Pharmaceutically Active Compounds include metformin, the most often prescripted drug for a treatment of the diabetes mellitus type 2. Metformin is used in high daily doses (up to 3000 mg per day) and it is eliminated by kidneys in its original non - metabolized form. Metformin is degraded in the wastewater treatment plants to guanylurea. The wastewater treatment plants aren't able to clean the waste water, so metformin and guanylurea enter the environment, especially surface water. This diploma thesis deals with the ability to remove metformin and its environmental metabolite guanylurea via phytoextraction technologies. First experiment was focused on phytoextraction of metformin using 5 plant species - Zea mays L., Pisum sativum L., Avena sativa L., Alternanthera reineckii Mini L. and Staurogyne repens L. Second experiment studied phytoextraction of guanylurea using Zea mays L. and Pisum sativum L. The third experiment deals with the phytoextraction of metformin and guanylurea together using Zea mays L. The media of all plants were contaminated by metformin or guanylurea at different concentration levels. The samples of media were taken in 24 hours intervals during the plant cultivation and the decrease of its concentration were studied by HPLC with UV detection at 233 nm for metformin and 210 nm...

Metformin is the most common first-line oral therapeutic agent used in the treatment of type-2 diabetes. Because of its widespread use, metformin has been increasingly detected in wastewater effluent. It is partially bio-transformed into guanylurea is subsequently released into aquatic environments. Since the literature concerning the effect of metformin and guanyl urea on early life stage of fish is scant, the aim of this research was to understand the potential influence of metformin and guanylurea on developmental, cardiometabolic and behavioral responses in zebrafish embryos, from the 4 cell stage (3 hours post fertilization, hpf) to first feed (120 hpf). To this end, embryos were exposed to environmentally relevant (0.4, 4, 40 μg·L−1) and supra-environmental (400 and 4000 μg·L−1) concentrations of the two chemicals. Metformin caused an increased mortality and spinal abnormalities in all concentrations compared to controls. and increased pericardial and yolk sac edema at the highest tested concentration. Metformin did not cause alterations in hatch or heart rate over the examined developmental stages. In addition, metformin did not cause alterations in general swimming, light-dark movement, startle response or thigmotaxis, irrespective of exposure concentration. Exposure to guanylurea over the same developmental stages caused a significant difference in mortality at 40 μg·L−1 only. Guanylurea did not cause alterations to any of the other tested endpoints. Our data suggests that metformin and guanylurea caused modest impacts to embryonic development of zebrafish at these concentrations. / Thesis / Master of Science (MSc) / Pharmaceuticals have been detected at the ng to µg L-1 range in aqueous environments for decades. These compounds are designed to be biologically active at low concentrations and can cause elicit adverse effects in non-target species. Among the more recently detected compounds are the antihyperglycemic drug metformin and its biotransformation product (guanylurea), which have been the focus of few studies in fish. This thesis addresses multiple knowledge gaps by examining the potential impacts of metformin and guanylurea during the embryonic and early larval zebrafish period (3-120 hours post-fertilization). Exposure to metformin resulted in increased mortality and abnormalities. Guanylurea exposure increased mortality at one dose. We suggest that metformin and guanylurea cause modest effects in developing larval zebrafish.

Drug-resistant pathogens are emerging rapidly and thwart the treatment of common bacterial infectious diseases that can lead to death. Many contagious diseases remain difficult to treat because of acquired drug resistance. Compared to small antibiotics, which interrupt the intracellular biochemical processes, antimicrobial polymers with relatively high molecular weights offer a promising strategy to overcome drug resistance by disrupting the physical integrity of the membrane. Because of the unique mechanism, bacteria need a much longer time to develop resistance. A new class of antimicrobial polymer in which the positive charge and hydrophobic/hydrophilic units are linearly connected in the amidinourea backbone was designed, synthesized, and tested for various bacteria including methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the effects of hydrophobicity and polymer molecular weights on antimicrobial activity by measuring minimum inhibitory concentrations (MIC) and hemolytic activities (HC50). Amidinourea antimicrobial polymers exhibit a promising MIC90 value (13 μg/mL) with low HC50, resulting in high selectivity (HC50/MIC90) against MRSA. Many bacteria have developed resistance against Ciprofloxacin. To overcome the antibiotic resistance associated with Ciprofloxacin, we hypothesized that a steady release of Ciprofloxacin at the bacteria membrane can overcome the drug resistance because the local drug concentration can be overwhelmingly high to suppress the drug efflux pump expressed on the membrane. A series of homo and di-block copolymers containing Ciprofloxacin, as the form of prodrugs, was synthesized using ring-opening metathesis polymerization (ROMP), and we evaluated their antimicrobial efficacy.While homo polymers only containing Ciprofloxacin were inactive against almost all bacteria tested, di-block copolymers containing Cipro and triphenylphosphine exhibited some antimicrobial activity against wild type M. smegmatis. Modulation of chemical environments at the positively charged polymeric materials can significantly influence the biophysical properties required for efficient cellular interaction and subsequent entry. Using intrinsic fluorescent conjugated polymers (CPs), we have demonstrated that the modulated guanidine group with various hydrophilic or hydrophobic moieties dramatically changed their cellular behaviors. We prepared a series of modified guanidine-containing CPs and examined their cellular behaviors by using confocal microscopic imaging. Details of the modification chemistry and modification-dependent cellular behaviors and a knockdown of a target protein in primary cells were discussed.

This research investigated the mechanical properties of laboratory manufactured, fire retardant treated (FRT) flakeboard in an effort to help establish proper manufacturing procedure and testing protocol for these types of composite products. Two sets of fire retardant treated and untreated panels were manufactured and tested to gauge the initial effects of treatment, as well as the effects of high temperature exposure on both panel types. Testing was also conducted on different bending specimen widths in an attempt to find the specimen size most suitable for testing flakeboard composites. Results indicated that FR treatment had an adverse effect on panel mechanical properties from both an initial standpoint as well as after the panels had been exposed. Results from the specimen width investigations revealed that using a wider dimension specimen for ASTM bending tests would reduce the amount of variation and error that can be found when testing smaller size samples.

This thesis focuses on preparation of novel compounds suitable for nonlinear optics (NLO). In particular, the target property is the second harmonic generation (SHG) and the group of interest are salts of the cations with delocalized electrons which can serve as carriers of the NLO properties. In particular, four derivatives of the highly interesting molecule of guanidine were selected and their NLO potential was proven by quantum chemical computations. In total, twenty new structures were described and those with the noncentrosymmetric structure assembly were examined for the SHG efficiency. Four of the prepared compounds exhibited a noticeable SHG efficiency, two of them even comparable to urea. The most promising compound, the guanylurea hydrogen phosphite (GUHP), was examined in more detail while many interesting NLO properties were revealed. The results of this work are presented also in 10 attached publications which are an integral part of the thesis. Keywords: nonlinear optics, second harmonic generation, guanidine derivatives, guanylurea, N-phenylbiguanide, N,N-dimethylbiguanide, N,N,N˝-triphenylguanidine