[Formulae and special characters can only be approximated here. Please see the pdf version of the Abstract for an accurate reproduction.] The kinetics for outer-sphere electron transfer between a series of cobalt(II) poly-aza cage ligand complexes and the iron(III) sarcophagine-type hexa-aza cage complex, [Fe(sar)]3+ (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane), in aqueous solution have been investigated and the Marcus correlation is used to deduce the electron self-exchange rate constant for the [Fe(sar)]3+/2+ couple from these cross-reactions. The deduced electron self-exchange rate constant is in relatively good agreement with the experimentally determined rate constant (k ex calc = 4 ´ 10 5 M -1 s -1 ; k ex obs = 8 ´ 10 5 M -1 s -1 ). The successful application of the Marcus correlation to the electron transfer reactions of the Fe cage complex is consistent with the trend for the Co, Mn, Ni and Ru cage complexes which all follow the pattern of outer-sphere electron transfer reactivity expected from the Marcus-Hush formalism. A comparison of predictions based on the Marcus correlation with the experimentally determined kinetics of an extended series of cross reactions involving cobalt cage complexes with low-spin-high-spin cobalt(III)/(II) couples shows that electron transfer reactions involving large spin changes at the metal centre are not necessarily anomalous in the context of the adiabatic Marcus-Hush formalism. The results of this study also show that for suitable systems, the Marcus correlation can be used to reliably calculate the rates of outer-sphere electron transfer cross-reactions, with reaction free-energy changes spanning the range -6 to -41 kJ mol -1 and many different combinations of initial electronic configurations. Together, these results provide a coherent and internally consistent set of experimental data in support of the Marcus-Hush formalism for outer-sphere electron transfer. The results with the caged metal-ion systems also highlight the special nature of the mechanism of electron transfer in reactions of metal-aqua ions. ¶ A new range of symmetrically disubstituted hexa-aza sarcophagine-type cage ligand complexes are prepared in this study by the base-catalysed co-condensation of formaldehyde and a-methylene aliphatic aldehydes with cobalt(III) tris(1,2-diamine) precursors in acetonitrile solution. Encapsulation reactions based on the condensation of the weak carbon di-acids propanal and decanal with formaldehyde and the cobalt(III) tris(1,2-diamine) precursors, [Co(en)3 ] 3+ (en = 1,2-ethanediamine) and D-lel3 -[Co((R, R)-chxn)3 ] 3+ (chxn = 1,2-cyclohexanediamine), yield unsaturated cobalt(III) cage complexes with an endo-cyclic imine function in each cap. The Co III -coordinated endo-cyclic imine units of the cage ligands are reactive electrophiles that are readily reduced by the BH4 - ion to give the corresponding symmetrically di-substituted hexaamine macrobicyclic cage ligands. The nitromethane carbanion is also shown to add at the endo-cyclic imine function to yield a novel nitromethylated cage ligand complex. The latter reaction introduces a new method for the regioselective functionalisation of cage ligands at sites removed from the more commonly substituted bridgehead positions. The capping of cobalt(III) tris(1,2-diamine)-type complexes with weak CH-acids developed in this study introduces a new and more direct route to symmetrically di-substituted cage ligand complexes. ¶ A new range of cobalt(III) surfactant cage complexes, with linear octyl, dodecyl and hexadecyl hydrocarbon chains built directly into the bridgehead structure of the cage ligand, have been prepared by the base catalysed co-condensation of formaldehyde and long chain aliphatic aldehydes with the tripodal cobalt(III) hexaamine complex, [Co(sen)]3+ (sen = 4,4',4''-ethylidynetris(3-azabutan-1-amine)), in acetonitrile solution. Chiral surfactant cage complexes are obtained by capping reactions beginning with the optically pure L-[Co(sen)]3+ precursor complex. The cobalt(III) cage complexes with octyl to hexadecyl substituents are surface active and reduce the surface tension of water to levels approaching those of organic solvents. The dodecyl substituted cage complex forms micelles in aqueous solution when the concentration of cage complex is > 1 ´ 10 -3 mol dm -3 at 25 °C. The cobalt(III) cage head-group of these surfactants undergoes an electrochemically reversible one-electron reduction to the corresponding cobalt(II) cage complex. The reduction potential of the surfactant head group can be tuned to more positive potentials by replacing the bridgehead hydrocarbon chain substituent with an ether linked hydrocarbon chain. The cobalt(III) surfactant-cage complexes are biologically active and are lethal to the tapeworm Hymenolepis diminuta, and the vaginal parasites, Trichomonas vaginalis and Tritrichomonas foetus. The surfactant cage complexes also cause lysis in red-blood cell membranes at concentrations as low 10 -5 mol dm -3 . Their biological activity is linked to the high head-group charge (3+) and size which cause distortions in biological membranes when the membrane is treated with these molecules. The combination of the chemically reversible outer-sphere redox properties of the cobalt cage head-groups and the chirality of the head group introduces a new and possibly unique series of chiral surfactant coordination complexes which are also redox active. ¶ The chiral carboxylic-acid ionophore, lasalocid A, has been used to promote the selective supramolecular transport and extraction of cobalt(III) hexa-aza cage cations and related tripodal cobalt(III) complexes. The conjugate base anion of lasalocid A forms stoichiometric outer-sphere complexes with the cobalt(III) cage and tripod complexes. These outer-sphere complexes are highly lipophilic and partition strongly from water into a chloroform phase. The extraction of the dissymmetric cobalt(III) complexes by the chiral polyether anion is enantioselective for many systems and results in the partial resolution of initially racemic complexes in the aqueous phase. A strong structural preference was demonstrated by the ionophore for symmetrically disubstituted cobalt(III) hexa-aza cage cations with a D-absolute configuration of the ligand about the metal-ion and an R configuration of the coordinated secondary amine N-H groups. The lasalocid A anion was also shown to promote the transport of the complexes, intact, across a chloroform bulk-liquid membrane against an NH4 + concentration gradient. The transport of the cobalt(III) complexes was also enantioselective and resulted in partial resolution of the initially racemic aqueous phase. The most efficiently transported enantiomer of each complex was also the most efficiently extracted isomer in all systems examined, consistent with a transport process limited by interfacial diffusion. The magnitude of the enantiomer separation obtained in some systems was sufficient to indicate that lasalocid A mediated extraction and transport may become a practical method for the resolution of particular types of kinetically-inert chiral metal-amine complexes.

Heparin binding (HB) proteins mediates a wide range of important cellular processes, which makes this class of proteins biopharmaceutically important. Engineering HB proteins could bring many advantages, but it necessitates cost effective and efficient purification methodologies compared to the currently available methods. One of the most important classes of heparin binding protein is the fibroblast growth factors (FGFs) and its receptors (FGFRs). In this study, we report an efficient off-column purification of FGF-1 from soluble fractions and purification of the D2 domain of FGFR from insoluble inclusion bodies, using a weak amberlite cation (IRC) exchanger. This approach is an alternative to conventional affinity column chromatography, which exhibit several disadvantages, including time-consuming experimental procedures and regeneration and results in high cost for production of recombinant proteins. Authenticity of the purified proteins was verified by SDS-PAGE and MALDI mass spectrum analysis. Results of the heparin binding chromatography and steady state fluorescence experiments showed that the FGF-1 and the D2 are in a native biologically active conformation. The findings of this study will not only aid an in-depth investigation of this class of proteins but will also provide avenues for inexpensive and efficient purification of other important biological macromolecules.

Pyridazines are heterocyclic compounds with an N-N bond in their ring structure. Heterocyclic aromatic compounds are of great interest as a result of their novel properties and commercial applications. Our current research is focused on the potential role of pyridazines in next generation electronic devices that utilize organics as the semiconducting material. The synthesis of 5, 6-fused ring pyridazines beginning from fulvenes (Scheme 1) is described herein. These fused heterocycles will serve as synthetic models and building blocks for potential organic or organometallic conducting polymers. Our goal was to modify the route of Snyder et al. previously reported for the direct synthesis of pyridazine 2. This required improved synthesis of fulvene 1 and higher yields of 5. Additionally, a thorough analysis of the x-ray data was obtained to better understand the 3D aspects of this compound (pyridazine 2).This route was quite general and features an efficient and convenient synthesis. Single crystal X-ray analysis confirms the molecular structure of pyridazine 2. Full synthesis and characterization of newly formed pyridazine 2 and Fulvene 1 are reported.

Tetrahydroisoquinoline alkaloids are a class of structurally complex natural products and a huge number of its natural product widely exist in nature which, from the discovery has been more than a century, it compounds with high anti-tumor activity, antibacterial and other physical activity, but also because of its special structure, with low oncentration of biological activity, but these alkaloids are not sold in the market mainly due to a less natural extraction, chemical synthesis method and multi-step, low yield. Therefore, we constructed a combination of tetrahydroisoquinoline alkaloids and the pyrazino [2,1-b] quinazoline-3,6-diones structure of the new compounds, which have the quinazolinone compounds which is the drug synthesis and drug activity on the bond, is also a kind of unique and widely used drug structure, and causes a lot of scientists and drug research interest and discussion, as we develop the motivation.

A systematic study was carried out for the synthesis of aziridine 2-phosphonates by using two methods. First method is the classical Gabriel-Cromwell reaction and the second one is the modified version of Gabriel-Cromwell reaction which was developed in this thesis. In the first method, vinyl phosphonate was used as the starting material, then it was brominated to get 1,2-dibromoethyl phosphonate. HBr elimination from this compound, then reaction with different primary amines gave desired aziridinyl phosphonates in good yields. In the second method, easily available acetyl phosphonate was used as the starting material which was reacted with DBU and tosyl chloride to get &alpha / -tosylated vinyl phosphonate. Reaction of this compound with the same amines gave aziridinyl phosphonates in good yields, as well. Biological activities of all newly synthesized compounds were studied against different bacteria.

The tetrahydroisoquinoline alkaloids have been studied thoroughly about their biological and chemical significance over the past 30 years. These natural products show great biological activity, especially ET-743 and saframycin A, makes them promising therapeutics, while their structural complexity and particularity provide challenging synthetic targets. These alkaloids or derivatives show interesting biological activity, but the most important drawback as potential market therapeutics is the minute amount of them available from nature, and the synthetic methods published are inconvenient, difficult, and hard to handle. Herein is described our researches about the tetrahydroisoquinoline alkaloids. Chapter 1 describes relevant background related to the biological significance of these alkaloids, and the currently synthetic studies toward these natural products. Chapter 2 describes our design and synthesis of the analogues based on the anticancer mechanism of the tetrahydroisoquinoline alkaloids, and the biological activities of these analogues. Chapter 3 describes a rapid synthetic route for the common structure of the bis-tetrahydroisoquinoline alkaloids via a controlled mono-Pictet-Spengler cyclization.

No description available.

Darbo tikslas: atlikti preparatų, turinčių augalinių žaliavų kaupiančių rozmarino rūgštį, sudėčių palyginamąją analizę, nustatyti bendrą fenolinių junginių kiekį, rozmarino rūgšties kiekį ir antioksidacinį aktyvumą. Darbo uždaviniai:  Išrinkti preparatus su rozmarino rūgštimi;  Atlikti šių preparatų sudėčių palyginamąją analizę;  Nustatyti ir palyginti bendrą fenolinių junginių kiekį preparatuose;  Nustatyti ir palyginti rozmarino rūgšties kiekį ESC metodu;  Nustatyti ir palyginti antioksidacinį aktyvumą. Tyrimo objektai ir metodai: preparatai, turintys augalines žaliavas, kaupiančias rozmarino rūgštį ir kvapiųjų rozmarinų skystasis ekstraktas. Bendras fenolinių junginių kiekio nustatymas atliktas spektrofotometriniu būdu, naudojant standartinį Folin – Ciocalteu reagentą. Rozmarino rūgšties kiekis preparatuose nustatytas ESC metodu. Antioksidacinis aktyvumas nustatytas DPPH radikalo sujungimo metodu. Literatūros analizės metodu atlikta rozmarino rūgšties preparatų sudėčių analizė. Išvados: Tyrimams išrinkti 3 kompleksiniai preparatai su kvapiųjų rozmarinų augaline žaliava ir skystasis rozmarinų ekstraktas. Daugiausia kvapiųjų rozmarinų žaliavos ir RR kiekio RPD buvo keturkomponentiniame Verdin. Žaliavos dalis sudaro 50,68 % preparato. Atlikus bendro fenolinių junginių kiekio tyrimą, nustatyta, kad didžiausias fenolinių junginių kiekis yra skystajame rozmarinų ekstrakte (160,34 RRE mg/ml) (P<0.05). Didžiausias rozmarino rūgšties kiekis rastas skystajame rozmarinų... [toliau žr. visą tekstą] / Aim: to make comparable analysis of preparations containing plant materials accumulating rosmarinic acid, determine the total phenolic compound content, rosmarinic acid content and compare antioxidant activity. Objective:  Elect the preparations with rosmarinic acid;  Make the comparative analysis of compositions of these preparations;  Determine and compare the total phenolic compound content;  Determine and compare the rosmarinic acid content using HPLC method;  Determine and compare their antioxidant activity. Objects and methods: products with plant materials accumulating rosmarinic acid and rosemary leaf liquid extract. Total content of phenolic compounds was carried out spectrophotometrically using a standart Folin- Ciocalteu reagent. Rosmarinic acid content was determined by HPLC method. Antioxidant activity determined by DPPH radical scavenging method. The comparable analysis of products composition performed by literary analysis method. Conclusion: For research were selected 3 complex preparations with rosemary plant material and liquid rosemary extract. The highest quantity of raw rosemary material and RR quantity in RDD had Verdin, the preparation containing 4 components. Rosemary plant material makes 50,68 % in the preparation. Total phenolic compounds study showed that the highest amount of phenolic coumpounds had liquid rosemary extract (160,34 RAE mg/ml). The biggest quantity of rosmarinic acid was found in liquid rosemary extract (0.03 mg/ml). Combined... [to full text]

Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.

Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.