<p> Semiconducting quantum dots (QDs) exhibit tunable size dependent properties, leading some to designate these materials as &ldquo;artificial atoms&rdquo;. Synthetic methods of CdSe QDs have been highly refined and typically involve one-pot seeding and growth, resulting in the generation of colloidal crystallites ranging in diameter from ~1nm to ~6nm and with size distributions as low as 10%. Several reports describe the observation of &ldquo;magic size&rdquo; QDs during the early stages of growth, characterized by a stepwise increase in QD size&mdash;as opposed to the typically-observed continuous growth of QD sizes. While postulated to result from QD structures of energetic stability, evidence of the nature of stable structures is limited in experiment by microscopy and in computational simulation by the sheer number of electrons present within even the smallest of QDs. This work highlights a new computational approach toward treatment of QD behavior that forgoes quantum mechanical (electronic state) information in lieu of computational speeds many orders of magnitude faster than ab initio methods. The modification of traditional charge equilibration (qEQ) methods to also account for the unique dielectric environment experienced by a QD during its synthesis (QD-qEQ) yields an approach that is fast and atomistic, providing rich information about the partial charge of each atom in the system at energetic equilibrium. When applied to a structure-set of 35,000+ unique wurtzite CdSe QDs with diameters &le; 2.50 nm, energetic depressions are apparent at certain QD sizes, which agree generally with the sizes at which CdSe magic size QDs have been reported experimentally. Further, analysis of QD surface characteristics associated with such magic sizes yield surfaces made up of highly coordinated and relatively low energy atoms, suggesting that the magic size phenomenon is due to a thermodynamic stability afforded by certain QD surface atom arrangements. The accuracy and versatility of QD-qEQ positions this method as a potential candidate for simulation of QD properties at much larger scales, an intractable problem with traditional computational methods.</p><p>

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2012. / In title on title-page, "[beta]" appears as the lower-case Greek letter. Cataloged from PDF version of thesis. / Includes bibliographical references. / The electrochemical splitting of water into hydrogen and oxygen has been proposed as an alternative means to store electrical energy. The limiting aspect of this reaction is the oxygen forming reaction, which can be catalyzed by transition metal species with varying degrees of efficiency. This thesis examines the characteristics of oxygen bonding that complicate the 0-0 bond formation reaction, and examines ligand platforms that can stabilize high valent metal oxo intermediates. Siloxide ligands were used to generate a series of 4-coordinate Cr, Mn, Fe, and Co complexes, but these could not support the corresponding high valent oxo species. Instead, a remarkably stable 4-coordinate Crv tetrasiloxide complex was isolated. Chelating triamide ligands were explored, which might generate pseudotetrahedral metal oxo species, but complexes of various metal ions could not be reliably isolated. Planar bis-pdiketiminate (NacNac) complexes were synthesized by reaction of acetonitrile with Fe and Co mesityl species. The Co complex undergoes a ligand centered oxidation event to yield the first structurally characterized NacNac radical cation. In contrast to known redox noninnocent ligand platforms, no significant changes in C-C or C-N bond lengths are observed by X-ray crystallography. DFT calculations and the electronic and structural characterization of the oxidized and reduced Co complex confirm these conclusions. / by Michael Pesek Marshak. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013. / 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. / Includes bibliographical references. / The niobium-phosphorus triple bond in [P=-Nb(N[Np]Ar)3]- (Np = CH2tBu; Ar = 3,5-Me2C6H3) has produced the first case of P4 activation by a metal-ligand multiple bond. Treatment of P4 with the sodium salt of the niobium phosphide complex in weakly-coordinating solvents led to the formation of the C3-symmetric cyclo-P3 anion, while in THF, it led to the formation of the cyclo-P5 anion [(Ar[Np]N)([eta]4-P5)Nb(N[Np]Ar)2]-. The latter represents a rare example of a substituted pentaphospha-cyclopentadienyl ligand and may be interpreted as the product of trapping an intermediate h5-P5 structure through the migration of one anilide ligand. A search for methods of activating P4 that avoid tedious metal-mediated steps led to the discovery of an incredibly simple procedure involving only commercial reagents. Irradiation of solutions containing P4 and readily available 1,3-dienes produced bicyclic organic diphosphanes in an atom-economical, one-step protocol. Use of 2,3-dimethylbutadiene allowed the isolation of the bicyclic diphosphane P2(C6H10)2 in gram-quantities, but other dienes such as 1,3-butadiene, isoprene, 1,3-pentadiene, and 1,3-cyclohexadiene also provided evidence for incorporation of P2 units via double Diels-Alder reactions. Theoretical investigations provided support for the formation of P2 molecules from photo-excited P4. Investigations into the physical and chemical characteristics of P2(C6H10)2 uncovered an unprecedented stability towards cleavage of the P-P bond relative to other diphosphanes. P2(C6H10)2 exhibits a flexible, yet robust bicyclic framework containing lone pairs disposed at an angle of ca. 45°, and proved to be ideally suited to form multiple bridges between two metal centers. Dinuclear complexes containing tetrahedral, zero-valent group 10 metals bridged by three diphosphane ligands were investigated in detail. These contain D3h-symmetric {M2P6} barrelene cages with metal-metal distances of 4 Å , and exhibited substitution reactions where the cages remain intact. Alternatively, diphosphane P2(C6H10)2 allowed for unprecedented selectivity towards functionalization of a single phosphorus lone pair. Additional functionalization proceeds at a significantly slower rate, thus enabling the selective isolation of various phosphoranes (EP2(C6H10)2 and E2P2(C6H10)2; E = O, S, N-R). Metalation reactions with the bulky diiminodiphosphorane ligand (MesN)2P2(C6H10)2 allowed for multiple metal complexes, showing that such ligands provide an attractive pre-organized binding pocket for transition metals, as well as post-transition metals. / by Daniel Tofan. / Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / Includes bibliographical references. / The use of the ketone biotin - benzophenone-biotin hydrazide system for detecting the formation of cyan fluorescent protein and NF-kappaB p50 dimers was assessed. A series of benzophenone-based probes were synthesized and tested for photocrosslinking activity to investigate the efficiency of photocrosslinking in these systems. Three series of small molecule probes were synthesized for the selection of ribozymes from a random sequence pool. Solid-phase immobilized fluorescein and fluorescein phosphates were synthesized for the indirect selection of a fluorescein phosphatase ribozyme. A corresponding thiophosphate analog was created for the in-gel selection of a thiophosphatase ribozyme via APM-PAGE. Finally, a series of fluorescein-nucleoside phosphate conjugates was designed and synthesized for use in the solution phase preparation of a fluorogenic ribozyme substrate, and later immobilization of this substrate on a silyl resin for direct ribozyme selection. / by Jeremy Adam Ryan. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996. / Includes bibliographical references. / by Erik Meyer. / Ph.D.

Thesis (Ph. D. in Biological Chemistry)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references. / Viruses are a major cause of human morbidity and mortality in the world. New effective approaches to stop their spread are paramount. Herein, two approaches toward this goal are explored: (i) developing multivalent therapeutics (multiple copies of an antiviral agent covalently attached to a polymeric chain) with superior potency against their viral targets, and (ii) creating antiviral surface coatings that detoxify aqueous solutions containing various viruses on contact. By harnessing the power of multivalency we endeavored to improve the potency of influenza inhibitors, as well as resurrect the potency of two FDA-approved influenza inhibitors for which widespread drug resistance now exists. In the former direction of research, we attached multiple copies of bicyclic naphthoquinone-like monomeric inhibitors to polymeric chains. When tested against the Wuhan strain of influenza, these multivalent conjugates were up to 240- fold more potent inhibitors than their monomeric predecessors. However, this improvement in potency was strain-dependent, as two other serotypically-different influenza strains were not inhibited nearly as well by multivalent inhibitors. This strategy was also employed to restore inhibition for the adamantane class of influenza inhibitors against drug-resistant strains. The chemical modifications to the adamantane scaffold necessary for polymer attachment imposed deleterious steric constraints which resulted in poorer inhibitory effect. Even despite these drawbacks, however, the drug-polymer conjugates were up to 30-fold more potent against drug-resistant strains than their monomeric counterparts. These efforts made strides toward the ultimate goal of recovery of influenza virus inhibition for the adamantanes. To diminish transmission of viral infections, we explored the action of antimicrobial PEIbased (PEI = polyethylenimine) hydrophobic polycations against both enveloped and nonenveloped viruses. When solutions containing herpes simplex viruses (both 1 and 2) were brought in contact with NN-dodecyl,methyl-PEI coated on either polyethylene slides or latex condoms, they could be disinfected by up to 6-logs of viral titers. Our hydrophobic polycation also could be formulated into a suspension to disinfect herpes simplex virus-containing solutions, suggesting potential utility in a therapeutic modality. We also investigated whether these findings were applicable to non-enveloped viruses, namely poliovirus and rotavirus. Aqueous solutions containing them indeed could be drastically disinfected by our hydrophobic polycation-coated slides; subsequent mechanistic studies suggested that this disinfection was due to adsorption of the viruses onto the coated surfaces from solution. / by Alyssa Maxine Larson. / Ph.D.in Biological Chemistry

Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, February 2015. / Cataloged from PDF version of thesis. "February 2015." / Includes bibliographical references (pages 61-65). / Multi-modality and stimuli responsive nanoparticles are promising platform materials for medical imaging and diagnostics. Specifically magnetic resonance imaging (MRI) and nearinfrared (NIR) fluorescent probes can be used in combination to visualize biodistribution and in vivo clearance rates. We reasoned that through the use of a nitroxide radical MRI contrast agent along with a NIR fluorophore it would be possible to study these phenomena along with nitroxide reduction in vivo. Thus, we have developed branched bottlebrush copolymers that display compensatory fluorescence response to nitroxide reduction that enables correlation of MRI contrast, fluorescence intensity, and spin concentration in tissues. These polymers were synthesized by ring-opening metathesis copolymerization of two new branched macromonomers: one carries a bis-spirocyclohexyl nitroxide and the other the NIR dye Cy5.5. Promising preliminary results with the resulting polymers in solution MRI and NIR imaging studies as well as in vitro toxicity led us to explore the potential of these materials for in vivo applications. Though nitroxide agents are promising organic agents for MRI applications, clinically, gadolinium-based MRI contrast agents are most common due to their high relaxivity and relatively low toxicity when bound to chelating ligands. We have also explored the idea of incorporation of gadolinium agents into our branched bottlebrush copolymer platform through the design of Gd-based branched macromonomers. While the fluorescence redox effects described in the nitroxide system above would not be applicable, chelated Gd could be used in much smaller concentration to provide similar MRI contrast. In this way, a small percentage of Gd could be added as an MRI tag to any polymer synthesized by ROMP. A natural extension of the work described above is the incorporation of cellular targeting moieties for tissue-selective imaging. Toward this end, we propose the incorporation of known cellular targeting ligands onto the surface of branched bottlebrush polymers through the synthesis of end-functionalized branched macromonomers. The synthesis of several targeting ligands is described, alongside synthesis and characterization of positively charged nanoparticles for improved cellular uptake and ionic coordination of hyaluronic acid or other negatively charged polymers. / by Molly A. Sowers. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1994. / Includes bibliographical references. / by Jeremy D. Selengut. / Ph.D.

Massachusetts Institute of Technology. Dept. of Chemistry. Thesis. 1974. Ph.D. / MICROFICHE COPY ALSO AVAILABLE IN SCIENCE LIBRARY. / Vita. / Includes bibliographical references. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 125-129). / This thesis describes the development and application of fast flow solid phase synthesis for the preparation of peptides and phosphorodiamidate morpholino oligomers (PMOs), as well as the application of fast, reliable peptide synthesis to study non-natural protein folding and function. In the first chapter, solid supported peptide synthesis was accelerated using flow by continuously delivering preheated solvents and reagents to the solid support at high flow rate, thereby maintaining maximal concentrations, quickly exchanging reagents, and eliminating the need to heat reagents after they were added to the vessel. In the second chapter, these chemical principles were expanded upon and mechanical challenges particular to accelerated solid phase synthesis were overcome to build a fully automated fast flow peptide synthesizer than incorporates amino acids in as little as 40 seconds each. First, mechanical systems were developed to rapidly switch between the many reagents needed for peptide synthesis while maintaining the proper stoichiometry of all reaction components at all times. Second, conditions under which reagents did not appreciably degrade during storage or synthesis were found. Finally, synthetic outcomes were substantially improved by increasing temperature without degrading the protected, resin bound peptide. The third chapter describes the expansion of fast flow synthesis to PMOs. A 10-fold acceleration of PMO synthesis was realized using mechanical systems adapted from chapter 1, increasing the reaction temperature to 90°C, and introducing a Lewis acid catalyst. The acidity of the deprotection reagent was reduced to prevent cleavage of the backbone during 3' detritylation. In the final chapter, a "D-scan" of two small proteins, the disulfide-rich Ecballium elaterium trypsin inhibitor II (EETI-II) and a minimized Z domain of protein A (Z33), is reported. For each protein, the chirality of one amino acid at a time was inverted to generate a series of diastereomers, and study the critical stereocenters of EETI-I and Z33. Twelve out of 30 EETI-II analogs folded and were high-affinity trypsin inhibitors, but most active analogs were less stable to reduction than EETI-II. Similarly, twelve Z33 analogs retained high binding affinity to IgG, but most were substantially less stable than WT-Z33. / by Mark David Simon. / Ph. D.