The synthetic approach was developed for the preparation of N-bridged diiron phthalocyanines substituted by different electron-withdrawing alkylsulfonyl substituents. Six novel phthalocyanines bearing small (methylsulfonyl, ethylsulfonyl and hexylsulfonyl) and bulky (t-butylsulfonyl, adamantylsulfonyl and cyclohexylsulfonyl) substituents have been prepared and characterized by electrospray ionization mass spectrometry (ESI-MS), UV-Vis, FT-IR and EPR. Two complexes (with hexylsulfonyl and t-butylsulfonyl substituents) were characterized in addition by Mössbauer techniques, X-ray photoelectron spectroscopy (XPS) and Fe K-edge X-ray absorption spectroscopy (XANES, EXAFS, high resolution Kβ emission spectroscopy). It has been evidenced that the electronic state of iron in these complexes depends on the size of the substituents. While N-bridged diiron phthalocyanines having methylsulfonyl, ethylsulfonyl and hexylsulfonyl substituents are cationic (PcFeIVNFeIVPc)+N3- complexes, N-bridged diiron phthalocyanines with bulkier t-butylsulfonyl, adamantylsulfonyl and cyclohexylsulfonyl substituents are formally neutral PcFeIIINFeIVPc species. The catalytic properties of six N-bridged diiron phthalocyanines have been studied, using tert-butyl hydroperoxide (tBuOOH) as the oxidant in the oxidation of toluene, p-xylene as well as in the oxidation of various alcohols. This thesis demonstrates the efficiency of N-bridged diiron phthalocyanines substituted by electron-withdrawing alkylsulfonyl groups as oxidation catalysts, in conditions required by environmental and industrial preoccupations

The original goal of this thesis was to develop process chemistry to yield boron subphthalocyanine (BsubPc) derivatives which were previously difficult to access. Retrospectively, it was found that these compounds show extremely high density crystal packing in comparison to other known BsubPcs, and thus this also became a focus of the thesis. A process to synthesize and purify fluoro-BsubPc was developed. This led to a detailed comparison of the physical and chemical properties of the three halo-BsubPcs in order to answer the question of which halo-BsubPc is appropriate for different purposes. Through this work, the previously unpublished crystal structure of the oxygen bridged dimer, µ-oxo-BsubPc, was found. A process was subsequently developed for the practical synthesis of µ-oxo-BsubPc for use in vacuum deposition and a number of µ-oxo-BsubPc crystal polymorphs were found and analyzed. The properties of this group of compounds are discussed in the context of other known BsubPcs.

The original goal of this thesis was to develop process chemistry to yield boron subphthalocyanine (BsubPc) derivatives which were previously difficult to access. Retrospectively, it was found that these compounds show extremely high density crystal packing in comparison to other known BsubPcs, and thus this also became a focus of the thesis. A process to synthesize and purify fluoro-BsubPc was developed. This led to a detailed comparison of the physical and chemical properties of the three halo-BsubPcs in order to answer the question of which halo-BsubPc is appropriate for different purposes. Through this work, the previously unpublished crystal structure of the oxygen bridged dimer, µ-oxo-BsubPc, was found. A process was subsequently developed for the practical synthesis of µ-oxo-BsubPc for use in vacuum deposition and a number of µ-oxo-BsubPc crystal polymorphs were found and analyzed. The properties of this group of compounds are discussed in the context of other known BsubPcs.

The Morse/Long Range (MLR) potential has become one of the most reliable and highly used potential energy functions for diatomic molecules. It includes the theoretical long range behaviour that diatomic molecules are known to exhibit as they approach the dissociation limit. Heavy alkali metals with adjacent electronic states often exhibit strong coupling between the spin and orbital angular momentum. The ground state X¹Σg⁺ and the lowest lying triplet state aᶟΣᵤ⁺ of Cs₂ exhibit such coupling effects and as a result, modeling the highest vibrational states of these states is a non-trivial problem. Utilizing scattering length values obtained from published analysis of 60 Feshbach resonances, the correct form of the potential energy function was determined. Moreover, the scattering length values were used to determine the correct leading dispersion coefficient that describes the true form of the long-range potential energy functions. All previous attempts to determine global potential energy functions for these states have considered only the optical spectroscopic data. This is the first ever effort attempting to use scattering lengths determined from cold atom collision experiments in a combined analysis with conventional spectroscopic data.

This thesis covers the combination of two seperate work accomplished during the throughout the study. In the first part of the study, xanthene based artificial enzymes were synthesized, and kinetic hydrolysis studies done. Artificial enzyme design is an active field of supramolecular chemistry and metalloenzymes are attractive targets in such studies. Enzymatic catalysis is essentially a &lsquo / multifuctional&rsquo / catalysis. As part of our work, we designed and synthesized three novel xanthene derivatives. All three model contain Zn(II) in their active sites. Using the model substrate p-nitrophenyl acetate, we showed that the bifunctional model is at least an order of magnitude more active in catalyzing the hydrolysis of the substrate. Compared to the uncatalyzed hydrolysis reaction of the p-nitrophenyl ester at pH 7.0, the bifunctional model complex showed a 5714-fold rate acceleration. The second part of the thesis involves the design of a dimeric calixpyrrole as a chromogenic chemosensor. Anions are involved in a large number of biological processes and there is an interest in developing molecular sensors for these charged species. The calixpyrroles are a class of old but new heterocalixarene analogues that show considerable promise in the area of anion sensing. In this work, we have designed, synthesized and characterized a calixpyrrole-dimer anion sensor for its anion binding strength. The dimer forms stable complexes with p-nitrophenolate ion. This formed complex is used as a colorimetric sensor by displacing the chromogenic anion with the addition of various anions. like fluoride and acetate. The receptor shows strong affinity and high selectivity for fluoride anion, and also show reasonable affinity toward acetate. Thus, effective optical sensing of biochemically relevant these anions is accomplished using the calixpyrrole dimer.

The following thesis focuses on two areas of chemistry, pi-pi interactions and radical cation dimers. Approximations to the exact solution to the Schrodinger equation are investigated for these types of chemical systems with a variety of theoretical methods. The first chapter provides an introduction to the various quatum mechanical methods used in this research. The second chapter focuses specifically on pi-pi interaction. In this chapter, high quality quantum mechanical methods are used to examine how substituents tune pi-pi interactions between monosubstituted benzene dimers in parallel-displaced geometries. In addition, the role of dispersion and coulombic interactions in these systems is investigated to determine the nature of the substituent effect. In the third chapter radical cation dimers are investigated. Benchmark results with full configuration interaction (FCI) and equation-of-motion coupled-cluster for ionized systems (EOM-IP-CCSD) are presented for prototypical charge transfer species. Conclusions regarding chapters 2 and 3 are presented in the final chapter. This work may form the basis for improved approaches to rational drug design, organic optical materials, and molecular electronics.

Ribosomal stalk proteins are known to play important role in protein synthesis. The ‘stalk’, an extended structure on the large subunit of the ribosome is composed mainly of two to three dimers of L12 and one L10 protein, which forms the base of the stalk. In E. coli, four copies of L12 molecules exist as dimer of dimers forming the pentameric L8 complex together with L10. This thesis is a collection of four interlinked studies on the structure, function and application of the ribosomal stalk protein L12. In the first study, we have mapped the interaction sites of the four major translation GTPase factors (IF2, EF-Tu, EF-G & RF3) on L12 molecule using heteronuclear NMR spectroscopy. Surprisingly, all these factors produced an overlapping interaction map spanning two α-helices on the C terminal domain of L12, thereby suggesting a general nature of the interaction between L12 and the GTPase factors. L12 is known to stimulate GTPase activity of the elongation factors EF-Tu and EF-G. Here, we have clarified the role of L12 in IF2 mediated initiation of protein synthesis. Our data suggest that rapid subunit association requires a specific interaction between the L12 protein on the 50S and IF2·GTP on the 30S preinitiation complex. We have also shown that L12 is not a GAP for IF2 and GTP hydrolysis triggers IF2 release from the 70S initiation complex. The next question we have addressed is why multiple copies of L12 dimer are needed on the ribosome. For this purpose, we created a pure E. coli strain JE105, where the terminal part of rplJ gene coding for the binding site of one L12 dimer on protein L10 was deleted in the chromosomal locus. Using ribosomes with single L12 dimer we have observed that the rate of the initiation and elongation involving IF2 and EF-G gets most compromised, which in turn decreases the growth rate of the bacteria.  This study also indicates that L12 can interact with different GTPase factors in a specialized manner. Lastly, we have developed an application making advantage of the multiple L12 dimers on the ribosome. By inserting a (His)6-tag at the C-terminus of the L12 protein we have created a novel E. coli strain (JE28), where all ribosomes are tetra-(His)6-tagged. Further, we have developed a single step method for purification of the active (His)6-tagged ribosomes from JE28.

Το φυσικό προϊόν αρτεμισινίνη και τα παράγωγά της αποτελούν σήμερα φάρμακα επιλογής για την αντιμετώπιση της ελονοσίας ενώ πολλά απ’αυτά παρουσιάζουν και ιδιαίτερα σημαντική αντικαρκινική δράση. Στο πλαίσιο της παρούσας διπλωματικής εργασίας έγινε χημική τροποποίηση του μορίου της αρτεμισινίνης, προκειμένου να συντεθούν διμερή συζεύγματά της με πολυαμίνες (πουτρεσκίνη, σπερμιδίνη, σπερμίνη). Αρχικά, η αρτεμισινίνη τροποποιήθηκε κατάλληλα έτσι ώστε, να φέρει συνδέτη με δεσμό C-O (10-oxo) στη θέση-10, προκειμένου στη συνέχεια να προσδεθεί στις πολυαμίνες μέσω δεσμού ουρεθάνης. Για το λόγο αυτό, συντέθηκε το ενεργοποιημένο ανάλογο(10-oxo , το οποίο μετά από αντίδραση με τις κατάλληλα προστατευμένες πολυαμίνες, έδωσαν τα διμερή συζεύγματα της αρτεμισινίνης 66-68. Επιπλέον, για προκαταρκτικές μελέτες βιολογικής δράσης, συντέθηκε ένα ασύμμετρο σύζευγμα της αρτεμισινίνης με το αντικαρκινικό χλωραμβουκίλη (69), χρησιμοποιώντας το 10-oxo ενεργοποιημένο ανάλογο και την πουτρεσκίνη ως πολυαμίνη. Όλα τα παραπάνω συζεύγματα, βρίσκονται στο στάδιο της αποτίμησης της βιολογικής τους δράσης, από συνεργαζόμενο εργαστήριο έναντι καρκινικών σειρών HL60. / The natural product Artemisinin and its derivatives are currently the drugs of choice for the treatment of malaria, with a large number of them showing important anticancer activity as well. In the context of the present dissertation, one chemical modification of artemisinin was accomplished towards the synthesis of several Artemisinin dimer conjugates with polyamines (putrescine, spermidine, spermine). Initially, artemisinin was modified at the 10- position, in order to synthesize analogue bearing suitable linkers, through C-O (10-oxo) bond, able to form urethane bonds with amino groups of polyamines. For this purpose, the activated intermediate(10-oxo) was synthesized, which upon reaction with suitably protected polyamines afforded the Artemisinin symmetric conjugates 66-68. In addition, for the sake of preliminary biological evaluation a new asymmetric conjugate (69) consisted of an 10-oxo Artemisinin and a chlorambucil moiety, using putrescine as a polyamine-type linker, was synthesized. All above conjugates are now under biological evaluation as anticancer agents, against HL60 cancer cells, by a collaborating research group. Further studies are underway, in order to evaluate the biological activity of the aforementioned analogues as antimalarials.

Faithful DNA replication is essential for the maintenance of genetic information. This complex process consists of 3 steps: initiation, elongation and termination. Although the first two steps are quite well understood in both eukaryotes and prokaryotes, many aspects of the termination of replication remain unclear. Escherichia coli is an ideal organism to study termination of DNA replication. In E. coli, DNA replication starts by bidirectional firing of two replication forks from a unique origin and terminates when those forks collide in the terminus region of the circular chromosome. The terminus region is flanked by specific ter sequences, which ensure that termination of replication occurs within specific boundaries. Due to the circularity of the E. coli chromosome, once the replication is finished the dimers can be formed. To resolve the dimers, the dif sequences are aligned together and two chromosomes are then separated into two daughter cells. Previous members of Prof. Leach laboratory have observed a stimulation of both double-strand break repair (DSBR) and DNA over-replication in the terminus region when DSBR was induced in the lacZ locus, half way between the origin and the terminus. In this work, I propose that these two phenomena, elevated levels of DSBR and DNA over-replication, are linked to each other. I confirm that the DSBs arise from the dif site and that the dif site is the source of DNA over-replication in the terminus. My results suggest that an attempted DSBR at dif leads to over-replication between terA and terB. Here, using next generation sequencing methods, I show that TopoIV and TopoIII topoisomerases introduce breaks in chromosome dimers that were not resolved by the XerCD/dif system, leading to DSBR and DNA over-replication.

Resolvemos o modelo de d´meros em duas redes planas diferentes, a rede 4-8 e a rede hexagonal (favo de mel). Na rede 4-8 ocorre uma transição do tipo Ising (bidimensional); na rede hexagonal há uma transição conhecida como 3/2. Após a definição do modelo mostramos que o cálculo da função de partição pode ser formulado em termos do traço de uma matriz de transferência escrita numa representação de matrizes de Pauli. Usando a transformação de Jordan-Wigner, os operadores de Pauli são transformados em operadores de criação e aniquilação de férmions, e a matriz de transferência pode ser diagonalizada pela redução a um problema de férmions livres. Comparamos as soluções do modelo de dímeros na rede 4-8 e do modelo de Ising bidimensional; em particular, comparamos o comportamento do calor específico e analisamos o espectro da matriz de transferência. Verificamos que as nossas soluções concordam com resultados obtidos pelas técnicas combinatórias. Utilizamos a formulação da matriz de transferência para construir uma versão de tempo contínuo dos modelos de dímeros nas redes quadrada, 4-8 e hexagonal. Ao contrário do modelo de Ising, no caso dos dímeros essa aproximação de tempo contínuo altera a natureza do comportamento crítico. / We solve the dimer model on two different planar lattices, the 4-8 lattice and the honeycomb lattice. In the dimer model on the 4-8 lattice there is a phase transition of the (two-dimensional) Ising type; on the honeycomb lattice there is a phase transition known as 3/2. After defining the model we show that the calculation of the partition function can be formulated as the trace of a transfer matrix that is written in terms of Pauli matrices. Using the Jordan-Wigner transformation, the Pauli matrices give rise to fermion creation and annihilation operators, and the problem is reduced to the diagonalization of a system of free fermions. We compare the solutions of the dimer model on the 4-8 lattice and of the two-dimensional Ising model; in particular, we compare the behavior of the specific heat and we analyze the spectrum of the transfer matrix. These solutions agree with well-known results from combinatorial techniques. We then use the transfer matrix approach to obtain a continuum time formulation for the dimer models on the square, 4-8 an d honeycomb lattices. In contrast to the Ising case, for the dimer models this approximation changes the nature of critical behavior.