Radiosensitizing derivatives of pyrimidine or purine nucleobases: Mass spectrometry and quantum chemical studies on low-energy electron interactions in gas phase, water clusters and solutions

The results of the current studies will lead to the in-depth understanding of relation between the efficiency of DEA in the gas phase and the effectiveness of potential radiosensitizer under physiological environment. It is difficult to overestimate access to such knowledge in the context of new, capable radiosensitizers. The most thorough studied radiosensitizing MNuc, 5-bromo-2’-deoxyuriudine, has not been used in the clinic so far. One of the reason for that could be insufficient understanding of the processes responsible for radiosensitizing properties of MNucs. Explaining the details of DEA, the influence of water in particular, should allow for rational designing of radiosensitizers. The identification of resonances leading to DEA in the gas phase as well as optimization of activation barriers and thermodynamic stimuli of degradation channels open in water will hopefully result in super-radiosensitizers which ultimately could be employed in the clinic.

Details

Financial Program Name:

CEUS

Organization:

Narodowe Centrum Nauki (NCN) (National Science Centre)

Agreement:

UMO-2020/02/Y/ST4/00110 z dnia 2021-07-12

Realisation period:

2021-07-12 - 2025-07-11

Research team leader:

dr hab. inż. Sebastian Demkowicz

Realised in:

Department of Organic Chemistry

External institutions participating in project:

Uniwersytet Gdański (Poland)

Project's value:

1 606 215.00 PLN

Request type:

International Research Programmes

Domestic:

International project

Verified by:

Gdańsk University of Technology

Papers associated with that project

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total: 2

Year 2024

Surprising Radiolytic Stability of 8‑Thiomethyladenine in an Aqueous Solution
Publication
- M. Datta
- A. Szczyrba
- M. Zdrowowicz
- D. Wyrzykowski
- O. Ciupak
- S. Demkowicz
- F. Izadi
- S. Denifl
- J. Rak
- JOURNAL OF PHYSICAL CHEMISTRY B - Year 2024
8-Thiomethyladenine (ASCH3), a potentially radiosensitizing modified nucleobase, has been synthesized in a reaction between 8-thioadenine and methyl iodide. Despite favorable dissociative electron attachment (DEA) characteristics, the radiolysis of an aqueous solution of ASCH3 with a dose of X-ray amounting to as much as 300 Gy leads to no effects. Nevertheless, crossed electron-molecule beam experiments in the gas phase on ASCH3...

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Year 2023

Electron-Induced Decomposition of 5-Bromo-4-thiouracil and 5-Bromo-4-thio-2′-deoxyuridine: The Effect of the Deoxyribose Moiety on Dissociative Electron Attachment
Publication
- F. Izadi
- A. Szczyrba
- M. Datta
- O. Ciupak
- S. Demkowicz
- J. Rak
- S. Denifl
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES - Year 2023
When modified uridine derivatives are incorporated into DNA, radical species may form that cause DNA damage. This category of molecules has been proposed as radiosensitizers and is currently being researched. Here, we study electron attachment to 5-bromo-4-thiouracil (BrSU), a uracil derivative, and 5-bromo-4-thio-20 -deoxyuridine (BrSdU), with an attached deoxyribose moiety via the N-glycosidic (N1-C) bond. Quadrupole mass spectrometry...

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