Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / Vita. / Includes bibliographical references. / Liquid water is a fascinating substance, ubiquitous in chemistry, physics, and biology. Its remarkable physical and chemical properties stem from the intricate network of hydrogen bonds that connect molecular participants. The structures and energetics of the network can explain the physical properties of the substance on macroscopic length scales, but the events that initiate many chemical reactions in water occur on the time scales of [similar to] 0.1 - 1 picosecond. The experimental challenges of measuring specific molecular motions on this time scale are formidable. The absorption frequency of the OH stretch of HOD in liquid D₂0 is sensitive to the hydrogen bonding and molecular environment of the liquid. Ultrafast IR experiments endeavor to measure fluctuations in the hydrogen bond network by measuring spectral fluctuations on femtosecond time scales, but the data do not easily lend themselves to a direct microscopic interpretation. Computer simulations of empirical models, however, offer explicit microscopic detail but must be adapted to include a quantum mechanical vibration. I have developed methods in computer simulation to relate spectral fluctuations of the OH stretch in liquid D₂0 to explicit microscopic information. The experiments also inform the simulation by providing important quantitative data about the fidelity and accuracy of a chosen molecular model, and help build a qualitative picture of hydrogen bonding in water. Our atomistic model reveals that ultrafast experiments of HOD in liquid D₂0 measure transient fluctuations of the liquid's electric field. On the fastest time scales, localized fluctuations drive dephasing, while on longer time scales larger scale molecular reorganization destroys vibrational coherence. / (cont.) Because electric fields drive vibrational dephasing, the frequency of the OH stretch is particularly sensitive to the microscopic details of the molecular potential. With collaborators, I have examined the accuracy of emerging fluctuating charge models for water and the role that molecular polarizability plays in the vibrational spectroscopy. In liquid water at ambient conditions, roughly 90 % of the hydrogen bonds are intact. I have examined the fates and the fundamental chemical nature of the remaining 10 % of the "broken" hydrogen bonds. We consider two reaction mechanisms that describe how hydrogen bonds change partners. In the first scenario, broken hydrogen bonds exist in stable chemical equilibrium with intact hydrogen bonds. In an alternate scenario, the broken hydrogen bond is not a meta-stable chemical state but instead a species that molecules visit during natural equilibrium fluctuations or when trading hydrogen bonding partners. I show how the methods of condensed phase reaction dynamics can be directly applied to vibrational spectroscopy of reactive systems and how experimental 2D IR spectra can distinguish between the two mechanistic scenarios. Our data support the notion that broken hydrogen bonds are an intrinsically unstable species in water and return to form hydrogen bonds on the time scale of intermolecular motions. / by Joel David Eaves. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references. / In this thesis, chemiresistive devices for the detection of volatile organic compounds to include chemical warfare agents are developed. Active sensing materials were produced by crafting composites of synthetic polymers and single walled carbon nanotubes. Sensitivity to and selectivity for target analytes were augmented by the introduction of molecular recognition elements into polymer side chains or by the addition of additives into a polymer/single walled nanotube composite. Additionally, methods to create n-type single walled carbon nanotubes through covalent side wall functionalization were explored. Chapter 1: Chemiresistive sensors are becoming increasingly important as they offer an inexpensive option to conventional analytical instrumentation, they can be readily integrated into electronic devices, and they have low power requirements. Nanowires (NWs) are a major theme in chemosensor development. High surface area, inter-wire junctions, and restricted conduction pathways give intrinsically high sensitivity and new mechanisms to transduce binding or action of analytes. This chapter details the status of NW chemosensors with selected examples from the literature. We begin by proposing a framework for understanding electrical transport and transduction mechanisms in NW sensors. Next, we offer the reader a review of device performance parameters. Then, we consider the different NW types followed by a summary of NW assembly and different device platform architectures. Subsequently, we discuss NW functionalization strategies. Finally, we propose a roadmap for future developments in NW sensing that addresses selectivity, sensor drift, sensitivity, response analysis, and emerging applications. The NW field is still in its infancy, and continuing advances present abundant opportunities. Chapter 2: Chemical warfare agents (CWA) continue to present a threat to civilian populations and military personnel in operational areas all over the world. Reliable measurements of CWAs are critical to contamination detection, avoidance, and remediation. The current deployed systems in United States and foreign militaries, as well as those in the private sector offer accurate detection of CWAs, but are still limited by size, portability and fabrication cost. Herein, we report a chemiresistive CWA sensor using single-walled carbon nanotubes (SWCNTs) wrapped with poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives. We demonstrate that a pendant hexafluoroisopropanol group on the polymer that enhances sensitivity to a nerve agent mimic, dimethyl methylphosphonate, in both nitrogen and air environments to concentrations as low as 5 ppm and 11 ppm, respectively. Additionally, these PEDOT/SWCNT derivative sensor systems experience negligible device performance over the course of two weeks under ambient conditions. Chapter 3: The detection of alkylating agents using carbon nanotube chemiresistive devices has confounded researchers in the sensor field for quite some time. In this work, we address this quandary by fabricating a chemiresistive device consisting of poly(4-vinylpyridine)/single walled carbon nanotube/lithium bromide composites that is able to detect gaseous ethylene oxide (EtO) and a mustard agent simulant, 2-chloroethyl ethylsulfide (CEES). Our devices were sensitive to EtO and CEES down to 1048 ppm and 33 ppm, respectively. We calculated theoretical detection limits of 212 ppm for EtO and 10 ppm for CEES. These results should encourage researchers in the field to tackle analytes once thought to be undetectable via carbon nanotube chemiresistive devices, as they offer a low cost and low power alternative to current options. Chapter 4: The covalent functionalization and characterization of single walled carbon nanotubes (SWCNTs) by dihalocarbenes and the trifluoromethylating Togni's reagent is explored in this chapter. Covalent functionalization reactions were performed to increase the SWCNT solubility, imparting n-type semiconducting behavior while maintaining the native conductivity of the conjugated sp² network. Previous computational studies predicted the conservation of the electrical conductivity of SWCNTS after carbene additions, but experimental work to verify the electrical properties has not been performed. In the studies presented herein, we utilized five different covalent functionalization methods to modify SWCNTs and utilized X-ray photoelectron spectroscopy (XPS) in tandem with Resonance Raman spectroscopy to characterize our products. Though electrical characterization was not performed, we improved upon literature methods concerning the dichlorocarbene addition of -CCl₂ groups to pristine SWCNTs. / by John F. Fennell Jr. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003. / Vita. / Includes bibliographical references. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Several methodological developments and applications of multidimensional solid-state nuclear magnetic resonance to biomolecular structure determination are presented. Studies are performed in uniformly 3C, 15N isotope labeled samples with magic-angle spinning for optimal resolution and sensitivity. Frequency selective rotational-echo double-resonance (FSR) and three-dimensional transferred-echo double-resonance (3D TEDOR) methods for carbon-nitrogen distance measurements in (U-'3C,S5N)-labeled peptides and proteins are described. FSR employs frequency selective Gaussian pulses in combination with broadband REDOR recoupling to measure dipolar couplings based on the isotropic chemical shifts of the selected 13C-15N spin pairs. The experiment is demonstrated in model peptides, N-acetyl-L-Val-L-Leu and N-formyl-L-Met-L-Leu-L-Phe, where multiple distances in the 3-6 A range are determined with high precision, and in a membrane protein, bacteriorhodopsin, where the distances between aspartic acids Asp-85 and Asp-212 and the retinal Schiff base nitrogen are measured in the active site. The 3D TEDOR methods employ 13C and 15N chemical shift dimensions for site-specific resolution and encode the distance information in the buildup of cross-peak intensities, allowing multiple distances to be measured simultaneously. The methods are demonstrated in N-acetyl-L-Val-L-Leu and N-formyl-L-Met-L-Leu-L-Phe, where 20 and 26 distances up to 6 A are determined, respectively. The molecular conformation of peptide fragment 105-115 of transthyretin in an amyloid fibril is investigated. / (cont.) Complete sequence-specific 13C and 15N backbone and side- chain resonance assignments are obtained using two-dimensional 13C-13C and 15N-13C-3C chemical shift correlation experiments. Backbone torsion angles are measured directly using three-dimensional dipolar-chemical shift correlation experiments, which report on the relative orientations of 3C-15N, 3C-1H and 15N-'H dipolar tensors, and intramolecular 13C-15N distances in the 3-5 A range are determined using 3D TEDOR, resulting in about 60 constraints on the peptide structure. An atomic-resolution structure of the peptide consistent with the NMR constraints is calculated using simulated annealing molecular dynamics, and the results indicate that the peptide adopts an extended β-strand conformation in the fibril. / by Christopher Peter Jaroniec. / Ph.D.

Thesis: Ph. D. in Physical Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student-submitted PDF version of thesis. Page 144 blank. / Includes bibliographical references (pages 127-143). / Visualizing structures deep within biological tissue is a central challenge in biomedical imaging, with both preclinical implications and clinical relevance. Using shortwave infrared (SWIR) light enables imaging with high resolution, high sensitivity, and sufficient penetration depth to noninvasively interrogate sub-surface tissue features. However, the clinical potential of this approach has been largely unexplored. Until recently, suitable detectors have been either unavailable or cost-prohibitive. Additionally, clinical adoption of SWIR imaging has been inhibited by a poor understanding of its advantages over conventional techniques. For fluorescence imaging in particular, there has further been a perceived need for clinically-approved contrast agents. Here, taking advantage of newly available detector technology, we investigate a variety of biomedical applications with SWIR-based imaging devices. We describe the development of a medical otoscope and our clinical observations using this device to evaluate middle ear pathologies in both adult and pediatric populations, showing that SWIR otoscopy could provide diagnostic information complementary to that provided by conventional visible otoscopy. We further describe fluorescence detection of an endogenous disease biomarker in animal models including nonalcoholic fatty liver disease and cirrhotic liver models and models of a neurodegenerative disease pathway. While this biomarker has been known for decades, we describe a method for its noninvasive detection in living animals using near infrared and SWIR light, as opposed to its conventional ex vivo detection. Furthermore, we show that SWIR image contrast and penetration depth are primarily mediated by the absorptivity of tissue, and can be tuned through deliberate selection of imaging wavelength. This understanding is crucial for rationally determining the optimal imaging window for a given application, and is a prerequisite for understanding which clinical applications could benefit from SWIR imaging. Finally, we show that commercially-available near infrared dyes, including the FDA-approved contrast agent indocyanine green, exhibit optical properties suitable for in vivo SWIR fluorescence imaging, including intravital microscopy, noninvasive, real-time imaging in blood and lymph vessels, and tumor-targeted imaging with IRDye 800CW, a dye being tested in clinical trials. Thus, we suggest that there is significant potential for SWIR imaging to be implemented alongside existing imaging modalities in the clinic. / by Jessica Ann Carr. / Ph. D. in Physical Chemistry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2005. / Vita. / Includes bibliographical references. / Mesomorphic organizations provide a powerful and efficient method for the preorganization of molecules to create synthetic materials with controlled supramolecular architectures. Incorporation of polymerizable groups within a liquid crystalline template can set the stage for the synthesis of anisotropic molecular networks. This dissertation details the synthesis and characterization of chiral liquid crystals and crosslinked polymer networks, with an eye toward applications in asymmetric catalysis. Chapter One gives an introduction to the study of liquid crystals and their phases. Chapters Two and Three describe the incorporation of terminal olefins as polymerizable groups within a columnar liquid crystalline template as an effective method for the synthesis of robust, anisotropic polymeric materials. Upon in situ acyclic diene metathesis (ADMET) polymerization, the original mesophase order is retained. Chapter Two involves the room temperature polymerization of iron(III) tris(diketonate) liquid crystals, resulting in densely crosslinked materials. The focus of Chapter Three is the polymerization of dioxomolydenum-based liquid crystals, performed at high temperature, and their potential to serve as catalysts for asymmetric epoxidation. In Chapter Four, a different approach towards the synthesis of catalytically active anisotropic materials is taken, incorporating well-established, transition metal catalysts within a liquid crystalline framework. Progress towards the formation of liquid crystal phases containing C₂- symmetric bis(oxazoline) and pincer ligands is detailed. Finally, Chapter Five describes the immobilization of chiral monodentate oxazoline ligands for use as catalysts in asymmetric cyclopropanation. Preliminary results indicate that the heterogeneous system gives higher enantioselectivities than the analogous homogeneous system. / by Karen Villazor Martin. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Includes bibliographical references. / This thesis addresses challenging aspects of drug design that require explicit consideration of more than a single drug-target interaction in an unchanging environment. In the first half, the common challenge of designing a molecule that recognizes a desired subset of target molecules amidst a large set of potential binding partners is explored. Using theoretical approaches and simulation of lattice-model molecules, relationships between binding specificity and molecular properties such as hydrophobicity, size, and conformational flexibility were achieved. Methods were developed to design molecules and molecular cocktails capable of recognizing multiple target variants, and some were integrated with existing methods to design drug cocktails that were predicted to inhibit seven variants of HIV-1 protease. In the second half of the thesis, computational modeling and designs that were used to understand how cytokine binding and trafficking events affect potency are described. A general cellular-level model was systematically explored to analyze how signaling and trafficking properties can help dictate a cytokine-receptor binding affinity appropriate for long-term potency. / (cont.) To help create an accurate cellular-level model of signaling and trafficking for one system in particular, the erythropoietin (Epo) system, we computationally designed mutant erythropoietin receptor (EpoR) molecules for use as experimental probes. By mutating a residue predicted to contribute to pH-dependent Epo-EpoR binding, reagents were designed to facilitate study of endosomal binding and trafficking. Furthermore, a pair of mutant Epo receptors was designed to form a specific, heterodimeric complex with Epo to facilitate study of each individual EpoR's role in signaling via the asymmetric Epo-(EpoR)2 complex. / by Mala Lakshmi Radhakrishnan. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Includes bibliographical references (leaves 133-137). / by Natasha M. Kablaoui. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996. / Includes bibliographical references. / by Stephani Ann Brandt Solina. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / Includes bibliographical references (leaves 198-208). / This thesis describes the construction of a novel, low-noise laser kinetics spectrometer. A quasi-CW (picosecond pulse), tunable Ti:Sapphire laser is used to detect various transient species in laser flash photolysis kinetics experiments via direct absorption. The spectral range of the laser, when used with a harmonic generator, covers most of the visible wavelength region, allowing for the detection of a wide array of organic radical species. Paired with a temperature-and pressure-controlled flow reactor equipped with a Herriott-type optical multiple pass cell, transient absorptions of ~0.0001 can be measured, corresponding to cross section - concentration products of less than 1x10-7 cm". The flexibility and high sensitivity of this instrument allows direct and accurate measurement of many important transient intermediates in combustion and atmospheric chemistry.Using this instrument, we report the self-reaction rate coefficient of vinyl and allyl radicals. Vinyl iodide and allyl iodide are used as precursors to generate respective radicals via laser-flash photolysis at 266 nm. Second order chemical reactions require an accurate determination of the initial radical concentration, which we determined using direct laser absorption by I atom at 1315 nm. The current study finds the self-reaction rate constant for vinyl radical to be more than a factor of two slower than previous studies and allyl self reaction rate constant to be 50% faster than values reported in the literature. The absorption cross sections of the vinyl radical at 404, 423.2, & 445 nm and allyl radical at 404 & 408 nm are also determined. This thesis also reports measurements of rate coefficients for the reaction of vinyl radical with various alkenes: ethylene, propene, isobutene, 1-butene, and 2-butene,performed over a temperature range of 300 K to 700 K at 100 Torr. The measured vinyl radical disappearance rates compare well with ab initio quantum calculations. The combined measurements and calculations provide improved estimates for other vinyl + alkene reactions. / by Huzeifa Ismail. / Ph.D.

Thesis: Ph. D. in Physical Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 185-232). / Organic photovoltaics (OPVs) and organic light-emitting diodes (LEDs) are organic optoelectronics offering a number of unique benefits that may play an important role in the future of clean energy generation and efficient energy consumption. In this thesis, we explore key electronic processes in OPVs and OLEDs, with a major focus on quantum-mechanical kinetic modeling of magnetic field effects (MFEs) that probe underlying subprocesses. Certain organics are capable of dividing excited states in a process termed singlet fission, which can increase the maximum theoretical efficiency of an OPV by a factor of nearly 1/3. The MFEs on photocurrent measurements from our collaborators are combined with theoretical models to determine optimal device architectures for singlet fission OPVs, allowing us to exceed the conventional limit of one electron per photon. We also use MFEs to determine the spin of charge transfer states most efficient at generating photocurrent and demonstrate microscopic insight into the mechanism of their diffusion, offering new design principles for the engineering of donor-acceptor interfaces in OPVs. Thermally activated delayed fluorescence (TADF) is becoming an increasingly important OLED technology that extracts light from non-emissive triplet states via reverse intersystem crossing (RISC) to the bright singlet state. We use MFEs to prove a rather surprising finding that in TADF materials composed of donor-acceptor bends, the electron-hole distance fluctuates as a function of time, resulting in spontaneous cycling between states that are advantageous to fluorescence at one moment and then advantageous to RISC at another. Combined with additional topics in the fields of metal organic frameworks and reaction pathfinding methods, the work in this thesis provides insight into how to achieve optimal performance in OPV and OLED devices, which may serve an important role in the future of our energy landscape. / by Eric Richard Hontz. / Ph. D. in Physical Chemistry