Krishnagiri Vinod, Jincy
(2024)
1) Synthesis and Fluorometric Characterizations of Pittsburgh Green Fluorescent Probes, FR901464 Analog, and a Suzuki-Miyaura Coupling Reaction. 2) Exploration of Chiral Induced Spin Selectivity Effect in Enantioselective Organic Reactions.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Fluorescent probes designed for biological studies are highly valued for their bioorthogonal properties, enabling them to function effectively in complex biological environments. A synthesis method for Pittsburgh Green derivatives has been developed, involving a streamlined one-step process to mask the compound into mono-alkylated or esterified forms. This approach accommodates a wide range of functional groups as masking agents, unlike previous methods, and is used to create various Pittsburgh Green-based fluorescent probes, demonstrating applications such as esterase and hydrogen peroxide detection. Notably, mono-alkylation has been shown to offer advantages over di-alkylation, specifically in metal detection assays, highlighting its use in sensor development.
In another study, a palladium-catalyzed deallylation reaction was employed to activate fluorescence, enabling the detection of catalytically active palladium species in organic reactions. In a proposed amine-catalyzed Suzuki-Miyaura coupling reaction, the reaction kinetics were found to be linearly dependent on the presence of a palladium impurity in the amine. A workflow was established to fluorometrically analyze the presence and activity of palladium impurity.
Next, the efforts toward synthesizing a hydroxymethyl-substituted FR901464 analog are discussed. FR901464 is a natural product splicing regulator with low nanomolar activity against various cancer cell lines. FR901464 binds to the splicing factor SF3B. Based on the crystal structure, axial methyl group modification on the right fragment pyran ring of FR901464 is tolerated. This hydroxy substitution serves as a versatile handle for further functionalization, potentially enabling the attachment of fluorescent tags or cancer-targeting moieties. Hydroxy substitution selectively on the axial methyl is achieved via a Hg-mediated cyclization in the presence of oxygen.
Furthermore, the study of the Chiral Induced Spin Selective (CISS) effect in enantioselective organic reactions was explored. The CISS (Chiral Induced Spin Selectivity) effect describes how the molecule's chirality significantly influences the displacement of electron spins through chiral molecules and materials. Although electrochemical ketone reduction experiments demonstrated successful yields, the expected enantioselectivity enhancement through the CISS effect was not observed in the current experimental setup
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
27 August 2024 |
| Date Type: |
Publication |
| Defense Date: |
22 July 2024 |
| Approval Date: |
27 August 2024 |
| Submission Date: |
12 August 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
446 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Fluorescence, synthesis, natural product, palladium catalysis, Chiral Induced Spin selectivity, Organophosphorus poisoning agents |
| Date Deposited: |
27 Aug 2024 11:45 |
| Last Modified: |
27 Aug 2024 11:45 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46913 |
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