Date on Master's Thesis/Doctoral Dissertation

12-2021

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemistry

Degree Program

Chemistry, PhD

Committee Chair

Kozlowski, Pawel M.

Committee Co-Chair (if applicable)

Grapperhaus, Craig

Committee Member

Grapperhaus, Craig

Committee Member

Thompson, Lee

Committee Member

Bert, Robert

Author's Keywords

B12; CarH; photoreceptors; photochemistry; computational chemistry; reaction mechanisms

Abstract

The photochemical properties of the B12 family of molecules (cobalamins = Cbls) have been known for many years yet only until the 21st century have applications for the light-sensitivity of Cbls come to the surface. Photolabile Cbls can be used for the delivery of therapeutics with spatial and temporal control, in the generation of hydroxyl radicals, and in nature, as demonstrated in the catalytic cycle of coenzyme B12-dependent photoreceptors. This dissertation describes the use of computational methods to explore the photochemical properties of Cbl systems including antivitamins B12, a thiolato-cobalamin, and the coenzyme B12-dependent photoreceptor CarH. Chapter 1 includes explanation of the light-sensitivity of B12 derivatives from both technical and historic standpoints. Descriptions of the structure and functions Cbls are included. The main target of Chapter 2 is to describe how experimental observations can inform theoretical investigations. The computational approach is also described. Chapter 3 describes the photolytic properties of two synthetic antivitamins B12 including ethylphenylcobalamin (EtPhCbl) and phenylethynylcobalamin (PhEtyCbl). EtPhCbl is photoactive and excitation leads to a branching between internal conversion (IC) to the ground state and photodissociation. PhEtyCbl is remarkably photostable and IC is the major photophysical event with nearly unit quantum yield (QY). The photolytic properties of a thiolato-cobalamin, N-acetylcysteinylcobalamin (NACCbl) are described in Chapter 4. Photoexcitation of NACCbl leads to Co(II)/Ado• radical pair (RP) formation from the ligand field region of the S1 potential energy surface (PES). A key difference in comparison to other photoactive Cbls is that the S1 LF field region can be directly accessed via S2 → S1 IC bypassing the involvement of the S1 metal-to-ligand charge transfer (MLCT) minimum. Also unique to NACCbl is that the LF region contains two local minima from which RP formation can occur from. Chapters 5-7 are devoted to the coenzyme B12-dependent photoreceptor CarH. While coenzyme B12 (aka adenosylcobalamin = AdoCbl) is best known as a ubiquitous cofactor, in CarH, AdoCbl takes on a new function as a chromophore. In Chapter 5, the evidence for how CarH operates using light linstead of substrate binding in its catalytic cycle is presented. Chapter 6 focuses on the description of the electronic and photolytic properties of hydridocobalamin (HCbl) and explores its potential role as an intermediate in CarH. Chapter 7 is devoted to proposing a mechanism for how CarH uses light to form the photoproduct, 4′,5′-anhydroadenosine (anhAdo) using insights from Chapters 5 and 6 as well as comparisons to experimental works.

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