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The ripening of fruits is a determinant factor on the composition of phytochemical compounds such as phenolic compounds. In this study the phenolic profile of quince fruits was determined as a function of its maturity index. Based on the total soluble solids (TSS) and the acidity (TA) of the fruits, four maturity indexes were established (12.55, 14.56, 21.86 and 24.77), using the ratio of TSS/TA. The phenolic profile of quince fruits with different maturity indexes were obtained by a reversed-phase HPLC-DAD and HPLC-DAD/MS. A PCA loading plot was generated to explain the relationship between physicochemical parameters and the phenolic compounds. The phenolic compounds identified in the quince fruits were 3-0-caffeoylquinic acid, catechin, 4-0-caffeoylquinic acid, 5-0-caffeoylquinic acid, coumaric acid, quercetin-3-0-rutinoside and quercetin-3-0-glycosides. The maturity index increase caused in general a reduction of phenolic compounds, these compounds were also influenced by pH and acidity of fruits. Quince is a valuable source of natural phenolic antioxidants, and can be used as raw material to elaborate diverse food products, providing important functional properties.

During the last decades, biomaterials have been deeply studied to perform and improve coatings for biomedical devices. Metallic materials, especially in the orthopedic field, represent the most common material used for different type of devices thanks to their good mechanical properties. Nevertheless, low/medium resistance to corrosion and low osteointegration ability characterizes these materials. To overcome these problems, the use of biocoatings on metals substrate is largely diffused. In fact, biocoatings have a key role to confer biocompatibility properties, to inhibit corrosion and thus improve the lifetime of implanted devices. In this work, the attention was focused on Hydroxyapatite-Chitosan (HA/CS) and Hydroxyapatite-Polyvinylacetate (HA/PVAc) composites, that have been studied as biocoatings for 304 SS based devices. Hydroxyapatite was selected for its osteoconductivity thanks to its chemical structure similar to bones. Furthermore, Chitosan and Polyvinylacetate are largely used yet in medical field (e.g. antibacterial agent or drug deliver) and in this work were used to create a synergic interaction with hydroxyapatite to increase the strength and bioactivity of coating. Biocotings were obtained by galvanic deposition process that does not require an external power supply. It is a spontaneous electrochemical deposition in which materials with different standard electrochemical potential were short-circuited and immersed in an electrolytic solution. Electrons supply for the cathodic reaction in the noblest material comes from oxidation of the less noble material. SEM, EDS, XRD and RAMAN were performed for chemical-physics characterization of biocoatings. Polarization and impedance measurements have been carried out to evaluate corrosion behavior. Besides, in-vitro cytotoxicity assays have been done for the biological features.

A galvanic method to deposit chitosan coatings on stainless steel substrate is reported. Deposition of suitable coatings is desired to improve biocompatibility and corrosion resistance of metallic medical devices to be implanted in human body. In the present work, a thin hydrogel layer of chitosan was deposited on 304SS by a galvanic displacement reaction, which is advantageous first as it does not require external power supply. 304SS was immersed into an aqueous solution of chitosan/lactic acid and electrochemically coupled with magnesium acting as a sacrificial anode. SEM images showed the formation of a uniform layer of chitosan with a thickness controlled by deposition time. Corrosion tests in simulating body fluid showed that chitosan coatings shift the corrosion potential of 304 substrates toward nobler values. Finally, the cytotoxicity of the coating was investigated through cell viability assays with osteoblastic cell MC3T3-E1. The results revealed highly satisfying biocompatibility of the coating.

Plankton food web dynamics were studied during a complete production season in a semi-intensive land-based facility for rearing of turbot (Scophthalmus maximus) larvae. The production season was divided into three production cycles of 3–5 weeks. Phytoplankton biomass (using chlorophyll a as biomass proxy) peaked in each production cycle. However, the maximum biomass decreased from spring (18 μg chlorophyll a L−1) to fall (ca. 7 μg chlorophyll a L−1), simultaneous with a decline in the concentration of dissolved nitrogen in the inoculating water. During the three production cycles, we observed decreasing copepod nauplii concentration from spring to fall in the rearing tanks. The decreasing nitrogen gave increasing carbon to chlorophyll a ratio in the seston (from 23 in spring to 73 in fall). The pool of free amino acids in seston was constant. We suggest that the decreasing nitrogen input in the inoculating water reduces the quality of the phytoplankton and thus the growth potential of the prey for fish larvae, copepods.

The food industry often utilizes flavor-enriched, semifinished food products as ingredients in more complex preparations. To the best of our knowledge, there are no methods to produce minimally processed food items to which flavorings have been added. In this investigation, apple sticks were enriched with a green apple aroma using different techniques. In particular, vacuum impregnation (VI), ultrasound technology (USI), and the combination of these two techniques (VUSI) were compared with atmospheric pressure impregnation (AI). An isotonic solution of fructose containing ascorbic acid and green apple flavoring was used for impregnation of apple sticks. Different treatment times (2.5, 5.0, and 12.5 min) were investigated, and the relative amount of the major compounds of impregnation flavoring was recorded. Significant differences between treatments were detected: VI and VUSI gave the highest aroma enrichment at 5.0 min of treatment. Different impregnation behaviors were recorded for alcohols and esters: the former increased even after 5.0 min of treatment, and the other components increased until 5.0 min and then decreased, mainly when ultrasound was applied (USI and VUSI). Some possible explanations of these results are proposed, although additional studies are needed to explain the mechanisms involved.

We evaluated dehydrofreezing in strawberries in terms of retention of healthy compounds (i.e. polyphenolics) and sensory qualities for direct consumption in substitution of fresh fruit. Different osmodehydration (OD at 30 °C and 5 °C), vacuum osmodehydration (VOD at 30 °C) and immersion chilling freezing (ICF) processes were applied in sucrose syrup. Samples were analyzed for dry matter, soluble solids, pH, titratable acidity, mass transfers, polyphenolic content by HPLC-DAD/MSD, volatile profile by SPME-GC/MSD and consumer acceptance. The results of sensory evaluation, in particular, confirmed the cryoprotective effects of osmotic processes of fruits with respect to untreated frozen control samples. The OD samples at 5 °C presented a water loss to solid gain ratio comparable to OD at 30 °C and VOD samples. Moreover, while osmo-dehydrofreezing at relatively high temperatures caused a slight depletion of phenolic compounds, the samples osmodehydrated at 5 °C showed higher polyphenolic retention. Data on aromatic compounds showed that some compounds increased (e.g. ethanol and acetaldehyde), while others did not appear to be affected by the pre-treatments.

Anthocyanins, the major colourants of strawberries, are polar pigments that are positively charged at low pH. Herein, we have assessed a new analytical method for the separation of anthocyanins using CZE. Acidic buffer solutions (pH a2) were employed in order to maintain pigments in the cation flavylium form and achieve high molar absorptivity at 510 nm. These spectral properties enabled us to identify strawberry anthocyanins in a preliminary stage by detection in the visible range, although the method was optimised at 280 nm to obtain the best S/N. The effects of buffer composition highlighted the necessity of adding an organic modifier to the running buffer to obtain a suitable separation. The electrophoretic method permitted the separation of the three main anthocyanins of strawberry extracts, namely pelargonidin 3-glucoside (Pg-glu), pelargonidin 3-rutinoside and cyanidin 3-glucoside. The electrophoretic results, expressed as retention time and separation efficiency of the major anthocyanin (Pg-glu), were compared to those achieved in HPLC, the analytical technique traditionally used for the investigation of anthocyanins in vegetable matrix. The content of Pg-glu in strawberries (cv. Camarosa), calculated with HPCE and HPLC methods, resulted respectively in 11.41 mg/L and 11.37 mg/L.

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) ⿿ a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound ⿿ has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180 days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200 mg DPV and 0, 16 or 32 mg LNG, Day 1 daily DPV release values were between 4132 and 6113 μg while Day 60 values ranged from 284 to 454 μg. Daily LNG release ranged from 129 to 684 μg on Day 1 and 2⿿91 μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180 days, and maintained daily drug release rates within much narrower windows (either 75⿿131 μg/day or 37⿿66 μg/day for DPV, and either 96⿿150 μg/day or 37⿿57 μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception. yes

The synthesis of a range of novel amine-containing structures and their primary potency as inhibitors of HIV-1 fusion via blocking of the CCR5 receptor is described. The development of the medicinal chemistry strategy and SAR's which led to the identification of the piperidine amide compounds 33 and 36 as excellent leads for further evaluation is described, along with key physicochemical data which highlighted their lead potential.

The discovery of maraviroc 17 is described with particular reference to the generation of high selectivity over affinity for the HERG potassium channel. This was achieved through the use of a high throughput binding assay for the HERG channel that is known to show an excellent correlation with functional effects.

Ring-opening metathesis polymerization (ROMP) of bicyclo[2,2,1]hept-2-ene (norbornene) has been effected in supercritical carbon dioxide (SC CO2) with two types of metal carbene catalysts. It has been found that the polynorbornenes prepared in SC CO2 are similar in molecular weight, molecular weight distribution and thermal stability to their counterparts prepared in tetrahydrofuran (THF). More important, the trans/cis ratio of the resulting polymers could be adjusted by varying the amount of cosolvent THF or metal carbene catalysts. However, neither the reaction temperature nor pressure significantly influenced the trans/cis ratio of the polymer. Copyright © 2005 John Wiley & Sons, Ltd.

Alkenyl-substituted six- and seven-membered cyclic enol ethers, which are potential building blocks for the synthesis of marine polyether natural products, can be prepared in high yield (70–97%) from alkynyl ethers by ruthenium-catalysed ring-closing enyne metathesis. The carbene-bearing ruthenium complex 9 is generally the most efficient catalyst for the reaction.

A previously known imidazole-initiated intramolecular ester migration was modified by replacing the imidazole with Cs2CO3 to effect the efficient conversion of 25, 27-bis-p-methoxy-, 25,27-bis-p-fluoro and 25, 27-bisbenzoyloxycalix[4]arene in the flattened cone conformation to the corresponding 25,26-benzoyloxy compounds in the 1,2-alt. The rearrangement was highly efficient for the unsubstituted and methoxy-substituted esters; the 1,2-alternate isomers were isolated in 80–88% yield, but less efficient for the fluoro-substituted ester (isolated yield 58%). The p-methoxy- and p-fluoroesters were further functionalized in subsequent alkylation reactions with methyl p-toluenesulfonate and pentaethyleneglycol-di-p-tosylate to produce dimethoxy- and calixcrown-ester derivatives in the 1,2-alt. in moderate to good yields. The high yields of the 1,2-alt. are attributed to a π-metal template effect involving the soft cesium ion from the base, two aryl rings and the two phenolate oxygens of the deprotonated calixarene.

The phenolic fraction modification was evaluated in untreated vacuum impregnated frozen apple slices from two varieties (Granny Smith and Stark Delicious) a few days after freezing and after 12 months of frozen storage. After 12 months the phenolic content of both fresh and vacuum impregnated apple slices varied greatly. The most important change was the increase of many polymeric flavan-3-ols, which may be due to hydrolysis of polymeric procyanidins. Furthermore, there was significant correlation (r2 = 0.52, P < 0.05) between the increase in flavan-3-ols and the decrease in pH. In fact, control Stark slices presented the highest pH, and had no statistically significant increase in favan-3-ols. Other classes of phenolic compounds were decreased in apple slices following frozen storage.

Nectarines (Prunus persica L. cv. Maria Laura) were manually selected, cut in slices and divided into four groups: fresh, untreated frozen, soaked in osmotic solution and subsequently frozen, and vacuum impregnated (VI) and subsequently frozen. This investigation was focused on evaluation of consumer acceptance with respect to treated versus untreated frozen nectarine slices. In a preliminary acceptance test of untreated frozen nectarine slices, fruits were generally rejected on the basis of a darkened appearance and ‘‘oxidized’’ taste. These negative attributes were probably linked to the activity of polyphenol oxidase (PPO) and depletion of phenols due to cell rupture during freeze–thaw procedures. For these reasons, in order to evaluate the tendency of fruit to oxidation, several analyses were performed: the antioxidant capacity of phenolic fraction and the o-diphenol content were estimated by spectrophotometric assays, whereas the hydroxycinnamic acid (chlorogenic and neochlorogenic acids) composition was evaluated by high performance liquid chromatography (HPLC). Phenolic content and antioxidant capacity were found to correlate well with the acceptance level of frozen nectarine slices. In this regard a higher phenolic content associated with a higher acceptance level of nectarine samples.

ABTS•+ test, o-diphenols (spectrophotometric) and HPLC-DAD phenolic content in vacuum impregnated apple slices from Stark Delicious and Granny Smith cvv. were studied. Vacuum impregnation (VI) was carried out in a pilot plant using an aqueous solution containing 37.9% dextrose, 15.2% sucrose, 1.0% ascorbic acid, 0.25% calcium chloride and 0.25% sodium chloride. The impregnation time was 30 min and the vacuum pressure was 100 mbar; the temperature was 25 C during all processing steps and the solution/fruit ratio was 11:1. At the end of VI, samples were left 5 min in syrup. They were then rinsed with water, drained in a vibrating screen and quickly frozen. A significant decrease (p < 0.05) of the o-diphenol content was seen (17.84 and 12.32% of the initial content in Stark and Granny varieties, respectively). The same trend was confirmed by HPLC-DAD where reductions in total phenols were 21.57 and 26.86% in Stark and Granny, respectively. Individual phenolic compounds showed different rates of depletion, although in some cases there was no reduction. The ABTS•+ test was strongly affected by the presence of ascorbic acid (AA), which was much higher in treated samples. Sensory evaluation showed higher values of hardness, crispness, juiciness and sourness in VI Granny Smith than VI Stark delicious, with a higher retention of texture parameters in the former. Finally, sweetness was slightly higher in VI Stark.

A rapid method for the screening of metal binding selectivities of host compounds in mixtures is presented. This method involves the separation of mixtures of hosts by HPLC, followed by postcolumn complexation with one or more metals, then analysis by mass spectrometry. The intensities of the host-guest complexes in the mass spectra correlate with the binding selectivities of the hosts. The method was applied to a series of lariat ethers that were synthesized as ion-selective reagents for ion-selective electrodes. The compounds most selective for Na+ vs Li+ and K+ were identified. Additionally, a mixture of substituted calixarenes was screened for alkali-metal-binding selectivity. These compounds were determined to be selective for Cs+ over Rb+, K+, and Na+.

Three new copolymers containing pendant calix[4]arene units have been synthesized via radical initiated reactions involving a vinylic calix[4]arene monomer with methylacrylate, acrylonitrile, and styrene. The calix[4]arene monomer was locked into tie cone conformation by appending four ethoxyethyl groups to its lower rim. The upper rim of the calix[4]arene monomer, which was the site of polymerization, was monofunctionalized with a modified acrylate ester moiety. A seven atom spacer group was incorporated between the bulky calixarene core and the acrylate moiety in order to minimize steric interactions which proved to impede the polymerization. The copolymers were designed to take advantage of the well-established binding interactions of calixarenes with neutral molecules and ions. The ultimate goal of this project is to develop materials that are suitable for incorporation into chemical sensor devices such as ion-specific electrodes, semipermeable membranes and quartz microbalances.

The de novo synthesis of the novel potent building blocks phenyl ( R )-3-acetoxymethyl-3,6-dihydro-2 H -pyridine-1-carboxylate (−)- 7 and phenyl ( S )-3-butyryl-oxymethyl-3,6-dihydro-2 H -pyridine-1-carboxylate (+)- 8 starting from commercially available methyl-1-benzyl-4-oxo-3-piperidinecarboxylate is described. The key steps are the enantioselective esterification of the racemic alcohol 6 and the enantioselective hydrolysis of the racemic acetate 5 , respectively, using lipase P from Pseudomonas caepacia .

A practical synthesis of N-p-anisyl-N-methyl-amino-3-(9-anthryl)-propane from 9-anthraldehyde is described. All the intermediates in this simple five step sequence are crystalline and simple re-crystallisation after each step allows the preparation of this exciplex fluorescence ‘thermometer’ molecule on a preparative scale without resort to chromatography.

Intramolecular [Pd2(dba)3]/tri(2‐furyl)phosphine‐catalysed (dba = dibenzylideneacetone, PhCH=CHCOCH=CHPh) cyclisations of olefinic propargylic carbonates I provided alk‐1‐enyl‐(3‐aza)bicyclo[3.1.0]‐hexanes VIII in good yields. A palladium cascade sequence I → II → III → IV → VII → VIII is proposed. Furthermore, chiral propargylic carbonates such as 23, 24 and 25 allowed diastereoselective formation of bicyclo[3.1.0]hexanes 29, 30 and 31, respectively. The first diastereoselective synthesis of the monoterpene, (−)‐α‐thujone 40 illustrates the potential of the method.

The initial synthesis of UK-427,857 (Maraviroc) is described including the preparation of 4,4-difluorocyclohexanoic acid and amide coupling utilizing a polymer supported reagent.

A practical synthesis of N-p-anisyl-N-methyl-amino-3-(9-anthryl)-propane from 9-anthraldehyde is described. All the intermediates in this simple five step sequence are crystalline and simple re-crystallisation after each step allows the preparation of this exciplex fluorescence ‘thermometer’ molecule on a preparative scale without resort to chromatography.

The de novo synthesis of the novel potent building blocks phenyl ( R )-3-acetoxymethyl-3,6-dihydro-2 H -pyridine-1-carboxylate (−)- 7 and phenyl ( S )-3-butyryl-oxymethyl-3,6-dihydro-2 H -pyridine-1-carboxylate (+)- 8 starting from commercially available methyl-1-benzyl-4-oxo-3-piperidinecarboxylate is described. The key steps are the enantioselective esterification of the racemic alcohol 6 and the enantioselective hydrolysis of the racemic acetate 5 , respectively, using lipase P from Pseudomonas caepacia .

Alkenyl-substituted six- and seven-membered cyclic enol ethers, which are potential building blocks for the synthesis of marine polyether natural products, can be prepared in high yield (70–97%) from alkynyl ethers by ruthenium-catalysed ring-closing enyne metathesis. The carbene-bearing ruthenium complex 9 is generally the most efficient catalyst for the reaction.

Experimental evidence was found for an electronic contribution favoring the cisoid conformation of α,β-unsaturated carbonyl compounds in thermal Diels-Alder transition states

The synthesis, crystal structure, and binding properties are reported for a globe-shaped hemicarcerand (4) composed of two rigid bowl-like units (polar caps) attached to one another at their rims through four o-xylyl units (equatorial spacers). Four pendant β-phenylethyl groups attached to each of the polar caps impart solubility to the system

We have synthesized seven new carceplexes involving two different hosts and six different guests that are soluble in organic solvents. They were prepared by shell closures of cavitands in 4-fold S N 2 reactions to give carcerands in 20-32% yeidls. High structural recognition for encapsulation of the more polar component in mixtures with benzene as a cosolvent was shown in the shell closures. Incarcerated molecules included two CH 3 OH, wo CH 3 CN, CH 3 CH 2 OH, (CH 3 ) 2 NCHO, CH 3 COC-H 2 CH 3 and CH 3 CH 2 COCH 2 CH 3 . All carcerands except H•CH 3 CN•NCCH 3 (2) were fully characterized. The degrees of rotational freedom of the guests relative to the host were studied with 1 H NMR spectral techniques

Avoiding cardiac liability associated with blockade of hERG (human ether a go-go) is key for successful drug discovery and development. This paper describes the work undertaken in the discovery of a potent CCR5 antagonist, maraviroc 34, for the treatment of HIV. In particular the use of a pharmacophore model of the hERG channel and a high throughput binding assay for the hERG channel are described that were critical to elucidate SAR to overcome hERG liabilities. The key SAR involves the introduction of polar substituents into regions of the molecule where it is postulated to undergo hydrophobic interactions with the ion channel. Within the CCR5 project there appeared to be no strong correlation between hERG affinity and physiochemical parameters such as pKa or lipophilicity. It is believed that chemists could apply these same strategies early in drug discovery to remove hERG interactions associated with lead compounds while retaining potency at the primary target.

The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades and diverse geographic origin (geometric mean 90% inhibitory concentration of 2.0 nM). Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes. There was little difference in the sensitivity of the 200 viruses to maraviroc, as illustrated by the biological cutoff in this assay (= geometric mean plus two standard deviations [SD] of 1.7-fold). The mechanism of action of maraviroc was established using cell-based assays, where it blocked binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry. Maraviroc did not affect CCR5 cell surface levels or associated intracellular signaling, confirming it as a functional antagonist of CCR5. Maraviroc has no detectable in vitro cytotoxicity and is highly selective for CCR5, as confirmed against a wide range of receptors and enzymes, including the hERG ion channel (50% inhibitory concentration, >10 μM), indicating potential for an excellent clinical safety profile. Studies in preclinical in vitro and in vivo models predicted maraviroc to have human pharmacokinetics consistent with once- or twice-daily dosing following oral administration. Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS.

A concise total synthesis of the potent cytotoxic marine natural products salicylihalamide A and B (la, b) is reported. Key steps of our approach were the asymmetric hydrogenation reactions of β-keto esters 18 and 32 catalyzed by [((S)-BINAP)Ru-Cl 2 ] 2 .NEt 3 and the cyclization of the macrolide core by ring closing olefin metathesis (RCM) using the "second-generation" ruthenium carbene complex 24 as the catalyst which bears an imidazol-2-ylidene ligand. The E/Z ratio obtained in this macrocyclization reaction was determined by the protecting groups at the remote phenolic OH group of the cyclization precursor. The elaboration of the resulting cycloalkene 37 into the final target involved a CrCl 2 -mediated synthesis of vinyliodide 49 which, after deprotection, did undergo a copper-catalyzed cross-coupling process with the (Z,Z)-configurated carboxamide 42 to form the labile enamide moiety of 1. Compound 42 was derived from a palladium-catalyzed Negishi coupling between butynylzinc chloride and 3-iodoacrylate 39 followed by a Lindlar reduction of enyne 40 thus obtained and a final aminolysis of the ester group.

Background: By extending the use duration of vaginal rings (VRs) the overall production cost per patient per month can be greatly reduced. Matrix-type ring designs produce an initial burst of drug release and concentrations during the burst must be maintained within safe limits. This constrains both the maximum drug load and in turn the use duration of a matrix ring. By contrast reservoir-type VRs comprise a drug-loaded reservoir surrounded by a rate-controlling non-medicated sheath such that initial burst release is minimised and constant daily release rates are achieved. In this way greater drug loadings and longer use periods are possible. Here we report the development of reservoir VRs formulations containing dapivirine (DPV) and various contraceptive steroids. Methods: Reservoir VRs were manufactured with injection molded cores containing ethinyl estradiol (EE) etonogestrel (ETO) levonorgestrel (LNG) or DPV. Addition- and condensation-cured silicone cores were tested. All cores were overmolded with a blank 1.5 mm addition-cured silicone sheath. In-vitro release was assessed for up to 60 days. Results: VRs comprising addition cured silicone cores and blank addition cured silicone sheath layers provided zero order release of DPV (95 µg/day) and LNG (30 µg/day) but not EE (detectable release on days 2 to 10 only) or ETO (no detectable release at any time). Rings comprising a condensation-cured silicone core provided zero order release of DPV (119 µg/day) EE (328 µg/day days 4 to 18) ETO (422 µg/day days 4 to 18) and LNG (69 µg/day). Conclusions: Reservoir-type VRs offering zero order release kinetics have potential as a multipurpose prevention technology (MPT) product for contraception and HIV-prevention with use duration of several months. However the contraceptive hormones require careful selection of the silicone polymer system to ensure adequate release while DPV is readily released from both types tested.

A catalysis-based approach to the core region 24 of the antitumor agents salicylihalamides A and B is reported. Key steps are two asymmetric hydrogenations of beta-keto esters 13 and 16 catalyzed by [(R)-BINAP.RuCl(2)](2).NEt(3) and an RCM-based macrocyclization effected by the NHC-containing ruthenium carbene 21. The stereochemical outcome of the latter reaction is controlled by remote substituents on the phenolic OH group of the cyclization precursor 23.

Carceplexes form with high structural recognition of their incarcerated guests (2MeOH, MeCN, 2MeCN, EtOH, Me2NCHO, MeCOEt, or Et2CO); the physical properties of these complexes depend on the structures of both host and guest.

Calixarenes of a variety of molecular weights and with several different functional attachments have been studied as high resolution, high contrast negative electron beam resists. In this article, results are presented for a new type of calixarene molecule to be used as an electron beam resist. The molecule differs from previous calixarene resists through the use of bridging groups to limit its conformational mobility and by having only a partial functionalization of the available phenol units with allyl groups to enhance the resist sensitivity. Both the sensitivity and contrast of the calixarene were measured. The measured contrast was found to be 4, while the sensitivity was 3.6mC∕cm2 which is comparable to other fully functionalized calix[6]arene resists. A closer comparison of this calixarene with similar calixarenes indicates that the measured sensitivity is better than would be expected for this partially functionalized molecule and that full functionalization might not be necessary to obtain a sign...

A hemicarcerand composed of two bowls attached at their rims with four O(CH2CH2O)2 units, when heated with 22 guests containing 6–12 rigidly-arranged non-hydrogen atoms, formed 22 isolable, characterized hemicarceplexes, but failed to form isolable complexes with 34 other potential guests of the same molecular size range.

This report updates and corrects information in Technical Report No. 6 (September 15, 1985). New data includes concentration effects on tin-119 chemical shifts, measurements of chemical shifts of dibutyltin dichloride (5) plus chloride ion at low concentrations, direct determination of relative complexing strengths of acyclic model 5 against macrocyclic hosts and modified calculations of host-guest binding energies in acetonitrile. Three macrocyclic Lewis acidic hosts containing two symmetrically disposed dichlorostanna moieties (1-3, ring sizes 18, 22, 26 atoms, respectively) have been prepared as has an acyclic di-tin model, 5,5-16,16-tetrachloro-5,16-distannadocosane (4). The complexation of 1-4 and dibutyltin dichloride (5) with chloride ion in acetonitrile was studied by tin-119 NMR spectroscopy. Rapid exchange of chloride between tin atoms occurred at all ratios of chloride to host studied. An iterative computer program was used to provide estimates of the binding constants of 1, 2, 4 and 5 with chloride. Competition experiments were performed wherein two hosts competed for limited chloride ion, and the tin-119 NMR spectra of the mixtures were analyzed to determine the relative amount of chloride bound by each host and hence the ratio of the binding constants for the two hosts. Good agreement between the relative binding constants found in the latter studies and the ratios of the absolute binding constants found in the former studies was found.

The preparation of eight symmetrical, macrobicyclic hosts containing two chloride or bromide substituted tin atoms at the bridgehead positions and linking chains of 6, 7, 8, 10, 12 methylene groups are described. In solution, the smaller members exist as one isomer with the halogens outside of the cavity (out-out isomer), but the larger members exist as a mixture of the major out-out isomer and a minor in-out isomer that contains one halogen inside the cavity. Complexation of chloride anion by the five chloride substituted hosts and of bromide anion by the three bromide substituted hosts in halogenated solvents was studied by 119 sub Sn NMR spectroscopy. All of the bicyclic hosts that bind halide form complexes with 1:1 stoichiometry with a guest anion encrypted within the cavity of the host. Equilibrium constants for formation of the complexes were measured. Temperature dependent dynamic NMR behavior was observed for four bicyclic hosts binding chloride and for one host binding bromide, and simulations of the spectra measured at various temperatures provided rate constants for binding guest anion within the cavity and for dissociation of the guest anion from cavity. Arrhenius functions for these processes were calculated. Size selective binding was observed in both chloride and bromide binding. For chloride complexation, the rate of formation of complexes at 20 deg C increased monotonically as a function of the linking chain length, but the rate of dissociation did not.

Reactions of the α,β-unsaturated aldehyde 1 with the O-silyl ketene acetals 10 have been investigated. Both Michael addition and [4+2] cycloaddition products were formed, depending on the reaction conditions.

Preparation of the title class of anion-binding hosts is described, and the chloride binding properties of one host are reported.

Crystalline complexes of 1,10-dichloro-1,10-distannabicyclo.8. 8hexacosane and benzyltriphenylphosphonium chloride (complex 3) and of 1,8- dichloro-1,8-distannabicyclo-6.6.6eicosane and tetrabutylammonium fluoride (complex 4) have been studied by X ray crystallography and solid state 119 Sn NMR spectroscopy. The halide ions are encrypted within the cavities of the bicyclic hosts in both complexes. Complex 3 is a stannates stannane species wherein one of the Lewis acidic tins binds the chloride strongly and the other interacts with the chloride only weakly. Complex 4 is a bis-hemistannate species wherein the Lewis acidic tin atoms bind the guest fluoride simultaneously. Low temperature species wherein the Lewis acidic tin the two complexes in halogenated solvents were studied. A chloride jump from one tin to the other was observed in complex 3; the dynamic process has an activation energy of 5.3 kcal/ mol. Line broadening of the tin signals in complex 4 was consistent with a similar fluoride jump with an activation energy of 2.9 kcal/mol. The crystalline complexes were reasonable models for the solution complexes in both cases, and the structural features in the solid state can be used to rationalize the binding in solution.