Synthetic studies of azulenyl and pseudoazulenyl nitrones

Free radicals have been implicated in various pathological conditions such as, stroke, aging and ischemic heart disease (IHD), as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease. The role of antioxidants in protection from the harmful effects of free radicals has long been recognized. Trapping extremely reactive free radicals and eliminating them from circulation has been shown to be effective in animal models. Nitrone-based free radical traps have been extensively explored in biological systems. Examples include nitrones such as PBN, NXY-059, MDL-101,002, DMPO and EMPO. However, these nitrones have extremely high oxidation potentials as compared to natural antioxidants such as Vitamin E (α-tocopherol), and glutathione. Becker et al. (1995) synthesized novel azulenyl nitrones, which were shown to have oxidation potentials much lower than that of any of the previously reported nitrone based spin traps. Another azulenyl nitrone derivative, stilbazulenyl nitrone (STAZN), was shown to have an even lower oxidation potential within the range of natural antioxidants. STAZN, a second generation free radical trap, was found to be markedly superior than the two most studied nitrones, PBN and NXY-059, in animal models of cerebral ischemia and in an in vitro assay of lipid peroxidation. In this study, a third generation azulenyl nitrone was synthesized with an electron donating group on the previously synthesized STAZN derivative with the aim to lower the oxidation potential even more. Pseudoazulenes, because of the presence of an annular heteroatom, have been reported to possess even lower oxidation potential than that of the azulenyl counterpart. Therefore, pseudoazulenyl nitrones were synthesized for the first time by extracting and elaborating valtrate from the roots of Centranthus ruber (Red valerian or Jupiter’s beard). Several pseudoazulenyl nitrones were synthesized by using a facile experimental protocol. The physical and biological properties of these pseudoazulenyl nitrones can be easily modified by simply changing the substituent on the heteroatom. Cyclic voltammetry experiments have shown that these pseudoazulenyl nitrones do indeed have low oxidation potentials. The oxidation potential of these nitrones was lowered even more by preparing derivatives bearing an electron donating group at the 3-position of the five membered ring of the pseudoazulenyl nitrone.

A thermally wavelength-tunable photonic switch based on silicon microring resonator

Silicon photonics is a very promising technology for future low-cost high-bandwidth optical telecommunication applications down to the chip level. This is due to the high degree of integration, high optical bandwidth and large speed coupled with the development of a wide range of integrated optical functions. Silicon-based microring resonators are a key building block that can be used to realize many optical functions such as switching, multiplexing, demultiplaxing and detection of optical wave. The ability to tune the resonances of the microring resonators is highly desirable in many of their applications. In this work, the study and application of a thermally wavelength-tunable photonic switch based on silicon microring resonator is presented. Devices with 10μm diameter were systematically studied and used in the design. Its resonance wavelength was tuned by thermally induced refractive index change using a designed local micro-heater. While thermo-optic tuning has moderate speed compared with electro-optic and all-optic tuning, with silicon’s high thermo-optic coefficient, a much wider wavelength tunable range can be realized. The device design was verified and optimized by optical and thermal simulations. The fabrication and characterization of the device was also implemented. The microring resonator has a measured FSR of ∼18 nm, FWHM in the range 0.1-0.2 nm and Q around 10,000. A wide tunable range (>6.4 nm) was achieved with the switch, which enables dense wavelength division multiplexing (DWDM) with a channel space of 0.2nm. The time response of the switch was tested on the order of 10 μs with a low power consumption of ∼11.9mW/nm. The measured results are in agreement with the simulations. Important applications using the tunable photonic switch were demonstrated in this work. 1×4 and 4×4 reconfigurable photonic switch were implemented by using multiple switches with a common bus waveguide. The results suggest the feasibility of on-chip DWDM for the development of large-scale integrated photonics. Using the tunable switch for output wavelength control, a fiber laser was demonstrated with Erbium-doped fiber amplifier as the gain media. For the first time, this approach integrated on-chip silicon photonic wavelength control.

Synthesis and characterization of photochromic indolyl substituted fulgides and fulgimides

The fulgide and fulgimide family constitutes an important class of organic photochromic compounds. The ability of fulgides and fulgimides to interconvert between two key forms by irradiation of different wavelength of light has made them promising material in optical memory devices, optical switches and sensors, and specialty dyes and inks. Thermal stability and hydrolytic stability of fulgides and fulgimides are essential for their practical applications. A deuterated trifluoromethyl indolylfulgide was synthesized based on the synthetic pathway of the proteo trifluoromethyl indolylfulgide using commercially available deuterated starting materials. Deuteration of the isopropylidene group improved the thermal stability of the indolylfulgide by a factor of 7. ^ Fulgimides are the most important fulgide derivatives. Fulgimides improve the hydrolytic stability of fulgides by replacing the succinic anhydride ring with a succinimide ring. A novel trifluoromethyl N-ethoxycarbonylmethyl indolylfulgimide was synthesized from trifluoromethyl indolylfulgide. The trifluoromethyl indolylfulgide was synthesized on a large scale in five steps with an overall yield of 18%. The indolylfulgide was then converted to indolylfulgimide by aminolysis follow by dehydration. The N-ethoxycarbonylmethyl indolylfulgimide showed enhanced hydrolytic stability and photochemical stability in 70/30 ethanol/water. ^ Three novel aqueous soluble fulgimides, trifluoromethyl carboxylic acid indolylfulgimide, dicarboxylic acid indolylfulgimide, and H-carboxylic acid indolylfulgimide, were synthesized. In sodium phosphate buffer (pH 7.4) at 37 ºC, an unusual hydrolysis of the trifluoromethyl group of the closed form of the carboxylic acid indolylfulgimide resulted in the dicarboxylic acid indolylfulgimide which has an additional carboxylic acid group. The closed form of dicarboxylic acid indolylfulgimide was further decarboxylated to generate H-carboxylic acid indolylfulgimide which was not photochromic. The trifluoromethyl dicarboxylic acid indolylfulgimide is the most robust fulgimide yet reported in aqueous solution. ^ A novel aqueous soluble methyl carboxylic acid indolylfulgimide was synthesized from methyl indolylfulgide. The methyl indolylfulgide was synthesized in five steps with an overall yield of 21%. The methyl carboxylic acid indolylfulgimide was synthesized by aminolysis follow by dehydration. The methyl carboxylic acid indolylfulgimide is expected to have improved thermal and photochemical stability in aqueous solutions relative to the trifluoromethyl analog.^

Multi-temporal monitoring of wetland water levels in the Florida Everglades using interferometric synthetic aperture radar (InSAR)

Interferometric synthetic aperture radar (InSAR) techniques can successfully detect phase variations related to the water level changes in wetlands and produce spatially detailed high-resolution maps of water level changes. Despite the vast details, the usefulness of the wetland InSAR observations is rather limited, because hydrologists and water resources managers need information on absolute water level values and not on relative water level changes. We present an InSAR technique called Small Temporal Baseline Subset (STBAS) for monitoring absolute water level time series using radar interferograms acquired successively over wetlands. The method uses stage (water level) observation for calibrating the relative InSAR observations and tying them to the stage's vertical datum. We tested the STBAS technique with two-year long Radarsat-1 data acquired during 2006–2008 over the Water Conservation Area 1 (WCA1) in the Everglades wetlands, south Florida (USA). The InSAR-derived water level data were calibrated using 13 stage stations located in the study area to generate 28 successive high spatial resolution maps (50 m pixel resolution) of absolute water levels. We evaluate the quality of the STBAS technique using a root mean square error (RMSE) criterion of the difference between InSAR observations and stage measurements. The average RMSE is 6.6 cm, which provides an uncertainty estimation of the STBAS technique to monitor absolute water levels. About half of the uncertainties are attributed to the accuracy of the InSAR technique to detect relative water levels. The other half reflects uncertainties derived from tying the relative levels to the stage stations' datum.

Synthetic Approaches to Flexible Fluorescent Conjugated Polymers

Conjugated polymers (CPs) are intrinsically fluorescent materials that have been used for various biological applications including imaging, sensing, and delivery of biologically active substances. The synthetic control over flexibility and biodegradability of these materials aids the understanding of the structure-function relationships among the photophysical properties, the self-assembly behaviors of the corresponding conjugated polymer nanoparticles (CPNs), and the cellular behaviors of CPNs, such as toxicity, cellular uptake mechanisms, and sub-cellular localization patterns. Synthetic approaches towards two classes of flexible CPs with well-preserved fluorescent properties are described. The synthesis of flexible poly(p-phenylenebutadiynylene)s (PPBs) uses competing Sonogashira and Glaser coupling reactions and the differences in monomer reactivity to incorporate a small amount (~10%) of flexible, non-conjugated linkers into the backbone. The reaction conditions provide limited control over the proportion of flexible monomer incorporation. Improved synthetic control was achieved in a series of flexible poly(p-phenyleneethynylene)s (PPEs) using modified Sonogashira conditions. In addition to controlling the degree of flexibility, the linker provides disruption of backbone conjugation that offers control of the length of conjugated segments within the polymer chain. Therefore, such control also results in the modulation of the photophysical properties of the materials. CPNs fabricated from flexible PPBs are non-toxic to cells, and exhibit subcellular localization patterns clearly different from those observed with non-flexible PPE CPNs. The subcellular localization patterns of the flexible PPEs have not yet been determined, due to the toxicity of the materials, most likely related to the side-chain structure used in this series. The study of the effect of CP flexibility on self-assembly reorganization upon polyanion complexation is presented. Owing to its high rigidity and hydrophobicity, the PPB backbone undergoes reorganization more readily than PPE. The effects are enhanced in the presence of the flexible linker, which enables more efficient π-π stacking of the aromatic backbone segments. Flexibility has minimal effects on the self-assembly of PPEs. Understanding the role of flexibility on the biophysical behaviors of CPNs is key to the successful development of novel efficient fluorescent therapeutic delivery vehicles.

Silicon photonic device for wavelength sensing and monitoring

Over the last decade advances and innovations from Silicon Photonics technology were observed in the telecommunications and computing industries. This technology which employs Silicon as an optical medium, relies on current CMOS micro-electronics fabrication processes to enable medium scale integration of many nano-photonic devices to produce photonic integrated circuitry. ^ However, other fields of research such as optical sensor processing can benefit from silicon photonics technology, specially in sensors where the physical measurement is wavelength encoded. ^ In this research work, we present a design and application of a thermally tuned silicon photonic device as an optical sensor interrogator. ^ The main device is a micro-ring resonator filter of 10 μm of diameter. A photonic design toolkit was developed based on open source software from the research community. With those tools it was possible to estimate the resonance and spectral characteristics of the filter. From the obtained design parameters, a 7.8 × 3.8 mm optical chip was fabricated using standard micro-photonics techniques. In order to tune a ring resonance, Nichrome micro-heaters were fabricated on top of the device. Some fabricated devices were systematically characterized and their tuning response were determined. From measurements, a ring resonator with a free-spectral-range of 18.4 nm and with a bandwidth of 0.14 nm was obtained. Using just 5 mA it was possible to tune the device resonance up to 3 nm. ^ In order to apply our device as a sensor interrogator in this research, a model of wavelength estimation using time interval between peaks measurement technique was developed and simulations were carried out to assess its performance. To test the technique, an experiment using a Fiber Bragg grating optical sensor was set, and estimations of the wavelength shift of this sensor due to axial strains yield an error within 22 pm compared to measurements from spectrum analyzer. ^ Results from this study implies that signals from FBG sensors can be processed with good accuracy using a micro-ring device with the advantage of ts compact size, scalability and versatility. Additionally, the system also has additional applications such as processing optical wavelength shifts from integrated photonic sensors and to be able to track resonances from laser sources.^

A Thermally Wavelength-tunable Photonic Switch Based on Silicon Microring Resonator

Silicon photonics is a very promising technology for future low-cost high-bandwidth optical telecommunication applications down to the chip level. This is due to the high degree of integration, high optical bandwidth and large speed coupled with the development of a wide range of integrated optical functions. Silicon-based microring resonators are a key building block that can be used to realize many optical functions such as switching, multiplexing, demultiplaxing and detection of optical wave. The ability to tune the resonances of the microring resonators is highly desirable in many of their applications. In this work, the study and application of a thermally wavelength-tunable photonic switch based on silicon microring resonator is presented. Devices with 10µm diameter were systematically studied and used in the design. Its resonance wavelength was tuned by thermally induced refractive index change using a designed local micro-heater. While thermo-optic tuning has moderate speed compared with electro-optic and all-optic tuning, with silicon’s high thermo-optic coefficient, a much wider wavelength tunable range can be realized. The device design was verified and optimized by optical and thermal simulations. The fabrication and characterization of the device was also implemented. The microring resonator has a measured FSR of ~18 nm, FWHM in the range 0.1-0.2 nm and Q around 10,000. A wide tunable range (>6.4 nm) was achieved with the switch, which enables dense wavelength division multiplexing (DWDM) with a channel space of 0.2nm. The time response of the switch was tested on the order of 10 us with a low power consumption of ~11.9mW/nm. The measured results are in agreement with the simulations. Important applications using the tunable photonic switch were demonstrated in this work. 1×4 and 4×4 reconfigurable photonic switch were implemented by using multiple switches with a common bus waveguide. The results suggest the feasibility of on-chip DWDM for the development of large-scale integrated photonics. Using the tunable switch for output wavelength control, a fiber laser was demonstrated with Erbium-doped fiber amplifier as the gain media. For the first time, this approach integrated on-chip silicon photonic wavelength control.

Synthesis of a PbTx-2 photoaffinity and fluorescent probe and an alternative synthetic route to photoaffinity probes

A natural phenomenon characterized by dense aggregations of unicellular photosynthetic marine organisms has been termed colloquially as red tides because of the vivid discoloration of the water. The dinoflagellate Karenia brevis is the cause of the Florida red tide bloom. K. brevis produces the brevetoxins, a potent suite of neurotoxins responsible for substantial amounts of marine mammal and fish mortalities. When consumed by humans, the toxin causes Neurotoxic Shellfish Poisoning (NSP). The native function of brevetoxin within the organism has remained mysterious since its discovery. There is a need to identify factors which contribute to and regulate toxin production within K. brevis. These toxins are produced and retained within the cell implicating a significant cellular role for their presence. Localization of brevetoxin and identification of a native receptor may provide insight into its native role as well as other polyether ladder type toxins such as the ciguatoxins, maitotoxins, and yessotoxins. In higher organisms these polyether ladder molecules bind to transmembrane proteins with high affinity. We anticipated the native brevetoxin receptor would also be a transmembrane protein. Photoaffinity labeling has become increasingly popular for identifying ligand receptors. By attaching ligands to these photophors, one is able to activate the molecule after the ligand binds to its receptor to obtain a permanent linkage between the two. Subsequent purification provides the protein with the ligand directly attached. A molecule that is capable of fluorescence is a fluorophore, which upon excitation is capable of re-emitting light. Fluorescent labeling uses fluorophores by attaching them covalently to biologically active compounds. The synthesis of a brevetoxin photoaffinity probe and its application in identifying a native brevetoxin receptor will be described. The preparation of a fluorescent derivative of brevetoxin will be described and its use in localizing the toxin to an organelle within K. brevis. In addition, the general utility of a synthesized photoaffinity label with other toxins having similar functionality will be described. An alternative synthetic approach to a general photoaffinity label will also be discussed whose goal was to accelerate the preparation and improve the overall synthetic yields of a multifunctional label.

Synthetic Studies of Azulenyl and Pseudoazulenyl Nitrones

Free radicals have been implicated in various pathological conditions such as, stroke, aging and ischemic heart disease (IHD), as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease. The role of antioxidants in protection from the harmful effects of free radicals has long been recognized. Trapping extremely reactive free radicals and eliminating them from circulation has been shown to be effective in animal models. Nitrone-based free radical traps have been extensively explored in biological systems. Examples include nitrones such as PBN, NXY-059, MDL-101,002, DMPO and EMPO. However, these nitrones have extremely high oxidation potentials as compared to natural antioxidants such as Vitamin E (á-tocopherol), and glutathione. Becker et al. (1995) synthesized novel azulenyl nitrones, which were shown to have oxidation potentials much lower than that of any of the previously reported nitrone based spin traps. Another azulenyl nitrone derivative, stilbazulenyl nitrone (STAZN), was shown to have an even lower oxidation potential within the range of natural antioxidants. STAZN, a second generation free radical trap, was found to be markedly superior than the two most studied nitrones, PBN and NXY-059, in animal models of cerebral ischemia and in an in vitro assay of lipid peroxidation. In this study, a third generation azulenyl nitrone was synthesized with an electron donating group on the previously synthesized STAZN derivative with the aim to lower the oxidation potential even more. Pseudoazulenes, because of the presence of an annular heteroatom, have been reported to possess even lower oxidation potential than that of the azulenyl counterpart. Therefore, pseudoazulenyl nitrones were synthesized for the first time by extracting and elaborating valtrate from the roots of Centranthus ruber (Red valerian or Jupiter’s beard). Several pseudoazulenyl nitrones were synthesized by using a facile experimental protocol. The physical and biological properties of these pseudoazulenyl nitrones can be easily modified by simply changing the substituent on the heteroatom. Cyclic voltammetry experiments have shown that these pseudoazulenyl nitrones do indeed have low oxidation potentials. The oxidation potential of these nitrones was lowered even more by preparing derivatives bearing an electron donating group at the 3-position of the five membered ring of the pseudoazulenyl nitrone.

Silicon Photonic Device for Wavelength Sensing and Monitoring

Over the last decade advances and innovations from Silicon Photonics technology were observed in the telecommunications and computing industries. This technology which employs Silicon as an optical medium, relies on current CMOS micro-electronics fabrication processes to enable medium scale integration of many nano-photonic devices to produce photonic integrated circuitry. However, other fields of research such as optical sensor processing can benefit from silicon photonics technology, specially in sensors where the physical measurement is wavelength encoded. In this research work, we present a design and application of a thermally tuned silicon photonic device as an optical sensor interrogator. The main device is a micro-ring resonator filter of 10 $\mu m$ of diameter. A photonic design toolkit was developed based on open source software from the research community. With those tools it was possible to estimate the resonance and spectral characteristics of the filter. From the obtained design parameters, a 7.8 x 3.8 mm optical chip was fabricated using standard micro-photonics techniques. In order to tune a ring resonance, Nichrome micro-heaters were fabricated on top of the device. Some fabricated devices were systematically characterized and their tuning response were determined. From measurements, a ring resonator with a free-spectral-range of 18.4 nm and with a bandwidth of 0.14 nm was obtained. Using just 5 mA it was possible to tune the device resonance up to 3 nm. In order to apply our device as a sensor interrogator in this research, a model of wavelength estimation using time interval between peaks measurement technique was developed and simulations were carried out to assess its performance. To test the technique, an experiment using a Fiber Bragg grating optical sensor was set, and estimations of the wavelength shift of this sensor due to axial strains yield an error within 22 pm compared to measurements from spectrum analyzer. Results from this study implies that signals from FBG sensors can be processed with good accuracy using a micro-ring device with the advantage of ts compact size, scalability and versatility. Additionally, the system also has additional applications such as processing optical wavelength shifts from integrated photonic sensors and to be able to track resonances from laser sources.

Synthetic approaches to flexible fluorescent conjugated polymers

Conjugated polymers (CPs) are intrinsically fluorescent materials that have been used for various biological applications including imaging, sensing, and delivery of biologically active substances. The synthetic control over flexibility and biodegradability of these materials aids the understanding of the structure-function relationships among the photophysical properties, the self-assembly behaviors of the corresponding conjugated polymer nanoparticles (CPNs), and the cellular behaviors of CPNs, such as toxicity, cellular uptake mechanisms, and sub-cellular localization patterns. ^ Synthetic approaches towards two classes of flexible CPs with well-preserved fluorescent properties are described. The synthesis of flexible poly( p-phenylenebutadiynylene)s (PPBs) uses competing Sonogashira and Glaser coupling reactions and the differences in monomer reactivity to incorporate a small amount (∼10%) of flexible, non-conjugated linkers into the backbone. The reaction conditions provide limited control over the proportion of flexible monomer incorporation. Improved synthetic control was achieved in a series of flexible poly(p-phenyleneethynylene)s (PPEs) using modified Sonogashira conditions. In addition to controlling the degree of flexibility, the linker provides disruption of backbone conjugation that offers control of the length of conjugated segments within the polymer chain. Therefore, such control also results in the modulation of the photophysical properties of the materials. ^ CPNs fabricated from flexible PPBs are non-toxic to cells, and exhibit subcellular localization patterns clearly different from those observed with non-flexible PPE CPNs. The subcellular localization patterns of the flexible PPEs have not yet been determined, due to the toxicity of the materials, most likely related to the side-chain structure used in this series. ^ The study of the effect of CP flexibility on self-assembly reorganization upon polyanion complexation is presented. Owing to its high rigidity and hydrophobicity, the PPB backbone undergoes reorganization more readily than PPE. The effects are enhanced in the presence of the flexible linker, which enables more efficient π-π stacking of the aromatic backbone segments. Flexibility has minimal effects on the self-assembly of PPEs. Understanding the role of flexibility on the biophysical behaviors of CPNs is key to the successful development of novel efficient fluorescent therapeutic delivery vehicles.^