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dc.contributor.advisor Drueckhammer, Dale G en_US Liang, Xiaofei en_US
dc.contributor.other Department of Chemistry en_US 2017-09-20T16:51:45Z 2017-09-20T16:51:45Z 2016-12-01
dc.identifier.uri en_US
dc.description 173 pg. en_US
dc.description.abstract As(III) compounds have high affinity for thiol groups and this affinity has been used in the prior development of FlAsH and related tags for cysteine peptides. We aimed to develop a series of arsenic-based receptors designed to bind to different arrangements of cysteines within native alpha-helical protein structures. Computer modeling was used to define the proper arrangement of arsenic functionality for binding to each targeted sequence. The computer program HostDesigner was then used to discover scaffold structures on which to display the arsenic functionality at the proper distance and relative orientation to bind the targeted sequence. Designed structures were then targeted for synthesis. The synthetic approach to initial probes was based on reaction of a dihaloalkyl-arsenic (III) or related reagent with one equivalent of an organolithium or Grignard reagent. This approach failed due to lack of selectivity for displacement of a single leaving group from arsenic and also due to the instability of products having arsenic attached to a benzylic carbon, as in most of the design targets. A second generation design relied on introduction of arsenic functionality ortho to the hydroxyl group of a phenol via a Pd-catalyzed coupling with an organomercury intermediate. While the ensuing synthetic work resulted in the development of a new method for the synthesis of arsinous acids, the synthesis of designed target molecules ultimately failed due to difficulties in synthesis and isolation of ortho mercuration intermediate in complex systems. The third generation approach relied on Pd-catalyzed coupling between an arylboronic acid and a dihaloalkylarsenic reagent. In contrast to the second generation approach, this approach does not require a phenolic hydroxyl group on the benzene ring. Further computational studies including new scaffold design using HostDesigner and further computational evaluation of selected scaffolds were conducted. Selected designs were then targeted for synthesis. The synthetic work resulted in development of a second new method for arsinous acid synthesis based on Pd-catalyzed coupling between an arylboronic acid and an arsenic dihalide. This reaction showed high selectivity for substitution of one halide group, leaving the second halide group for displacement by thiol substituents in forming an arsenic-thiol complex. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Chemistry en_US
dc.title PhD en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US

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