Dissociative Electron Attachment Dynamics of a Promising Cancer Drug Indicates Its Radiosensitizing Potential

Area of Science:

• Chemical Physics
• Radiation Chemistry
• Computational Chemistry

Background:

• RRx-001 is a hypoxic cell chemotherapeutic agent.
• Synergistic effects of RRx-001 in chemo-radiation therapy are known.
• Low-energy electrons are generated during irradiation and interact with RRx-001.

Purpose of the Study:

• Investigate the initial interaction between RRx-001 and low-energy electrons.
• Characterize the formation and fragmentation of the transient anion of RRx-001.
• Elucidate the mechanisms governing RRx-001 anion decay.

Main Methods:

• Experimental techniques to study electron-RRx-001 interactions.
• Time-resolved measurements to disentangle anion decay pathways.
• Quantum chemical calculations to model reaction mechanisms.

Main Results:

• Electron interaction causes rapid dissociation of NO2 and HNO2 neutrals.
• NO2- and Br- anions are produced directly and via intermediate complexes.
• Bidirectional state switching between π*(NO2) and σ*(C-Br) states explains experimental findings.

Conclusions:

• The study provides insights into the fast dynamics of RRx-001 anion fragmentation.
• Understanding these dynamics is crucial for predicting condensed phase chemistry.
• Findings contribute to the comprehension of RRx-001's synergistic effects in therapy.