UMBC Chemistry & Biochemistry Department
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Item Design, Synthesis, and Biological Evaluation of Modified Acyclic Fleximer Nucleoside Analogues(2024/01/01) Thames, Joy Elizabeth; Seley-Radtke, Katherine L; Chemistry & Biochemistry; ChemistryAs the SARS-CoV-2 pandemic left lingering effects worldwide, it remains clear there is a need for the development of broad-spectrum antiviral therapeutics to not only help fight the pandemic at hand but help fight future pandemics to come. With this in mind nucleos(t)ides have had a rich history as antivirals. A commonly employed modification is the use of an acyclic sugar (lack of 2’ and/or 3’ carbons on the sugar moiety), such as that found in Acyclovir (ACV), an FDA-approved drug for herpes simplex virus or the FDA-approved drug Cidofovir (CDV) for CMV retinitis. Research in the Seley-Radtke group focuses on investigating nucleos(t)ide analogues known as “fleximers”, which feature a purine nucleobase “split” into its imidazole and pyrimidine moieties via a carbon-carbon single bond, thus introducing flexibility to the nucleobase. This novel design has endowed the fleximer analogues with potent activity not seen in the rigid parent nucleosides. Combining the acyclic sugar, with the fleximer technology produced a series of first-generation, doubly flexible Flex-ACV analogues. Some of these analogues have exhibited activity against filoviruses, flaviviruses, and coronaviruses. Given the broad-spectrum activity exhibited by these fleximers, optimization of previously synthesized Flex-ACV analogues was carried out for further investigation into the biological effects of these nucleosides. The first-generation Flex-ACV nucleosides were synthesized using modern organic chemistry techniques such as various cross-coupling methods, as well as microwave assisted chemistry. Synthesis of various monophosphate and triphosphate analogues allowed for elucidation of the metabolism and mechanism of action of the first-generation analogues. A new series of Flex-ACV analogues that feature a bond between carbon 5 of imidazole and carbon 5 of the pyrimidine moiety have been designed and synthesized. The newly designed analogues are of interest to compare them to the typical proximal fleximer design and evaluate their antiviral activity as well as the potential to reach new residues in a viral enzyme binding pocket. Overall, the flexible acyclic nucleosides continue to show broad-spectrum antiviral activity and have the potential to become an antiviral therapeutic.Item Surface Modifications of InSe and MXene Two-Dimensional (2D) Materials and their Impact on the Chemical Stability and Interactions with Bacterial Models Relevant to the Environment(2024/01/01) Sengupta, Shreyasi; Rosenzweig, Dr. Zeev; Chemistry & Biochemistry; ChemistryNanosheets are layered two-dimensional nanostructures with thickness in the nano-range, but with properties completely different from the bulk precursors or 3D nanomaterials. Layered materials are defined as solids with strong in-plane chemical bonds, but weak out-of-plane van der Waals interactions. Their unique structural properties enable new functional properties that are important for a multitude of applications. The goal of my research project is to investigate the impact of surface chemistry modifications of 2D materials like InSe and MXenes on their stability and interactions with environmentally relevant bacterial organisms. From a basic science perspective, this study increases the molecular level understanding of the interactions between hydrophobic 2D materials like InSe and amphiphilic adsorbates. The primary choice of our 2D material is InSe, which is an emerging semiconductor 2D material having a direct band gap, already used in broadly distributed nanotechnologies. Usage of InSe and similar 2D materials is expected to grow exponentially in the next decade. However, their unique morphology and ability to produce reactive oxygen species (ROS) could adversely affect human health and the environment. There is an urgent need to address these environmental concerns before the expected exponential growth of their use. Aim 1 of the project is to perform surface modifications on originally hydrophobic InSe nanosheets by physisorption of an amphiphilic molecule and a natural organic matter (NOM) simulant to make them water soluble and understand the impact of this modification on the chemical stability of the nanosheets. Physisorption of NOM components on InSe nanosheets is likely to naturally happen in the environment (natural water) when InSe nanosheets are disposed at the end of devices lifetime, and thus they act as model environmental aqueous solutions. Aim 2 is to investigate the impact of the surface-modified InSe 2D materials soluble in aqueous media on Shewanella oneidensis MR-1, which is an environmentally relevant Gram-negative bacterial cell model. Aim 3 is to investigate the environmental impact of a different highly conducting and water-soluble emerging set of 2D material, MXenes, in unmodified and surface-modified forms with different functional groups as well as fabricated on thermoelectric composite materials, on Shewanella oneidensis MR-1.Item Bioimaging system using acousto-optic tunable filter(SPIE, 2000-05-03) Kasili, Paul M.; Mobley, Joel; Cullum, Brian; Vo-Dinh, TuanThe interaction of light with tissue has ben used to recognize disease since the mid-1800s. The recent developments of light sources, detectors, and fiber optic probes provide opportunities to measure these interactions, which yield information for tissue diagnosis at the biochemical, structural, or physiological level. In this paper, we describe a bioimaging system designed for biomedical applications and show laser-indued fluorescence (LIF) images mammalian brain tissue. The LIF imaging of tissue was carried out in vitro using two laser excitations: 488 nm and 514 nm. Images were recorded through an acousto- optic tunable filter over the range 500 nm-650 nm with a charged coupled device camera. Background subtracted images were generated across the fluorescent wavelength. Subtraction allowed a safe comparison to be made with well- contrasted images. Of the two tested excitation wavelengths, 488 nm excitation gave the more distinctive contrast.Item Development of a compact, handheld Raman instrument with no moving parts for use in field analysis(AIP, 2000-04-01) Cullum, Brian; Mobley, Joel; Chi, Zhenhuan; Stokes, David L.; Miller, Gordon H.; Vo-Dinh, TuanThis article describes a lightweight, self-contained, field portable Raman instrument that has been developed for rapid on-site determination of primary mixture components. The instrument consists of a helium neon (HeNe) laser for excitation, an acousto-optic tunable filter (AOTF) for wavelength discrimination, and an avalanche photodiode for detection. The AOTF is the primary component of this system and has been selected based on its spectral range (600–900 nm) along with its high resolution, ∼7.5 cm⁻¹. Labview™ based software for controlling the AOTF frequency and the signal acquisition has also been developed. Several different samples were analyzed (both solids and liquids) using this instrument for the evaluation of parameters such as spectral resolution, sensitivity, and data acquisition speed for certain environmentally important compounds. The results from these measurements are compared with those using a conventional laboratory Raman system consisting of a grating-based spectrograph and a charge-coupled device.Item Antibody-based nanoprobe for measurement of a fluorescent analyte in a single cell(Nature, 2000-07) Vo-Dinh, Tuan; Alarie, Jean-Pierre; Cullum, Brian; Griffin, Guy D.We report here the application of an antibody-based nanoprobe for in situ measurements of a single cell. The nanoprobe employs antibody-based receptors targeted to a fluorescent analyte, benzopyrene tetrol (BPT), a metabolite of the carcinogen benzo[a]pyrene (BaP) and of the BaP–DNA adduct. Detection of BPT is of great biomedical interest, since this species can serve as a biomarker for monitoring DNA damage due to BaP exposure and for possible precancer diagnosis. The measurements were performed on the rat liver epithelial clone 9 cell line, which was used as the model cell system. Before making measurements, the cells were treated with BPT. Nanoprobes were inserted into individual cells, incubated 5 min to allow antigen–antibody binding, and then removed for fluorescence detection. We determined a concentration of 9.6 ± 0.2 × 10⁻¹¹ M for BPT in the individual cells investigated. The results demonstrate the possibility of in situ measurements inside a single cell using an antibody-based nanoprobe.Item Intracellular Measurements in Mammary Carcinoma Cells Using Fiber-Optic Nanosensors(Elsevier, 2000-01-01) Cullum, Brian; Griffin, Guy D.; Miller, Gordon H.; Vo-Dinh, TuanSubmicrometer fiber-optic biosensors have been developed and used to measure toxic chemicals within single cells. Optical fibers that have been pulled to a distal-end diameter of less than 1 μm are coated with antibodies to selectively bind the species of interest. This paper describes the use of these fibers to selectively measure the concentration of benzo[a]pyrene tetrol (BPT), a metabolite of benzo[a]pyrene, within individual cells of two different cell lines, human mammary carcinoma cells and rat liver epithelial cells. The results from these measurements have been used to determine the sensitivity, reproducibility, and usefulness of these nanosensors. The detection limit of these biosensors has been determined to be 0.64 ± 0.17 × 10⁻¹¹ M for BPT.Item Three-Dimensional Optical Random Access Memory Materials for Use as Radiation Dosimeters(ACS, 2000-10-13) Cullum, Brian; Mobley, Joel; Bogard, James S.; Moscovitch, Marko; Phillips, Gary W.; Vo-Dinh, TuanThis article describes the development of the first three-dimensional optical random access memory (3D-ORAM) material and readout system for monitoring energetic neutrons. Two different photochromic dyes, 5‘-chloro-6-nitro-1‘,3‘,3‘-trimethylspiro-[2H-1-benzopyran-2,2‘-indoline] (spirobenzopyran) and anthracene, have been investigated for use in these 3-D ORAM dosimeter materials. These dyes were immobilized in a poly(methyl methacrylate) support, and the resulting dosimeter materials were irradiated with neutrons from a Cf-252 source. Fluorescence measurements from the dosimeter show a dramatic decrease in the overall fluorescence intensity of the 3D-ORAM dosimeter exposed to the Cf-252, relative to a nonirradiated dosimeter. In addition, a two-photon excitation readout system has been developed for determining characteristics of the radiation that are necessary for estimating dose.Item Development of Nanosensors and Bioprobes(Springer, 2000-03-01) Vo-Dinh, Tuan; Griffin, Guy D.; Alarie, Jean Pierre; Cullum, Brian; Sumpter, Bobby; Noid, DonaldWe describe the development and application of nanosensors having bioreceptor probes for bioanalysis. The nanoprobes were fabricated with optical fibers pulled down to tips having distal end sizes of approximately 30–60 nm. The use of two different types of receptors was investigated. Fiberoptic nanoprobes were covalently bound either with bioreceptors, such as antibodies, or with other receptors, such as cyclodextrins that are selective for the size and chemical structure of the analyte molecules. Theoretical calculations were performed to model the binding of beta-cyclodextrin with pyrene and 5,6-benzoquinoline, and to illustrate the possibility of comparing experimental data with theoretical data. The antibody-based nanoprobe was used for in situ measurements of benzopyrene tetrol in single cells. The performance of the nanosensor is illustrated by intracellular measurements performed on a rat liver epithelial cell line (Clone 9) used as the model cell system. The usefulness and potential of these nanotechnology-based biosensors in biological research and applications are discussed.Item The development of optical nanosensors for biological measurements(Elsevier, 2000-08-21) Cullum, Brian; Vo-Dinh, TuanThis article discusses and documents the basic concepts of, and developments in, the field of optical nanosensors and nanobiosensors. It describes the progression of this field of research from its birth up to the present, with emphasis on the techniques of sensor construction and their application to biological systems. After a brief overview of the techniques for fabricating nanometer-sized optical fibers, we describe the various types of transducer and bioreceptor molecule presently used for nanosensor and nanobiosensor fabrication.Item Biosensors and biochips: advances in biological and medical diagnostics(Springer, 2000-03-01) Vo-Dinh, T.; Cullum, BrianIn the past two decades, the biological and medical fields have seen great advances in the development of biosensors and biochips capable of characterizing and quantifying biomolecules. This review is meant to provide an overview of the various types of biosensors and biochips that have been developed for biological and medical applications, along with significant advances over the last several years in these technologies. It also attempts to describe various classification schemes that can be used for categorizing the different biosensors and provide relevant examples of these classification schemes from recent literature.Item Vapor detection of polyaromatic compounds using laser-induced fluorescence(SPIE, 2001-02-14) Chi, Zenhuan; Cullum, Brian; Mobley, Joel; Miller, Gordon H.; Vo-Dinh, Tuan12 In this work, we present the fluorescence spectra of anthracene and pyrene vapors at different elevated temperatures (from 150 to 650 degree(s)C) excited with the 337 nm line of a nitrogen laser. We describe the high temperature effects on the resulting spectral properties including spectral intensity, spectral bandwidth and spectral shift. We found that the PAH fluorescence spectral bandwidths become very broad as the temperature increases. The broadening is mainly due to thermal vibrational sequence congestion. We also have found that the fluorescence intensity of pyrene vapor increases with increasing temperature, which results from the increase of the pyrene vapor absorption cross section at 337 nm.Item Ultrasonic diffraction in the design of photoacoustic probes(SPIE, 2001-06-04) Mobley, Joel; Cullum, Brian; Vo-Dinh, TuanIn this work, we examine the role of diffraction in the design of ring-shaped ultrasonic receivers for photoacoustic probes. The sensitivity patterns of ultrasonic receiving rings are calculated at 1 MHz using the angular spectrum technique. Three separate series of simulations are considered: flat ring with a fixed outer diameter and a variable inner diameter, flat ring with a fixed inner diameter and variable outer diameter, and a spherically focused ring with a variable inner diameter. From these results the focal zone characteristic and sensitivities are calculated. For the planar rings, we find that the spatial sensitivity varies markedly with ring width but the overall sensitivities are comparable. For the focused (spherically curved) rings, the focal distances and beam volumes were similar while the sensitivity grew with ring thickness.Item Nanosensors for analysis of a single cell(SPIE, 2001-06-04) Cullum, Brian; Griffin, Guy D.; Vo-Dinh, TuanSubmicron fiber-optic biosensors have been developed and used to measure toxic chemicals within single cells. These sensors are fabricated by pulling the distal-end of an optical fiber to a diameter of less than one micron and coating them with antibodies to selectively bind the species of interest. This paper describes the use of these fibers to selectively measure the concentration of benzo[a]pyrene tetrol, a metabolite of benzo[a]pyrene, within individual cells of two different cell lines, human mammary carcinoma cells and rat liver epithelial cells. The results from these measurements have been used to evaluate the analytical figures of merit of these sensors such as detection limits, which were found to be 0.64 +/- 0.17 X 10⁻¹¹ M for BPT. In addition, measurements were performed both extracellularly and intracellularly, and an increase in variation of approximately 4% was determined for the intracellular measurements, relative to the extracellular measurements.Item High-temperature vapor detection of polycyclic aromatic hydrocarbon fluorescence(Elsevier, 2001-09-13) Chi, Zhenhuan; Cullum, Brian; Stokes, David L.; Mobley, Joel; Miller, Gordon H.; Hajaligol, Mohammad R.; Vo-Dinh, TuanPolycyclic aromatic hydrocarbons (PAHs) are generated from the incomplete combustion of organic matters in a wide variety of natural and man-made materials, such as fuels. It is important to develop an analytical technique for rapidly monitoring PAH generation at high temperatures during pyrolysis processes. This work describes a real-time and in situ technique using laser-induced fluorescence to detect PAH vapors at elevated temperatures. We report fluorescence spectra of several typical PAH model compounds, such as pyrene, phenanthrene and chrysene. We have also examined the temperature effects on PAH fluorescence spectra such as spectral shift, intensity and band width.Item Nanosensors and biochips: frontiers in biomolecular diagnostics(Elsevier, 2001-04-06) Vo-Dinh, Tuan; Cullum, Brian; Stokes, David LIn the past two decades, the biotechnology and medical fields have seen great advances in the development of novel technologies that open new horizons for identifying and quantifying biomolecules, and diagnosing diseases. This manuscript provides an overview of two of those important technologies, nanosensors and biochips. We describe various types of nanosensors and biochips that have been developed for biological and medical applications, along with significant advances achieved over the last several years in these technologies. Some applications of nanosensors, developed in our laboratory for single-cell analysis, and applications of biochips for biological sensing of pathogenic agents and medical diagnostics are described to illustrate the usefulness and potential of these technologies.Item Laser-induced fluorescence studies of polycyclic aromatic hydrocarbons (PAH) vapors at high temperatures(Elsevier, 2001-06-01) Chi, Zhenhuan; Cullum, Brian; Stokes, David L; Mobley, Joel; Miller, Gordon H; Hajaligol, Mohammad R; Vo-Dinh, TuanIn this work, we present the fluorescence spectra of anthracene and pyrene vapors at different elevated temperatures (from 150 to 650°C) excited with the 337 nm line of a nitrogen laser. We describe the high temperature effects on the resulting spectral properties including spectral intensity, spectral bandwidth and spectral shift. We found that the PAH fluorescence spectral bandwidths become very broad as the temperature increases. The broadening is mainly due to thermal vibrational sequence congestion. We also have found that the fluorescence intensity of pyrene vapor increases with increasing temperature, which results from the increase of the pyrene vapor absorption cross section at 337 nm.Item Crossed-beam two-photon readout system for three-dimensional radiation dosimeters(AIP, 2002-12-01) Song, Joon Myong; Cullum, Brian; Mobley, Joel; Bogard, James S.; Moscovitch, Marko; Phillips, Gary W.; Vo-Dinh, TuanThree-dimensional optical random access memory (3D ORAM) materials with enormous capacity and fast access speed have shown a great potential in overcoming limitations of access and storage capacity in current memory devices. As another useful development of this 3D ORAM, we have shown the application of 3D ORAM materials as a practical dosimeter. The local heating of the polymer matrix by the deposited energy of ionizing radiation is thought to contribute to the conversion of the fluorescent photochromic dye to a nonfluorescent form. The two-photon readout system is very useful in tracking the interactions of energy of ionizing radiation deposited in a polymer matrix. However, the polymer fracturing that has occurred during two-photon readout has been an obstacle in utilization of 3D ORAM materials as a dosimeter. In this work, we further evaluated the readout system using a high-energy variable attenuator in order to prevent polymer fracturing due to the strong absorption of the 1064 nm beam by the polymer matrix. Through adjustment of the 1064 nm beam intensity using this attenuator, two-photon excited fluorescence of anthracene-doped 3D ORAM materials could be obtained without polymer fracturing. As a result of this improved procedure, a highly spatially resolved fluorescence image of anthracene-doped 3D ORAM material could be observed with the two-photon readout system.Item Real-time detection of PAH mixtures in the vapor phase at high temperatures(Elsevier, 2002-12-03) Allain, Leonardo R.; Stratis, Dimitra N.; Cullum, Brian; Mobley, Joel; Hajaligol, Mohammad R.; Vo-Dinh, TuanLaser-induced fluorescence (LIF) spectroscopy can serve as a rapid analytical method for the quantitative analysis of polycyclic aromatic hydrocarbons (PAHs). The high quantum yields of this class of compounds, along with large absorption cross-sections, make fluorescence a very attractive technique for trace analysis determination of PAHs. Furthermore, fluorescence can provide in situ and online information regarding the composition and concentration of PAHs formed during combustion or pyrolysis processes. In this paper, we utilize a fiber-optic probe coupled to a spectrometer to collect fluorescence spectra of several PAH vapors at elevated temperatures using excitation at 337 nm. We have collected the fluorescence of standards as well as complex mixtures of PAHs at 300°C. The expected band broadening induced by temperature effects was observed, but did not compromise the spectrum signature for each PAH studied. We have measured fluorescence spectra of benzo[a]pyrene, pyrene, anthracene, and phenanthrene vapors. Determination of trace amounts of the toxicologically important benzo[a]pyrene has been shown to be feasible. Experimental results show that at 337 nm, benzo[a]pyrene is the most quantum efficient fluorophore among the PAHs studied. Furthermore, fluorescence lifetime measurements were found to be helpful in the characterization of PAH mixtures.Item Development of a multi-spectral imaging system for medical applications(IOP, 2003-07-01) Vo-Dinh, Tuan; Cullum, Brian; Kasili, PaulWe describe the development of a multi-spectral imaging (MSI) system based on a rapid-scanning solid-state device, an acousto-optic tunable filter (AOTF), for wavelength selection and a two-dimensional charge-coupled device for detection. The MSI device is designed for in vivo optical detection in medical diagnostic applications. Unlike conventional grating spectrometers, the AOTF is a miniature solid-state device that has no moving parts, and can be rapidly tuned to any wavelength within its operating range. The large aperture of the AOTF and its high spatial resolution allows the optical image from an imaging fibre optic probe to be recorded by the detector. These characteristics, combined with their small size, make AOTFs important new alternatives to conventional monochromators, especially for spectral imaging in biomedical applications. The MSI can also be used for dual-modality diagnostics to detect both fluorescence and diffuse reflectance images. The usefulness and potential of the MSI system is illustrated in several applications of biomedical interest, such as reflectance fluorescence imaging of skin and brain tissues.Item Single-board computer based control system for a portable Raman device with integrated chemical identification(AIP, 2004-06-01) Mobley, Joel; Cullum, Brian; Wintenberg, Alan L.; Shane Frank, S.; Maples, Robert A.; Stokes, David L.; Vo-Dinh, TuanWe report the development of a battery-powered portable chemical identification device for field use consisting of an acousto-optic tunable filter (AOTF)-based Raman spectrometer with integrated data processing and analysis software. The various components and custom circuitry are integrated into a self-contained instrument by control software that runs on an embedded single-board computer (SBC), which communicates with the various instrument modules through a 48-line bidirectional TTL bus. The user interacts with the instrument via a touch-sensitive liquid crystal display unit (LCD) that provides soft buttons for user control as well as visual feedback (e.g., spectral plots, stored data, instrument settings, etc.) from the instrument. The control software manages all operational aspects of the instrument with the exception of the power management module that is run by embedded firmware. The SBC-based software includes both automated and manual library searching capabilities, permitting rapid identification of samples in the field. The use of the SBC in tandem with the LCD touchscreen for interfacing and control provides the instrument with a great deal of flexibility as its function can be customized to specific users or tasks via software modifications alone. The instrument, as currently configured, can be operated as a research-grade Raman spectrometer for scientific applications and as a “black-box” chemical identification system for field use. The instrument can acquire 198-point spectra over a spectral range of 238–1620 cm⁻¹, perform a library search, and display the results in less than 14 s. The operating modes of the instrument are demonstrated illustrating the utility and flexibility afforded the system by the SBC–LCD control module.