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Combination of matrix isolation techniques with theoretical methods for identification and characterization of some dithiiranes and oxathiiranes is presented. In general, both dithiiranes and oxathiiranes were generated via flask vacuum pyrolysis of suitable sulfur-containing precursors such as 1,2,4-trithiolanes, 1,3-dithietane 1,3-dioxide or thiocarbonyl S-oxides (sulfines). Novel applications of dimethyldioxirane (DMDO) and (trifluoromethyl)methyl dioxirane (TFMDO) as versatile oxidizing reagents published in the period 2008–2018 are summarized. Methods applied for manufacturing of new polymeric materials functionalized with dioxirane moieties and reported in patents are presented. Mechanisms involving Criegee intermediates in reactions of carbonyl compounds with dioxiranes using experimental and theoretical methods are discussed in the light of recent results.

In contrast to monotopic receptor 3, the anthracene functionalized squaramide dual-host receptor 1 is capable of selectively extracting sulfate salts, as was evidenced unambiguously by DOSY, mass spectrometry, fluorescent and ion chromatography measurements. The receptors were investigated in terms of anion and ion pair binding using the UV–vis and 1H NMR titrations method in acetonitrile. The reference anion receptor 3, lacking a crown ether unit, was found to lose the enhancement in anion binding induced by the presence of cations. Besides the ability to bind anions in an enhanced manner exhibited by ion pair receptors 2 and 4, changing the 1-aminoanthracene substituent resulted in their exhibiting a lower anion affinity than receptor 1. By using receptor 1 and adjusting the water content in organic phase it was possible to selectively detect sulfates both by “turn-off” and “turn-on” fluorescence, and to do so homogenously and under interfacial conditions. Such properties of receptor 1 have allowed the development of a new type of sensor capable of recognizing and extracting potassium sulfate from the aqueous medium across a phase boundary, resulting in an appropriate fluorescent response in the organic solution.

The title thiacrown ethers were prepared in a one-step procedure to give a series of unique macrocycles possessing two unsubstituted hydroxy groups that can be easily functionalized. In addition, epoxides and macrocycles derived from Cookson’s birdcage diketone, were prepared. The nucleophilic ring opening of epoxides synthesis can be classified in the frame of click chemistry. Surprisingly, some of the prepared allyl substituted polyglycols as well as bis-epoxides, especially sulfur analogues, were prepared for the first time.

Bisphenol A (BPA) is considered to be an endocrine disrupting chemical (EDC), which mimics endogenous hormones and is linked to various cancers. Bisphenol S (BPS) is a BPA analogue, often used in plastics. BPS can leach into food and drink products, exposing humans to these chemicals. Evidence suggests BPS is also an EDC with similar endocrine disrupting effects. Despite hopes for a safer alternative, research has shown BPS possesses estrogenic activity due to its structural similarities with its analogue BPA. Previously we have shown the effects of BPS on estrogen receptor-alpha (ERα) and BRCA-1 in both MCF-7 and T-47D breast cancer cells. The wild-type p53 and BRCA-2 work to prevent cancer by monitoring and repairing DNA damage; however, in breast cancer patients these genes are often mutated. Mutated p53 will induce the cell cycle protein p21 to act as an oncogenic transcription factor. In the present study, we have examined the effects of BPS, alone and in combination with hormones and anti-hormones, on p53, BRCA-2, and p21 in both MCF-7 and T-47D cell lines by utilizing western blot analyses, cellular viability assays, confocal microscopy, apoptosis assay, and RT-qPCR analyses. Western blot studies revealed alterations in the expression of p53, BRCA-2, and p21 related with varying concentrations of BPS (4-20 µM). In comparison to the control, p53 expression increased (65-95%) in the presence of BPS in both MCF-7 and T-47D cells. In addition, BRCA-2 expression revealed a similar increase in both cell lines when treated with BPS. However, p21 expression decreased (approximately 50%) with increasing concentrations in both cell lines. For further evaluation, an optimal concentration of 8 µM BPS was then used in combination with various hormones and anti-hormones. Compared to the control, BPS and E2 were up regulated in a similar fashion to p53. A similar trend in the effects on BRCA-2 expression was depicted in T-47D and MCF-7 cells. However, in p21, BPS and E2 were down regulated in both MCF-7 and T-47D breast cancer cells. In order to determine the influence of BPS on the growth of breast cancer cells, image cytometric analysis with propidium iodide staining was utilized to quantify alterations in T-47D and MCF-7 cell numbers and viability. Upon treatment of BPS concentrations (4-20 µM), an increase in cellular proliferation (12-60% increase) occurred in both cell lines. These cellular proliferative effects of BPS and E2 were sensitive to combination treatments with anti-estrogens. Confocal microscopy was utilized to examine the cytolocalization of p53 upon exposure to BPS alone and in combination with hormones and anti-hormones. The results from this study will yield a greater understanding of the molecular regulation of BPS action via the p53, BRCA-2, and p21 signaling pathways linked with breast cancer.

The telomerization of 1,3-dienes with functionalized nucleophiles presents an atom efficient and selective synthesis of potential non-ionic surfactants. Crucial for application of these synthetic pathways is the effective recycling of the homogeneous palladium catalyst. In this work, we present the telomerization of 1,3-butadiene with the renewable aminopolyol N -methylglucamine to a non-ionic surfactant in an aqueous solvent system. In order to achieve phase separation, the addition of freshly added 1,3-butadiene instead of an additional solvent offers an elegant way of catalyst recycling. With this method, recycling of the catalyst is feasible; a total turnover number of 1456 was reached.

Hydrogen sulfide (H2S), as one of the important gasotransmitters, plays an essential role in a many physiological and pathological processes. Commonly used methods for real-time detection and quantification of H2S are rather complicated. This report presents a simple fluorescence and colorimetry dual-mode assay based on ethers (Nq-Cm and Nq-2Cm) derived from hymecromone (7-hydroxy-4-methylcoumarin, Cm) and naphthoquinone (Nq). In these compounds an electron-deficient naphthoquinone unit was used as a suitable reagent for nucleophilic aromatic substitution (SNAr) reaction. Thiolysis of Nq-Cm and Nq-2Cm at physiological pH releases Cm and causes an significant fluorescence enhancement at 448 nm (with excitation at 320 nm). At the same time, the resulting naphthoquinone derivative Nq-2SH causes the solution a purple color, which allows naked-eye detection. Thus Nq-Cm and Nq-2Cm are colorimetrically selective for H2S. The efficacy of the Nq-Cm and Nq-2Cm were demonstrated in buffer with associated submicromolar detection limit as low as 130 nM and 150 nM, respectively. Presented results suggest that both probes are excellent quantitative detection tool for H2S.

Tert-butyl hydroquinone (TBHQ) is an aromatic compound that is commonly used as a preservative in processed food to prevent rancidity and lengthen shelf life. TBHQ is known to act as an antioxidant by protecting cells from radical oxygen species and thus preventing DNA damage. Although previous studies have found TBHQ to cause cancer cell death at high concentrations, they have also contrastingly found TBHQ, when studied in animal models, to enhance carcinogenic effects. However, the effect of TBHQ on breast cancer has not been thoroughly explored. With the prevalence of breast cancer and the wide use of TBHQ in processed food items, it is imperative that we explore their possible relationship. This study examined the effects of TBHQ, alone and in combination with hormones and anti-hormones, on ERα and p53 expression in both MCF-7 and T-47D breast cancer cell lines. To ensure treatment conditions without the presence of endogenous steroids or growth factors, the cells were cultured with a 5% charcoal-stripped fetal bovine serum (FBS) for six days. Western blot analysis revealed alterations in the expression of ERα and p53 protein levels after 24 hours of treatment with varying concentrations of TBHQ (0.005 to 1 mM). A concentration-dependent decrease of ERα protein levels was observed in both cell lines, with a 49% reduction occurring with 100 µM TBHQ as compared to the control. P53 levels portray a continued increase of expression through concentrations of TBHQ (0.005 to 1 mM), found similarly in both cell lines. To gain further insight into possible similarities between BPS and other known effectors of ERα, the optimal concentration of TBHQ (100 μM) was used in combination with hormones and anti-hormones. Down-regulation of ERα protein levels was observed after 24-hour co-treatment of T-47D & MCF-7 cells with a combination of TBHQ and E2. Antiestrogen ICI with TBHQ showed a significant down-regulation as compared to TBHQ alone, and TBHQ with TAM portrayed no significant differences. A similar trend in the effects on p53 expression was depicted in T-47D and MCF-7 cells. Image cytometric analysis with propidium iodide staining was utilized to quantify cell values and viability changes to further portray the effects of TBHQ on T-47D and MCF-7 cellular growth. The viability assay shows a biphasic effect with increasing concentrations of TBHQ, with a maximum decrease in proliferation seen at a concentration of 100 uM TBHQ. TBHQ alone and in combination with E2 and antiestrogens showed a decreased proliferation compared to the control in T-47D cells. However, cytolocalization of ERα upon treatment with estradiol and TBHQ remained unaltered. Our studies offer a unique perspective on the effects of TBHQ on two different breast cancer cell lines, and provide valuable insight for further exploration of the mechanism of action of TBHQ on tumor suppressor gene and steroid receptors.

A new selective probe containing the thiomorpholine unit (TM) was synthesized and examined for the fluorescence-based detection of hypochlorous acid (HOCl). Connection of TM with the fluorophore, 7-nitrobenz-2-oxa-1,3-diazole (NBD) effectively suppresses NBD fluorescence, whereas a HOCl-induced oxidation of TM to its S-oxide turns on a green emission. HPLC analysis shows that the reaction is stoichiometric and no sulfone is formed. Moreover, neither hydrogen peroxide nor peroxynitrite are able to oxidize the probe. Experimental data indicates that NBD-TM probe can be used to detect HOCl generated by myeloperoxidase (MPO). Presented results may be helpful in developing a novel class of fluorescent and luminogenic probes for the imaging of HOCl.

Long chain amines are of great importance for industrial chemistry as they are precursors for surfactants like amine oxides or quaternary ammonia compounds. The atom efficient, homogeneously catalyzed hydroamination using 1,3-dienes offers linear linkage of the amine group to renewables like β‐farnesene, offering a C15 skeletal structure, which is a desired size for surfactants, the so called laurics. The presented paper describes the development of a catalytic system for the hydroamination of the industrially available terpene β‐farnesene in good to excellent yields. The reaction works with a broad range of amines, aliphatic and aromatic ones. Furthermore, functionalities, like alcohol or ether groups, are tolerated, yielding functionalized farnesylamines. With two model nucleophiles, a scale-up to a 5000 mL reactor was accomplished; the obtained products were functionalized to surfactants and afterwards characterized by their surface activity.

In the investigation presented here the synthesis of new lariat ether derivative obtained from the modification of tetrapyrrolidinyl-PNP-crown ether macrocycle is described. The polyheterotopic molecular coreceptor consisted of the replacement of chlorine atoms with an optically active (S)-(1-benzylpyrrolidin-2-yl) methanamine. The structure was confirmed by using elemental analysis, mass spectrometry, and NMR spectroscopy. This work covers results concerning the complexing properties of the new ligand towards Ag+, Cu2+, Co2+, Ni2+, and Zn2+ ions. The formation of non-covalent complexes of 1:1 stoichiometry with the Cu2+, Co2+, Ni2+, and Zn2+ ions have been confirmed by mass spectrometry. Due to the previous work and application possibilities, a large emphasis was put on the investigation of the complexation ability of lariat ether with silver (I) cation to determine stability constants by direct potentiometric method. In this case, the formation of four different forms of complexes AgL, Ag2L, Ag3L, and Ag4L has been proved. The observed unusual binding through the nitrogen atoms from the exocyclic substituents may provide the structural unit to build a new coordination polymers.

Therapy of acute myeloid leukemia (AML) is unsatisfactory. Histone deacetylase inhibitors (HDACi) are active against leukemic cells in vitro and in vivo. Clinical data suggest further testing of such epigenetic drugs and to identify mechanisms and markers for their efficacy. Primary and permanent AML cells were screened for viability, replication stress/DNA damage, and regrowth capacities after single exposures to the clinically used pan-HDACi panobinostat (LBH589), the class I HDACi entinostat/romidepsin (MS-275/FK228), the HDAC3 inhibitor RGFP966, the HDAC6 inhibitor marbostat-100, the non-steroidal anti-inflammatory drug (NSAID) indomethacin, and the replication stress inducer hydroxyurea (HU). Immunoblotting was used to test if HDACi modulate the leukemia-associated transcription factors &beta, catenin, Wilms tumor (WT1), and myelocytomatosis oncogene (MYC). RNAi was used to delineate how these factors interact. We show that LBH589, MS-275, FK228, RGFP966, and HU induce apoptosis, replication stress/DNA damage, and apoptotic fragmentation of &beta, catenin. Indomethacin destabilizes &beta, catenin and potentiates anti-proliferative effects of HDACi. HDACi attenuate WT1 and MYC caspase-dependently and -independently. Genetic experiments reveal a cross-regulation between MYC and WT1 and a regulation of &beta, catenin by WT1. In conclusion, reduced levels of &beta, catenin, MYC, and WT1 are molecular markers for the efficacy of HDACi. HDAC3 inhibition induces apoptosis and disrupts tumor-associated protein expression.

A key challenge in the synthesis of non-ionic surfactants is the opposite polarity of the substrates and the connected challenge of using homogeneous catalysis. We present the telomerisation of β-myrcene with N-methylglucamine to C20-N-alkylated polyols, which show surface activity. The use of aqueous solvent systems along with amphiphilic ligands bridges the polarity gap and generates high reactivities.

The efficient synthesis of new macrocyclic systems via nucleophilic ring opening reaction of epoxides by thiols was described. Initially new macrocyclic compounds were obtained as a mixture of dias...

Crown ethers possessing an external chain are called lariat ethers. Huisgen cycloaddition is the 1,3-dipolar cycloaddition occurs between a suitable azide and terminal alkyne to give a stable 1,2,3...

Catalytic telomerization of 1,3-butadiene with alcohols is a catalytic reaction and an effective tool to synthesize 2,7-octadienyl ethers with different characteristics depending on the alcoholic substrate. While Pd/phosphine type catalysts were studied in depth, highly active Pd/NHC (=N-heterocyclic carbene) catalysts have been studied in the telomerization almost exclusively along with methanol. In the course of employing alcohols from renewables, e.g., lignin, cellulose or terpenes etc., a deeper understanding of the reactivity of these catalysts is needed. In this work, we present comprehensive investigations with linear and branched alcohols of different chain-lengths. Distinct tendencies in reaction behavior between primary and secondary alcohols were found and the lower reactivity of secondary alcohols could clearly be attributed to electronic properties, along with steric hindrance. Furthermore, the influence of double bonds in the alcohol chain has been studied. Interestingly, alcohols with double bonds that are not conjugated to the hydroxyl groups were shown to be more active than saturated alcohols. Allylic alcohols, however, are significantly less reactive than their saturated analogs. With the gathered information, we were able to deduce a structure reactivity-relationship of certain functional groups and substitution patterns. These findings were proved by employing terpenols to gain new allylic terpenol ethers.

A series of diazides and dithiols were prepared in a one-pot protocol from commercially available alcohols by a modified Appel reaction. Selected dithiols were converted into α,ω-dipropargyl sulfides and combined with thioglycol-derived diazides under Huisgen–Sharpless–Meldal reaction conditions to give a new class of 1,2,3-triazole-linked sulfur-rich crown ethers.

The atmospherically highly relevant methylsulfinyl radical (CH3(O)S˙) readily reacts with molecular triplet oxygen in cryogenic argon matrices containing small amounts of (3)O2. Comparison of experimental and computed IR- and UV/Vis spectra, including isotope exchange, show that the initially formed (3)O2 adduct has the structure of a peroxyl radical (CH3(O)SOO˙), which upon irradiation with UV light isomerizes to the methylsulfonoxyl radical (CH3SO3˙). The latter transforms into the methansulfonic acid radical (˙CH2SO3H) by irradiation with visible light. During the matrix photolysis small amounts of SO3 and the methyl radical were detected indicating competitive direct photodissociation.

Why cobalt outperforms other matrix materials in its capacity for diamond retention in cutting tools is considered. To this end diamond loading conditions were modelled to establish the magnitude of stress and strain in the matrix surrounding a working diamond crystal. Only at 315 N did the contact force in Co result in plastic strain of 4-8%, which has a destructive influence on diamond retention. The strain field generated in a poorly performing Cu-40%Co-6%Sn matrix under a load of 190 N closely resembled that generated by 315 N in Co. It is postulated that diamond retention is related to the yield strength and work hardening characteristics of the metallic matrix.

The atmospherically highly relevant methylsulfonyl radical (CH3SO2(•)) was generated by high-vacuum flash pyrolysis (HVFP) of allylmethylsulfone and isolated in an argon matrix at 10 K; the allyl radical formed as the cofragment. Upon thermolysis, the methylsulfonyl radical undergoes partial decomposition, leading to substantial amounts of sulfur dioxide in the matrix. The title compound was characterized through the assignment of eight fundamental IR bands of its CD3 and (13)CH3 isotopologues and the excellent agreement with the B3LYP/6-311+G(3df,3pd) computed harmonic vibrational frequencies. The two most intense absorptions were found at 1267.1 and 1067.6 cm(-1). In extension of this study S-methyl methanethiosulfonate was found to be another suitable, although less efficient, precursor for the gas-phase generation of the methylsulfonyl radical.

The synthesis of novel Cookson’s birdcage-annulated thiacrowns as well as noncage oligomers with an incorporated 1,2,3-triazole moiety are described. The title compounds were prepared applying a click alkyne–azide cycloaddition reaction in the final macrocyclization step. Using this methodology a series of oligomers containing oxygen, nitrogen, and sulfur were prepared. The effective cycloaddition process was carried out under nonaqueous conditions in the presence of a catalytic amount of copper(I) iodide and N , N -diisopropylethylamine; the yields of oligomers were moderate to good.

Results from twin control simulations of the preindustrial CO2 gas exchange (natural flux of CO2) between the ocean and the atmosphere are presented here using the NASA-GISS climate model, in which the same atmospheric component (modelE2) is coupled to two different ocean models, the Russell ocean model and HYCOM. Both incarnations of the GISS climate model are also coupled to the same ocean biogeochemistry module (NOBM) which estimates prognostic distributions for biotic and abiotic fields that influence the air-sea flux of CO2. Model intercomparison is carried out at equilibrium conditions and model differences are contrasted with biases from present day climatologies. Although the models agree on the spatial patterns of the air-sea flux of CO2, they disagree on the strength of the North Atlantic and Southern Ocean sinks mainly because of kinematic (winds) and chemistry (pCO2) differences rather than thermodynamic (SST) ones. Biology/chemistry dissimilarities in the models stem from the different parameterizations of advective and diffusive processes, such as overturning, mixing and horizontal tracer advection and to a lesser degree from parameterizations of biogeochemical processes such as gravitational settling and sinking. The global meridional overturning circulation illustrates much of the different behavior of the biological pump in the two models, together with differences in mixed layer depth which are responsible for different SST, DIC and nutrient distributions in the two models and consequently different atmospheric feedbacks (in the wind, net heat and freshwater fluxes into the ocean).

Substitution of the 1,3,5-triphenyl-6-oxoverdazyl radical with n-alkylsulfanyl groups lead to derivatives 1[n], which exhibit a columnar rectangular phase (Colr ) below 60 °C. Compounds 1[n] have a broad absorption band in the visible region with maxima at 540 and 610 nm and redox potentials E0/+1 1/2 = +0.99 V and E0/−1 1/2 = −0.45 V vs. SCE. Time-of-flight (TOF) investigation of 1[8] revealed hole mobility of μh = 1.52 × 10−3 cm2 V−1 s−1 in the columnar phase with an activation energy Ea = 0.06 ± 0.01 eV. Magnetization studies of 1[8] demonstrated nearly ideal paramagnetic behavior in both solid and fluid phases above 200 K and weak antiferromagnetic interactions at low temperatures. Verdazyl derivatives 1[n] were prepared in a sequence of reactions starting from 1-bromo-3,4,5-trifluorobenzene by alkylsulfanylation, followed by hydrazinylation, and finally 6-oxoverdazyl ring assembly using the Milcent method.

The compression behavior of binary mixtures with a large size disparity has been investigated using an instrumented tableting emulator. The stress–strain correlations obtained during the compaction of blends of microcrystalline cellulose and varying amounts of micronized active ingredient have been analyzed in order to identify the nature of the phenomena controlling the densification of the different ingredients throughout the tableting process. It has been discovered that, cocurrently to the elastic and plastic deformation of the excipient, the API particles can migrate into the intrinsic void spaces of the powder bed. This secondary rearrangement step occurs on a characteristic time scale and, therefore, exhibits a strong sensitivity to the speed of compaction. The implications of this phenomenon can be far reaching, with the most significant impact manifesting in the area of tablet weight control. Most currently-implemented tableting control schemes (usually found in development and research-scale devices) rely on empirical models correlating compaction force measured by the tablet press instrumentation to the composition/mass of powder in the die. Based on these correlations the die-fill settings can be adjusted to maintain tablet weight. Since the secondary rearrangement mechanism effectively shields the smaller particles from deformation, their mass cannot be detected by the strain gauges measuring compaction force, which renders the control scheme unreliable.

This paper presents off-line and on-line orientation results obtained with the new on line nuclear orientation device NICOLE in CERN. Magnetic moments of 187,185Pt g and 186Ir m, electric quadrupole moment ratios between Pt isotopes with mass number 185, 187 and 189, the spin of the 2 h isomer of 186Ir and a new decay scheme of 184Au involving a metastable state are established. The shape variation versus mass number of the Pt isotopes leads to sign change of the spectroscopic quadrupole moment between A=187 and 185. © 1990 J.C. Baltzer A.G., Scientific Publishing Company.

A series of racemic phosphoryloxy-substituted (η4-cyclohexadiene)Fe(CO)3 complexes was synthesized by exploiting the O-phosphorylation of (dienol)Fe(CO)3 intermediates generated in situ from the corresponding triisopropylsiloxy-protected complexes. The phosphorylated products were fully characterized by spectroscopic methods, including single-crystal X-ray diffraction in four cases. Monodeprotection of two dimethyl phosphate derivatives with trimethylamine led to the tetramethylammonium salts of the (cyclohexadienyl methyl phosphate)Fe(CO)3 complexes. These compounds are the first water-soluble enzyme-trigged CO-releasing molecules (ET-CORMs). The phosphatase-induced CO release was monitored by means of GC. The biological activity was assessed in different cellular assays. The compounds were shown to be only slightly toxic, and a moderate anti-inflammatory potential was determined in an assay based on the inhibition of inducible NO synthase (iNOS)-induced NO production.

Flash vacuum pyrolysis of 3,3,5,5-tetramethyl-1,2,4-trithiolane 1-oxide performed at 700 °C yields the 1-oxatrisulfan-3-yl radical (HOSS·) along with disulfur monoxide (S2O) and diisopropyl sulfide, which were isolated in argon matrices at 10 K. Upon irradiation with UV light, the 1-oxatrisulfan-3-yl radical undergoes isomerization to the 1-oxatrisulfan-1-yl radical (HSSO·). Both radicals were identified by comparison of their computed and experimental IR and UV/Vis spectra. In addition, density functional theory (DFT) computations offer a plausible explanation of the most likely reaction mechanism, suggesting that the initial step is a 1,3-H shift with simultaneous ring opening. A 1-oxatrisulfane derivative formed thereby undergoes fragmentations via a radical and a competitive concerted pathway leading to the observed final products. The same mechanism also governs the thermal fragmentation of di-tert-butyl disulfide S-oxide. Its pyrolysis at 700 °C affords an analogous set of products, including the 1-oxatrisulfan-3-yl radical (HOSS·) as the key intermediate.

The production and stabilization of crystalline pharmaceutical suspensions, an area of great importance to the pharmaceutical industry, was investigated through exploration of the ability of surfactants and polymers to affect the growth and stability of poorly water soluble pharmaceutical crystals on a molecular scale using molecular dynamics simulations coupled with anti-solvent crystallizations. Griseofulvin, a model poorly soluble drug, was simulated in an aqueous system containing individual non-ionic surfactant Tween 80, polymer HPMC, polymer Pullulan, and anionic surfactant SDS, as well as binary surfactant–polymer mixtures. To evaluate the stability and growth potential of the crystals, the interfacial binding energies between three elementary faces were calculated and compared, based on which HPMC was determined to be the most effective individual additive of those tested. Additionally, the potential synergism of additives was evaluated by the simulation of binary mixtures containing each of the non-ionic additives with the anionic surfactant SDS at different starting configurations. The combination of HPMC with SDS proved to be the most effective and significantly greater than HPMC when used alone. Simulation results were validated by observing both crystal growth rates, as well as final particle sizes of griseofulvin crystals grown using an antisolvent crystallization in the presence of individual and mixtures of additives, suggesting that the simulation approach may be used as a screening tool for selection of additives.

Thiocarbonyl S-oxides (sulfines) derived from aliphatic and cycloaliphatic thioketones were irradiated in argon matrices at 10 K, and the resulting oxathiiranes were identified by comparison of computed and experimental IR spectra. Upon photolysis at 10 K, depending on the substitution pattern, the oxathiiranes underwent either H-shift reactions or regioselective ring enlargements to form the corresponding thioesters. After warming of the matrix material to 38–40 K, the oxathiiranes underwent fast desulfurization to yield the corresponding ketones. Density functional theory (DFT) computations at the B3LYP/6-311+G(3df,3pd) level suggest that the desulfurizations of oxathiiranes occurred as bimolecular processes with activation enthalpies near 0 kcal mol–1.

In recent years, high-pressure homogenization has been used with increasing frequency to reduce the size of pharmaceutical suspensions to the micron, submicron, and nano scales with the goal of increasing the dissolution rate of the drug, and consequently, the in vivo bioavailability. As particle suspensions become smaller in size, increased concentrations of surfactants and stabilizers are required to prevent particle agglomeration. Recently, relatively high concentrations of biocompatible polymers have been used to stabilize suspensions by imparting surface-active steric stability as well as kinetic stability through an increase in suspension viscosity and/or a transition to non-Newtonian rheological properties. While the benefits of stable suspensions are known, little is known about the effect of the high polymer concentration on the actual breakup of the particles in suspension. In this work, designed experiments were used to identify the key parameters that govern the final particle size of a drug suspension following homogenization. In particular, drug loading, operating pressure, and polymer concentration were all found to be statistically significant factors in determining the resulting size of particles in suspension. In addition, it was found that an optimal polymer concentration of 2% (w/w) was required to adequately stabilize the particle suspension while simultaneously avoiding a decrease in homogenizer performance. Concentrations higher than 2% (w/w) resulted in size reduction limitations due to the increased viscosity (>10 cP) and the transition to non-Newtonian behavior.

The matrix isolation technique in combination with vacuum pyrolysis, photochemistry, and quantum mechanical computations was applied to study the structures and reactivities of dimethoxycarbene (DMC) and 1,3-dithian-2-ylidene. 1,2,4-Trithiolane was used for the generation of thioformaldehyde S-sulfide and the isomeric dithiirane. Irradiation of thioformaldehyde S-oxide in argon matrix at 10 K led to the first isolation of parent oxathiirane as well as HCSOH, a remarkable species with a rare formal carbon–sulfur triple bond.

It is currently of great interest to the pharmaceutical industry to control the size and agglomeration of nano- and micro-particles for the enhancement of drug delivery. Typically, surfactants and polymers are used as additives to interact with and stabilize the growing crystal surface, thus controlling size and agglomeration; however, selection is traditionally done empirically or using heuristics. The objective of this study was to use molecular dynamic simulations to investigate and predict additive interactions, and thus, evaluate the stabilization potential of individual and multiple additives on the surface of the model drug fenofibrate. Non-ionic surfactant Tween 80, anionic surfactant sodium dodecyl sulfate (SDS), and polymers hydroxypropyl methylcellulose (HPMC) and Pullulan were evaluated individually on three distinct crystal surfaces [(001), (010), (100)], as well as in surfactant-polymer combinations. HPMC was determined to have the strongest interaction with the surfaces of the fenofibrate crystal, and therefore, was predicted to be the most effective individual additive. A mixture of HPMC with SDS was determined to be the most effective mixture of additives, and more effective than HPMC alone, indicating a synergistic effect. The predictions of mixed additives indicated a relative order of effectiveness as follows: HPMC-SDS>HPMC-Tween 80>Pullulan-Tween 80>Pullulan-SDS. The simulations were subsequently validated by an anti-solvent crystallization of fenofibrate where it was found that HPMC individually, and a mixture of HPMC-SDS, produced the smallest and most stable crystals, as measured by laser diffraction; this, in combination with measurements of the crystal growth rate in the presence and absence of additives confirmed the results of the simulations.

The products of the gas-phase pyrolysis of two regioisomeric 1,2,4-trithiolane S-oxides were collected in an argon matrix at 10 K and studied by means of spectroscopic as well as computational methods. Whereas the main products of the pyrolysis of the "symmetrical" S-oxide were identified as thioformaldehyde S-oxide and thioformaldehyde S-sulfide, the "non-symmetrical" S-oxide gave predominantly dithioformic acid, which exists as a mixture of s-cis and s-trans conformers. We present a rationalization of the reaction pathways including density functional theory computations.

A small library of 17 modular and easily accessible phenol-derived chiral phosphine−phosphite ligands was evaluated in the asymmetric Rh-catalyzed hydroformylation of styrene. It was found that the stereochemical outcome of the reaction is highly dependent on the chiral phosphite moiety and the substituents on the phenolic backbone. Among the ligands studied, Taddol-based ligands of type 10 bearing bulky substituents in ortho-position to the phosphite performed best, with enantioselectivities of up to 85% ee and regioselectivities of ≥98:2. High-pressure NMR of the active catalyst [HRh(P−P)(CO)2] (P−P = 10h) revealed an equatorial-apical coordination of the ligand at rhodium. Temperature dependency of the coupling constants observed during the experiment indicates equilibrium between the two equatorial-apical isomers, with the isomer in which the phosphite occupies the equatorial position being the dominant species.

New 1-alkoxy-3-alkyl-4,5-dimethylimidazolium bromides were synthesized by alkylation of the corresponding 1-alkylimidazole 3-oxides, which were conveniently prepared via condensation of α-(hydroxyimino)ketones, primary aliphatic amines, and formaldehyde. By using enantiomerically pure chiral amines, optically active imidazolium salts were obtained. Treatment with sodium tetrafluoroborate in acetone yielded the corresponding imidazolium tetrafluoroborates. All these compounds, with only one exception, were obtained as oils, which are considered as potential ionic liquids and ‘chiral ionic liquids’. The reduction of the chiral or non-chiral 1-alkylimidazole 3-oxides with Raney-Ni, followed by alkylation with alkyl bromides and subsequent ion exchange to tetrafluoroborates, gave the corresponding 1,3-dialkylimidazolium salts, most of them showing properties of ionic liquids. The alkylation of 1-butyl-4,5-dimethylimidazole 3-oxide and the corresponding imidazole, respectively, with 1,3-dibromopropane led to the first bis-imidazolium dibromides and bis-tetrafluoroborates.

The current case study focuses on the generation, identification, and characterization of two representative mono- and disubstituted alkyl phosphonatocarbenes by means of matrix isolation techniques in conjunction with density functional theory [B3LYP/6-311++G(d,p)] and coupled cluster [CCSD(T)/cc-pVXZ, X = D, T] computations. The EPR measurements identify both carbenes as triplet ground-state species with D values of 0.660 and 0.623 cm(-1), respectively, exhibiting persistency toward intramolecular reactions (the EPR signal observable in perfluoromethylcyclohexane up to around 70 K for the disubstituted molecule). While the reaction of the carbene center of the conformationally rich tetramethyl bisphosphonatocarbene with the CH bonds of the methyl groups leads to phosphaoxetane at room temperature, its fragmentation via a Wittig-type reaction during high vacuum flash pyrolysis (HVFP) results in dimethyl vinylphosphonate and methyl metaphosphate. The latter has been observed for the first time as an isolated entity.

Polycyclic 'cage' ketones, such as pentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-one (10), pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione (11), and adamantan-2-one (16) were treated with the nucleophilic dimethoxycarbene (DMC; 1), which was generated thermally from 2,5-dihydro-2,2-dimethoxy-5,5-dimethyl-1,3,4-oxadiazole (4a) in boiling toluene. In this 'one-pot' procedure, the ahydroxycarboxylic acid ester 12 or a corresponding derivative 15 or 17 was obtained (Schemes 4 – 7). Additionally, 'cage' thione 21 was treated with DMC under the same conditions yielding dimethoxythiirane 22 (Scheme 8). Subsequent hydrolysis or desulfurization (followed by hydrolysis on silica gel) of 22 gave alpha-mercaptocarboxylate 25 and the corresponding desulfurized ester 24, respectively. In all cases, the addition of DMC occurred stereoselectively, and the addition from the exo-face is postulated to explain the structures of the isolated products.

The present paper describes the effect of oxygen and hard phase (diamond) content on the allotropic phase transformation in hot pressed cobalt. Investigations were carried out both on samples made of cobalt and cobalt–diamond materials. All specimens were obtained by hot pressing in graphite moulds. X-ray diffraction (XRD) was used in order to estimate the regular and hexagonal phase content of the cobalt. The XRD measurements were supplemented with microstructural observations by means of scanning electron microscopy and transmission electron microscopy. The obtained results provided evidence that occurrence of phase transformation in hot pressed cobalt upon cooling to room temperature strongly depends on the oxygen content, and it is hindered by a very fine grain structure and the cobalt oxides. The effect of residual stress produced in cobalt–diamond materials, which is the effect of the difference between linear expansion coefficients of metal matrix and diamond on the phase composition of the...

Ruppert’s reagent (CF3-SiMe3) was used in the reaction with derivatives of pentacyclo[5.4.0.0.0.0]undecane-8,11-dione (‘cage’ dione) in the presence of dry CsF to yield trifluoromethyl O-silylated products. Subsequent acidic hydrolysis gave the corresponding hydroxy derivatives. In the case of the ‘cage’ dione the transannular cyclization leading to oxahexacyclic (O-bridged) product was observed.

The syntheses of thiocarbonyl derivatives of pentacyclo[5.4.0.02,6.03,10.05,8]-8,10-dione (1) using bis(trimethylsilyl)sulfide 12 or H2S/HCl as a thionating agent are reported. The complexation reactions of monothioketone 3, dimethoxythioketone 5, and thioxoketone 6 with bisphosphine platinum(0) complexes were investigated. The formed complexes 9a–c and 11 were characterized by 1H, 31P NMR, IR spectroscopy, as well as mass spectrometry and elemental analysis. X-ray crystal structure analyses of 5 and complexes 9a and 11 were performed. The structure analyses show that thiocarbonyl derivatives are coordinated in the η2-mode. In each case, only one isomer is formed, with the platinum complex fragment selectively coordinated in the exo-position. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:584–590, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20332

The kinetics of sintering of Co-Fe materials was studied. The main objective of the work was to establish the effects of iron content and sintering parameters on the microstructure and phase composition of the as-sintered materials. Specimens containing from 3 to 25 wt.% iron were sintered in a dilatometer for one hour at 900, 1000 and 1150OC in either hydrogen or nitrogen atmosphere. The length of specimens during the heating, hold at the temperature and cooling steps were monitored to establish the sample’s shrinkage. Microstructural observations were carried out on polished and etched transverse sections which were also subjected to the X-ray phase analysis.