Structure and biological activities of metal complexes of flumequine

The reaction of CoCl2·6H2O with the quinolone antimicrobial agent flumequine (Hflmq) in the absence or presence of the α-diimines 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2′-bipyridylamine (bipyam) resulted in the formation of four mononuclear complexes which were characterized with physicochemical and spectroscopic techniques. The crystal structures of [Co(flmq)2(bipy)]·2H2O, [Co(flmq)2(phen)]·1.6MeOH·0.4H2O and [Co(flmq)2(bipyam)]·H2O were determined by X-ray crystallography. The interaction of the complexes with calf-thymus DNA (CT DNA) was investigated by UV spectroscopy, viscosity measurements, cyclic voltammetry and competitive studies with ethidium bromide in order to evaluate the possible DNA-binding mode and to calculate the corresponding DNA-binding constants. The binding of the complexes to human or bovine serum albumin was studied by fluorescence emission spectroscopy and the corresponding binding constants were determined. The antimicrobial activity of the Co(II)–flumequine and the recently reported Cu(II)–flumequine complexes was tested against four different microorganisms (Escherichia coli, Xanthomonas campestris, Staphylococcus aureus and Bacillus subtilis) and was found to be similar to that of free Hflmq. The antiproliferative activity of previously reported complexes [Cu(flmq)(phen)Cl], [Zn(flmq)(phen)Cl] and [Ni(flmq)2(phen)] against human ovarian (A2780) and lung (A549) cancer cell lines is also reported in comparison to the cobalt analogue, [Co(flmq)(phen)Cl], 3, highlighting important differences among the various complexes which may be due to different uptake and modes of action

Urban plans and public space during Otto's period (1833 - 1862) in Greece: cities’ urban planning through the Official Government Gazette

The research investigates the fundamentals and principles that govern the planning, design and organization of the modern Greek city and public space, as well as the design and localization of public buildings and monuments during the Otto’s period in Greece, 1833-1862. Three are the main phases investigated in the research: Initially, the role of the Regency period (1833 - 1835) is examined, then the period of Absolute Monarchy (1836 - 1843) is analysed and finally the role of Governments during Constitutional Monarchy (1843 - 1862) is studied. The ideological views of the Kingdom of Hellas in space organization – related aspects are also considered.Moreover, focus is given on state interventions aimed at urban and residential reconstruction and the composition of public space. The research monitors and records the development of the relevant legislation during the first thirty years of the new Greek State (1833-1862), analyses its influences from the European area, highlighting issues of creating "colonial" settlements in various cities, the management of national lands, the localization and construction of the first public buildings. It also records and analyses the policy pursued by the State during the same period for antiquities and monuments and explores the correlation of politics with the planning of cities. The research is based on the Official Government Gazette (GG) of the Kingdom, in which the Laws and Royal Decrees, the Decisions and the Circulars that were published were issued by King Otto and his Ministers. More than 1,400 GGs of the Otto’s period and about 200 GGs of the period after Otto were studied, to investigate whether there was policy continuity or change. As concluded from the research, the planning and design of the cities was attempted with a “top-down approach". The state perception, which is recorded in the Laws and Decrees of the Official Government Gazette, was the dominant one in the governmental system imposed by Otto together with all the positive aspects that were planned and implemented, but also with those omitted. The urban planning process that followed was the means by which the urbanization of the State was sought. The study also concludes that the State has been pursuing a policy through the distribution of national lands, which it has been implementing with several relevant laws since 1835. In this context, many settlements were formed, or co-formed, the plans of large and small cities (such as Piraeus, Eretria, etc.). Local communities, through the Municipal Councils, expressed an opinion on design issues, as stated in the first relevant Decrees (1834), however, their view was conclusive. The Councils expressed their views on issues at local level, but the decisions were taken by the relevant Prefect and the Minister of Interior. The research is not limited to exploring the parameters that contributed to the design of the largest Greek cities of the time (Athens, Piraeus, Ermoupolis in Syros island, Patras, Lamia), but extends to city plans throughout the Hellenic Territory, which at that time included only the Peloponnese, Central Greece, the island of Evia and some of the Aegean islands. Every city plan, from the administrative centres of the time and the historic cities (Nafplio) to the smallest ones (Galatas), is examined in detail, as long as they are recorded in the Official Government Gazette. Many of the decisions made at that time laid the foundations for city plans until the 20th century. The public buildings presented in the study include those built to serve a public function, such as the Parliament building, the University, the Observatory, the Archaeological Museum of Athens, temples. Buildings that served public use (theaters, etc.), for which there is information published in the Government Gazette are also included. Furthermore, the study analyses the policy implemented during the Otto’s period for antiquities and presents monuments in public, whether they were planned to be located or erected (e.g. Karaiskaki monument in Salamis, Guilford bust in Athens, etc.).Finally, the research investigates, through the Government Gazette: the role of architects and engineers in the design processes of cities and of public buildings,the importance of infrastructure projects and their interconnection with the evolution of cities and the organization of the space,the location of Museums during this period. The thesis is structured in five chapters, the Preface, three Chapters forming the main body and the Conclusions and Future Work, while Bibliography follows. The Appendix includes detailed tables with the legislation and plans of cities and public buildings of the Otto’s period. In more detail:The Preface refers to the purpose of the study, the methodology followed, the sources, the structure of the content and the problems that arose during its elaboration. The first Chapter of the study, entitled "The European Framework for Cities and Public Space in the 19th Century", provides background information about the concept of the city and then approaches the concept of public space and its evolution. In particular, the developments and characteristics of the urban space are presented, in the context of shifting the boundaries between private and public space. Following there is a reference to the corresponding European framework, which is based on bibliographical research carried out. This discusses the development of the European city after the Middle Ages, design issues of European cities and public space in the 19th century, the dominant trends of neoclassicism and romanticism in European architecture at that time, the role of industrial revolution and the new materials that are beginning to be used in construction. Some examples of large urban centres of the time are given in various European countries (France, Germany, Britain, Spain, etc.). The urban legislative framework, the policy on public space and public buildings applied by the Ottoman Empire at the same time are also presented. Particular reference is made to the Parliament buildings of the European states, which were designed and built in the 19th century. The European developments of the 19th century in politics, in the design of cities, in architecture, influenced what was happening in Greece. These influences are recorded. The first Chapter closes with conclusions. The second Chapter entitled "Greece during the Otto’s Period" consists of two (2) Parts. Part A refers to people and events of this period. The Government Gazette is presented in detail and follows the political and institutional framework per specific period (Regency, absolute monarchy, constitutional monarchy). The political figures highlighted in the research, are mainly those who have taken on the duties of Minister of the Interior, i.e. those responsible for the city planning. Part B of the Chapter discusses issues of state organization, legislation, education and infrastructure. The administrative organization and the institutions associated with the city planning (e.g. Council of the State) are presented. At the legislative framework, its influences from respective European countries and the legislative regulations of the Otto’s period that had a general application in the city planning are presented and analysed. Following is the presentation of the Building Regulations that were applied and their development until today. What is more, issues related to the building permits (content, sanctions, etc.) and how they are issued are presented. The following are the archaeological legislation, the Archaeological Society (founded in 1837) and its work, and the monuments. The responsibilities of the Ministries of Interior and Military in urban planning and public buildings’ design, educational issues and the first educational institutions (University of Athens, School of Arts, Polytechnic School, etc.), technical professions and their professional rights and funding issues for the implementation of city plans are further discussed. Regarding the infrastructure, the road and railway connection works of the cities at the beginnings of the Greek State, as well as water supply and lighting systems of the largest urban centres and port infrastructures are pointed out. Each Part of the second Chapter closes with conclusions. The third Chapter is entitled "The city, the public space, the public buildings" and it presents a detailed list of information about each studied city separately. Particularly, for each of eleven (11), initially, cities (Athens, Patras, Messolonghi, Chalkida, Nafplio, Tripoli, Sparta, Corinth, Lamia, Agios Andreas, Katakolo) information are presented. These are cities for which there are many and substantial laws that have been published in the Government Gazette. This is followed by a group of twenty-nine (29) other cities, for which references in the Government Gazette are limited. Then the issue of "colonies" is analysed, which includes important cities, such as Piraeus, Ermoupolis and Eretria, but also smaller populated cities or towns (e.g. Petalidi, Elafonisos). Finally, some cities (e.g. Nafpaktos) are mentioned, for which there are no references in the Government Gazette during the Otto’s period, but their plans were found in the Map Archives of the Ministry of Environment, presented in the Annex. The study then focuses on the public buildings in Athens that were designed or erected during the Otto’s period (Palace, Old Parliament, Library, etc.). Special cases are the Archaeological Museum and the theatre of Athens, buildings for which there is important material published in the Government Gazette. Public buildings in other cities (e.g. lazaret in Ermoupolis, etc.) are also on display, including temples, as well as the legislation on which they were designed. The environmental issues of the cities are also analysed and the rudimentary way of dealing with them is discussed. Finally, through Ministerial Announcements and Proclamations, an attempt is made to seek the ideological framework of the Governments of Otto. Last but not least, the Conclusions of the study and the proposals for future work follow, which are summarized in numerous sections, namely: fundamentals of urban planning legislation, design principles of cities and settlements, colonies, as well as public space and public buildings. Finally, issues of the policy pursued for antiquities and for the few monuments in the public space during the Otto’s period are summarized. What is more, further research fields are proposed focusing on the unpublished legislative framework, future investigation of urban design and development of the coastal areas of the new Greek State based on coastal shipping growth from 1849. The study concludes with the Bibliography Section and the Appendix presents fourteen (14) Tables and ninety-eight (98) Plans.Η παρούσα διδακτορική διατριβή εστιάζει στη διερεύνηση των αρχών και των συντελεστών που διέπουν τον σχεδιασμό, τη δημιουργία και οργάνωση της πόλης και του δημόσιου χώρου, καθώς και τον σχεδιασμό και τη χωροθέτηση δημόσιων κτιρίων και μνημείων κατά την πρώτη τριακονταετία του νέου Ελληνικού Κράτους, 1833 – 1862, επί βασιλείας Όθωνα. Αρχικά, διερευνώνται οι παρεμβάσεις του Κράτους με στόχο την πολεοδομική και οικιστική αναδημιουργία του και τη συγκρότηση του δημόσιου χώρου. Παρακολουθείται και καταγράφεται η εξέλιξη της σχετικής νομοθεσίας κατά την Οθωνική περίοδο, αναλύονται οι επιρροές της από τον ευρωπαϊκό χώρο και επισημαίνονται θέματα της δημιουργίας αποικιών, της διαχείρισης των εθνικών γαιών, της διαμόρφωσης του δημόσιου χώρου, της χωροθέτησης και ανέγερσης των πρώτων μεγάλων δημόσιων κτιρίων στην Αθήνα και σε άλλες πόλεις. Το Κράτος ασκούσε πολιτική διαχείρισης της γης μέσω σειράς Νόμων (περί προικοδοτήσεως οικογενειών και Δήμων, περί εκποιήσεως εθνικών κτημάτων, περί κτηματολογίου, κ.α.), που εφάρμοζε από το 1835 μέχρι το τέλος της Οθωνικής περιόδου. Στη διατριβή, καταγράφεται και αναλύεται επίσης η πολιτική που εφάρμοσε το Κράτος την ίδια περίοδο για τις αρχαιότητες και τα μνημεία σε δημόσιο χώρο και διερευνάται ο συσχετισμός αυτής της πολιτικής με τον σχεδιασμό των πόλεων. Η μελέτη δεν περιορίζεται στη διερεύνηση των παραμέτρων που συνέβαλαν στον σχεδιασμό των μεγαλύτερων ελληνικών πόλεων της εποχής (Αθήνα, Ερμούπολη, Πάτρα, κ.α.), αλλά εκτείνεται σε σχέδια πόλεων ανά την Επικράτεια, η οποία από το 1832 περιελάμβανε την Πελοπόννησο, τη Στερεά Ελλάδα, την Εύβοια και ορισμένα άλλα νησιά του Αιγαίου. Εξετάζεται αναλυτικά κάθε σχέδιο πόλεως, από τις ιστορικές πόλεις και τα διοικητικά κέντρα (Ναύπλιο, Τρίπολη), μέχρι τις πλέον μικρές (Γαλατάς), εφ’ όσον αυτές είναι καταγεγραμμένες στην Εφημερίδα της Κυβερνήσεως. Στα δημόσια κτίρια που παρουσιάζονται στη διατριβή, περιλαμβάνονται όσα οικοδομήθηκαν για να εξυπηρετήσουν δημόσιες λειτουργίες, όπως το Πανεπιστήμιο και οι ναοί. Η μελέτη βασίζεται στην Εφημερίδα της Κυβερνήσεως του Βασιλείου, στην οποία δημοσιευόταν η νομοθεσία που εξέδιδε ο Όθωνας και οι Υπουργοί του. Μελετήθηκε το σύνολο των Φύλλων της Εφημερίδας της Κυβερνήσεως (περισσότερα από 1.400 ΦΕΚ) της Οθωνικής περιόδου, αλλά και 200 (διακόσια) περίπου ΦΕΚ της περιόδου μετά τον Όθωνα, προκειμένου να ερευνηθεί εάν υπήρξε συνέχεια της μέχρι τότε ακολουθούμενης πολιτικής ή αν αυτή άλλαξε, για τα μελετώμενα θέματα. Όπως προκύπτει από την έρευνα, ο σχεδιασμός των πόλεων επιχειρήθηκε «εκ των άνω». Για όλα τα θέματα αποφάσιζε ο αρμόδιος Υπουργός Εσωτερικών ή ο διορισμένος Νομάρχης. Η κρατική αντίληψη, όπως καταγράφεται στους Νόμους και στα Διατάγματα της Εφημερίδας της Κυβερνήσεως, ήταν η κυρίαρχη στο σύστημα διακυβέρνησης που επέβαλε ο Όθωνας και σε αυτήν οφείλονται όσα θετικά σχεδιάστηκαν και υλοποιήθηκαν, αλλά και όσα παραλείφθηκαν. Επισημαίνεται ότι πολλές από τις αποφάσεις που λήφθηκαν εκείνη την εποχή για ορισμένες πόλεις, διαμόρφωσαν τα σχέδια αυτών των πόλεων μέχρι τον 21ο αιώνα. Τέλος, στη μελέτη παρουσιάζονται δεκατέσσερις (14) Πίνακες με τη σχετική νομοθεσία που έχει δημοσιευθεί σε ΦΕΚ και τα ενενήντα οκτώ (98) σχέδια πόλεων και δημόσιων κτιρίων, που βρέθηκαν μετά από αναζήτηση σε διάφορα Αρχεία και αφορούν την Οθωνική περίοδο

Validation of a HILIC UHPLC-MS/MS Method for Amino Acid Profiling in Triticum Species Wheat Flours

Amino acids are essential nutritional components as they occur in foods either in free form or as protein constituents. An ultra-high-performance (UHPLC) hydrophilic liquid chromatography (HILIC)-tandem Mass Spectrometry (MS) method has been developed and validated for the quantification of 17 amino acids (AA) in wheat flour samples after acid hydrolysis with 6 M HCl in the presence of 4% (v/v) thioglycolic acid as a reducing agent. The developed method proved to be a fast and reliable tool for acquiring information on the AA profile of cereal flours. The method has been applied and tested in 10 flour samples of spelt, emmer, and common wheat flours of organic or conventional cultivation and with different extraction rates (70%, 90%, and 100%). All the aforementioned allowed us to study and evaluate the variation of the AA profile among the studied flours, in relation to other quality characteristics, such as protein content, wet gluten, and gluten index. Significant differences were observed in the AA profiles of the studied flours. Moreover, AA profiles exhibited significant interactions with quality characteristics that proved to be affected based mainly on the type of grain. A statistical and multivariate analysis of the AA profiles and quality characteristics has been performed, as to identify potential interactions between protein content, amino acids, and quality characteristics

Effects of cadmium and 17\u3b2-estradiol on Mytilus galloprovincialis redox status. Prooxidant\u2013antioxidant balance (PAB) as a novel approach in biomonitoring of marine environments

Cadmium and 17\u3b2-estradiol are rapidly accumulated in mussel tissues, making mussels excellent pollution sentinel organisms. The aim of the present study was to compare the oxidative responses of the mussels after 1, 3 and 7 days of exposure to cadmium with those to 17\u3b2-estradiol and subsequently, to suggest a multi-parametric approach for biomonitoring studies. Our results showed that environmentally relevant concentrations of either cadmium or 17\u3b2-estradiol for 1, 3 and 7 days induced oxidative stress in hemocytes of exposed mussels. The latter was determined by significantly increased ROS levels and apoptosis, by suppression of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) expression levels and subsequent increased prooxidant levels, as measured by prooxidant-antioxidant balance (PAB) assay. To our knowledge this is the first time that prooxidant-antioxidant balance is evaluated in invertebrates as an index of oxidative stress. The simultaneous use of the parameters of prooxidant-antioxidant balance and antioxidant enzymes expression patterns, in combination with ROS production levels and apoptosis, in mussel hemocytes is suggested as an approach that may help to better evaluate the impact of environmental pollution on marine organisms and thereupon ecosystems

Palladium(II) Complexes of Substituted Salicylaldehydes: Synthesis, Characterization and Investigation of Their Biological Profile

Five palladium(II) complexes of substituted salicylaldehydes (X-saloH, X = 4-Et2N (for 1), 3,5-diBr (for 2), 3,5-diCl (for 3), 5-F (for 4) or 4-OMe (for 5)) bearing the general formula [Pd(X-salo)2] were synthesized and structurally characterized. The crystal structure of complex [Pd(4-Et2N-salo)2] was determined by single-crystal X-ray crystallography. The complexes can scavenge 1,1-diphenyl-picrylhydrazyl and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and reduce H2O2. They are active against two Gram-positive (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative (Escherichia coli and Xanthomonas campestris) bacterial strains. The complexes interact strongly with calf-thymus DNA via intercalation, as deduced by diverse techniques and via the determination of their binding constants. Complexes interact reversibly with bovine and human serum albumin. Complementary insights into their possible mechanisms of bioactivity at the molecular level were provided by molecular docking calculations, exploring in silico their ability to bind to calf-thymus DNA, Escherichia coli and Staphylococcus aureus DNA-gyrase, 5-lipoxygenase, and membrane transport lipid protein 5-lipoxygenase-activating protein, contributing to the understanding of the role complexes 1–5 can play both as antioxidant and antibacterial agents. Furthermore, in silico predictive tools have been employed to study the chemical reactivity, molecular properties and drug-likeness of the complexes, and also the drug-induced changes of gene expression profile (as protein- and mRNA-based prediction results), the sites of metabolism, the substrate/metabolite specificity, the cytotoxicity for cancer and non-cancer cell lines, the acute rat toxicity, the rodent organ-specific carcinogenicity, the anti-target interaction profiles, the environmental ecotoxicity, and finally the activity spectra profile of the compounds

Metal(II) Complexes of the Fluoroquinolone Fleroxacin: Synthesis, Characterization and Biological Profile

A series of complexes of divalent transition metals (Cu(II), Mn(II), Zn(II), Co(II) and Ni(II)) with the quinolone antibacterial agent fleroxacin, in the absence or presence of an α-diimine such as 2,2′-bipyridine, 1,10-phenanthroline or 2,2′-bipyridylamine, were prepared and characterized. The complexes were characterized by various physicochemical and spectroscopic techniques and by single-crystal X-ray crystallography. The in vitro antibacterial activity of the complexes was studied against the bacterial strains Staphylococcus aureus, Bacillus subtilis and Xanthomonas campestris and was higher than that of free quinolone. The affinity of the complexes for bovine and human serum albumin was studied by fluorescence emission spectroscopy and the determined binding constants showed tight and reversible binding to the albumins. The interaction of the complexes with calf-thymus DNA was studied by various techniques, which showed that intercalation was the most plausible mode of interaction

Development, Validation and Application of an Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC-MS/MS) Method after QuEChERS Cleanup for Selected Dichloroanilines and Phthalates in Rice Samples

Dichloroanilines and phthalic acid esters (phthalates) are food contaminants, stable in solution even at high temperatures, which exhibit considerable toxic effects, while acting as endocrine disruptors. In the present study, a quick and easy UHPLC-MS/MS method for simultaneously analyzing two dichloroanilines (3,4-DCA and 3,5-DCA) and six phthalates (DMP, DnBP, BBP, DnOP, DEHP, and mBP) in commercial rice samples was developed, validated, and applied. For the cleanup process, the methodology of quick, easy, cheap, effective, rugged, and safe (QuEChERS) was applied, whereas different dispersants (GCB, C18, and PSA) were tested. What was developed and presented had limits of detection ranging from 0.017 up to 0.12 mg/kg, recoveries (trueness) below 120%, and relative standard deviations (RSD; precision) <15% for all target analytes, whilst no significant matrix effects occurred for all analytes. It was determined that the rice samples analyzed using this developed technique did not contain any of the two dichloroaniline compounds (3,4-DCA and 3,5-DCA) nor two of the six phthalate (DMP and mBP) compounds analyzed, while the levels of other phthalates (DEHP, BBP, DnBP and DnOP) were within the legal limits. The current method ensures a fast and easy approach for the high-throughput quantification of the selected food contaminants in rice

Cost-Effective Simultaneous Determination of tau- and pi-Methylhistidine in Dairy Bovine Plasma from Large Cohort Studies Using Hydrophilic Interaction Ultra-High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry

The isomeric metabolites τ- and π-methylhistidine (formerly referred to as 3- and 1-methylhistidine) are known biomarkers for muscle protein breakdown and meat protein intake, frequently used in studies involving humans and animals. In the present study, we report the development and validation of a simple HILIC-MS/MS method for individual determination of τ-MH and π-MH in a large cohort of blood plasma samples from dairy cows. Their separate determination was achieved mainly through a mass spectrometry fragment ion study, which revealed that the two isomers exhibited distinct mass spectrometric behaviors at different collision energies. Chromatographic conditions were optimised to achieve better separation, minimizing inter-channel interference to less than 1% in both directions. A simple and effective sample clean-up method facilitated low laboratory manual workload. The analytical method was validated for the determination of τ-MH and π-MH in bovine plasma within a concentration range of 80 to 1600 μg/L and provided good linearity (&gt;0.99 for both curves) and precision (&lt;10%). Overall, the developed method enabled the determination of the two isomers in an efficient and economic-friendly manner suitable for large cohort bovine studies (involving hundreds to thousands of samples) mainly to provide data for statistical use.</jats:p