Authors' Affiliations

Sarah Osei Addae, Department of Chemistry, East Tennessee State University, Johnson City, TN Dr. Marina Roginskaya, Department of Chemistry, East Tennessee State University, Johnson City, TN Dr. Yuriy Razskazovskiy, Department of Physics and Astronomy, East Tennessee State University, Johnson City, TN

Location

Culp Center Ballroom

Start Date

4-25-2023 9:00 AM

End Date

4-25-2023 11:00 AM

Poster Number

41

Faculty Sponsor’s Department

Chemistry

Name of Project's Faculty Sponsor

Marina Roginskaya

Additional Sponsors

Yuriy Razskazovskiy, Abbas Shilabin, Aleksey Vasiliev

Classification of First Author

Graduate Student-Master’s

Competition Type

Competitive

Type

Poster Presentation

Project's Category

Biological and Chemical Sciences

Abstract or Artist's Statement

Oxidative damage to DNA has been implicated in a plethora of pathologies, such as cancer, neurodegenerative diseases, cardiovascular diseases, and aging. One-electron transfer (OET) plays a significant role in oxidative DNA damage in vivo. Guanine as the most oxidizable part of DNA is the major focus of studies on oxidation damage to DNA initiated by OET. Until recently, the pathway of guanine one-electron oxidation via its neutral guanine radical, G·, has been poorly studied. Our recent research has discovered a novel type of products of G· dimerization, D1 and D2, formed as a result of oxidation reaction of guanine derivatives, initiated by OET. A proposed reaction mechanism contains an early intermediate (Int1) generated by recombination of the two G· radicals. We were not able to isolate Int1, so that its role in the proposed reaction mechanism is only hypothetical. Literature data have reported that 8-arylamino-substituted 2´-deoxyguanosine (dGuo) compounds can be oxidized to create structural analogs of D1 and D2. As a result, the original 8-substituted dGuo compounds can serve as analogs of Int1. The goal of this work is therefore to confirm that Int1 is a precursor to D1 and D2 using the analogy approach.

Two 8-aryl- and three 8-alkyl-substituted dGuo compounds were synthesized, purified by semipreparative HPLC, and their structures were confirmed by 1H-NMR. 8-subsituted oxidation products analogous to D1 and D2 were obtained from 8-substituted dGuo analogs upon illumination the reaction mixture in the presence of S2O82- as a oxidant and Ru(II)bpy32+ as a photosensitizer at 470 nm. The products were purified by semipreparative HPLC, and their structures were confirmed by 1H-NMR. The purified analogs of D1 were successfully tested for conversion into the D2 analog. Finally, the analogs of D2 were successfully tested for the reaction with primary amines to form analogs of 2-aminoimidozalone (AIz), in agreement with the mechanism characteristic of D2.

Share

COinS
 
Apr 25th, 9:00 AM Apr 25th, 11:00 AM

Analysis of Novel Intermediate of Guanine-Guanine Crosslink Produced in Reactions of One-Electron Oxidation of Guanine Derivatives by Using 8-Substituted 2´-Deoxyguanosines as Analog Compounds

Culp Center Ballroom

Oxidative damage to DNA has been implicated in a plethora of pathologies, such as cancer, neurodegenerative diseases, cardiovascular diseases, and aging. One-electron transfer (OET) plays a significant role in oxidative DNA damage in vivo. Guanine as the most oxidizable part of DNA is the major focus of studies on oxidation damage to DNA initiated by OET. Until recently, the pathway of guanine one-electron oxidation via its neutral guanine radical, G·, has been poorly studied. Our recent research has discovered a novel type of products of G· dimerization, D1 and D2, formed as a result of oxidation reaction of guanine derivatives, initiated by OET. A proposed reaction mechanism contains an early intermediate (Int1) generated by recombination of the two G· radicals. We were not able to isolate Int1, so that its role in the proposed reaction mechanism is only hypothetical. Literature data have reported that 8-arylamino-substituted 2´-deoxyguanosine (dGuo) compounds can be oxidized to create structural analogs of D1 and D2. As a result, the original 8-substituted dGuo compounds can serve as analogs of Int1. The goal of this work is therefore to confirm that Int1 is a precursor to D1 and D2 using the analogy approach.

Two 8-aryl- and three 8-alkyl-substituted dGuo compounds were synthesized, purified by semipreparative HPLC, and their structures were confirmed by 1H-NMR. 8-subsituted oxidation products analogous to D1 and D2 were obtained from 8-substituted dGuo analogs upon illumination the reaction mixture in the presence of S2O82- as a oxidant and Ru(II)bpy32+ as a photosensitizer at 470 nm. The products were purified by semipreparative HPLC, and their structures were confirmed by 1H-NMR. The purified analogs of D1 were successfully tested for conversion into the D2 analog. Finally, the analogs of D2 were successfully tested for the reaction with primary amines to form analogs of 2-aminoimidozalone (AIz), in agreement with the mechanism characteristic of D2.