STRUCTURAL STUDIES OF BIOPOLYMERS USING COMPUTER SIMULATIONS, OPTICAL AND MAGNETIC SPECTROSCOPY
Author:
Subhasish Chatterjee
Year of Dissertation:
2009
Biopolymers are essential components of numerous natural and synthetic macromolecular assemblies. In the present study, the structural properties of biopolymers ranging from fungal melanins to synthetic nucleic acids were investigated using spectroscopic methods and theoretical modeling. (1) Computational modeling and molecular dynamics simulations were used to study the structural properties of a short single-stranded (ss) DNA. The dependence of the conformational stability and flexibility of the ssDNA on the thermodynamic conditions of the system was demonstrated. (2) Time-resolved fluorescence spectroscopy involving an organic donor-quencher pair was utilized to study the conformational properties of Y-shaped DNA. Results highlighted the different distances between the arms of the Y-DNA and indicated the overall structural stability of the Y-DNA system. Time-resolved fluorescence techniques were applied to investigate the distance dependence of the non-radiative energy transfer process between an organic donor (fluorescein) and a gold nanoparticle quencher connected by double stranded (ds) DNA. (3) Synthesis of phospholipid-conjugated gold nanoparticles and their self-assembly onto an aqueous subphase were tested. The resulting lipid-capped nanoparticles were characterized by optical methods such as UV-Vis absorption spectroscopy and dynamic light scattering. The effects of bio-functionalization on the size of biotin-capped gold nanoparticles were investigated using optical techniques. (4) Solid-state nuclear magnetic resonance (NMR) spectroscopy was utilized to elucidate the structural characteristics of fungal melanins. Various spinning speeds, temperatures, magnetic field strengths, and isotopic labels were utilized with 1D and 2D 13C MAS NMR, revealing distinctive structural fingerprints of the fungal melanins generated biosynthetically with L-dopa, methyldopa, epinephrine, and norepinephrine. These pigments exhibited differences in their aromatic and aliphatic structures and probable biosynthetic pathways, and it was possible to delineate proximities between particular melanin and membrane-related molecular groups.
I. The RCM Approach Towards 1,6-methano-bridged[12] & [14]Annulenes and their Bisdehydro-derivatives II. 1,5-bisdehydro[10]Annulene Revisited
Year of Dissertation:
2010
Part I of my dissertation presents a new efficient synthesis of 3,4-benzo-1,6-methano[12]annulene (3). This novel synthetic approach involves a grignard addition to 3,4-benzo-cycloheptatriene-1,6-dialdehyde followed by a ring closing olefin metathesis (RCM) reaction giving the bridged 12-menber ring of 3,4-benzo-1,6-methano[12]annulene (3) was obstained in six steps and an overall yield 44%. This allowed the complete structural and spectroscopic characterization as a paratropic ethano-bridged benzo[12]annulene with a 28% reduction of the paramagnetic ring current relative to the non-benzannulated molecule. A careful comparison of the 1H NMR of (3) with its 9,10-dihydro derivative (104) suggests an extended paratropic 16π system. The RCM approach is general and thus formally presents a 6 steps route to the parent 1,6-methano[12]annulene, previously reported by E. Vogel et al. Combination of cis-selective Wittig reaction of (36) with the ylide derived from 4-bromo-1-butene followed by RCM reaction yielded the 9,12-dihydro-3,4-benzo-1,6-methano[14]annulene (35). Attempts to convert this molecular in to the expectedly diatropic 14π system did not succeed so far. In course of this investigation, an efficient synthesis for 3,4-benzo-1,6-ethynylcycloheptatriene was developed. Diketone (37) obtained through Jones oxidation of the diasteromeric alcohols (26) was converted into the 3,4-benzo-1,6-methano-7,12-bis(dibromomethylene)-8,11-dihydro[12]annulene (38). Treatment of this molecule with two moles of n-butyllithium did not yield the anticipated diacetylene (39). From diketone (37) a series of 7,12-disubstituted bridged [12]annulene can be synthesized, this illustrating the generality of this approach.
MULTIFERROIC AND CORE-SHELL NANOSTRUCTURES - ADVANCES IN PREPARATIONS AND NOVEL PROPERTIES
Year of Dissertation:
2010
This dissertation reports the research findings in two nanoscience areas: (i) facile methods for the preparation of multiferroic bismuth ferrites nanoparticles and the observation of room temperature magnetoelectric coupling and optically induced magnetic and electric orderings in BiFeO3 (BFO) thin film; (ii) preparation and characterization of core-shell nanomaterials based on conducting polymer as components for shell and core. Controlled cargo release from the core as well as from the shell surface was examined for nanospheres with conjugate polymer shell. An unusual enhanced electric polarization was observed for nanospheres with high-k strontium titanate (STO) nanocrystals embedded in conductive polyaniline (PANI) matrix.
Synthesis of Drug/Dye Incorporated Copolymer-Protein Hybrids and Novel Curcumin Derivatives for Imaging and Therapeutic Applications.
Year of Dissertation:
2010
Advisor:
Krishnaswami Raja
This thesis describes novel synthetic methodologies towards: (a) novel polymer-protein hybrids with a significantly increased number of functional units attached per protein and (b) the synthesis of curcumin derivatives with increased solubility and amplified bioactivity.
Probing Reaction Dynamics in Complex Gas-Phase Systems Using Guided-Ion-Beam Scattering and Computational Methods
Year of Dissertation:
2013
An electrospray ionization (ESI) guided-ion-beam tandem mass spectrometer was developed in our research lab, including vacuum systems, electronics and instrument control and data acquisition (DAQ) systems using LabVIEW programming. Capitalizing on this instrument, two experimental projects have been accomplished as described below.
SYNTHESIS, CRYSTAL GROWTH AND CHARACTERIZATION OF PHOSPHIDES, SELENIDES, SULFIDES AND OXIDES
Year of Dissertation:
2010
The desire to build smaller, faster, inexpensive electronics has prompted researchers to exploit electron "spin" in transistors. Spin in semiconductors offers a pathway towards integration of storage and processing in a single material. These "spintronic" transistors
GROUND- AND EXCITED-STATE CHEMISTRY OF [BIS(2,2'-BIPYRIDINE)(2-(2-PYRIDYL)PYRAZINE) RUTHENIUM(II)]: PROTONATION AND COORDINATION
Year of Dissertation:
2012
Ruthenium(II) diimines have been extensively studied for their notable photo physical properties. Of particular interest are compounds with ligands with peripheral base sites, where the metal-to-ligand charge transfer shifts electron density onto the ligand yielding an emissive state of increased in basicity. One well known example of such complexes, (bis(2,2'-bipyridine) (2-3-bis(2-pyridyl) pyrazine) ruthenium(II), [Ru(bpy)2dpp]2+, has been studied extensively, yet questions remained regarding the sequence of protonation steps at the two peripheral dpp nitrogens in the ground and excited states and the magnitude of the photo-induced change in acid-base properties at each site. In order to reach a deeper understanding of the kinetic and thermodynamic steps involved in its protonation and coordination, a similar complex was synthesized and studied, (bis(2,2'-bipyridine) (2-(2-pyridyl) pyrazine) ruthenium(II), [(bpy)2Ru(pypz)]2+. The alternative ligand is identical in almost every respect to dpp except for the absence of the free pyridyl ring and the fact that it has only one possible protonation site instead of two. The pypz ligand, thus, represents an ideal candidate to elucidate how the pyrazinyl nitrogen on the coordinated dpp would behave if the additional pyridyl ring on dpp was not present. The differences and similarities in the properties of [(bpy)2Ru(pypz)]2+ and [Ru(bpy)2dpp]2+ in the same environment are highlighted here, describing the peculiar behavior of the acid-base sites of each complex upon excitation and their role in protonation reactions and coordination reactions to d10 metals, namely zinc.
BIOPHYSICAL STUDIES OF MOLECULAR RECOGNITION IN PERIPHERAL AND INTEGRAL MEMBRANE PROTEINS
Year of Dissertation:
2012
The molecular interactions of peripheral and integral membrane proteins with ligands and model biological membranes play important roles in the regulation of human nutrition, cell signaling, and other physiological processes. In the current study, we have used solution- and solid-state nuclear magnetic resonance (NMR) and computational modeling methods to study the interactions of fatty acid-binding proteins (FABPs) with ligands and membrane mimetics, and to examine the conformation of a transmembrane peptide fragment of the Ste2p G protein-coupled receptor (GPCR) in lipids.
Synthesis of Biologically important C-glycoinositols
Year of Dissertation:
2009
Glycosylinositol subunits comprise important glycoproteins on eurkayotic cell membranes and oligosaccharide components of the cell wall of mycobacteria. Glycosylinositols are also believed to function as secondary messengers in cellular processes, such as the mediation of insulin action. Analogues of glycoinositols in which the ring or glycosidic oxygen of the acetal residue is replaced with a methylene group (C- and carba- glycoside respectively), have attracted interest as mechanistic probes because of their greater hydrolytic stability and different conformational behavior compared with the native O-glycosides.
Design of Ultra-large-pore Ordered Mesoporous Silicas and Grafting of Organic Groups on Their Surfaces
Year of Dissertation:
2012
Developing novel methods to synthesize ordered mesoporous silicas with ultra-large pores and exploring robust approaches to functionalize their surfaces are two attractive topics in material science. Focused on these two aspects, this dissertation includes the selection of swelling agents for the synthesis of ordered mesoporous silicas templated by commercially available surfactants, and the development of diverse surface modification strategies to graft functional molecules on the surface of ordered mesoporous silicas.