Novel Hetrocyclic Constructions Mediated by Nucleophilic Carbenes and Related Chemistry

The thesis entitled novel heterocyclic constructions mediated by nucleophilic carbenes and related chemistry, embodies the results of the investigations carried out to explore the reactivity patterns of the 1:1 zwitterions, generated in situ from various nucleophilic carbenes and DiMethyl AcetyleneDicarboxylate(DMAD) towards aldehydes and ketones. The traditional synthesis of complex organic molecules employs stepwise formation of bonds and involves multiple steps. Besides the sequential synthesis, in several instances, the desired product can also be obtained in one pot reactions of three or more starting compounds. Such reactions in which more than two starting materials react to form a product in such a way that the majority of the atoms of the starting materials can be found in the products are called multicomponent reactions(MCRs). The results of our investigations on the application of N-heterocyclic carbenes in multicomponent reaction with DMAD and aromatic aldehydes leading to the one pot synthesis of 2-oxy-maleate and furanone derivatives. It is interesting to note that dihydrofuran and lactone motifs are present in a number of biologically active natural products and other heterocyclic compounds. It is conceivable that the novel multicomponent reactions described herein will find application in the synthesis of a variety of heterocyclic compounds, and in natural product synthesis.

Analysis and Design of an Adaptive Polynomial Predistorter with the Loop Delay Estimator

Most adaptive linearization circuits for the nonlinear amplifier have a feedback loop that returns the output signal oj'tne eunplifier to the lineurizer. The loop delay of the linearizer most be controlled precisely so that the convergence of the linearizer should be assured lot this Letter a delay control circuit is presented. It is a delay lock loop (ULL) with it modified early-lute gate and can he easily applied to a DSP implementation. The proposed DLL circuit is applied to an adaptive linearizer with the use of a polynomial predistorter, and the simulalion for a 16-QAM signal is performed. The simulation results show that the proposed DLL eliminates the delay between the reference input signal and the delayed feedback signal of the linearizing circuit perfectly, so that the predistorter polynomial coefficients converge into the optimum value and a high degree of linearization is achieved

Light amplification in dye doped polymer films

We report unusual spectral narrowing and laser emission from polymer thin films doped with Coumarin 540 dye. The laser emission from the polymer films is found to be highly dependent upon the excitation length of the medium. Even a short length of 1.75 mm of the dye doped film gave rise to laser emission with FWHM of 0.3 nm for a pump intensity of 825 kW cm−2. The partial reflections from the broad lateral surfaces of the free standing films provided the optical feedback for the laser emission. Occurrence of well-resolved equally spaced resonant modes confirmed the effect of a Fabry–Perot-like optical cavity between the film surfaces

Semiconductor Oxides Mediated Photocatalytic Removal of Chemical and Bacterial Pollutants from Wastewater

School of Environmental Studies, Cochin University of Science and Technology

Sulfated titania mediated regioselective nitration of phenol in solid state

Titania, sulfated titania and chromium loaded sulfated titania were prepared by sol–gel method and characterized using different technique. Phenol is nitrated regioselectively by nitric acid using chromium loaded sulfated titania catalysts. A remarkable ortho selectivity is observed in solid state nitration to yield exclusively ortho-nitrophenol. Compared to the conventional process, phenol nitration over solid acid catalyst is a clean and environment friendly process. Catalytic activity well correlates with the Brönsted acid sites of these catalysts.

Fabrication and characterisation of polymer optical fibers for smart sensing and optical amplification

The thesis presented the fabrication and characterisation of polymer optical fibers in their applications as optical amplifier and smart sensors.Optical polymers such as PMMA are found to be a very good host material due to their ability to incorporate very high concentration of optical gain media like fluorescent dyes and rare earth compounds. High power and high gain optical amplification in organic dye-doped polymer optical fibers is possible due to extremely large emission cross sections of oyes. Dye doped (Rhodamine 6G) optical fibers were fabricated by using indigenously developed polymer optical fiber drawing tower. Loss characterization of drawn dye doped fibers was carried out using side illumination technique. The advantage of the above technique is that it is a nondestructive method and can also be used for studying the uniformity in fiber diameter and doping. Sensitivity of the undoped polymer fibers to temperature and microbending were also studied in its application in smart sensors.Optical amplification studies using the dye doped polymer optical fibers were carried out and found that an amplification of l8dB could be achieved using a very short fiber of length lOcm. Studies were carried out in fibers with different dye concentrations and diameter and it was observed that gain stability was achieved at relatively high dye concentrations irrespective of the fiber diameter.Due to their large diameter, large numerical aperture, flexibility and geometrical versatility of polymer optical fibers it has a wide range of applications in the field of optical sensing. Just as in the case of conventional silica based fiber optic sensors, sensing techniques like evanescent wave, grating and other intensity modulation schemes can also be efficiently utilized in the case of POF based sensors. Since polymer optical fibers have very low Young's modulus when compared to glass fibers, it can be utilized for sensing mechanical stress and strain efficiently in comparison with its counterpart. Fiber optic sensors have proved themselves as efficient and reliable devices to sense various parameters like aging, crack formation, weathering in civil structures. A similar type of study was carried out to find the setting characteristics of cement paste used for constructing civil structures. It was found that the measurements made by using fiber optic sensors are far more superior than that carried out by conventional methods. More over,POF based sensors were found to have more sensitivity as well.

Light amplification in dye doped polymer films

We report unusual spectral narrowing and laser emission from polymer thin films doped with Coumarin 540 dye. The laser emission from the polymer films is found to be highly dependent upon the excitation length of the medium. Even a short length of 1.75 mm of the dye doped film gave rise to laser emission with FWHM of 0.3 nm for a pump intensity of 825 kW cm−2. The partial reflections from the broad lateral surfaces of the free standing films provided the optical feedback for the laser emission. Occurrence of well-resolved equally spaced resonant modes confirmed the effect of a Fabry–Perot-like optical cavity between the film surfaces.

Development of Compact Microwave Filters Using Microstrip Loop Resonators

Study of the characteristics of planar loop resonators and their use in the construction of filters at microwave frequencies are presented in this thesis.A detailed investigation of parameters affecting the strength of coupling and the resonant frequency are also carried out .Techniques for size reduction in bandstop and bandpass filters using planar loop resonators are developed.Different configurations of bandstop and bandpass filters using loop resonators are simulated and experimental results on optimal filter configurations are presented.

Microstrip band rejection filter using open loop resonator

Design of a compact microstrip band reject filter is proposed. The device consists of an Open Loop Rectangular Resonator (OLRR) coupled to a microstrip line. The transmission line has a U-bend which enhances the coupling with the OLRR element and reduces the size of the filter. The filter can be made tunable by mounting variable capacitance to the system. Simulated and experimental results are presented.

Organic Synthesis Mediated by Heterogeneous Catalysts

Catalysis is a technologically important field which determines the quality of life in future. Catalyst research in pharmaceutical industry,fine chemical synthesis and emission control demands supported catalysts in bulk quantities.In the present work it was observed that clay supported catalysts mentioned in various chapters could also be used for the synthesis of similar molecules. The K10Ti catalyst can be used for the synthesis similar substituted imidazole derivatives under solvent free conditions and synthetically important Mannich bases of substrates containing various substitutes.Al-pillared saponite can be used for acetalation of other polyhydroxy compounds like glycerol,mannitol etc.Cu-Pd KSF catalyst has found application in C-C bond forming reactions which can be applied to other reactions and similar methods can be adopted for the synthesis of other catalyst by changing the transition metals. Montmorillonite K10 catalysed synthesis of triarylpyridines can be extended to the synthesis tetrasubstuted pyroles.K10Ti can also be utilized for the synthesis of similar heterocycles.

Serotonin receptor subtypes functional regulation and oxidative stress mediated apoptosis in 6-hydroxydopamine lesioned Parkinsonian rats

Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the SNpc resulting in severe motor impairments. Serotonergic system plays an important regulatory role in the pathophysiology of PD in rats, the evaluation of which provides valuable insight on the underlying mechanisms of motor, cognitive and memory deficits in PD. We observed a decrease in 5-HT content in the brain regions of 6-OHDA infused rat compared to control. The decreased 5-HT content resulted in a decrease of total 5-HT, 5-HT2A receptors and 5-HTT function and an increase of 5-HT2C receptor function. 5-HT receptor subtypes - 5-HT2A and 5-HT2C receptors have differential regulatory role on the modulation of DA neurotransmission in different brain regions during PD. Our observation of impaired serotonergic neurotransmission in SNpc, corpus striatum, cerebral cortex, hippocampus, cerebellum and brain stem demonstrate that although PD primarily results from neurodegeneration in the SNpc, the associated neurochemical changes in other areas of the brain significantly contributes to the different motor and non motor symptoms of PD. The antioxidant enzymes – SOD, CAT and GPx showed significant down regulation which indicates increased oxidative damage resulting in neurodegeneration. We also observed an increase in the level of lipid peroxidation. Reduced expression of anti-apoptotic Akt and enhanced expression of NF-B resulting from oxidative stress caused an activation of caspase-8 thus leading the cells to neurodegeneration by apoptosis. BMC administration in combination with 5-HT and GABA to PD rats showed reversal of the impaired serotonergic neurotransmission and oxidative stress mediated apoptosis. The transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the SNpc along with an increase in DA content and an enhanced expression of TH. Neurotrophic factors – BDNF and GDNF rendered neuroprotective effects accompanied by improvement in behavioural deficits indicating a significant reversal of altered dopaminergic and serotonergic neurotransmission in PD. The restorative and neuroprotective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of PD.

Withania somnitera and withanolide a mediated restoration of AMPA and NMDA receptor function in pilocarpine induced temporal lobe epilepsy

The onset of spontaneous seizures triggers a cascade of molecular and cellular events that eventually leads to neuronal injury and cognitive decline. The present study investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring behavioural deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. The subdued performance in behavioural tests shows impaired motor coordination and memory. Histopathological investigations revealed significant neuronal loss in hippocampus of epileptic rats indicating glutamate mediated excitotoxicity. The treatment with WS and WA restored behavioural deficit and ameliorated neuronal loss. An altered redox homeostasis leading to oxidative stress is a hallmark of TLE. The antioxidant potential was afflicted in epileptic rats, evident from altered activity of SOD and CAT, down regulation of SOD and GPX expression and enhanced lipid peroxidation. The antioxidant property of WS and WA restored altered antioxidant capacity. Alteration in GDH activity and down regulation of GLAST expression resulted in enhanced glutamate content in the brain regions. The metabolism of glutamate was altered in the form of down regulated GAD expression. The alteration in synthesis, transport and metabolism resulted in further increase of the glutamate concentration at the synapse leading to glutamate mediated excitotoxicity. The decreased NMDA and AMPA receptor binding and down regulated NMDA R1, NMDA 2B and AMPA (GluR2) mRNA expression indicated altered glutamergic receptor function. The treatment with WS and WA reversed altered glutamergic receptor function, synthesis, transport and metabolism. The enhanced levels of second messenger IP3 responsible for Ca2+ mediated toxicity was reversed after treatment with WS and WA. Neurotoxics concentration of glutamate resulted in up regulation of pro apoptotic factors Bax and Caspase 8 and down regulation of anti apoptotic factor Akt resulting in neuronal death. The treatment with WS and WA resulted in activation of Akt and down regulation of Bax and caspase 8 leading to blocking of apoptotic pathway. The treatment with WS and WA resulted in reduced seizure frequency and amelioration of associated alterations suggesting the therapeutic role of Withania somnifera in temporal lobe epilepsy

Molecular genetic profiling of functional genes of pearl oyster, Pinctada fucata

There are a number of genes involved in the regulation of functional process in marine bivalves. In the case of pearl oyster, some of these genes have major role in the immune/defence function and biomineralization process involved in the pearl formation in them. As secondary filter feeders, pearl oysters are exposed to various kinds of stressors like bacteria, viruses, pesticides, industrial wastes, toxic metals and petroleum derivatives, making susceptible to diseases. Environmental changes and ambient stress also affect non-specific immunity, making the organisms vulnerable to infections. These stressors can trigger various cellular responses in the animals in their efforts to counteract the ill effects of the stress on them. These include the expression of defence related genes which encode factors such as antioxidant genes, pattern recognition receptor proteins etc. One of the strategies to combat these problems is to get insight into the disease resistance genes, and use them for disease control and health management. Similarly, although it is known that formation of pearl in molluscs is mediated by specialized proteins which are in turn regulated by specific genes encoding them, there is a paucity of sufficient information on these genes.In view of the above facts, studies on the defence related and pearl forming genes of the pearl oyster assumes importance from the point of view of both sustainable fishery management and aquaculture. At present, there is total lack of sufficient knowledge on the functional genes and their expressions in the Indian pearl oyster Pinctada fucata. Hence this work was taken up to identify and characterize the defence related and pearl forming genes, and study their expression through molecular means, in the Indian pearl oyster Pinctada fucata which are economically important for aquaculture at the southeast coast of India. The present study has successfully carried out the molecular identification, characterization and expression analysis of defence related antioxidant enzyme genes and pattern recognition proteins genes which play vital role in the defence against biotic and abiotic stressors. Antioxidant enzyme genes viz., Cu/Zn superoxide dismutase (Cu/Zn SOD), glutathione peroxidise (GPX) and glutathione-S-transferase (GST) were studied. Concerted approaches using the various molecular tools like polymerase chain reaction (PCR), random amplification of cDNA ends (RACE), molecular cloning and sequencing have resulted in the identification and characterization of full length sequences (924 bp) of the Cu/Zn SOD, most important antioxidant enzyme gene. BLAST search in NCBI confirmed the identity of the gene as Cu/Zn SOD. The presence of the characteristic amino acid sequences such as copper/zinc binding residues, family signature sequences and signal peptides were found out. Multiple sequence alignment comparison and phylogenetic analysis of the nucleotide and amino acid sequences using bioinformatics tools like BioEdit,MEGA etc revealed that the sequences were found to contain regions of diversity as well as homogeneity. Close evolutionary relationship between P. fucata and other aquatic invertebrates was revealed from the phylogenetic tree constructed using SOD amino acid sequence of P. fucata and other invertebrates as well as vertebrates

Differential induction, isolation, physicochemical and molecular characterization of temperate phages of environmental Vibrio cholerae as evidence of phage mediated Horizontal Gene Transfer

The resurgence of the enteric pathogen Vibrio cholerae, the causative organism of epidemic cholera, remains a major health problem in many developing countries like India. The southern Indian state of Kerala is endemic to cholera. The outbreaks of cholera follow a seasonal pattern in regions of endemicity. Marine aquaculture settings and mangrove environments of Kerala serve as reservoirs for V. cholerae. The non-O1/non-O139 environmental isolates of V. cholerae with incomplete ‘virulence casette’ are to be dealt with caution as they constitute a major reservoir of diverse virulence genes in the marine environment and play a crucial role in pathogenicity and horizontal gene transfer. The genes coding cholera toxin are borne on, and can be infectiously transmitted by CTXΦ, a filamentous lysogenic vibriophages. Temperate phages can provide crucial virulence and fitness factors affecting cell metabolism, bacterial adhesion, colonization, immunity, antibiotic resistance and serum resistance. The present study was an attempt to screen the marine environments like aquafarms and mangroves of coastal areas of Alappuzha and Cochin, Kerala for the presence of lysogenic V. cholerae, to study their pathogenicity and also gene transfer potential. Phenotypic and molecular methods were used for identification of isolates as V. cholerae. The thirty one isolates which were Gram negative, oxidase positive, fermentative, with or without gas production on MOF media and which showed yellow coloured colonies on TCBS (Thiosulfate Citrate Bile salt Sucrose) agar were segregated as vibrios. Twenty two environmental V. cholerae strains of both O1 and non- O1/non-O139 serogroups on induction with mitomycin C showed the presence of lysogenic phages. They produced characteristic turbid plaques in double agar overlay assay using the indicator strain V. cholerae El Tor MAK 757. PCR based molecular typing with primers targeting specific conserved sequences in the bacterial genome, demonstrated genetic diversity among these lysogen containing non-O1 V. cholerae . Polymerase chain reaction was also employed as a rapid screening method to verify the presence of 9 virulence genes namely, ctxA, ctxB, ace, hlyA, toxR, zot,tcpA, ninT and nanH, using gene specific primers. The presence of tcpA gene in ALPVC3 was alarming, as it indicates the possibility of an epidemic by accepting the cholera. Differential induction studies used ΦALPVC3, ΦALPVC11, ΦALPVC12 and ΦEKM14, underlining the possibility of prophage induction in natural ecosystems, due to abiotic factors like antibiotics, pollutants, temperature and UV. The efficiency of induction of prophages varied considerably in response to the different induction agents. The growth curve of lysogenic V. cholerae used in the study drastically varied in the presence of strong prophage inducers like antibiotics and UV. Bacterial cell lysis was directly proportional to increase in phage number due to induction. Morphological characterization of vibriophages by Transmission Electron Microscopy revealed hexagonal heads for all the four phages. Vibriophage ΦALPVC3 exhibited isometric and contractile tails characteristic of family Myoviridae, while phages ΦALPVC11 and ΦALPVC12 demonstrated the typical hexagonal head and non-contractile tail of family Siphoviridae. ΦEKM14, the podophage was distinguished by short non-contractile tail and icosahedral head. This work demonstrated that environmental parameters can influence the viability and cell adsorption rates of V. cholerae phages. Adsorption studies showed 100% adsorption of ΦALPVC3 ΦALPVC11, ΦALPVC12 and ΦEKM14 after 25, 30, 40 and 35 minutes respectively. Exposure to high temperatures ranging from 50ºC to 100ºC drastically reduced phage viability. The optimum concentration of NaCl required for survival of vibriophages except ΦEKM14 was 0.5 M and that for ΦEKM14 was 1M NaCl. Survival of phage particles was maximum at pH 7-8. V. cholerae is assumed to have existed long before their human host and so the pathogenic clones may have evolved from aquatic forms which later colonized the human intestine by progressive acquisition of genes. This is supported by the fact that the vast majority of V. cholerae strains are still part of the natural aquatic environment. CTXΦ has played a critical role in the evolution of the pathogenicity of V. cholerae as it can transmit the ctxAB gene. The unusual transformation of V. cholerae strains associated with epidemics and the emergence of V. cholera O139 demonstrates the evolutionary success of the organism in attaining greater fitness. Genetic changes in pathogenic V. cholerae constitute a natural process for developing immunity within an endemically infected population. The alternative hosts and lysogenic environmental V. cholerae strains may potentially act as cofactors in promoting cholera phage ‘‘blooms’’ within aquatic environments, thereby influencing transmission of phage sensitive, pathogenic V. cholerae strains by aquatic vehicles. Differential induction of the phages is a clear indication of the impact of environmental pollution and global changes on phage induction. The development of molecular biology techniques offered an accessible gateway for investigating the molecular events leading to genetic diversity in the marine environment. Using nucleic acids as targets, the methods of fingerprinting like ERIC PCR and BOX PCR, revealed that the marine environment harbours potentially pathogenic group of bacteria with genetic diversity. The distribution of virulence associated genes in the environmental isolates of V. cholerae provides tangible material for further investigation. Nucleotide and protein sequence analysis alongwith protein structure prediction aids in better understanding of the variation inalleles of same gene in different ecological niche and its impact on the protein structure for attaining greater fitness of pathogens. The evidences of the co-evolution of virulence genes in toxigenic V. cholerae O1 from different lineages of environmental non-O1 strains is alarming. Transduction studies would indicate that the phenomenon of acquisition of these virulence genes by lateral gene transfer, although rare, is not quite uncommon amongst non-O1/non-O139 V. cholerae and it has a key role in diversification. All these considerations justify the need for an integrated approach towards the development of an effective surveillance system to monitor evolution of V. cholerae strains with epidemic potential. Results presented in this study, if considered together with the mechanism proposed as above, would strongly suggest that the bacteriophage also intervenes as a variable in shaping the cholera bacterium, which cannot be ignored and hinting at imminent future epidemics.