Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid-Spermine Conjugates

Natural and abundant plant triterpenoids are attractive starting materials for the synthesis of conformationally rigid and chiral building blocks for functional soft materials. Here, we report the rational design of three oleanolic acid-triazole-spermine conjugates, containing either one or two spermine units in the target molecules, using the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The resulting amphiphile-like molecules 2 and 3, bearing just one spermine unit in the respective molecules, self-assemble into highly entangled fibrous networks leading to gelation at a concentration as low as 0.5% in alcoholic solvents. Using step-strain rheological measurements, we show rapid self-recovery (up to 96% of the initial storage modulus) and sol ⇔ gel transition under several cycles. Interestingly, rheological flow curves reveal the thixotropic behavior of the gels. To the best of our knowledge, this kind of behavior was not shown in the literature before, neither for a triterpenoid nor for its derivatives. Conjugate 4, having a bolaamphiphile-like structure, was found to be a nongelator. Our results indicate that the position and number of spermine units alter the gelation properties, gel strength, and their self-assembly behavior. Preliminary cytotoxicity studies of the target compounds 2-4 in four human cancer cell lines suggest that the position and number of spermine units affect the biological activity. Our results also encourage exploring other triterpenoids and their derivatives as sustainable, renewable, and biologically active building blocks for multifunctional soft organic nanomaterials.acceptedVersionPeer reviewe

British Foreign Policy: the Iraq-Kuwait Matter in the UN Security Council from 1997 to 2003

This diploma thesis "British Foreign Policy: the Iraq-Kuwait Matter in the United Nations Security Council from 1997 to 2003" deals with the policy of the British Government of the Prime Minister Tony Blair in the UN Security Council charged with maintaining international peace and security against the Saddam Hussein's regime in Iraq. The research starts with the victory of the Labour Party in the general election in Great Britain in May 1997 and ends with the use of military power of the coaliton led by the USA against the Iraqi regime in March 2003. The main objective of this diploma thesis is to examine the relationship between the foreign policy of the British Government formulated in basic documents (The Labour Party's 1997 and 2001 General Election Manifestos) and foreign minister Robin Cook's The FCO Mission Statement of May 1997 and its practical fullfilment in a concrete crisis situation. The thesis also aims to define the main strategic goal of the British policy in the Iraq-Kuwait matter in researching time, and to decide if the policy was succesful.Diplomová práce s názvem "Britská zahraničí politika: irácko-kuvajtská otázka v Radě bezpečnosti OSN v letech 1997 až 2003" se zabývá politikou britské labouristické vlády premiéra Tonyho Blaira v nejvyšším orgánu Organizace spojených národů, který nese hlavní zodpovědnost za udržování světového míru a bezpečnosti, vůči režimu Saddáma Husajna v Iráku. Výzkum začíná od května 1997, kdy Labouristická strana zvítězila v britských parlamentních volbách a ujala se vlády, a je ukončen vojenským zásahem koalice států v čele v březnu roku 2003. Diplomová práce si klade za cíl formou případové studie prozkoumat vztah mezi britskou zahraniční politikou tak, jak ji formulují základní dokumenty (volební manifesty Labouristické strany pro parlamentní volby v letech 1997 a 2001) a prohlášení britského ministra zahraničních věcí v prvním volebním období labouristické vlády Robina Cooka z 12. května 1997, a jejím praktickým uplatněním v konkrétní krizové situaci. Práce má zároveň definovat hlavní strategický cíl britské politiky v iráckokuvajtské otázce ve zkoumaném období, popsat její vývoj a pokusit se určit, zda byla tato politika úspěšná a definovaného cíle dosáhla.Department of European StudiesKatedra evropských studiíFaculty of Social SciencesFakulta sociálních vě

Franco-German Cooperation in the European Union in Context of Enlargement of the European Union of Eastern and Central European Countries in 1993 - 2004

Department of European StudiesKatedra evropských studiíFaculty of Social SciencesFakulta sociálních vě

Altered biochemical specificity of G-quadruplexes with mutated tetrads

A fundamental motif in canonical nucleic acid structure is the base pair. Mutations that disrupt base pairs are typically destabilizing, but stability can often be restored by a second mutation that replaces the original base pair with an isosteric variant. Such concerted changes are a way to identify helical regions in secondary structures and to identify new functional motifs in sequenced genomes. In principle, such analysis can be extended to non-canonical nucleic acid structures, but this approach has not been utilized because the sequence requirements of such structures are not well understood. Here we investigate the sequence requirements of a G-quadruplex that can both bind GTP and promote peroxidase reactions. Characterization of all 256 variants of the central tetrad in this structure indicates that certain mutations can compensate for canonical G-G-G-G tetrads in the context of both GTP-binding and peroxidase activity. Furthermore, the sequence requirements of these two motifs are significantly different, indicating that tetrad sequence plays a role in determining the biochemical specificity of G-quadruplex activity. Our results provide insight into the sequence requirements of G-quadruplexes, and should facilitate the analysis of such motifs in sequenced genomes

Altered biochemical specificity of G-quadruplexes with mutated tetrads

A fundamental motif in canonical nucleic acid structure is the base pair. Mutations that disrupt base pairs are typically destabilizing, but stability can often be restored by a second mutation that replaces the original base pair with an isosteric variant. Such concerted changes are a way to identify helical regions in secondary structures and to identify new functional motifs in sequenced genomes. In principle, such analysis can be extended to non-canonical nucleic acid structures, but this approach has not been utilized because the sequence requirements of such structures are not well understood. Here we investigate the sequence requirements of a G-quadruplex that can both bind GTP and promote peroxidase reactions. Characterization of all 256 variants of the central tetrad in this structure indicates that certain mutations can compensate for canonical G-G-G-G tetrads in the context of both GTP-binding and peroxidase activity. Furthermore, the sequence requirements of these two motifs are significantly different, indicating that tetrad sequence plays a role in determining the biochemical specificity of G-quadruplex activity. Our results provide insight into the sequence requirements of G-quadruplexes, and should facilitate the analysis of such motifs in sequenced genomes

Reaction of N-Acetylcysteine with Cu2+: Appearance of Intermediates with High Free Radical Scavenging Activity: Implications for Anti-/Pro-Oxidant Properties of Thiols

We studied the kinetics of the reaction of N-acetyl-l-cysteine (NAC or RSH) with cupric ions at an equimolar ratio of the reactants in aqueous acid solution (pH 1.4–2) using UV/Vis absorption and circular dichroism (CD) spectroscopies. Cu2+ showed a strong catalytic effect on the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical (ABTSr) consumption and autoxidation of NAC. Difference spectra revealed the formation of intermediates with absorption maxima at 233 and 302 nm (ε302/Cu > 8 × 103 M−1 cm−1) and two positive Cotton effects centered at 284 and 302 nm. These intermediates accumulate during the first, O2-independent, phase of the NAC autoxidation. The autocatalytic production of another chiral intermediate, characterized by two positive Cotton effects at 280 and 333 nm and an intense negative one at 305 nm, was observed in the second reaction phase. The intermediates are rapidly oxidized by added ABTSr; otherwise, they are stable for hours in the reaction solution, undergoing a slow pH- and O2-dependent photosensitive decay. The kinetic and spectral data are consistent with proposed structures of the intermediates as disulfide-bridged dicopper(I) complexes of types cis-/trans-CuI2(RS)2(RSSR) and CuI2(RSSR)2. The electronic transitions observed in the UV/Vis and CD spectra are tentatively attributed to Cu(I) → disulfide charge transfer with an interaction of the transition dipole moments (exciton coupling). The catalytic activity of the intermediates as potential O2 activators via Cu(II) peroxo-complexes is discussed. A mechanism for autocatalytic oxidation of Cu(I)–thiolates promoted by a growing electronically coupled –[CuI2(RSSR)]n– polymer is suggested. The obtained results are in line with other reported observations regarding copper-catalyzed autoxidation of thiols and provide new insight into these complicated, not yet fully understood systems. The proposed hypotheses point to the importance of the Cu(I)–disulfide interaction, which may have a profound impact on biological systems