Synthesis, Characterization and Cell Viability of Novel Tripodal Amines

Cancer, over the years, has become a much more prevalent focus for the scientific community. Organizations and laboratories all over the world have spent countless hours searching for a cure, trying to learn more about what makes cancer so powerful and what is the best way to stop its growth. Iron-chelation drugs were already on the market, and it was shown that they did have the ability to act as both iron-chelators and anticancer drugs. Most of these iron-chelating drugs are not as effective at killing cancer cells as the medical field desires. Novel iron-chelating tris-indolyl derivatives, GSO2, GSO4 and GSO6, were synthesized and tested for their potential anti-cancer properties. These compounds were characterized using both melting points and NMR. Apoptosis was the chosen method for cell death of the PC3 cells. The compounds, GSO2 and GSO4 did show promising results when tested on human prostate cancer cell lines. The success of these compounds does sanction further research into apoptosis of other human cancer cell lines

Cyclic AMP in The Normal State and Depressive Illness.

Two methods for the measurement of cyclic AMP, enzymic radioisotopic displacement and protein binding (saturation) assay, were established. Vitamins B12 and C were found, in in vitro studies, to be more effective inhibitors of cyclic AMP phosphodiesterase than theophylline. Plasma and urinary levels of cyclic AMP were found to exhibit a diurnal variation in normal volunteers. The majority gave a plasma pattern with a maximum at 24.00h and a minimum at 16.00h. The minority plasma pattern showed a peak at 12.00h. The urinary excretion gave a pattern in the majority with a maximum between 04.00 -08.00h and a minimum between 12.00 - 16.00h. The minority showed a peak urine value between 12.00 - 16.00h and a trough between 24.00 - 04.00h. A further pattern was noted in menstrual cycle with a mid-cycle peak. This was absent in males, and was lost in secondary amenorrhoea, pregnancy and after prolonged ingestion of oral contraceptives. The amplitude was more pronounced in pre-menstrual tension syndrome, suggesting the possibility of overswing. Muscular activity produced a transient increase in plasma cyclic AMP, but this was not reflected in the urinary level. Limited studies on dietary change showed no significant influence. Patients suffering from endogenous depression showed low plasma and urinary levels of cyclic AMP. On clinical improvement urinary levels returned to the normal range. The urinary excretion of cyclic AMP in endogenous depression showed a peak between 08.00 - 12.00 h. On clinical improvement the pattern became bimodal with peaks between 04.00 - 08.00h and 16.00 - 20.00h. The reactive depression group showed a bimodal pattern (peaks between 24.00 - 04.00h and 12.00 - 16.00h) both before and after clinical improvement. Electroconvulsive therapy caused a marked rise in both plasma and urinary levels of cyclic AMP on the day of treatment. The plasma concentration doubled and remained elevated for up to 90 min after electrical stimulation. Patients who did not respond to E. C. T. in terms of cyclic AMP increase also showed no clinical improvement

Alkali metal solutions in low-polarity solvents

Alkali metal solutions comprising alkali metal anions, the ‘alkalides’, and complexed alkali cations side by side provide a large untapped potential with respect to future applications. This is due to their unique properties such as a strongly reducing nature and a high polarizability. The use of organic complexing agents such as crown ethers and cryptands allows for the stabilization of high concentrations of charge carriers in a weakly polar medium. Nevertheless, the currently available knowledge about those solutions is very limited and their characterization is mostly centered around alkali metal NMR techniques. A significant upfield shift and exceptionally narrow width of the alkalide NMR signal were ascribed to the high shielding and high symmetry of an effectively unperturbed ‘gas-like’ anion in solution with little to no interaction with its local environment. Our investigations extend this traditional picture of the alkalide in solution and unveil the underlying effect of coulomb interactions on the properties of alkalides in low-polarity solvents by a comprehensive combination of spectroscopic methods. Concentration dependent measurement of both conductivity and permittivity of alkalide solutions revealed that ion pairing is a key factor in determining the kinetic properties and the stability of alkali metal solutions. Furthermore, the effect of dissolved metal on the mesoscopic structure of solutions of macrocyclic complexants was probed by small angle neutron scattering. Ultimately, we present a rationale for the rather obscure and unexpected temperature- and concentration-dependence of alkali metal dissolution in organic media and provide a multi-facetted understanding of the remarkable preparatory and spectroscopic characteristics of alkalide solutions. Finally, the synthesis of sterically congested amides and their unique fragmentation under dissolving metal reduction conditions are presented. Synthetic access to amide substrates was achieved by the use of highly electrophilic nitrimine precursors in the formation of imine intermediates.Open Acces

The Photochemistry of <i>N</i>-Arylsulfonyl Amino Acids and Peptides

The photochemistry of arylsulfonamides has received continuing interest for the last four decades for three main reasons: 1) arylsulfonamides offer convenient acceptor properties for studying photo-induced electron transfer (PIET.) processes in chromophorically modified peptide models, 2) arylsulfonamides have potential as photoremovable protecting groups in organic synthesis, but this has so far remained largely unrealized, 3) arylsulfonamide pharmaceuticals are generally photolabile and photostability is an important consideration in the development of new drugs. We have studied a series of p-toluenesulfonyl amino acid derivatives and undertaken comprehensive product analysis to elucidate the photoproducts and identify common pathways of photodegradation. We found that the tosyl a-amino acids formed toluenesulfinic acid as a major photoproduct in conjunction with ammonia, carbon dioxide and a carbonyl compound. Upon changing the carboxylate to an ester or an amide, a Cɑ-H abstraction became the dominant process to give a carbonyl compound, toluenesulfinic acid and ammonia. These were also the major photoproducts with a tosyl ß-amino acid. A mechanism is proposed that involves an initial electron transfer (ET) from the carboxyl function to the sulfonyl moiety to give a biradical intermediate that could react to produce most of the observed products. Some differences in product distribution were found with different amino acid side-chains, although bulky aliphatic or sulfur containing side-chains produced little variation. A tyrosine derivative underwent side-chain cleavage, implying electron transfer from the side-chain rather than the carboxyl function. Peptide bond cleavages occurred in the majority of amide derivatives, which can also be explained by an electron transfer mechanism. The results showed that S-N cleavage to form the free amino acid moiety occurs in very poor yield due to a complex array of competing photoreactions. A photoyellowing was seen in many of the amide compounds which may be due to photochromism, a process that is consistent with our photo-induced electron transfer hypothesis

Pd0-Catalyzed Formal 1,3-Diaza-Claisen Rearrangement. Design And Development Of Cationic 1,3-Diaza-Claisen Rearrangement.

The dissertation describes Pd0-catalyzed formal 1,3-diaza-Claisen rearrangement and the design and development of cationic 1,3-diaza-Claisen rearrangement. Our previous work has shown that isocyanates react with azanorbornenes and azabicyclo[2.2.2]octenes under thermal conditions to afford zwitterionic intermediates that undergo a thermal 1,3-diaza-Claisen rearrangement to give both ureas and isoureas. However, some azanorbornenes and azabicyclooctenes failed to rearrange or proceeded in low yields. To address these challenging substrates for the thermal 1,3-diaza-Claisen rearrangement, we have developed a Pd0-catalyzed formal 1,3-diaza-Claisen rearrangement. Interestingly, under Pd0-catalyzed condition, both isocyanates with electron-withdrawing groups and isocyanates without electron-withdrawing groups react with azanorbornenes and azabicyclo[2.2.2]octenes to provide ureas as the only products in high yields. More importantly, the reactions that failed under thermal conditions were all successful under Pd0-catalysis. In addition to azanorbornenes and azabicyclo[2.2.2]octenes, other ring systems were also investigated. Pd0 catalysis has broadened the scope of tertiary allylic amines that react with isocyanates to afford 1,3-diaza-Claisen rearrangement products. In the presence of p-TsCl and NEt3, allylaminopropyl benzyl ureas were initially dehydrated to form protonated carbodiimides whose presence was confirmed by the infrared absorption frequency at 2100 cm-1 which is the characteristic band of -N=C=N-; then the in situ generated protonated carbodiimides were poised for further cationic 1,3-diaza-Claisen rearrangement to afford synthetically challenging guanidines. The effect of acid on the rearrangement was ascertained by the fact that no rearrangement product was observed by simply heating free base carbodiimide 3.10 in benzene at reflux. Other dehydration reagents, such as Tf2O, Ts2O, MsCl were also investigated, and none of them provide satisfactory results. A selection of allyamino benzyl ureas with different tether length, substituents, or in varied ring systems, were synthesized to explore the scope of this methodology. This methodology works best at allylaminopropyl benzyl ureas, and the substituents on the benzyl group does not seem to affect the reaction rate in a significant way

The preparation, metal binding ability and catalytic activity of poly itaconate copolymers with pendant ethylene amine groups

A polymeranalogous reaction in homogeneous medium was carried out to prepare poly itaconate copolymers with pendant ethylene imine groups. Three copolymers, poly- (MHpI+DHpI), poly (MBI+DBI) and poly (MMI+DMI) were prepared, characterised and their composition analysed. The acid groups in the monoesters were reacted with ethylene diamine, diethylenetriamine, triethylenetetramine or tetraethylenepentamine in the presence of dicyclohexyl car bodiimide. Two types of polymer-metal complexes, polymer chelates and pendant-type polymer-metal complexes were prepared. The complexation between the polymeric ligands and cobalt(II) chloride or copper(II) chloride was studied by visible spectroscopy. The electron microscopy study of these polymer-metal complexes shows that the size and the number of the metal ion clusters increases proportionally with the mole percentage of the metal ions. The catalytic activity of the polymer-metal complexes on the decomposition of hydrogen peroxide has been studied. Graphical and mathematical methods were used to show and compare the catalytic activity of these polymer-metal complexes. It was found that the catalyst efficiencies were in the decreasing order of: poly(MHpI+DHpI)/EN/ Co(en)2Cl] 2+ 2Cl" ^ poly(MMI+DMI)/EN/[ Co(en)2Cl] 2+ 2C1~ ^ poly(MHpI+DHpI)/TEPA/CoCl2 ^ poly(MHpI+DHpI)/TEPA/CuCl2^ poly (MMI+DMI) /TEPA/CoCl^ poly (MMI+DMI) /TEPA/CuC12. The thermal stability of these modified polymers and polymer-metal complexes confirms that degradation was a random chain scission process and that the thermal stability of the polymer-metal complexes were higher than the polymeric ligands due to crosslinking. The viscoelasticity study shows that the modulus in the rubbery region increases when the mole percentage of the pendant ethylene amine group was less than 6.3. The glass transition temperature increases and becomes broader and ill-defined as the mole percentage of pendant ethylene amine group increases due to enhanced inter molecular interactions in the system

Эндокринные механизмы регуляции приспособления организма к мышечной деятельности. Стероидные и пептидные гормоны при мышечной деятельности

• A.А. Виру. Общие закономерности изменений гормонального ансамбля крови во время физического упражнения • Summary • Ы.Н. Яковлев. Энзимная адаптация к повышенной мышечной деятельности и вопросы ее эндокринной регуляции • Summary • Г.Н. Кассиль, P.C. Суздалытацкий, A.A. Левандо, Б.Б. Першин, С.Н. Кузьмин. Нейрогуморально- горыональные механизмы нарушения ишунного гомеостаза при напряженной спортивной деятельности • Summary • B.В. Меньшиков, Т.Д. Большакова, Е.П. Гитель, В.В. Городецкий, И.И. Егиазарян, С.А. Потекаева, Е.А. Лапшин. Изменения концентрации некоторых пептидных гормонов и энергетических оубстратов в крови у спортсменов и нетренированных людей при нагрузке повышающейся мощности • Summary • М.И. Митшов, А. А. Филаретов, Л.П. Филаретова, А.И. Богданов. Иммобилизация и гипоталамо-гипофизарно- адренокортикальная система • Summary • П.К. Кырге, Л.Х. Медияйнен. Значение ATP и состояния энергетики миокарда в механизме действия глюкокортикоидов в этой ткани • Summary • Т.П. Коцегуб, Б.И. Фельдкорен. Концентрация кортикостерона в крови и активность миофибркялярной протеазы при физической нагрузке • Summary • Э.В. Варрик, Т.П. Сээне, A.A. Виру. Экскреция 3 метилгистидина при тренирующих нагрузках у адреналэктомироваяннх животных • Summary • Т.П. Сээне, К.П. Алев. Круговорот белков актомиозинового комплекса в скелетных мышцах при хронической физической перегрузке • Summary • И.А. Држевецкая, O.A. Бутова. Угнетающее влияние длительного потребления алкоголя на реактивность гипоталамо-гипофизарно-адренокортикальной системы к мышечным нагрузка • Summary • Е.И. Джураева, С.А. Хорева, С.И. Ксенц. Влияние суточной периодики не динамику активности кортикотропина, свободных и связанных с белком II-оксикортикостероидов у собак при мышечной работе • Summary • P.B. Ялак. Динамика акскреции I7-оксикортикоидов в тренировочном микроцикле у баскетболистов высшей квалификации • Summary • B.C. Чайковский, Б.М. Иванова, B.A. Рогозкин. Влияние различных физических нагрузок на содержание и утилизацию тестостерона • Summary • Е.И. Осипова, Б.И. Фельдкорен. Определение цитоплазматических рецепторов андрогенов в скелетных мышцах интактних белых крыс • Summary • E.P. Иванов, Г.Н. Кассиль, И.С. Морозов. Роль симпато-адреналовой системы в происхождении расстройств тонких двигательных навыков при повышенной психоэмоциональной напряженност • Summary • В.Я. Русин, В.В. Насолодин, B.A. Воробьев. Влияние однократного введения адреналина и физического напряжения на гематологически показатели и микроэлементный состав крови • Summary • Л.А. Шитов, И.А. Криволапчук, A.B. Шаров. О роли адренорецепторов в регуляции концентрации инсулина и сахара крови в реакции организма собак на экстремальные статические нагрузки • Summary • Оглавлениеhttp://tartu.ester.ee/record=b1174892~S1*es

Alkyyliamiinit pohjoisissa metsä- ja kaupunkiympäristöissä

Low-molecular-weight alkyl amines are reactive organic nitrogen compounds that are im- portant precursors in secondary aerosol formation. Atmospheric aerosols have direct and indirect effects on Earth's climate system. Alkyl amines are emitted from marine and terrestrial ecosystems, agricultural activities and other anthropogenic sources. In terrestrial ecosystems, the quantities in the different parts of an ecosystem and formation processes are not well understood. Alkyl amine soil concentration and biosphere atmosphere exchange measurements are scarce. The main focus of this thesis is to determine concentrations of alkyl amines in ambient air in boreal forest and urban area, and further identify possible sources and reservoirs of alkyl amines in boreal forest. The main results presented in the thesis consist of a timeseries of gas- phase concentrations of alkyl amines measured over several months, concentrations of alkyl amines in the soil and fungal biomass, and an emission estimation based on the measured concentrations. Alkyl amines were studied in two northern latitude environments: in a boreal Scots pine (Pinus sylvestris L.) forest at the SMEAR II station in Hyytiälä and in an urban background area at the SMEAR III station in Helsinki. To quantify ambient air concentrations of alkyl amines in these environments, sample collection and analytical methods were developed. Ambient air concentrations of alkyl amines were measured from May to October 2011 in the forest site and from May to August 2011 in the urban site. The effect of the measured ambient air concentrations of alkyl amines on the local air chemistry was also assessed together with aromatic hydrocarbons and terpenoids. To assess boreal forest soil as a source of alkyl amines, a pot-scale experiment was set up. In the experiment Scots pine seedlings were grown on humus soil collected from the forest site, and the effects of Scots pine and soil organic matter (SOM) degrading enzymes on alkyl amine soil concentrations were studied. In addition, fungal strains common in boreal forest soils were cultured, and the alkyl amine concentrations in the grown fungal biomass were quanti- fied. The role of boreal forest soil as a source or as a sink of atmospheric alkyl amines was studied using a gradient-diffusion approach. In the approach, the soil atmosphere exchange of selected alkyl amines was estimated. This was done by describing dissolution/volatilisation on water and transport processes, and utilizing the quantified soil and ambient air gas-phase concentrations of the selected alkyl amines found in the studied boreal forest. The gas-phase concentrations of alkyl amines in ambient air were found to be higher in the forest site than in the urban site. In the forest site, the atmospheric concentrations appeared to be linked to soil and vegetation activity based on the seasonal course of the measured alkyl amines. Litterfall, a phenological event, coincides with the concentration maxima of some of the measured alkyl amines. In the pot-scale experiment, the SOM degrading enzymes were found to have no effect on the soil concentrations of alkyl amine while the presence of Scots pine was found to have an effect on the concentrations of some of the measured alkyl amines. The soil concentrations of alkyl amines were found to be lower than those measured from the fungal biomass. The most abundant fungal groups (ectomycorrhizal and saprotrhopic fungi) in the forest soil contained the highest quantities of alkyl amines revealing that fungal biomass may be an important reservoir of alkyl amines in boreal forest soil. Based on the flux estimate, the boreal forest soil was found to act as both a source and a sink of alkyl amines. The direction of the flux was dependent on the studied alkyl amines and environmental conditions in the forest site. Soil pH was found to be one of the most critical factors determining the direction of the flux between the soil and the atmosphere.Alkyyliamiinit ovat typpipitoisia orgaanisia yhdisteitä. Ilmakehässä nämä yhdisteet osallistuvat moniin kemiallisiin reaktioihin sekä pienhiukkasten muodostumis- ja kasvuprosesseihin. Riittävän suuret pienhiukkasten voivat toimia pilvipisaroiden tiivistymisytiminä. Pienhiukkaset vaikuttavat pilvien heijastukseen, elinikään sekä sateisuuteen. Alkyyliamiineilla on todettu olevan monia lähteitä ilmakehään. Lähteet voivat olla luonnollista alkuperää tai ihmistoiminnasta aiheutuvia. Alkyyliamiinien ilmakehälähteitä ei ole tarkasti määritetty, ja erityisesti maaekosysteemeissä alkyyliaminiien pitoisuuksia, muodostumisprosesseja ja kulkeutumista ei juurikaan tunneta. Koska alkyyliamiinien pitoisuuksia maaekosysteemeissä tai kaasunvaihtoa ekosysteemien ja ilmakehän välillä ei juurikaan tunneta, alkyyliamiinien ilmapitoisuuksia mitattiin kahdesta erilaisesta ympäristöstä, mäntymetsässä ja kaupunkialueella. Mäntymetsän maaperän kykyä toimia alkyyliamiinien lähteenä tutkittiin kokeellisesti sekä laskennallisin menetelmin. Alkyyliamiinien vaikutusta metsä- ja kaupunkiympäristön ilmakemiaan arvioitiin suhteessa muihin reaktiivisiin ilmakehän orgaanisiin hivenkaasuihin. Väitöskirjan päätulokset koostuvat kuukausien mittaisista ilmapitoisuusaikasarjoista, alkyyliamiinien metsämaan ja sienirihmastojen pitoisuuksista. Näiden avulla tehtiin kaasunvaihtoarvioita maaperän ja ilmakehän välillä metsäympäristössä erilaisissa ympäristöolosuhteissa. Kaasunvaihtoarvion perusteella maaperän toimintaa mahdollisena lähteenä pystyttiin arvioimaan. Ilmakehäpitoisuudet metsäympäristössä olivat korkeammat kuin kaupunkiympäristössä. Metsäympäristön korkeimmat pitoisuudet ajoittuivat syksyyn ja ovat mahdollisesti yhteydessä esimerkiksi maaperän mikrobiologiseen toimintaan ja metsäkasvillisuuteen. Alkyyliamiinien suhteellinen vaikutus ilmakehän hapetusreaktioihin oli samaa suuruusluokkaa tai hieman vähemmän kuin haihtuvilla hiilivedyillä. Alkyyliamiineja todettiin olevan eloperäisessä pintamaassa sekä metsämaassa yleisesti esiintyvissä sienirihmastoissa. Alkyyliamiinien pitoisuus oli tutkitussa maassa suuri ja mitattujen alkyyliamiinien yhteispitoisuus oli samaa suuruusluokkaa kuin nitraatilla. Metsämaassa yleisesti esiintyvät sienet sisälsivät alkyyliamiineja pintamaata enemmän. Laskennallisesti pystyttiin osoittamaan, että metsämaa voi toimia lähteenä ilmakehän alkyyliamiineille. Maaperän happamuudella huomattiin olevan merkittävä rooli. Väitöskirjan tärkein tulos on kuitenkin luoda tiekartta jatkotutkimuksille, joissa selvitetään tarkemmin alkyyliamiinien lähteitä ja nieluja pohjoisessa metsäympäristössä

Synthesis of biodegradable polymers for delivery of diagnostic agents

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN004506 / BLDSC - British Library Document Supply CentreGBUnited Kingdo