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A new two-electron photosensitizer, H2BBQ2+[ZnCl4]2−/[(ZnCl)2(μ-BBH)] (BBQ stands for 2,5-bis[bis(pyridin-2-ylmethyl)amino]-1,4-quinone and BBH stands for 2,5-bis[bis(pyridin-2-ylmethyl)amino]-1,4-hydroquinone), has been synthesized and the oxidation state of the ligand was determined by X-ray crystallography and NMR spectroscopy. Under light illumination the H2BBQ2+[ZnCl4]2− + ZnCl2 is reduced quantitatively to [(ZnCl)2(μ-BBH)] (pH ∼ 5) oxidizing H2O to H2O2 as is evident by trap experiments. Electrochemistry gave a reversible two-electron ligand-centered redox wave for [(ZnCl)2(μ-BBH)]. UV-Vis, luminescence and EPR spectroscopies reveal the slow formation of a stable quinone diradical, intermediate of the reaction. DFT calculations are in agreement with the proposed mechanism. Based on this property an aqueous {[(ZnCl)2(μ-BBH)] H2O2} solar rechargeable galvanic cell has been constructed. © The Royal Society of Chemistry. 46 11 3688 3699

Reaction of NH4VO3 with (phenolate/hydroquinonate) iminodiacetate tripod ligands in aqueous solution in the pH range 7–8 results in the isolation of three new dioxido vanadium(V) complexes, one dinuclear (NH4)4{(VVO)2[μ-bicah(6-)-N,O,O,O]}·8H2O, (H6bicah, 2,5-bis[N,N'-bis(carboxymethyl)aminomethyl]-hydroquinone), and two mononuclear (NH4)2{(VVO)2[Hcah(3-)-N,O,O,O]·2H2O, (H4cah, 2-[N,N'-bis(carboxymethyl)aminomethyl]-hydroquinone) and (NH4)2{(VVO)[Hcacp(3-)-N,O,O,O]}·4H2O, (H4cacp, 2-[N,N'-bis(carboxymethyl)aminomethyl]-4-carboxyphenol). The 51V, 1H, and 13C NMR spectra in D2O show the coordination environment of vanadium in the above complexes to be octahedral, with four out of six positions to be occupied by the two carboxylate oxygen, one hydroquinonate oxygen, and one amine nitrogen atoms of the tripod ligand. The two acetate arms are in cis position to each other. Variable-temperature 1H and 13C NMR measurements show that the complexes are kinetically labile. An intramolecular exchange that proceeds through the opening of the phenolate/hydroquinonate chelate ring has been revealed by 2D{1H} NMR EXSY (exchange spectroscopy).

Incidences of fungal infections are on the rise in immunosuppressed people. Predominant causative agents for these mycoses are species of the genus Candida, including Candida albicans, Candida glabrata and Candida dublieniensis. Despite a wide range of emerging pathogens, C. albicans remains the leading cause. According to recent epidemiological studies, blood stream infections with C. albicans cause annually ~55% mortality in approximately 300,000 patients from intensive care units worldwide. Furthermore, the percentage of morbidity linked to oral, esophageal and vulvovaginal mycoses cause by C. albicans reach up to 90%. Reasons for these medical concerns are the lack of efficient diagnostics and antifungal therapy. Here, we therefore sought to find novel antifungal strategies inspired by innate immune cells, such as neutrophils. These phagocytes are able to block the fungal pathogenicity. Neutrophils are bloodstream leukocytes serving as the first line of defense against pathogenic microbes. It has been shown that neutrophils have a strong antifungal activity by impairing the conversion of the dimorphic C. albicans from yeast to hyphal form (Y-H). Consequently, we raised the question whether other immune cells, such as mast cells, with less phagocytic cabapilities may have similar activity to neutrophils. Mast cells are tissue-dwelling cells. Mucosal tissue is rich in mast cells and usually constitutes the entry ports for fungal pathogens into the human body. A contribution of mast cells in antifungal defense is, thus, very likely. We human explored mast cell functions upon encounter with fungal pathogens. Interestingly, human mast cells show a transient potential to impair fungal viability. To understand the mechanism behind this impairment we analyzed the human mast cell functions in more detail. We found that human mast cells challenged with C. albicans, immediately degranulate and secrete distinct cytokines and chemokines in an orchestrated manner. The chemokines secreted attract neutrophils. Mast cells moreover are able to internalize fungal cells and to ‘commit suicide’ by releasing extracellular DNA traps that ensnare the pathogen. The effectiveness of future antifungals is depended on targeting the pathogen virulence with more efficiency. The dimorphism of C. albicans is proven to be essential its virulence. Blockage of this switching ability could render the pathogen avirulent. Consequently, we screened for compounds that mimic the neutrophils anti-dimorphic activity by screening small chemical molecule libraries that block Y-H transition. The screening of big chemical libraries requires a reliable, reproducible and rapid high-throughput screening assay (HTS). We developed an HTS assay based on automated microscopy and image analysis, thereby allowing to distinguish between yeast and filamentous forms. In order to find the ideal Y-H blocker, we also evaluated the cell viability via the count of ATP levels when challenged with the respective small chemical molecules. Drug development is an elaborate and expensive process. We therefore applied our screening setup to identify antidimorphic/antifungal activity in compounds from two different chemical libraries including FDA-approved drugs. The study disclosed 7 off-patent antifungal drugs that have potent antimycotic activity, including 4 neoplastic agents, 2 antipsychotic drugs and 1 antianemic medication. In a nutshell, we aimed to mimic the anti-dimorphic/antifungal activity of neutrophils with small chemical molecules. Furthermore, we elucidated how immune cells contribute to antifungal defense to exploit these mechanisms for the development of novel antifungal therapies. Thus, this thesis provides novel tools for the discovery of more efficient compounds, identifies previously unknown antifungal aspect of off-patent FDA-approved drugs and highlights the interplay of mast cells with pathogenic fungi with the aim to define new screening strategies.

The reaction of 2,5-bis[N,N′-bis(2-pyridyl-aminomethyl)aminomethyl]-p-hydroquinone (H2bpymah) with VO2+ salts in acetonitrile or water at a low pH (2.2-3.5) results in the isolation of [{VIV(O)(Cl)}2(μ-bpymah)], the p-semiquinonate complex [{VIV(O)(Cl)}2(μ-bpymas)](OH), the cyclic mixed-valent hexanuclear compound [{VV(O)(μ-O)VIV(O)}(μ-bpymah)]3, and [(VVO2)2(μ-bpymah)]. [{VIV(O)(Cl)}2(μ-bpymas)](OH) is an intermediate of the radical-mediated oxidation of [{VIV(O)(Cl)}2(μ-bpymah)] from O2. At lower pH values (2.2), a reversible intramolecular electron transfer from the metal to the ligand of [{VIV(O)(Cl)}2(μ-bpymas)](OH) is induced with the concurrent substitution of chlorine atoms by the oxygen-bridging atoms, resulting in the formation of [{VV(O)(μ-O)VIV(O)}(μ-bpymah)]3. The metal complexes were fully characterized by X-ray crystallography, infrared (IR) spectroscopy, and magnetic measurements in the solid state, as well as by conductivity measurements, UV-vis spectroscopy, and electrochemical measurements in solution. The oxidation states of the metal ions and ligands were determined by the crystallographic data. The [{VIV(O)(Cl)}2(μ-bpymah)]-[{VIV(O)(Cl)}2(μ-bpymas)](OH) redox process is electrochemically reversible. The VIV ion in the semiquinonate compound exhibits a surprisingly low oxophilicity, resulting in the stabilization of OH- counterions at acidic pH values. An investigation of the mechanism of this reaction reveals that these complexes induce the reduction of O2 to H2O2, mimicking the activity of enzymes incorporating two redox-active centers (metal-organic) in the active site. © 2015 American Chemical Society. 54 15 7218 7229 Cited By :7

Αριθμός δεδηλωμένων πηγών στη βιβλιογραφία: 270 Διατριβή (διδακτορική) -- Πανεπιστήμιο Κύπρου, Σχολή Θετικών και Εφαρμοσμένων Επιστημών, Τμήμα Χημείας, Μάιος 2007. Η βιβλιοθήκη διαθέτει αντίτυπο της διατριβής σε έντυπη μορφή. Η μελέτη της αλληλεπίδρασης φαινολικών παραγώγων με μεταλλοϊόντα μετάπτωσης είναι πολύ σημαντική στην κατανόηση των μηχανισμών που επιτελούνται σε μεταλλοένζυμα. Επιπλέον, στα πλαίσια οικολογικής συνείδησης, τα τελευταία χρόνια το επιστημονικό ενδιαφέρον εστιάστηκε στην ανάπτυξη καταλυτικών συστημάτων για τη δέσμευση και αναγωγή ρυπαντών, όπως είναι το CO2. Στην εργασία αυτή παρασκευάστηκαν νέα σύμπλοκα CuII με καρβοξυλικά παράγωγα υδροκινόνης σε υδατικό διάλυμα. Απομονώθηκαν μονο- και δι-πυρηνικές ενώσεις (pH 3.0-4.0), πολυμερή (pH 5.0-7.0) και διπυρηνικά διμερή [CuII2O2] (pH 8.0-9.0). Τα μόρια μελετήθηκαν στη στερεή κατάσταση με κρυσταλλογραφία ακτίνων-Χ σε μονοκρυστάλλους, FT−IR και μαγνητοχημικά. Για πρώτη φορά, η μαγνητική συμπεριφορά των διμερών [CuII2O2] συσχετίστηκε με βάση το μήκος δεσμού Cu-O(φαινολικό) και διαπιστώθηκε ότι η συγκεκριμένη παράμετρος μπορεί να εξηγήσει το μέγεθος μαγνητικής αλληλεπίδρασης. Η μελέτη των ενώσεων σε υδατικό διάλυμα με UV−vis έδειξε ότι τα μόρια είναι δομικά σταθερά και ότι η ηλεκτροχημεία τους εξαρτάται απο το pH. Επίσης, παρασκευάστηκαν νέα μονο- και δι-υποκατεστημένα p-υδροκινονικά παράγωγα με πυριδύλ ομάδες που συμπλοκοποιήθηκαν με ZnII σε υδατικό διάλυμα. Η δομή των ενώσεων προσδιορίστηκε με κρυσταλλογραφία ακτίνων-Χ. H σύνθεση των ενώσεων VIV/V με δι-υποκατεστημένο p-υδροκινονικό παράγωγο με πυριδύλ ομάδες έδειξε ότι το συγκεκριμένο σύστημα p-υδροκινόνης με VIV δραστηριοποιείται σε pH 2.2-3.4. Για πρώτη φορά, σταθεροποιήθηκε η οξειδωτική κατάσταση ημικινόνης σε διπυρηνική ένωση VIV. Επιπρόσθετα, παρασκευάστηκαν ανθρακικές πολυοξομεταλλικές ενώσεις MoV και VVI/V, τα οποία δεσμεύουν ισχυρά τα ανθρακικά ανιόντα. Η ηλεκτροχημεία των ενώσεων έδειξε ότι η πολυοξομεταλλική ένωση MoV καταλύει την αναγωγή των ανθρακικών. The interaction study between phenol derivatives and transition metal ions is of importance in order to understand the mechanisms in metalloenzymes. Moreover, in view of environmental conscience, in the last years scientists were focused in the growth of catalytic systems with regard to the binding and reduction of pollutants like CO2. In this work, novel CuII complexes were synthesized with hydroquinone carboxylate derivatives in aqueous solution. This study has led to the isolation of mono- and bi-nuclear complexes (pH 3.0-4.0), polymers (pH 5.0-7.0) and [CuII2O2] dimers (pH 8.0-9.0). These compounds were characterized in the solid state by crystallography, FTIR and magnetochemically. We report for the first time a correlation between the magnetic properties of [CuII2O2] dimers and the Cu-O(phenolate) bond length and it was observed this parameter can explain the magnitude of their interaction. These compounds were found to be structural stable in solution by means of UV-vis and their electrochemistry is pH-dependent. Additionally, novel mono- and bi-substituted hydroquinone/s with pyridyl groups were synthesized and complexed with ZnII in aqueous solution. These compounds were characterized by crystallography. The synthesis of VIV/V complexes in aqueous solution with bisubstituted hydroquinone with pyridyl groups has shown this system is efficient in low pHs (2.2-3.4). For the first time semiquinone was stabilized in a binuclear VIV complex. Additionally, polyoxoMoV and polyoxoVIV/V carbonate compounds were synthesized, which bind strongly to the carbonates. The electrochemistry of these compounds demonstrated the polyoxoMoV compounds provoke the reduction of carbonates.

Reaction of the N,N-disubstituted bis(hydroxylamino) ligand 2,6-bis[hydroxy(methyl)amino]-4-morpholino-1,3,5-triazine (H2bihyat) with cis-[MoVIO2(acac)2] in tetrahydrofuran resulted in isolation of the mononuclear compound cis-[MoVIO 2(bihyat)] (1). The treatment of Na2MoVIO 4·2H2O with the ligand H2bihyat in aqueous solution gave the dinuclear compounds cis-[MoVI 2O4(bihyat)2(H2O)2] (2) and trans-[MoVI2O4(bihyat)2(H 2O)2] (3) at pH values of 3.5 and 5.5, respectively. The structures for the three molybdenum(VI) compounds were determined by X-ray crystallography. Compound 1 has a square-pyramidal arrangement around molybdenum, while in the two dinuclear compounds, each molybdenum atom is in a distorted pentagonal-bipyramidal environment of two bridging and one terminal oxido groups, a tridentate (O,N,O) bihyat2- ligand that forms two five-membered chelate rings, and a water molecule trans to the terminal oxido group. The dinuclear compounds constitute rare examples containing the {Mo 2VIO2(μ2-O2)} 4+ moiety. The potentiometry revealed that the Mo VIbihyat2- species exhibit high hydrolytic stability in aqueous solution at a narrow range of pH values, 3-5. A subtle change in the coordination environment of the five-coordinate compound 1 with ligation of a weakly bound water molecule trans to the oxido ligand (1w) renders the equatorial oxido group in 1w more nucleophilic than that in 1, and this oxido group attacks a molybdenum atom and thus the dinuclear compounds 2 and 3 are formed. This process might be considered as the first step of the oxido group nucleophilic attack on organic substrates, resulting in oxidation of the substrate, in the active site of molybdenum enzymes such as xanthine oxidase. Theoretical calculations in the gas phase were performed to examine the influence of water on the dimerization process (1 → 2/3). In addition, the molecular structures, cis/trans geometrical isomerism for the dinuclear molybdenum(VI) species, vibrational spectra, and energetics of the metal-ligand interaction for the three molybdenum(VI) compounds 1-3 have been studied by means of density functional theory calculations. © 2012 American Chemical Society. 51 24 13138 13147 Cited By :3

Bisphosphonates are biologically relevant therapeutics for bone disorders and cancer. Reaction ofγ-chlorobutyric acid, phosphorus acid, and phosphorus trichloride without the use of solvent gave the tetrahydrofuranyl-2,2-bisphosphonate sodium salt (Na2H2L). TheNa2H2Lwas isolated, characterized in solution byH,C, andPNMR spectroscopy and in solid state by single X-Ray crystallography. The crystal structure showed that theNa2H2Lforms in the crystal infinite two-dimensional sheets stacked one parallel to the other. A comparison of the chelating properties ofH2L2−with similar hydroxyl bisphosphonate ligands shows that the strength of the Na–O(furanyl/hydroxyl) bond is directly related to the total charge of the ligand anion.

Copper ions in the active sites of several proteins/enzymes interact with phenols and quinones, and this interaction is associated to the reactivity of the enzymes. In this study the speciation of theCu2+with iminodiacetic phenolate/hydroquinonate ligands has been examined by pH-potentiometry. The results reveal that the iminodiacetic phenol ligand forms mononuclear complexes withCu2+at acidic and alkaline pHs, and a binuclearOphenolate-bridged complex at pH range from 7 to 8.5. The binucleating hydroquinone ligand forms only 2 : 1 metal to ligand complexes in solution. The pK values of the protonation of the phenolate oxygen of the two ligands are reduced about 2 units after complexation with the metal ion and are close to the pK values for the copper-interacting tyrosine phenol oxygen in copper enzymes.

Partial oxidation of an aqueous solution of CoIICl 2·6H2O with (NH4)6[Mo 7VIO24]·4H2O in the presence of (NH4)2SO3·H2O and LiCl, at pH ≈ 5.3, leads to isolation of the octanuclear cluster (NH 4)11(Li⊂[Co4IICo 4III(SO3)16(NH3) 8]·10H2O), 1. The structure of the anion of 1 consists of a central [Co4II], almost ideal square planar unit, and a pair of symmetry-related CoIII dimers above and below the Co4II plane grafting onto the tetramer by 16 bridging sulfite groups. The [Co8(SO3)16(NH 3)8]12- cluster encapsulates a lithium cation which lies at the center of the Co4II square. © 2008 American Chemical Society. 47 11 4451 4453 Cited By :19

Reaction of the ligand 2,6-bis[hydroxy(methyl)amino]-4-morpholino-1,3,5- triazine (H2bihyat) with NaVVO3 in aqueous solution followed by addition of either Ph4PCl or C(NH 2)3Cl, respectively, gave the mononuclear vanadium(V) compounds Ph4P[VVO2(bihyat)]·1.5H 2O (1) and C(NH2)3[VVO 2(bihyat)] (2). Treatment of VIVOSO4· 5H2O with the ligand H2bihyat in methyl alcohol under specific conditions gave the oxo-bridged dimer [VV2O 2(μ2-O)(bihyat)2] (3). The structures for 1 and 3 were determined by X-ray crystallography and indicate that these compounds have distorted square-pyramidal arrangement around vanadium. The ligand bihyat2- is bonded to vanadium atom in a tridentate fashion at the pyridine-like nitrogen atom and the two deprotonated hydroxylamino oxygen atoms. The high electron density of the triazine ring nitrogen atoms, which results from the resonative contribution of electrons of exocyclic nitrogen atoms (Scheme 4), leads to very strong V-N bonds. The cis-[VVO 2(bihyat)]- species exhibits high hydrolytic stability in aqueous solution over a wide pH range, 3.3-11.0, as it was evidenced by 1H and 51V NMR spectroscopy and potentiometry. The high affinity of the H2bihyat ligand for the VVO 2+ unit, its tridentate character, as well as its small size, paves the way for potential applications in medicine, analysis, and catalysis for the C(NH2)3[VVO 2(bihyat)] compound. The molecular structures, vibrational and electronic spectra, and the energetics of the metal-ligand interaction for compounds 1 and 3 have been studied by means of density functional calculations. © 2008 American Chemical Society. 47 24 11698 11710 Cited By :17

Future Communication Networks are envisioned to be based upon a common, flexible and scalable convergence platform, where different access networks, different terminals and different services can coexist. The new user capabilities spawn a demand for Always Best Connectivity (ABC), i.e. that a user can always have the best possible connection regardless of place and time. This brings forth a new communication paradigm, which is user-centric, i.e. the user is no longer bound to only one access network but can choose the best available access network to satisfy a specific service request. The IP Multimedia Subsystem (IMS) is the technology promoted to enable this ubiquitous converged network. This paper considers the selection of access network, specifically for multicast/broadcast users and proposes a novel RAN selection scheme implemented using IMS signalling. © 2007 IEEE. Conference code: 72105 Cited By :1

It is shown that Enhanced UMTS will be an affordable solution for providing the required network quality and to reduce infrastructure investments in offices scenarios. System capacity results are obtained by using a system level simulator which considers traffic characterisation parameters and services usage in detail, among other. Results for the most profitable cell radius are obtained via an optimisation procedure based in economic aspects. A higher number of pico cells (with a smaller radius, around 30-32 m) can be installed in the future, when costs of deploying and maintaining the network decreases, allowing for supporting higher system capacity, and reducing prices. Our approach is based in a detailed services analysis, which represents a worst case situation relatively to the total services approach, because the later does not discriminate results for the different traffic classes. The impact of call blocking, handover failure, end-to-end delay, and delay variation are taken into account. © 2006 IEEE. Conference code: 72218 Cited By :2

Enhanced UMTS traffic characterisation parameters have been addressed for the offices scenario. By using a system level simulator, results concerning QoS measures as packet delay, blocking and handover failure probabilities have been obtained. If the cell radius decreases and the number of BSS increases the blocking probability decreases with a linear trend. One concludes that the supported traffic and the corresponding throughput significantly increase when the cell radius decreases. However, increasing system capacity by decreasing the cell radius causes an increase in the intensity of hand overs and a decrease in the throughput per BS. Hence, optimum values for the coverage distance will correspond to higher cell radius. Delay and delay variation are not a limitation. Sponsors: Conference code: 114330 Cited By :2