmf)(2)], and geometric isomers (both pentagonal bipyramidal) of [(dmso)(2)F(3)M(μ-F)(2)MF(3)(dmso)(2)]. The failed attempts to make IDiPP adducts led to crystals of [IDiPPH](3)[M(3)F(15)] containing discrete anions based upon a triangle of M atoms with single F bridges. The results are compared with previous work on TiF(4) adducts and with complexes of MCl(4), and demonstrate that the MF(4) are very hard Lewis acids, with a marked preference for O- over N-donors.

PERA/Ei (PE) mice are susceptible to tumor induction by polyomavirus (Py), while C57BR/cdJ (BR) mice are resistant. Antigen-presenting cells from BR mice respond to the virus with interleukin-12 (IL-12) and those from PE mice with IL-10. These polarized cytokine responses underlie the development of effective antitumor immunity in BR mice and the lack thereof in PE mice. An ex vivo cytokine production assay using spleen cells from infected [PE × BR] F2 mice together with a genome-wide SNP (single-nucleotide polymorphism)-based QTL (quantitative trait locus) analysis was used to map the determinant of cytokine production to a region of chromosome 4 carrying the Toll-like receptor 4 (TLR4) gene. Genotyping of infected F2 mice showed concordance of TLR4 allele-specific DNA sequences with the cytokine profile. Cytokine responses elicited by Py are MyD88 dependent. Bacterial lipopolysaccharide (LPS), a known TLR4 ligand, induced the same polarized responses as the virus in these host strains. Spleen cells from C3H/HeJ and C57BL/10ScNJ LPS-nonresponsive mice challenged in vitro with Py showed an impaired IL-12 response but were unaffected in IL-10 production. TLR4s of strains PE and BR differ by 3 amino acid substitutions, 2 in the extracellular domain and 1 in the intracellular domain. cDNAs encoding the TLR4s signaled equally to an NF-κB reporter in 293 cells in a ligand-independent manner. When introduced into TLR2/TLR4 double-knockout macrophages, the TLR4 cDNA from BR mice conferred a robust IL-12 response to Py and no IL-10 response. The TLR4 cDNA from PE mice failed to confer a response with either cytokine. These results establish TLR4 as a key mediator of the cytokine response governing susceptibility to tumor induction by Py.

Methyldihalobismuthines, BiMeX2 (X = Cl or Br) prepared from MeLi and a stoichiometric amount of BiX3 in thf, react with 1,10-phenanthroline, 2,2′-bipyridyl or Me2NCH2CH2NMe2 (L−L) in thf or MeCN to give [BiMeX2(L−L)], which are poorly soluble in non-polar solvents. X-Ray structures of [BiMeBr2(L−L)] and of [BiMeCl2(Me2NCH2CH2NMe2)] show discrete square pyramidal molecules with apical methyl groups, and no intermolecular contacts within the sum of the appropriate Van der Waals radii. The structure of BiMe2Br is a 1-D polymer chain with bromine bridges containing a pseudo-trigonal bipyramidal geometry at bismuth. The reactions of BiMe2X with the bidentate N-donor ligands result in disproportionation to also form [BiMeX2(L–L)]. An unusual [BiMeBr4]2− anion in the salt [Li(H2O)(1,10-phen)2][Li(1,10-phen)2(μ-Br)BiMeBr3]·thf, was isolated as a by-product and shows a Li−Br−Bi bridge to one of the Li cations. BiMe2Br disproportionates on reaction with [M(CO)5(thf)] (M = Cr or W) to form [M(CO)5(BiMe3)].

Summary The glycosphingolipid GM1 binds cholera toxin (CT) on host cells and carries it retrograde from the plasma membrane (PM) through endosomes, the trans -Golgi (TGN), and the endoplasmic reticulum (ER) to induce toxicity. To elucidate how a membrane lipid can specify trafficking in these pathways, we synthesized GM1 isoforms with alternate ceramide domains and imaged their trafficking in live cells. Only GM1 with unsaturated acyl chains sorted efficiently from PM to TGN and ER. Toxin binding, which effectively crosslinks GM1 lipids, was dispensable, but membrane cholesterol and the lipid raft-associated proteins actin and flotillin were required. The results implicate a protein-dependent mechanism of lipid sorting by ceramide structure and provide a molecular explanation for the diversity and specificity of retrograde trafficking by CT in host cells.

The hybrid dibismuthines O(CH(2)CH(2)BiPh(2))(2) and MeN(CH(2)-2-C(6)H(4)BiPh(2))(2) react with [M(CO)(5)(thf)] (M = Cr or W) to form [{M(CO)(5)}(2){O(CH(2)CH(2)BiPh(2))(2)}] and [{Cr(CO)(5)}(2){MeN(CH(2)-2-C(6)H(4)BiPh(2))(2)}] containing bridging bidentate (Bi(2)) coordination. The unsymmetrical tertiary bismuthine complexes [M(CO)(5){BiPh(2)(o-C(6)H(4)OMe)}] are also described. Depending upon the molar ratio, the hybrid distibines O(CH(2)CH(2)SbMe(2))(2) and MeN(CH(2)-2-C(6)H(4)SbMe(2))(2) react with [M(CO)(5)(thf)] to give the pentacarbonyl complexes [{M(CO)(5)}(2){O(CH(2)CH(2)SbMe(2))(2)}] and [{Cr(CO)(5)}(2){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] or tetracarbonyls cis-[M(CO)(4){O(CH(2)CH(2)SbMe(2))(2)}] and cis-[M(CO)(4){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}]. The latter can also be obtained from [Cr(CO)(4)(nbd)] or [W(CO)(4)(pip)(2)], and contain chelating bidentates (Sb(2)-coordinated) as determined crystallographically. S(CH(2)-2-C(6)H(4)SbMe(2))(2) coordinates as a tridentate (SSb(2)) in fac-[M(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}] (M = Cr or Mo) and fac-[Mn(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)]. Fac-[Mn(CO)(3){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)] contains NSb(2)-coordinated ligand in the solid state, but in solution a second species, Sb(2)-coordinated and with a κ(1)-CF(3)SO(3) replacing the coordinated amine is also evident. X-ray crystal structures were also determined for fac-[Cr(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}], fac-[Mn(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)] and fac-[Mn(CO)(3){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] [CF(3)SO(3)]. Hypervalent N···Sb interactions are present in cis-[M(CO)(4){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] (M = Mo or W), but absent for M = Cr.

The hybrid dibismuthines O{(CH2)2BiPh2}2, MeN(CH2-2-C6H4BiR2)2, and S(CH2-2-C6H4BiR2)2 (R = Me, Ph), have been prepared and characterized by microanalysis, 1H and 13C{1H} NMR spectroscopy, and FAB mass spectrometry. The X-ray structures of O{(CH2)2BiPh2}2 and S(CH2-2-C6H4BiPh2)2 show close to symmetrical hypervalent interactions between the O or S atoms and both bismuth centers. The antimony analogue S(CH2-2-C6H4SbMe2)2 is quaternized by MeI to [S(CH2-2-C6H4SbMe3)2]I2, which also shows a hypervalent S···Sb interaction, but in this case to only a single antimony center. Complexes of these and related ligands with the CpFe(CO)2+ group, of the type [{CpFe(CO)2}2L][BF4]2 (L = O{(CH2)2BiPh2}2, MeN(CH2-2-C6H4BiR2)2, S(CH2-2-C6H4BiR2)2, O{(CH2)2SbR2}2, S(CH2-2-C6H4SbMe2)2, MeN(CH2-2-C6H4SbMe2)2, Ph2Sb(CH2)3SbPh2), have been prepared and characterized by microanalysis (antimony complexes only), 1H and 13C{1H} NMR and IR spectroscopy, and ES+ mass spectrometry. The X-ray crystal structure of [{CpFe(CO)2}2{O{(CH2)2SbMe2}2}][BF4]2 shows a hypervalent Sb···O contact to one of the antimony centers, whereas no hypervalent contacts are seen in the structure of [{CpFe(CO)2}2{MeN(CH2-2-C6H4SbMe2)2}][BF4]2. IR (carbonyl region) and NMR spectroscopy indicate that, uniquely, [{CpFe(CO)2}2{MeN(CH2-2-C6H4BiPh2)2}][BF4]2 shows hypervalent N···Bi interactions in both the solid and solution, but for the other dibismuthine complexes, there is evidence for inequivalence of the iron centers (and hence hypervalency) only in the solid state. Spectroscopic data indicate that hypervalent interactions are absent in [{CpFe(CO)2}2{MeN(CH2-2-C6H4SbMe2)2}][BF4]2 and [{CpFe(CO)2}2{S(CH2-2-C6H4SbMe2)2}][BF4]2, but present in solid [{CpFe(CO)2}2{O{(CH2)2SbR2}2}][BF4]2. The preparation and X-ray structure of [CpFe(CO)2{BiPh2(o-C6H4OMe)}][BF4] is also reported, but attempts to isolate [CpFe(CO)2(BiPhMe2)]][BF4] resulted in rapid scrambling of the substituents at bismuth to give [CpFe(CO)2(BiPh3?nMen)][BF4] (n = 0?3).

A number of 3-substituted 1D-myo-inositols were synthesized and evaluated as substrates for phosphatidylinositol synthase and uptake by intact cells. 1D-3-Amino-, -3-chloro-, and -3-(acetylthio)-3-deoxy-myo-inositols were all synthesized by nucleophilic displacement of the 6-O-(trifluoromethyl)sulfonyl group of 1L-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-6-O-[(trifluoromethyl)-sulfon yl] - chiro-inositol (which was prepared from L-quebrachitol), respectively, by reaction with LiN3, followed by reduction of the azido function, and with LiCl and KSAc to give the O-protected compounds. O-Demethylation using BBr3 and concomitant acetal hydrolysis furnished the free-hydroxy 3-amino- and 3-chloro-3-deoxy-1D-myo-inositols. The 3-mercapto analogue was obtained by removal of the acetal groups of the acetylthio analogue, followed by acetylation and purification of the peracetate, and subsequent O-demethylation and deacetylation. The 3-deoxy derivative was synthesized from the 6-O-(imidazol-1-ylthiocarbonyl) compound via Barton-McCombie deoxygenation. The 3-azido derivative was directly synthesized from 1L-1-O-tosyl-chiro-inositol via displacement with azide. The 3-keto analogue was prepared by Pt-catalyzed air oxidation of 1L-chiro-inositol. The compounds were all evaluated as substrates for phosphatidylinositol (PtdIns) synthase from mouse brain. The 3-NH2, 3-F, 3-deoxy, and 3-keto analogues all showed activity as substrates, as measured by liberation of cytidine monophosphate. These compounds also showed inhibition of the reaction of myo-[3H]inositol with PtdIns synthase. These results taken together indicate that these compounds are likely to be incorporated into phospholipids. As a further indication that these compounds might be useful as probes for the PtdIns pathway, it was demonstrated that the 3-NH2, 3-F, and 3-deoxy compounds are taken up by intact fibroblast cells as evidenced by their competing with myo-[3H]inositol uptake.