Antibiotic use is a vital method for the treatment of most diseases involving bacterial infections. Unfortunately, in certain cases these agents are not effective in treatments against diseases for either some limitation in antibiotic usage because of the side effects or some distribution problems caused by physiological or pathological barriers in the body. Such problems are thought to be minimized by development of controlled release systems which involve implantation of antibiotic loaded polymeric systems directly to the site of infection. Present study involves Vancomycin, a very strong antibiotic with a wide spectrum of activity, and two biocompatible and biodegradable polymers, poly(3-hydroxybutyrate-co-3-valerate) PHBV and poly(L-lactide-co-glycolide) PLGA, in the construction of rod shaped controlled release systems designed for the aim of local treatment of osteomyelitis. Vancomycin carrying rods of either PHBV 8 or PLGA (50:50) polymers were prepared by the use of cold paste and hot extrusion methods in two different loading ratios (2:1 and 1:1 P:V). In situ release kinetics of each type of rod was determined by spectrophotometric measurement of vancomycin concentration. For determination of drug content of the controlled release rods initially and at the end of the release experiments, extraction and IR (infrared) studies were carried out. The efficacy of the system was measured in vitro on the bacterial strain, B. subtilis. Characterization of the rods was made by the use of stereomicroscopy and SEM (scanning electron microscopy). In situ release results of the controlled Vancomycin release formulations revealed that for both polymer types, hot extrusion process enabled the formation of a more compact system that provided slower release of the agent compared to the cold paste method. With the combined effect of variable loading proportion and polymer type the most prolonged release was obtained by PHBV rods having 2:1, P:V, ratio (prepared by hot extrusion method). In general, the release kinetics from the rods obeyed the Fickian diffusion kinetics except for PLGA rods prepared by cold paste method with 1:1 and 2:1 (P:V) loading ratios, which had a first order rate of drug release. According to in vitro bioactivity assays, all the groups effectively inhibited bacterial growth with the first day release samples. On the seventh day, however, only two cold paste samples, PHBV:Vancomycin 1:1 and PLGA:Vancomycin 1:1 had drug content barely sufficient for MEC while the others were in the ineffective range. The IR and grinding-extraction studies proved that Vancomycin was still present within the rods after a ten day release period. The PHBV rods with 2:1 (P:V) ratio prepared by hot extrusion method seem to be the most promising drug delivery system in terms of providing prolonged release as an implantable drug delivery system for the treatment of bacterial infections of the bone, namely osteomyelitis.

In this study the effects of compatibilizer type, organoclay type, and the addition order of components on the morphological, thermal, mechanical and flow properties of ternary nanocomposites based on low density polyethylene, LDPE were investigated. As compatibilizer, ethylene/methyl acrylate/glycidyl methacrylate, ethylene/glycidyl methacrylate, and ethylene/butyl acrylate/maleic anhydride / as organoclay Cloisite&amp / #61666 / 15A, Cloisite&amp / #61666 / 25A and Cloisite&amp / #61666 / 30B were used. All samples were prepared by a co-rotating twin screw extruder, followed by injection molding. Before producing the ternary nanocomposites, in order to determine the optimum amount of the organoclay and compatibilizer, binary mixtures of LDPE/organoclay and LDPE/compatibilizer blends with different compositions were prepared. Based on the results of the mechanical tests, compatibilizer and organoclay contents were determined as 5 wt. % and 2 wt % respectively. After that, ternary nanocomposites were prepared with each compatibilizer/organoclay system and characterization of these nanocomposites was performed. Among the investigated addition orders, mechanical test results showed that the best sequence of component addition was (PCoC), in which LDPE, compatibilizer and organoclay were simultaneously compounded in the first run of the extrusion. Considering the ternary nanocomposites, compositions of LDPE/E-MA-GMA/15A, LDPE/E-GMA/15A and LDPE/E-nBA-MAH/30B showed the highest improvement in mechanical properties. According to the DSC analysis, addition of organoclay and compatibilizer does not influence the melting behavior of the compositions and both compatibilizers and organoclay types have no nucleation activity in LDPE. In the X-Ray analysis, the highest increase of the basal spacing for ternary nanocomposites obtained for LDPE/E-BA-MAH/organoclay nanocomposites. This increase was 83 %, 198 %, and 206 % for samples containing 15A, 25A and 30B respectively.

In this study, N-vinylcaprolactam was polymerized by radiation in the solid state. The polymerization was carried out at room temperayure under vacuum and open to atmosphere respectively. The polymerization mechanism showed autoacceleration and the rate of polymerization was higher in the presence of oxygen. However the limiting conversion was 100% under vacuum conditions and 90% in the present of oxygen. This is due to the low molecular weight olgomer formation in the presence of oxygen. The polymers were characterized by FT-IR, NMR, DSC, TGA, Light Scattering, GPC, Viscosity, X_Ray and mass spectrometry methods. FT-IR and NMR results showed that polymerization proceded through the vinyl groups and caprolactam is a pendent group. DSC results show that the polymer produced could be polymerized further or crosslink by heat treatment. The Tg value for the polymerobtained from radiation induced polymerization was about 147 C. It increased to 174 C after thermal treatment. Solution properties were studied by Light Scattering, GPC and viscosity measurements. The solutionbehavioor of the polymer was highyl dependent on the molecular weight of the polymer. This effect was also the conformation of polymer in solution and the viscosity properties. Since the polymer obtained had low molecular weight a regular relation could not be obtained for the radius of gyration, hydrodynamic radius and viscosity. X-ray diffraction studies showed that the monomer structure was retained up to about 86% conversion of monomer to polymer. The chain structure of the polymer was confirmed further by mass spectroscopic results.

Terephthalic acid bis-(thiophen-3-ylmethyl)thioester (TTMT) was synthesized via the reaction of thiophen-3-ylmethanethiol with terephthaloyl dichloride. Nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FTIR) spectroscopies were utilized for the characterization of the monomer. This 3-functionalized thiophene monomer was polymerized in the presence of thiophene (Th) and pyrrole (Py) upon constant potential application in acetonitrile/tetrabutylammonium tetrafluoroborate (TBAFB). The resulting copolymers were characterized via cyclic voltammetry (CV), FTIR, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), four-probe technique conductivity measurement and UV-Vis spectroscopy. Spectroelectrochemical analysis of P(TTMT-co-Th) revealed &amp / #960 / to &amp / #960 / * transition at 476 nm with a band gap of 2.0 eV whereas, &amp / #955 / max and Eg were found as 375 nm and 2.4 eV for P(TTMT-co-Py), respectively. Dual type electrochromic devices (ECDs) of P(TTMT-co-Th) and P(TTMT-co-Py) with poly(3,4-ethylenedioxythiophene) (PEDOT) were constructed. Spectroelectrochemistry, switching ability, open circuit memory and stability of the devices were examined by UV-Vis spectroscopy and cyclic voltammetry. The device P(TTMT-co-Th)/PEDOT switches between brown and blue upon application of 0.0 V and +2.6 V, respectively with 11% optical contrast and 1.1 s as the switching time. On the other hand, P(TTMT-co-Py)/PEDOT ECD exhibits greenish yellow, grayish red and blue colors with the application of -2.4 V, 0.0 V and +0.8 V, respectively and the contrast between extreme potentials was 17.5% with a switching time of 1.6 s. 1-(4-Fluorophenyl)-2,5-di(thiophen-2-yl)-1H-pyrrole (FPTP) was synthesized and polymerized both chemically and electrochemically. Several analytical techniques, such as NMR, FTIR, CV, gel permeation chromatography (GPC), four-probe conductivity measurement, SEM were utilized when applicable. Spectroelectrochemistry experiments reflected a &amp / #960 / to &amp / #960 / * transition at 398 nm with a band gap energy of 1.94 eV for the polymer. A dual type electrochromic device (ECD) of PFPTP and poly(3,4-ethylenedioxythiophene) (PEDOT) was constructed. The device switches between yellowish brown and blue upon application of &amp / #8211 / 0.8 V and +1.1 V, respectively. Optical contrast was calculated as 19.4% with a switching time of 1.4 s at maximum contrast point.

ACTIVITY ANALYSIS OF IMMOBILIZED TYROSINASE ENZYME IN THE PRESENCE OF DIFFERENT INHIBITORS Narli, ISil M.Sc., Department of Chemistry Supervisor: Prof. Dr. Levent Toppare May 2006, 97 pages Immobilization of tyrosinase enzyme was performed in the matrices obtained via copolymerization of terephthalic acid bis-(2-thiophen-3-yl ethyl) ester (TATE) with pyrrole. During electrochemical polymerization of pyrrole, enzyme molecules were entrapped in the copolymer matrice. Activity measurements were performed by using Besthorn&amp / #8217 / s Hydrazone method which includes spectrophotometric analysis of quinones produced by the enzyme. Enzyme electrodes were characterized in terms of maximum reaction rate (Vmax) and Michaelis-Menten constant (Km). In addition to kinetic parameters, stability of enzyme electrodes towards environmental conditions such as pH and temperature was investigated. Usage stability and shelf-life analysis were also examined. Wines, especially red wines, contain numerous biologically active compounds, the most important of which are polyphenols, whose nutritional importance is attributed to their antioxidant power. The amounts of phenolic compounds in different red wines were analyzed by using obtained enzyme electrodes. The phenolic compound determination using free enzyme cannot reflect the actual values since there are also naturally found inhibitors in red wines. Benzoic acid, cinnamic acid and sorbic acid were utilized to understand the behavior of immobilized tyrosinase in the conducting polymer matrices toward inhibition.

2,5-Di(thiophen-2-yl)-1-p-tolyl-1H-pyrrole (DTTP) was synthesized via reaction of 1,4-di(2-thienyl)-1,4-butanedione with p-toluidine in the presence of catalytical amount of p-toluenesulfonic acid (PTSA). Homopolymer P(DTTP) was achieved both by chemical and electrochemical techniques. Chemical polymerization of the monomer yielded a soluble polymer. The average molecular weight was determined by gel permeation chromatography (GPC) as Mn: 2.5x103 g/mol. The monomer was electrochemically polymerized in the presence of LiClO4, NaClO4 (1:1) as the supporting electrolyte in acetonitrile. Copolymer of DTTP in the presence of EDOT was synthesized via potentiodynamic method in ACN/ NaClO4/LiClO4 (0.1 M) solvent-electrolyte couple. Structural characterizations of samples were carried out via 1H, 13C Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). Electrochemical behaviors of monomer and polymers were determined by Cyclic Voltammetry (CV). The morphologies of the polymer films were examined by Scanning Electron Microscopy (SEM). Conductivities of the films were measured by four probe technique. Electrochromic and spectroelectrochemical behavior of the polymers coated on ITO glass electrode were investigated, and their ability of employment in device construction was examined. Spectroelectrochemistry analysis of P(DTTP) revealed an electronic transition at 428 nm corresponding to &amp / #1087 / &amp / #8211 / &amp / #1087 / * transition with a band gap of 2.1 eV whereas P(DTTP-co-EDOT) revealed an electronic transition at 448 nm corresponding to &amp / #1087 / - &amp / #1087 / * transition with a band gap of 1.8 eV. Electrochromic investigations showed that P(DTTP) switches between greenish yellow and blue while P(DTTP-co-EDOT) was found to be multichromic, switching between red, yellow and blue. Switching time of the polymers was evaluated by a kinetic study upon measuring the percent transmittance (%T) at the maximum contrast point. Dual type polymer electrochromic devices (ECDs) based on P(DTTP) and P(DTTP-co-EDOT) with poly(3,4-ethylenedioxythiophene) (PEDOT) were constructed. Spectroelectrochemistry, electrochromic switching and open circuit stability of the devices were studied. They were found to have good switching times, reasonable contrasts and optical memories.

Zinc xanthates are active catalysts in stereoregular polymerization of propylene oxide and markedly more stable than that of known classical stereoregular catalysts. But steric control of zinc xanthates is weaker. To find more effective catalyst systems the isopropyl xanthates of Cu, Pb, Ni, Fe, Al and Sn are investigated and only copper (Cu(isoPr)Xt) and tin (Sn(isoPr)Xt) isopropyl xanthates were appeared to be active, but Cu(isoPr)Xt yielded only low molecular weight product. Therefore Sn(isoPr)Xt system was investigated in detail in polymerization of propylene oxide (PO). Polymerization of PO with this catalyst produced two contrasting polymers / high molar mass, crystalline (K-polymer) and low molar mass (D-polymer). Formation of double bonds in D-polymer was thought to be due to as an anionic process. Polymerization reactions were studied by changing polymerization conditions and reacting catalyst with predetermined amount of water. It&amp / #8217 / s found that Sn(isoPr)Xt have considerably low efficiency than that of Zn(isoPr)Xt catalyst. The yield linearly increases by increasing catalyst concentration. The propagation is competed by termination or transfer process hence overall activation energy is negative. Some mechanistic features of this system was also discussed. The catalytical activity of carbamates in this field has also been reported, without any information about catalytical efficiency and stereoregularity of the process. Therefore zinc diethyl dithiocarbamate was also studied and found as an active catalyst in stereoregular polymerization but it showed weaker efficiency in the PO polymerization than that of Zn(isoPr)Xt catalyst (about 12 times weaker).

Zinc xanthates polymerize propylene oxide into high polymer (PPO) with coordination mechanism. In order to identify structure and stereoisomerisms of this polymer, PPO was subjected to thermal and column fractionation. Obtained fractions were characterized by end-group analysis, cryoscopy, viscometry, IR and 13C-NMR spectroscopy, melting temperature. PPO is composed of a high molecular weight, stereoregular, crystallizable polymer (K-polymer) with low molecular weight (=500 g/mol) D-polymer. Presence of double bonds and hydroxyl terminals was interpreted as the product of an anionic mechanism. K-Polymers can be thermally fractionated on the basis of their melting temperature (Tm) rather than molecular weight (Mwt). It&amp / #8217 / s found that higher Tm fractions have lower Mwt, but they precipitate at higher temperatures than higher Mwt but lower Tm fractions. In column fractionation, K-polymers were deposited on glass beads from isooctane solution in a narrow temperature interval. Then the precipitated samples were split into a number of fractions by using again isooctane but at a higher temperature than the precipitation temperature by increasing residence time from 5 minutes to several hours. It&amp / #8217 / s found that rate of solubility is not controlled by molecular weight, but controlled by percentage crystallinity and Tm. Highest Tm polymers, with relatively higher Mwt showed faster rate of solution than that of lower Tm, lower Mwt but higher percent crystalline fractions. This discrepancy was accounted by suggesting a stereo-block structure where tactic blocks are bound each other with non-crystallizable atactic blocks. The mechanism of polymerization was also discussed in some detail.

In this study, glucose oxidase and polyphenol oxidase were immobilized in conducting copolymer poly(N-(4-(3-thienyl methylene)-oxycarbonylphenyl)maleimide)-co-pyrrole(P(MBThi-co-Py)). A copolymer was electrochemically synthesized by using sodium dodecyl sulfate (SDS) as supporting electrolyte and characterized by FTIR, scanning electron microscopy (SEM) and conductivity measurements. Immobilization of glucose oxidase (GOD) and polyphenol oxidase (PPO) enzymes were performed in conducting PPy and P(MBThi-co-Py) matrices by electropolymerization. Kinetic parameters, maximum reaction rate (Vmax) and Michaelis-Menten constant (Km) were determined for the enzyme electrodes by help of Lineweaver-Burk plot. Effect of temperature and pH on GOD and PPO activity was examined. Operational stability and long term stability of the enzyme electrodes were investigated. The immobilized GOD and PPO electrodes were used for determination of glucose amount in Turkish orange juices and analyzing the concentration of phenolic compounds in Turkish red wines respectively.

Electrochemical polymerization of pyrrole functionalized polystyrene (PStPy) with pyrrole was carried out in water-sodium dodecyl sulfate solvent-electrolyte couple. Characterization of the resulting copolymer was performed via Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and four probe conductivity measurements. Glucose oxidase and polyphenol oxidase enzymes were immobilized in polypyrrole (PPy) and conducting copolymer of pyrrole functionalized polystyrene with pyrrole (P(PStPy-co-Py). Resulting enzyme electrodes were characterized by kinetic parameters / Vmax and Km. Behavior of enzyme electrodes upon temperature and pH changes were investigated. Glucose oxidase electrode was used for the determination of glucose in orange juice and polyphenol oxidase electrode was used for the determination of polyphenolic compounds in red wine.