Novel Photochemical Methodologies For Diversity Oriented Synthesis And Screening Of Combinatorial Libraries

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups. Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds. To develop this novel methodology further and explore its generality, we directed our attention to the Diels-Alder adducts based on various chromones. We discovered that the Diels-Alder adducts of chromones are capable of photoinduced alkene-arene [2+2] cycloaddition producing different dienes, which can either dimerize or be introduced into a double-tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] synthetic sequence, followed by an acid-catalyzed oxametathesis, leading to a rapid expansion of molecular complexity over a few experimentally simple steps. In view of the fact that oxametathesis previously was primarily observed in aromatic oxetanes, we decided to prepare model aliphatic oxetanes with a conformationally unconstrained or "flexible" methyl group based on the Diels-Alder adducts of cyclohexadiene or cyclopentadiene with methyl vinyl ketone. Upon addition of an acid, the expected oxametathesis occurred with results similar to those observed in the aromatic series proving the generality of this approach. Also we synthesized polycyclic oxetanes resulting from the Diels-Alder adducts of cyclic ketones. This not only gave us access to remarkably strained oxetane systems, but also the mechanism for their protolytic ring opening provided a great deal of insight to how the strain affects the reactivity. Additionally, we discovered that although the model Hetero-Diels-Alder adducts did not undergo [2+2] cycloaddition, both exo- and endo-Sulfa-Diels-Alder products, nonetheless, were photochemically active and various products with defined stereochemistry could be produced upon photolysis. In conclusion, we have developed an approach to the encoding and screening of solution phase libraries based on the photorelease of externally sensitized photolabile tags. The encoding tags can be released into solution only when a binding event occurs between the ligand and the receptor, equipped with an electron transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.

Stabilisation of low softening point petroleum pitch fibres by iodine treatment

A method using iodine has been developed for the stabilisation of low softening point (SP) pitch fibres that avoids air stabilisation in the production of carbon fibres (CF). The interaction between iodine and petroleum pitches has been studied by following the changes in the hydrogen content, aromatic or aliphatic, during the heat treatment of iodine-treated pitch fibres. Two low SP petroleum pitches were used and the iodine-treated pitch fibres were analysed by TGA, DSC, DRIFT, XPS and SEM. The results confirm that using this novel method pitches with low SP can be used to prepare CF with two advantages, compared with conventional methods. The stabilisation time is considerably reduced and treatments to increase the SP, usually required when low SP pitches are used to prepare CF, can be avoided.

Asymmetric aldol reaction with BINAM-sulfonyl polymeric organocatalyst

The BINAM-sulfonyl polymeric organocatalysts was prepared by the AIBN-promoted copolymerization of BINAM-derived sulfonamide, styrene and divinylbenzebe. The polymer catalyzed the asymmetric aldol reaction of aliphatic ketones with aromatic aldehydes to give the aldol products in up to 83% yield and with up to 95% ee. The catalysts could be recovered upt to 6 times with only a slight decrease on its activity.

Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee’s up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary.

Synthesis of Nitrogenated Heterocycles by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)haloimines

Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.

The structure of a PII signaling protein from a halophilic archaeon reveals novel traits and high-salt adaptations

To obtain insights into archaeal nitrogen signaling and haloadaptation of the nitrogen/carbon/energy-signaling protein PII, we determined crystal structures of recombinantly produced GlnK2 from the extreme halophilic archaeon Haloferax mediterranei, complexed with AMP or with the PII effectors ADP or ATP, at respective resolutions of 1.49 Å, 1.45 Å, and 2.60 Å. A unique trait of these structures was a three-tongued crown protruding from the trimer body convex side, formed by an 11-residue, N-terminal, highly acidic extension that is absent from structurally studied PII proteins. This extension substantially contributed to the very low pI value, which is a haloadaptive trait of H. mediterranei GlnK2, and participated in hexamer-forming contacts in one crystal. Similar acidic N-extensions are shown here to be common among PII proteins from halophilic organisms. Additional haloadaptive traits prominently represented in H. mediterranei GlnK2 are a very high ratio of small residues to large hydrophobic aliphatic residues, and the highest ratio of polar to nonpolar exposed surface for any structurally characterized PII protein. The presence of a dense hydration layer in the region between the three T-loops might also be a haloadaptation. Other unique findings revealed by the GlnK2 structure that might have functional relevance are: the adoption by its T-loop of a three-turn α-helical conformation, perhaps related to the ability of GlnK2 to directly interact with glutamine synthetase; and the firm binding of AMP, confirmed by biochemical binding studies with ATP, ADP, and AMP, raising the possibility that AMP could be an important PII effector, at least in archaea.

Microwave-Enhanced Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)imines

Microwave irradiation has considerably enhanced the efficiency of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropyl alcohol catalyzed by a ruthenium complex bearing the achiral ligand 2-amino-2-methylpropan-1-ol. In addition to shortening reaction times for the transfer hydrogenation processes to only 30 min, the amounts of ruthenium catalyst and isopropyl alcohol can be considerably reduced in comparison with our previous procedure assisted by conventional heating, which diminishes the environmental impact of this new protocol. This methodology can be applied to aromatic, heteroaromatic and aliphatic N-(tert-butylsulfinyl)ketimines, leading, after desulfinylation, to the expected primary amines in excellent yields and with enantiomeric excesses of up to 96 %.

Detritylation of Protected Tetrazoles by Naphthalene-Catalyzed Lithiation

Treatment of N-tritylated tetrazoles bearing aliphatic, aromatic, or heteroaromatic substituents (including functionalized ones) with lithium powder and a catalytic amount of naphthalene led to reductive removal of the trityl group to give excellent yields of the corresponding free tetrazoles without decomposition of the tetrazole ring. The detritylation process was successfully extended to several tetrazoles that are components of sartans, an interesting class of drugs. The chemoselectivity between trityl–tetrazole and trityl­–amine bond-cleavage reactions was also studied. This method represents an efficient technique for deprotection of tritylated tetrazoles under non-acidic conditions.

New hybrid materials based on the grafting of Pd(II)-amino complexes on the graphitic surface of AC: preparation, structures and catalytic properties

A novel procedure for the preparation of solid Pd(II)-based catalysts consisting of the anchorage of designed Pd(II)-complexes on an activated carbon (AC) surface is reported. Two molecules of the Ar–S–F type (where Ar is a plane-pyrimidine moiety, F a Pd(II)-ligand and S an aliphatic linker) differing in F, were grafted on AC by π–π stacking of the Ar moiety and the graphene planes of the AC, thus favouring the retaining of the metal-complexing ability of F. Adsorption of Pd(II) by the AC/Ar–S–F hybrids occurs via Pd(II)-complexation by F. After deep characterization, the catalytic activities of the AC/Ar–S–F/Pd(II) hybrids on the hydrogenation of 1-octene in methanol as a catalytic test were evaluated. 100% conversion to n-octane at T = 323.1 K and P = 15 bar, was obtained with both catalysts and most of Pd(II) was reduced to Pd(0) nanoparticles, which remained on the AC surface. Reusing the catalysts in three additional cycles reveals that the catalyst bearing the F ligand with a larger Pd-complexing ability showed no loss of activity (100% conversion to n-octane) which is assigned to its larger structural stability. The catalyst with the weaker F ligand underwent a progressive loss of activity (from 100% to 79% in four cycles), due to the constant aggregation of the Pd(0) nanoparticles. Milder conditions, T = 303.1 K and P = 1.5 bar, prevent the aggregation of the Pd(0) nanoparticles in this catalyst allowing the retention of the high catalytic efficiency (100% conversion) in four reaction cycles.

Kinetic study and thermal decomposition behavior of viscoelastic memory foam

A systematic investigation of the thermal decomposition of viscoelastic memory foam (VMF) was performed using thermogravimetric analysis (TGA) to obtain the kinetic parameters, and thermogravimetric analysis coupled to Fourier Transformed Infrared Spectrometry (TGA-FTIR) and thermogravimetric analysis coupled to Mass Spectrometry (TGA-MS) to obtain detailed information of evolved products on pyrolysis and oxidative degradations. Two consecutive nth-order reactions were employed to correlate the experimental data from dynamic and isothermal runs performed at three different heating rates (5, 10 and 20 K/min) under an inert atmosphere. On the other hand, for the kinetic study of the oxidative decomposition, the data from combustion (synthetic air) and poor oxygen combustion (N2:O2 = 9:1) runs, at three heating rates and under dynamic and isothermal conditions, were correlated simultaneously. A kinetic model consisting of three consecutive reactions presented a really good correlation in all runs. TGA-FTIR analysis showed that the main gases released during the pyrolysis of VMF were determined as ether and aliphatic hydrocarbons, whereas in combustion apart from the previous gases, aldehydes, amines and CO2 have also been detected as the main gases. These results were confirmed by the TGA-MS.

Potential Shifts in Canadian High Arctic Sedimentary Organic Matter Composition With Permafrost Active Layer Detachments

Increased temperature and precipitation in Arctic regions have led to deeper thawing and structural instability in permafrost soil. The resulting localized disturbances, referred to as active layer detachments (ALDs), may transport organic matter (OM) to more biogeochemically active zones. To examine this further, solid state cross polarization magic angle spinning 13C nuclear magnetic resonance (CPMAS NMR) and biomarker analysis were used to evaluate potential shifts in riverine sediment OM composition due to nearby ALDs within the Cape Bounty Arctic Watershed Observatory, Nunavut, Canada. In sedimentary OM near ALDs, NMR analysis revealed signals indicative of unaltered plant-derived material, likely derived from permafrost. Long chain acyclic aliphatic lipids, steroids, cutin, suberin and lignin occurred in the sediments, consistent with a dominance of plant-derived compounds, some of which may have originated from permafrost-derived OM released by ALDs. OM degradation proxies for sediments near ALDs revealed less alteration in acyclic aliphatic lipids, while constituents such as steroids, cutin, suberin and lignin were found at a relatively advanced stage of degradation. Phospholipid fatty acid analysis indicated that microbial activity was higher near ALDs than downstream but microbial substrate limitation was prevalent within disturbed regions. Our study suggests that, as these systems recover from disturbance, ALDs likely provide permafrost-derived OM to sedimentary environments. This source of OM, which is enriched in labile OM, may alter biogeochemical patterns and enhance microbial respiration within these ecosystems.

Organic geochemistry of ODP Hole 162-985A sediments

Dark, organic-rich sediments were recovered from the lower Miocene section (~16.6 Ma) in Hole 985A in the Norway Basin during Ocean Drilling Program Leg 162. Organic carbon and total sulfur contents of the dark sediments showed a maximum concentration of 5.6 and 26.1 wt%, respectively. Sulfur enrichment in the sediments indicates that these dark layers were formed under anoxic conditions in bottom water. Four dark and eight greenish gray sediment samples, ranging in age from early Miocene to Pleistocene, were analyzed for lipid-class compounds (aliphatic hydrocarbons, fatty alcohols, and sterols) using gas chromatography (GC) and GC/mass spectrometry to better understand the formation processes of the organic-rich dark layers and to reconstruct the paleoenvironmental changes. The molecular distributions of n-alkanes and fatty alcohols indicate that terrigenous organic matter largely contributed to both types of sediments. Significant amounts of hopanoid hydrocarbons, such as diploptene and hop-17(21)-ene, however, were detected characteristically in the dark sediments, which suggests that prokaryotes such as methane-oxidizing bacteria or cyanobacteria may have significantly contributed to the formation of these organic-rich, dark sediments. These results indicate that the bottom waters of the Norway Basin had been subjected to anoxic conditions during the early Miocene.

(Table 1) Concentration and geological parameters of n-alkanes and n-alkenes in surface sediments from the Gulf of Gabes, Tunisia

Abstract Hydrocarbons in surface sediments were studied quantitatively and qualitatively in 18 stations along the coastline of Gabes Gulf in Tunisia. The results show that the total hydrocarbon levels vary along a wide range from 90 to 1,800 ppm. The GC-MS profiles of aliphatic hydrocarbons vary according to the stations and show that the hydrocarbons were derived from various sources. A special feature prevalent in several stations was identified: aliphatic hydrocarbons with distinctive chemical features. This includes a high abundance of even-numbered n-alkanes (n-C14 - n-C26, maximizing at n-C18, n-C20 and n-C22) and n-alk-1-enes (n-C14:1 - n-C24:1, maximizing at n-C16:1, n-C18:1, n-C20:1 and n-C22:1). This unusual predominance of even-numbered n-alkanes/alkenes is reported for the first time in the Gulf of Gabes and it thus contributes to the information on the rare occurrence of such distributions in the geosphere.