Dissertations, Theses, and Capstone Projects

Date of Degree

9-2023

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biochemistry

Advisor

Alexander Greer

Committee Members

Lesley Davenport

Jianbo Liu

Susan Rotenberg

Orrette Wauchope

Subject Categories

Biochemistry, Biophysics, and Structural Biology | Computational Chemistry | Organic Chemistry

Keywords

singlet oxygen, disulfide, S–S bond rotation, conformational analysis, isomerization, antioxidant

Abstract

Three chapters are included in this dissertation, each of which describes non-oxidative reactions, with peroxy intermediates formed between singlet oxygen (1O2) and substrate. (1) Novel discoveries related to the intermediate formed by 1O2 and dimethyl disulfane are explored. (2) A new mechanism is proposed, wherein the dihedral angle CS–SC (θ) determines the pro- or antioxidant activity of an organic disulfide. (3) A review of 1O2's ability to facilitate the geometric isomerization of alkenes and polyenes is presented in Chapter 3.

Chapter 1 investigates the role of singlet oxygen potentially mediating increased conformational flexibility of a disulfide. Density functional theory calculations indicate that the singlet oxygenation of 1,2-dimethyldisulfane produces a peroxy intermediate. This intermediate adopts a structure with a longer S–S bond distance and a more planar torsional angle CS–SC (θ) compared to the 1,2-dimethyldisulfane itself. The lengthened S–S bond enables a facile rotation about the torsional angle in the semicircle region 0° < θ < 210°, that is ~5 kcal/mol lower in energy than the disulfane. Subsequent departure of O2 from the disulfane peroxy intermediate is reminiscent of peroxy intermediates which also expel O2, yet facilitate cis-trans isomerizations of stilbenes, hexadienes, cyanines, and carotenes.

In Chapter 2, a mechanistic and structural clarification as to why organic disulfides will function as prooxidants under some conditions and antioxidants under others has been explored. Disulfides are sufficiently oxophilic to react with 1O2, and reactions of disulfides with oxidants occur in both synthetic and biological contexts; thus, these reactions are of particular interest. 1O2 reactivity appears to be a function of the disulfide CS⎼SC (θ) angle. At θ ≤ ~45°, the disulfide prepares 1O2 for deactivation concurrent with a unique pirouette movement of its trigonal bipyramidal (TBP) thiadioxirane intermediate. In contrast, 1O2 reactivity increases favoring persulfoxide formation when θ ≥ ~90°. The resulting persulfoxide is a more potent oxidant than 1O2.

Chapter 3 presents a review describing O2-dependent photoreactions for possible routes to double-bond isomerizations. E,Z-isomerizations triggered by O2 and visible light are a new area of potential synthetic interest. The reaction involves the reversible addition of O2 to form a peroxy intermediate with oxygen evolution and partial regeneration of the compound as its isomer. Targeting of O2-dependent photoisomerizations also relates to a practical use of visible light, for example the improved light penetration depth for visible as opposed to UV photons in batch sensitized reactions. This review is intended to draw a link between visible-light formation of a peroxy intermediate and its dark degradation with O2 release for unsaturated compound isomerization. It should be of interest both to photochemists and synthetic organic chemists, as it ties together mechanistic and synthetic work, drawing attention to an overlooked subject.

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