Late transition metal complexes bearing nitrogen-containing ligands have many applications in biotechnology or industrial catalysis. Imidazole is one of the most common biofunctional ligands to play critical roles in meta1loenzymes, since the imidazole moiety of the histidyl residues often constitutes all or part of the binding sites of various transition metal ions. We use the newly synthesized tetradentate ligand containing the imidazolyl and pyridyl functional group to react with zinc, copper, nickel, and iron ions in order to carry out biomimetic studies. We have obtained two crystal structures via different methods of crystallization. One of them is a mononuclear complex while the other is a polymeric structure. The polymeric structure has demonstrated the spontaneous deprotonation on the imidazolyl nitrogen on binding to the metal ion followed by the intermolecular self-assembly process.We believe that the imidazolate -bridged complexes undergo the pH-dependent interconversions between mononuclear (protonated ligand) and self-assembled oligomer (deprotonated ligand). In addition, we have measured the titration curves of the tetradentate ligand and its corresponding metal complexes to determine the preferential binding sites at varying pH. From the titration processes, we got the protonation constant of ligand and stability constants of its corresponding metal complexes.

Late transition metal complexes bearing nitrogen-containing ligands may act as catalyst in biotechnology or industrial catalysis. Imidazole is one of the most common biofunctional ligands that play critical roles in meta1loenzymes, since the imidazole moiety of the histidyl residues often constitutes all or part of the binding sites of various transition metal centers. In this work, some new zinc(II), copper(II) and nickel(II) complexes containing the imidazolate and pyridyl moieties incorporated in the imine (ImPyI) and amine (ImPyA) ligands were obtained. Different methods of crystallization yield crystals of complexes (2), (6), (8), (9), (10), (17) and (18). Subsequent structural analyses revealed their interesting structures. In zinc(II) and nickel(II) complexes, facial isomers were isolated while none of the meridional isomers were observed. Particularly interesting is the zinc(II) complexes where two facial complexes with different geometries were identified. The mixture of the different nitrogen donor groups in the same ligand provides handy comparison of these structural variations due to the different nature of these donor groups. One tridentate ligand with bromide substitution on the imidazolate and a tetradentate ligand with an additional pyridyl group were synthesized as an extension of this work. One crystal structure of each of the corresponding metal complex bearing these ligands is also discussed here. Most metal complexes are consolidated by extensive weak hydrogen bonds among them in the crystal lattices.

Η προστασία των μετάλλων με δραστικές ενώσεις που έχουν τη δυαντότητα σχηματισμού επιφανειακών ενώσεων εντάξεως είναι ένας κλάδος της Χημείας και της Επιστήμης των Υλικών μεγάλης επιστημονικής, αρχαιολογικής και τεχνολογικής σημασίας. Οι αντιδιαβρωτικές ιδιότητες του βενζοτριαζολίου και μικρού αριθμού υποκατεστημένων βενζοτριαζολίων για ορισμένα μέταλλα, ειδικά του χαλκού και των κραμάτων του, έχουν προσελκύσει το ενδιαφέρον για τη χημεία ένταξης του βενζοτριαζολίου και της συζυγούς του βάσεως, του βενζοτριαζολάτο ανιόντος. Έχουμε ξεκινήσει ένα ανόργανο μοντέλο προσέγγισης της παρεμπόδισης της διάβρωσης του Zn με βενζοτριαζόλια. Στην παρούσα εργασία έχουμε μελετήσει λεπτομερώς τη χημεία ένταξης του 1-μεθυλοβενζοτριαζολίου (Mebta) με Zn(II). Παρασκευάσθηκαν τα νέα σύμπλοκα [ZnCl2(Mebta)2](1), [ZnBr2 (Mebta)2](2), [ZnI2(Mebta)2](3), τετ-[Zn(ΝΟ3)2(Mebta)2](4), οκτ-[Zn(ΝΟ3)2(Mebta)2] (5), [Zn(Mebta)4](ClO4)2(6), [Zn(Mebta)4](PF6)2(7) και [Zn3(Ο2CPh)6(Mebta)2](8). Οι μοριακές και κρυσταλλικές δομές των συμπλόκων έχουν προσδιορισθεί με κρυσταλλογραφία ακτίνων-Χ μονοκρυστάλλου. Η γεωμετρία ένταξης του ZnΙΙ στα 1-4, 6 και 7 είναι τετραεδρική, ενώ στο σύμπλοκο 5 το μεταλλοϊόν έχει παραμορφωμένη οκταεδρική στερεοχημεία. Τα μεταλλικά κέντρα στο 8 υιοθετούν τετραεδρικές και οκταεδρικές γεωμετρίες. Το Mebta συμπεριφέρεται στα σύμπλοκα ως μονοδοντικός υποκαταστάτης με το άτομο δότης να είναι το άζωτο της θέσης 3 του αζολικού δακτυλίου. Τα σύμπλοκα χαρακτηρίσθηκαν με φασματοσκοπία IR. Τα δεδομένα συσχετίζονται με τον τρόπο ένταξης των υποκαταστατών και τις γνωστές δομές. Επίσης αναλύεται η τεχνολογική σημασία των αποτελεσμάτων μας. Φαίνεται ότι τα Ν-υποκατεστημένα βενζοτριαζόλια με ομάδες που δεν περιέχουν άτομα δότες δεν μπορεί να οδηγήσουν σε αποτελεσματικούς παρεμποδιστές της διάβρωσης εξ’αιτίας της αδυνμίας αυτών των μορίων να σχηματίζουν πολυμερικά είδη. / Protection of metals with reactive compounds capable of forming surface-phase coordination compounds is an area of chemistry and materials science which is of considerable scientific, archaeological and technological importance. The anticorrosion properties of benzotriazole and few substituted benzotriazoles towards certain metals, particularly copper and its alloys, have focused interest on the coordination chemistry of the parent molecule and its conjugate base, the benzotriazolate anion An inorganic model approach to the corrosion inhibition of Zn by benzotriazoles has been initiated. The coordination chemistry of 1-methylbenzotriazole (Mebta) with Zn(II) has been studied in detail. The new complexes [ZnCl2(Mebta)2](1), [ZnBr2 (Mebta)2](2), [ZnI2(Mebta)2](3), tet-[Zn(ΝΟ3)2(Mebta)2](4), οkt-[Zn(ΝΟ3)2(Mebta)2](5), [Zn(Mebta)4](ClO4)2(6), [Zn(Mebta)4](PF6)2(7) and [Zn3(Ο2CPh)6(Mebta)2](8) have been prepared. Their molecular and crystal structures have been determined by single crystal, X-ray crystallography. The coordination geometry of ZnII in 1-4, 6 and 7 is tetrahedral, while complex 5 has a distorted octahedral stereochemistry. The metal sites in 8 adopt both tetrahedral and octahedral geometries. Mebta behaves as a monodentate ligand in the complexes; the donor atom is nitrogen of the position 3 of the azole ring. The complexes were characterized by IR spectroscopy; the data are discussed in terms of the coordination modes of the ligands and known structures. The technological relevance of our results is also discussed. It seems that benzotriazole N-substitution with groups containing no donor atoms cannot lead to effective corrosion inhibitors due to the inability of these molecules to form polymeric species.

Tyrosine (4-hydroxyphenylalanine) is one of the naturally occurring 22 amino acids. The importance of tyrosine is due to the presence of its phenolic side chain. In biological systems, the tyrosyl residue in proteins is found to be sulfated, phosphorylated and nitrated. Upon oxidation with dioxygenases, Tyr residue forms dopaquinone which undergoes a series of reactions ultimately leading to the formation of melanin. Tyr is also a precursor to neurotransmitters (catechol amines namely dopamine, epinephrine and norepinephrine) and thyroid harmones T4 and T3. Tyr residue is also found to be cross linked with other amino acid residues in the active site of certain proteins. Tyr-Tyr cross link has also been associated with neurodegenerative diseases. Tyr residue in proteins has been targeted widely for site selective modifications. A series of chemical modifications like acylation, allylation, ene-type reaction, iodination with radiolabeled iodine, formation of Tyr-Tyr cross link with oxidants and aminoalkylation have been carried out on surface exposed Tyr residues in proteins. Apart from these chemical modifications of Tyr on protein surface, a couple of free Tyr-based scaffolds have also been developed for different applications. Similar to tyrosine-based scaffolds, several phenolate-based scaffolds have also been developed for various applications. Several phenolate-based binuclear metal complexes have been developed as mimics of the active site of metalloenzymes. Moreover, by varying the substituent in the phenolate scaffold, the redox properties of metal bound in these systems can be tuned. The thesis consists of five chapters. The first chapter gives general idea about tyrosine-and phenolate-based scaffolds. The first chapter also gives introduction to zinc(II)-containing enzymes metallo-β-lactamases (mβls) and phosphotriesterase (PTE) and their functional mimics. The importance of copper(II)-containing enzyme, catechol oxidase and its mimics has also been discussed. The significance and formation of o-dityrosine (Tyr-Tyr cross link) has also been briefly discussed. In chapters 2 and 3, a couple of phenolate-based ligands and their corresponding zinc(II)- and copper(II)- complexes have been synthesized and have been checked as mimics of zinc(II)-containing enzymes (mβl and PTE) and copper-containing enzyme catechol oxidase, respectively. In chapter 4, a series of tyrosine-based ligands have been designed and their in situ copper(II) complexes have been tested as mimics of catechol oxidase. In chapter 5, the effect of neighboring amino acid in the formation of Tyr-Tyr cross link has been studied. In chapter 2, a couple of zinc(II) complexes have been synthesized and studied as mimic of zinc(II)-containing enzymes mβl and PTE. Metallo-β-lactamases (mβls) are zinc(II)-containing enzymes which exist in both mono- and binuclear forms. Mβls are capable of hydrolyzing β-lactam ring in antibiotics and make them inactive (Scheme 1(A)). To date, an effective inhibitor for this enzyme is not known. Hence, in order to understand the nature of the enzyme a couple of synthetic mimics are known. However, in most of the synthetic mimics both the metal ions are in symmetrical environment. Therefore, we have attempted to design a few unsymmetrical phenolate- based ligands and their zinc(II) complexes. The unsymmetrical phenolate-based ligands HL1 and HL2 have been synthesized by sequential mannich reaction with formaldehyde and two different amines. Complexes 1 and 2 are obtained from ligands HL1 and HL2, respectively (Figure 1). For comparative purpose, the symmetrical ligands HL3 and HL4, and their zinc(II)-complexes 3 and 4 have been synthesized by reported procedures (Figure 1). The efficiency of the complexes 1-4 towards the hydrolysis of oxacillin has been studied. It has been observed that the binuclear zinc(II) complexes with metal-bound water molecule 1 and 4 are able to hydrolyze oxacillin at much faster rates compared to that of mononuclear complexes 2 and 3. However, between 1 and 4, there is no appreciable change in activity, indicating that the slight change in ligand environment has no significant role. PTE is a binuclear zinc(II)-containing enzyme, capable of hydrolyzing toxic organphosphotriesters to less toxic diesters (Scheme 1(B)). As the binuclear active site of mβl is comparable with that of phosphotriesterase (PTE), PTE activity of complexes 1-4 has been studied. Although the binuclear zinc(II)-complexes 1 and 4 are able to hydrolyze PNPDPP (p-nitrophenyl diphenyl phosphate) initially, these complexes are not able to effect complete hydrolysis. This is due to the inhibition of complexes 1 and 4 by hydrolyzed product, diester. However with mononuclear complexes 2 and 3 no such inhibitions is possible, and are capable of hydrolyzing PNPDPP at comparatively faster rates than 1 and 4. Scheme 1. Function of metallo-β-lactamase and phosphotriesterase. (A) Hydrolysis of β-lactam ring in antibiotics by metallo-β-lactamase. (B) Hydrolysis of organophosphotriesters to diesters by phosphotriesterase. Figure 1. Chemical structures of ligands HL1-HL4 and their corresponding zinc(II)complexes 1-4. In chapter 3, a couple of copper(II) complexes have been synthesized and their catechol oxidase activity has been studied. Catechol oxidase belongs to the class of oxidoreductase and it catalyzes the oxidation of a wide range of o-diphenols to o-quinones through the reduction of molecular oxygen to water (Scheme 2). A four new µ4-oxo-bridged tetranuclear copper(II) complexes (5-8) have been synthesized (Figure 2). The ability of these complexes to catalyze the oxidation of 3,5-DTBC (3,5-Di-tert-butylcatechol) to 3,5-DTBQ (3,5-Di-tert-butylquinone) has been studied. A detailed kinetic study has been carried out which reveals that the complexes with exogenous acetate ligands (5 and 6) are better catechol oxidase mimics compared to complexes with exogenous chloride ligands (7 and 8). This observation is due to the labile nature of acetate compared to chloride, as the displacement of exogenous ligand is essential for the binding of substrate to the catalyst. Based on mass spectral analysis a plausible mechanism has been proposed for the oxidation of 3,5-DTBC by these complexes. Scheme 2. Oxidation of catechol by catechol oxidase. Figure 2. Chemical structures of copper(II) complexes 5-8. In chapter 4, by following the analogy between phenol and tyrosine, a series of binucleating ligands of tyrosine or tyrosyl dipeptides (Figures 3 and 4) have been synthesized by Mannich reaction under mild conditions. The in situ complexation of these fifteen new binucleating ligands (HL5-HL19) with copper(II) chloride has been observed. In situ complexation was followed by UV-visible and mass spectral analysis. These in situ complexes were able to oxidize 3,5-DTBC at slower rate compared to that of the tetranuclear complexes reported in chapter 3. The catecholase activity has also been tested with the addition of base. A slight enhancement in activity of in situ complexes has been observed in the presence of base. Based on mass spectral evidences, a plausible mechanism for the oxidation of catechol by these in situ complexes has been proposed. Figure 3. Binucleating ligands (Mannich bases) of boc-protected tyrosine and tyrosyl dipeptides. Figure 4. Binucleating ligands (Mannich bases) of boc-deprotected tyrosyl dipeptides. In chapter 5 of the thesis, the effect of neighboring amino acid residue in the formation of o,o-dityrosine (Tyr-Tyr cross link) has been studied. o,o’-Dityrosine is a specific marker for oxidative/nitrosative stress. The increase in concentration of dityrosine is associated with several disease states. A detailed study has been carried out in order to find out the effect of neighboring amino acid residues in the rate of formation of dityrosine of several tyrosyl dipeptides. The formation of dityrosine has been carried out with horseradish peroxidase(HRP) and H2O2 (Scheme 3). Except Cys-Tyr, all other tyrosyl dipeptides, form corresponding dityrosine with HRP/ H2O2. With Cys-Tyr, the formation of corresponding disulfide is observed. The appreciably higher rate of dityrosine formation of Phe-Tyr is attributed to the presence of strong hydrophobic environment around the active site of HRP. Among the polar tyrosyl peptides, the positively charged peptides (Arg-Tyr, Lys-Tyr) undergo dityrosine formation at much faster rate compared to that of negatively charged dipepptides (Asp-Tyr, Glu-Tyr). This trend is in accordance with the pKa of neighboring amino acid residues. The positively charged neighboring residues with higher pKa stabilizes ionized tyrosine, hence the rate of dityrosine formation is higher for them. As positively charged neighboring residue enhances the rate of dityrosine formation, the effect of externally added L-Arg has been studied. A coupling of a few biologically relevant tyrosine derivatives has been studied. The derivatives in which one of the ortho-positions of tyrosine is blocked, does not undergo coupling under the experimental conditions employed. Scheme 3. Formation of dityrosine of Ile-Tyr from Ile-Tyr in the presence of H2O2 catalyzed by HRP. (For structural formula and figures pl refer the abstract pdf file)