Skin adhesive hydrogels for the topical delivery of active agents

This thesis illustrates the development of tailor-made, partially hydrated skin adhesive hydrogels as a vehicle for the topical delivery of moisturising agents. Maintaining an optimum hydration level of the stratum corneum ensures that the barrier properties of the skin are preserved. An unsaturated ionic monomer 2-acrylamido-2-methylpropanesulfonic acid sodium salt, glycerol, water, a photoinitiator Irgacure 184 and crosslinker Ebacryl II facilitated the production of monophasic sheet skin adhesives using photopolymerisation. The exploration and modification of the hydrogel components coupled with their influence on the adhesive and dynamic mechanical behaviour led to the development of novel monophasic and biphasic hydrogels. Biphasic pregels comprising of a hydrophobic monomer (epoxidised soybean oil acrylate, lauryl acrylate or stearyl acrylate) micellised with a non ionic surfactant Tween 60 allowed a homogeneous distribution throughout a predominantly hydrophilic phase (2-acrylamido-2-methylpropanesulfonic acid sodium salt, 4-acryloylmorpholine, glycerol and water). Further development of biphasic hydrogel technology led to the incorporation of preformed commercial O/W emulsions (Acronal, Flexbond 150, DM137 or Texicryl 13056WB) allowing the hydrophobic component to be added without prior stabilisation. The topical release of moisturising agents 2-pyrrolidone-5-carboxylic acid, lactobionic acid and d-calcium pantothenate results in the deposition onto the skin by an initial burst mechanism. The hydration level of the stratum corneum was measured using a Comeometer CM 825, Skin Reader MY810 or FT-ATR. The use of hydrophilic actives in conjunction with lipophilic agents for example Vitamin E or Jojoba oil provided an occlusive barrier, which reduced the rate of transepidermal water loss. The partition coefficients of the release agents provided invaluable information which enabled the appropriate gel technology to be selected. In summary the synthetic studies led to the understanding and generation of transferable technology. This enabled the synthesis of novel vehicles allowing an array of actives with a range of solubilities to be incorporated.

Thermo-chemical behaviour and chemical product formation from Polar seaweeds during intermediate pyrolysis

Fundamental analytical pyrolysis studies of biomass from Polar seaweeds, which exhibit a different biomass composition than terrestrial and micro-algae biomass were performed via thermogravimetric analysis (TGA) and pyrolysis-gas chromatography/mass-spectrometry (Py-GC/MS). The main reason for this study is the adaptation of these species to very harsh environments making them an interesting source for thermo-chemical processing for bioenergy generation and production of biochemicals via intermediate pyrolysis. Several macroalgal species from the Arctic region Kongsfjorden, Spitsbergen/Norway (Prasiola crispa, Monostroma arcticum, Polysiphonia arctica, Devaleraea ramentacea, Odonthalia dentata, Phycodrys rubens, Sphacelaria plumosa) and from the Antarctic peninsula, Potter Cove King George Island (Gigartina skottsbergii, Plocamium cartilagineum, Myriogramme manginii, Hymencladiopsis crustigena, Kallymenia antarctica) were investigated under intermediate pyrolysis conditions. TGA of the Polar seaweeds revealed three stages of degradation representing dehydration, devolatilization and decomposition of carbonaceous solids. The maximum degradation temperatures Prasiola crispa were observed within the range of 220-320 C and are lower than typically obtained by terrestrial biomass, due to divergent polysaccharide compositions. Biochar residues accounted for 33-46% and ash contents of 27-45% were obtained. Identification of volatile products by Py-GC/MS revealed a complexity of generated chemical compounds and significant differences between the species. A widespread occurrence of aromatics (toluene, styrene, phenol and 4-methylphenol), acids (acetic acid, benzoic acid alkyl ester derivatives, 2-propenoic acid esters and octadecanoic acid octyl esters) in pyrolysates was detected. Ubiquitous furan-derived products included furfural and 5-methyl-2-furaldehyde. As a pyran-derived compound maltol was obtained by one red algal species (P. rubens) and the monosaccharide d-allose was detected in pyrolysates in one green algal (P. crispa). Further unique chemicals detected were dianhydromannitol from brown algae and isosorbide from green algae biomass. In contrast, the anhydrosugar levoglucosan and the triterpene squalene was detected in a large number of pyrolysates analysed. © 2013 Elsevier B.V. All rights reserved.

Controlled RAFT polymerization and zinc binding performance of catechol-inspired homopolymers

Incorporation of catechols into polymers has long been of interest due to their ability to chelate heavy metals and their use in the design of adhesives, metal-polymer nanocomposites, antifouling coatings, and so on. This paper reports, for the first time, the reversible addition-fragmentation chain transfer (RAFT) polymerization of a protected catechol-inspired monomer, 3,4-dimethoxystyrene (DMS), using commercially available trithiocarbonate, 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT), as a chain transfer agent. Our identified RAFT system produces well-defined polymers across a range of molecular weights (5-50 kg/mol) with low molar mass dispersities (Mw/Mn < 1.3). Subsequent facile demethylation of poly(3,4-dimethoxystyrene) (PDMS) yields poly(3,4-dihydroxystyrene) (PDHS), a catechol-bearing polymer, in quantitative yields. Semiquantitative zinc binding capacity analysis of both polymers using SEM/EDXA has demonstrated that both PDMS and PDHS have considerable surface binding (65% and 87%, respectively), although the films deposited from PDMS are of a better quality and processability due to solubility and lower processing temperatures. © 2014 American Chemical Society.

Titanium dioxide photocatalytic degradation of aliphatic ethers and their primary oxidation products

Two studies were performed to obtain fundamental mechanistic information on the TiO2 catalyzed degradation of organic substrates irradiated at 350 nm in dilute aqueous solutions under oxygenated conditions: (a) The photodecomposition of methyl tert-butyl ether (MTBE) and its intermediate products from β-oxidation, 2-methoxy-2-methylpropanol and 2-methoxy-2-methylpropanol. (b) The photodecomposition of two haloethers, bis-(2-chloroethyl) ether, and bis-(2-chloroisopropyl) ether. Controls were carried out throughout the two studies in the absence of light, and without the semiconductor in order to evaluate the role of photolysis. ^ The syntheses of proposed intermediate products, 2-methoxy-2-methylpropanol, 2-methoxy-2-methylpropanal, 2-methoxy-2-methylpropanoic acid, 2-chloroethyl formate, and 1-chloro-2-propyl acetate, were performed. The formation of these products in the titanium dioxide photocatalytic oxidation of the substrates of interest was also confirmed. TiO2 photocatalysis is a very effective method for the mineralization of aliphatic ethers and their primary oxidation products. ^

Pore water and solid-phase data from site Scharendijke (Lake Grevelingen, NL)

Will be submitted by the author

Seasonal variations in surface metabolite composition of Fucus vesiculosus and Fucus serratus sampled at outer Kiel Fjord (August 2012 - July 2013)

The chemical composition of surface associated metabolites of two Fucus species (Fucus vesiculosus and Fucus serratus) was analysed by means of gas chromatography-mass spectrometry (GC-MS) to describe temporal patterns in chemical surface composition. Method: The two perennial brown macroalgae F. vesiculosus and F. serratus were sampled monthly at Bülk, outer Kiel Fjord, Germany (54°27'21 N / 10°11'57 E) over an entire year (August 2012 - July 2013). Per month and species six non-fertile Fucus individuals were collected from mixed stands at a depth of 0.5 m under mid water level. For surface extraction approx. 50 g of the upper 5-10 cm apical thalli tips were cut off per species. The surface extraction of Fucus was performed according to the protocol of de Nys and co-workers (1998) with minor modifications (see Rickert et al. 2015). GC/EI-MS measurements were performed with a Waters GCT premier (Waters, Manchester, UK) coupled to an Agilent 6890N GC equipped with a DB-5 ms 30 m column (0.25 mm internal diameter, 0.25 mM film thickness, Agilent, USA). The inlet temperature was maintained at 250°C and samples were injected in split 10 mode. He carrier gas flow was adjusted to 1 ml min-1. Alkanes were used for referencing of retention times. For further details (GC-MS sample preparation and analysis) see the related publication (Rickert et al. submitted to PLOS ONE).

Comparative study of bioactive potential of Fueniculum vulgare Mill. and Matricaria recutita L. phenolic rich extracts to functionalize cottage chesse

Synthetic additives used in a wide variety of food products have been associated to some toxic effects. This conducted to an increasing interest of consumers for natural additives, including food preservers [1]. Many aromatic herbs have been used to prepare bioactive extracts with benefits to the consumer's health. Foeniculum vulgare Mill. (fennel) and Matricaria recutita L. (chamomile) are examples of popular herbs rich in phenolic compounds with documented antioxidant and antimicrobial properties [2,3]. The present work confirms the antioxidant (DPPH scavenging activity, reducing power and lipid peroxidation inhibition) and antimicrobial (against bacteria such as Bacillus cereus and Salmonella Typhimurium and fungi such as Aspergillus niger, A. versicolor and PenicilliumfimicuJosum) activities of fennel and chamomile extracts, obtained by decoction. The chemical characterization of the extracts, performed by HPLC-DAD-ESIIMS, revealed the presence of five flavonoids (mainly qercetin-3-0- glucoside) and twelve phenolic acids (mainly 5-0-caffeolyquinic acid) for fennel extract and the presence of nine flavonoids (mainly luteolin-0-glucuronide) and ten phenolic acids (mainly di-caffeoyl-2,7- anhydro-3-deoxy-2-octulopyranosonic acid) for chamomile extract. Due to their high antioxidant and antimicrobial activities, both extracts were then incorporated (at DPPH scavenging activity EC25 value: 0.35 mg/mL and 0.165 mg/mL for fennel and chamomile, respectively) in cottage cheeses (prepared by Queijos Casa Matias Lda) as natural additives with two objectives: to increase the shelf-life of the cottage cheeses and to provide bioactive properties to the final products. The results showed that the use of these natural extracts did not alter significantly the nutritional characteristics of the cottage cheese in comparison with control samples (cottage cheese without extracts), but improved its antioxidant potential (more evident in the samples with chamomile extract). After 14 days of storage, only the control samples showed signs of degradation. Overall, the present study highlights the preservation potential of fennel and chamomile extracts in cottage cheeses, improving also their bioactivity.

Ammonia effects on proton conductivity properties of coordination polymers

Crystalline metal phosphonates are referred to as a type of structurally versatile coordination polymers [1]. Many of them contain guest molecules (H2O, heterocyclics, etc.), acidic sites and, furthermore, their structure can be also amenable for post‐synthesis modifications in order to enhance desired properties [2]. In the present work, we examine the relationships between crystal structure and proton conductivity for several metal phosphonates derive from multifunctional ligands, such as 5-(dihydroxyphosphoryl)isophthalic acid (PiPhtA) [3] and 2-hydroxyphosphonoacetic acid (H3HPAA). Crystalline divalent metal derivatives show a great structural diversity, from 1D to 3D open-frameworks, possessing hydrogen-bonded water molecules and acid groups. These solids present a proton conductivity range between 7.2·10-6 and 1.3·10−3 S·cm-1. Upon exposure to ammonia vapor, from an aqueous solution, solid state transformations are observed accompanied of enhance proton conductivities. The stability of these solids under different environment conditions (temperature and relative humidities) as well as the influence of the ammonia adsorption on the proton conduction properties of the resulting solids will be discussed.

Synthetic polymers blend used in the production of high activated carbon for pesticides removals from liquid phase

For the activated carbon (AC) production, we used the most common industrial and consumer solid waste, namely polyethyleneterephthalate (PET), alone or blended with other synthetic polymer such polyacrylonitrile (PAN). By mixing PET, with PAN, an improvement in the yield of the AC production was found and the basic character and some textural and chemical properties were enhanced. The PET–PAN mixture was subjected to carbonisation, with a pyrolysis yield of 31.9%, between that obtained with PET (16.9%) or PAN (42.6%) separately. The AC revealed a high surface area (1400, 1230 and 1117 m2 g−1) and pore volume (0.46, 0.56 and 0.50 cm3 g−1), respectively, for PET, PAN and PET–PAN precursors. Selected ACs were successfully tested for 4- chloro-2-methylphenoxyacetic acid (MCPA) and diuron removal from the liquid phase, showing a higher adsorption capacity (1.7 and 1.2 mmol g−1, respectively, for MCPA and diuron) and good fits with the Langmuir (PET) and Freundlich equation (PAN and PET–PAN blend). With MCPA, the controlling factor to the adsorption capacity was the porous volume and the average pore size. Concerning diuron, the adsorption was controlled essentially by the external diffusion. A remarkable result is the use of different synthetic polymers wastes, as precursors for the production of carbon materials, with high potential application on the pesticides removals from the liquid phase.

Sugarcane herbicide leaching risk evaluation in Guarany Aquifer.

he region of Ribeirão Preto, São Paulo State, Brazil, is located over recharge area of the Guarany aquifer, the most important source of groundwater in the South Central region of the country. This region is also the most important sugarcane producing area of the country which produces a large amount of the ethanol. This study was conducted to determine the potential risk of herbicide groundwater contamination. The leaching risk potential of herbicides to groundwater was conducted using the weather simulator ?Weather Generator? (WGEN) coupled with the model ?Chemical Movement Trough Layered Soils? (CMLS94). The following herbicides were evaluated in clayey and sandy soils (Typic Haplorthox and Typic Quartzipsamment soils) found in the region: ametryn (N-ethyl-N\'-(1- methylethyl)-6-(methylthio)-1,3,5-triazine-2,4-diamine), atrazine (6-chloro-N-ethyl-N\'-(1-methylethyl)-1,3,5-triazine- 2,4-diamine), clomazone (2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone), diuron (3,4-dichlorophenyl)- N,N-dimethylurea), halosulfuron (3-chloro-5-[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl], hexazinone (3- cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4 (1H,3H)-dione), imazapic ((±)-2-[4,5-dihydro-4-methyl-4- (1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-methyl-3-pyridinecarboxylic acid), imazapyr ((±)-2-[4,5-dihydro-4-methyl- 4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridinecarboxylic acid), MCPA (4-chloro-2-methylphenoxy)acetic acid), metribuzin (4-amino-6-(1,1-dimethylethyl)-3-(methylthio)-1,2,4-triazin-5(4H)-one), MSMA (Amonosodium salt of MAA), paraquat (1,1\'-dimethyl-4,4\'-bipyridinium ion), pendimethalin (N-(1-ethylpropyl)-3,4-dimethyl-2,6- dinitrobenzenamine), picloram (4-amino-3,5,6-trichloro-2-pyridinecarboxylic acid), simazine (6-chloro-N,N\'-diethyl- 1,3,5-triazine-2,4-diamine), sulfentrazone [N-[2,4-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H- 1,2,4-triazol-1-yl]phenyl]methanesulfonamide], and tebuthiuron [N-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-N,N\'- dimethylurea]. Results obtained by our simulation study have shown that the herbicides picloram, tebuthiuron, and metribuzin have the highest leaching potential, in either sandy or clayey soils, with picloram reaching the root zone of sugarcane at 0.6m in less than 150 days.

The Monocarboxylate Transporter 8 and L-Type Amino Acid Transporters 1 and 2 Are Expressed in Mouse Skeletons and in Osteoblastic MC3T3-E1 Cells

Background: Several plasma membrane transporters have been shown to mediate the cellular influx and/or efflux of iodothyronines, including the sodium-independent organic anion co-transporting polypeptide 1 (OATP1), the sodium taurocholate co-transporting polypeptide (NTCP), the L-type amino acid transporter 1 (LAT1) and 2 (LAT2), and the monocarboxylate transporter 8 (MCT8). The aim of this study was to investigate if the mRNAs of these transporters were expressed and regulated by thyroid hormone (TH) in mouse calvaria-derived osteoblastic MC3T3-E1 cells and in the fetal and postnatal bones of mice. Methods: The mRNA expression of the iodothyronine transporters was investigated with real-time polymerase chain reaction analysis in euthyroid and hypothyroid fetuses and litters of mice and in MC3T3-E1 cells treated with increasing doses of triiodothyronine (T(3); 10(-10) to 10(-6) M) or with 10(-8) M T(3) for 1-9 days. Results: MCT8, LAT1, and LAT2 mRNAs were detected in fetal and postnatal femurs and in MC3T3-E1 cells, while OATP1 and NTCP mRNAs were not. LAT1 and LAT2 mRNAs were not affected by TH status in vivo or in vitro or by the stage of bone development or osteoblast maturation (analyzed by the expression of osteocalcin and alkaline phosphatase, which are key markers of osteoblastic differentiation). In contrast, the femoral mRNA expression of MCT8 decreased significantly during post-natal development, whereas MCT8 mRNA expression increased as MC3T3-E1 cells differentiated. We also showed that MCT8 mRNA was up-regulated in the femur of hypothyroid animals, and that it was down-regulated by treatment with T(3) in MC3T3-E1 cells. Conclusions: This is the first study to demonstrate the mRNA expression of LAT1, LAT2, and MCT8 in the bone tissue of mice and in osteoblast-like cells. In addition, the pattern of MCT8 expression observed in vivo and in vitro suggests that MCT8 may be important to modulate TH effects on osteoblast differentiation and on bone development and metabolism.

4-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoic acid: X-ray and DFT-calculated structure

In the title compound, C(11)H(7)NO(4), there is a dihedral angle of 45.80 (7)degrees between the planes of the benzene and maleimide rings. The presence of O-H...O hydrogen bonding and weak C-H...O interactions allows the formation of R (3) 3(19) edge-connected rings parallel to the (010) plane. Structural, spectroscopic and theoretical studies were carried out. Density functional theory (DFT) optimized structures at the B3LYP/6-311 G(d,p) and 6-31++G(d,p) levels are compared with the experimentally determined molecular structure in the solid state. Additional IR and UV theoretical studies allowed the presence of functional groups and the transition bands of the system to be identified.

2-(Phenylcarbonothioylsulfanyl)acetic acid

The title compound, C(9)H(8)O(2)S(2), can be used as a chain transfer agent and may be used to control the behavior of polymerization reactions. O-H center dot center dot center dot O hydrogen bonds of moderate character link the molecules into dimers. In the crystal, the dimers are linked into sheets by C-H center dot center dot center dot O interactions, forming R(4)(2)(12) and R(2)(2)(8) edge-fused rings running parallel to [101]. There are no intermolecular interactions involving the S atoms.

2-[(2-Carboxyphenyl)disulfanyl]benzoic acid-4,4 '-bipyridyl N,N '-dioxide (1/2)

In the title 2:1 adduct, C(14)H(10)O(4)S(2)center dot 0.5C(10)H(8)N(2)O(2), which arose from an unexpected oxidation of a precursor, the dihedral angle between the aromatic rings in the disulfide is 82.51 (11)degrees. In the crystal, the molecules are linked by O-H center dot center dot center dot O, OH center dot center dot center dot N and C-H center dot center dot center dot O interactions, generating sheets.

Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-Hydrazides Active against MRSA

In this preliminary study eighteen p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. The computer programs Sybyl and CORINA were used, respectively, for the design and three-dimensional conversion of the ligands. Molecular interaction fields were calculated using GRID program. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response.