Precise Definition of a "Monolayer Point" in Polymer Brush Films for Fabricating Highly Coherent TiO2 Thin Films by Vapor-Phase Infiltration.

In this work, we show that in order to fabricate coherent titania (TiO2) films with precise thickness control, it is critical to generate a complete polymer brush monolayer. To date, demonstrations of such dense polymer monolayer formation that can be utilized for inorganic infiltration have been elusive. We describe a versatile bottom-up approach to covalently and rapidly (60 s processing) graft hydroxyl-terminated poly(2-vinyl pyridine) (P2VP-OH) polymers on silicon substrates. P2VP-OH monolayer films of varying thicknesses can subsequently be used to fabricate high-quality TiO2 films. Our innovative strategy is based upon room-temperature titanium vapor-phase infiltration of the grafted P2VP-OH polymer brushes that can produce TiO2 nanofilms of 2-4 nm thicknesses. Crucial parameters are explored, including molecular weight and solution concentration for grafting dense P2VP-OH monolayers from the liquid phase with high coverage and uniformity across wafer-scale areas (>2 cm2). Additionally, we compare the P2VP-OH polymer systems with another reactive polymer, poly(methyl methacrylate)-OH, and a relatively nonreactive polymer, poly(styrene)-OH. Furthermore, we prove the latter to be effective for surface blocking and deactivation. We show a simple process to graft monolayers for polymers that are weakly interacting with one another but more challenging for reactive systems. Our methodology provides new insight into the rapid grafting of polymer brushes and their ability to form TiO2 films. We believe that the results described herein are important for further expanding the use of reactive and unreactive polymers for fields including area-selective deposition, solar cell absorber layers, and antimicrobial surface coatings.

Nitrogen reactive ion etch processes for the selective removal of poly-(4-vinylpyridine) in block copolymer films.

Self-assembling block copolymer (BCP) patterns are one of the main contenders for the fabrication of nanopattern templates in next generation lithography technology. Transforming these templates to hard mark materials is key for pattern transfer and in some cases, involves selectively removing one block from the nanopattern. For poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP), a high χ BCP system which could be potentially incorporated into semiconductor nanofabrication, this selective removal is predominantly done by a wet etch/activation process. Conversely, this process has numerous disadvantages including lack of control and high generation of waste leading to high cost. For these reasons, our motivation was to move away from the wet etch process and optimise a dry etch which would overcome the limitations associated with the activation process. The work presented herein shows the development of a selective plasma etch process for the removal of P4VP cores from PS-b-P4VP nanopatterned film. Results have shown that a nitrogen reactive ion etch plasma has a selectivity for P4VP of 2.2:1 and suggest that the position of the nitrogen in the aromatic ring of P4VP plays a key role in this selectivity. In situ plasma etching and x-ray photoelectron spectrometry measurements were made without breaking vacuum, confirming that the nitrogen plasma has selectivity for removal of P4VP over PS.

In Situ XPS Chemical Analysis of MnSiO3 Copper Diffusion Barrier Layer Formation and Simultaneous Fabrication of Metal Oxide Semiconductor Electrical Test MOS Structures.

Copper/SiO2/Si metal-oxide-semiconductor (MOS) devices both with and without a MnSiO3 barrier layer at the Cu/SiO2 interface have been fabricated in an ultrahigh vacuum X-ray photoelectron spectroscopy (XPS) system, which allows interface chemical characterization of the barrier formation process to be directly correlated with electrical testing of barrier layer effectiveness. Capacitance voltage (CV) analysis, before and after tube furnace anneals of the fabricated MOS structures showed that the presence of the MnSiO3 barrier layer significantly improved electric stability of the device structures. Evidence of improved adhesion of the deposited copper layer to the MnSiO3 surface compared to the clean SiO2 surface was apparent both from tape tests and while probing the samples during electrical testing. Secondary ion mass spectroscopy (SIMS) depth profiling measurements of the MOS test structures reveal distinct differences of copper diffusion into the SiO2 dielectric layers following the thermal anneal depending on the presence of the MnSiO3 barrier layer.

Practical synthesis of a renin inhibitor via a diastereoselective Dieckmann cyclization.

A scalable synthesis of a potent renin inhibitor (1) is described. The absolute stereochemistry is set via an unprecedented diastereoselective Dieckmann cyclization directed by a remote chiral protecting group. This transformation enables preparation of chiral 1,3-[3.3.1]-diazabicyclononenes by desymmetrization of alkyl-esters, with selectivities ranging from 4 to 17:1.

Scalable synthesis of a prostaglandin EP4 receptor antagonist.

The evolution of scalable, economically viable synthetic approaches to the potent and selective prostaglandin EP4 antagonist 1 is presented. The chromatography-free synthesis of multikilogram quantities of 1 using a seven-step sequence (six in the longest linear sequence) is described. This approach has been further modified in an effort to identify a long-term manufacturing route. Our final synthesis involves no step requiring cryogenic (< -25 degrees C) conditions; comprises a total of four steps, only three of which are in the longest linear synthesis; and features the use of two consecutive iron-catalyzed Friedel-Crafts substitutions.

Practical synthesis of a potent bradykinin B(1) antagonist via enantioselective hydrogenation of a pyridyl N-acyl enamide.

A practical and efficient synthesis of bradykinin B(1) antagonist 1 is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of 1 in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.

Synthesis of 3-aminoisoxazoles via the addition-elimination of amines on 3-bromoisoxazolines.

A novel two-step procedure for the synthesis of 3-amino-5-substituted-isoxazoles is described. In the presence of a base, readily available 3-bromoisoxazolines react with amines to afford 3-aminoisoxazolines. An oxidation protocol was developed for these heterocycles to provide 3-aminoisoxazoles in consistently high yield.

A practical enantioselective synthesis of odanacatib, a potent Cathepsin K inhibitor, via triflate displacement of an alpha-trifluoromethylbenzyl triflate.

An enantioselective synthesis of the Cathepsin K inhibitor odanacatib (MK-0822) 1 is described. The key step involves the novel stereospecific S(N)2 triflate displacement of a chiral alpha-trifluoromethylbenzyl triflate 9a with (S)-gamma-fluoroleucine ethyl ester 3 to generate the required alpha-trifluoromethylbenzyl amino stereocenter. The triflate displacement is achieved in high yield (95%) and minimal loss of stereochemistry. The overall synthesis of 1 is completed in 6 steps in 61% overall yield.

Magnesiation of electron-rich aryl bromides and their use in nickel-catalyzed cross-coupling reactions.

Electron-rich aryl bromides are rapidly converted to the corresponding lithium triarylmagnesiates with (n-Bu)3MgLi, which undergo efficient nickel-catalyzed Kumada-Corriu cross-coupling reactions with a variety of aryl and alkenyl bromides, chlorides, tosylates, and triflates.

Niche-based modelling as a tool for predicting the risk of alien plant invasions at a global scale.

Predicting the probability of successful establishment of plant species by matching climatic variables has considerable potential for incorporation in early warning systems for the management of biological invasions. We select South Africa as a model source area of invasions worldwide because it is an important exporter of plant species to other parts of the world because of the huge international demand for indigenous flora from this biodiversity hotspot. We first mapped the five ecoregions that occur both in South Africa and other parts of the world, but the very coarse definition of the ecoregions led to unreliable results in terms of predicting invasible areas. We then determined the bioclimatic features of South Africa's major terrestrial biomes and projected the potential distribution of analogous areas throughout the world. This approach is much more powerful, but depends strongly on how particular biomes are defined in donor countries. Finally, we developed bioclimatic niche models for 96 plant taxa (species and subspecies) endemic to South Africa and invasive elsewhere, and projected these globally after successfully evaluating model projections specifically for three well-known invasive species (Carpobrotus edulis, Senecio glastifolius, Vellereophyton dealbatum) in different target areas. Cumulative probabilities of climatic suitability show that high-risk regions are spatially limited globally but that these closely match hotspots of plant biodiversity. These probabilities are significantly correlated with the number of recorded invasive species from South Africa in natural areas, emphasizing the pivotal role of climate in defining invasion potential. Accounting for potential transfer vectors (trade and tourism) significantly adds to the explanatory power of climate suitability as an index of invasibility. The close match that we found between the climatic component of the ecological habitat suitability and the current pattern of occurrence of South Africa alien species in other parts of the world is encouraging. If species' distribution data in the donor country are available, climatic niche modelling offers a powerful tool for efficient and unbiased first-step screening. Given that eradication of an established invasive species is extremely difficult and expensive, areas identified as potential new sites should be monitored and quarantine measures should be adopted.

A murine model to study leukocyte rolling and intravascular trafficking in lung microvessels.

The cascade of leukocyte interactions under conditions of blood flow is well established in the systemic microcirculation, but not in lung microcirculation. We have developed a murine model to study lung microcirculation by transplanting lung tissue into dorsal skin-fold window chambers in nude mice and examining the ability of leukocytes to traffic within revascularized lung microvessels by intravital microscopy. The revascularized lung allograft demonstrated a network of arterioles, capillaries, and postcapillary venules with continuous blood flow. Stimulation of the lung allograft with TNF-alpha induced leukocyte rolling and adhesion in both arterioles and venules. Treatment with function-blocking anti-selectin mAb revealed that P- and L-selectin are the predominant rolling receptors in the lung microvessels, with E-selectin strengthening P-selectin-dependent interactions. Intravital microscopic studies also demonstrated that during their transit in capillaries, some leukocytes undergo shape change and continue to roll as elongated cells in postcapillary venules. Furthermore, the revascularized microvessels demonstrated the ability to undergo vasoconstriction in response to superfusion with endothelin-1. Overall, these studies demonstrate that the revascularized lung allograft is responsive to various external stimuli such as cytokines and vaso-active mediators and serves as a model to evaluate the interaction of leukocytes with the vascular endothelium in the lung microcirculation under acute as well as chronic experimental conditions.