Synthesis of novel polyhedral borane and carborane derivatives with applications in materials science and medicine.

摘要

Chapter 1. The alkylation of [closo-B 12(OH)12]2- using fourteen alkyl- and aralkyl halides and two p-toluenesulfonic acid esters was investigated. The dodeca-(alkoxy)-closo-dodecaborate products, [ closo-B12(OR)12]2-, and their hypercloso two-electron oxidation products were explored. Several oxidizing reagents were investigated for the chemical oxidation of [closo-B 12(OR)12]2- and [hypercloso-B 12(OR)12]- to [hypercloso-B 12(OR)12]. Both FeCl3·6H2O and K3Fe(CN)6 were found to be the reagents of choice. The use of elevated reaction temperatures attained by employing an autoclave led to drastic reductions in reaction times and increased efficiency. X-ray diffraction studies of substituted dodecabenzyl ether derivatives were also investigated.;Chapter 2. The electronic and spectroscopic properties of [B12(OR)12]n (where n= -2, -1 and 0) were explored. Half-wave potentials for the (-2/-1) and (-1/0) redox reactions range from -0.73 to -0.06 and -0.21 to +0.49 volts, respectively, versus a standard hydrogen electrode. A Hammett linear free-energy analysis was performed on the substituted benzyl ether closomers. Furthermore, a linear correlation between hydrophobicity and molar refractivity substituent descriptors and the redox potential of alkyl, allyl and benzyl closomers was demonstrated. Peak separation for each redox process of alkyl closomers was analyzed, revealing electron transfer to be inversely proportional to substituent length. UV/Vis spectroscopy revealed unique absorbances for each closomer according to the oxidation state.;Chapter 3. Transthyretin (TTR), a thyroxine-transport protein found in the blood, has been implicated in a variety of amyloid related diseases. Previous investigations have identified a variety of non-steroidal anti-inflammatory drugs (NSAIDs), which can imbue kinetic stabilization to TTR, inhibiting dissociation and subsequent aggregation to the toxic amyloid fibrils. Cyclooygenase (COX) activity associated with NSAIDs limits their potential as a long-term therapy for TTR-associated amyloid diseases. Replacement of a phenyl ring in the NSAIDs with a carborane moiety greatly decreases the COX activity while retaining similar efficacy as an inhibitor of TTR dissociation.;Chapter 4. A novel homotrifunctional conjugation reagent, 1,3,5-tris-(N-maleimidomethyl) benzene, was synthesized in high yield. Its reactivity was examined by using L-cysteine as a nucleophile. Its utility was validated through trimerization and then crystallization of T4 lysozyme. The ability to produce crystals in two days could make this reagent a valuable tool for protein crystallization.