Ring-Selective Fragmentation in the Tirapazamine Molecule upon Low-Energy Electron Attachment.

Eugene Arthur-Baidoo,Joao Ameixa,Stephan Denifl,Milan Ončák

doi:10.3390/ijms22063159

Eugene Arthur-Baidoo, Joao Ameixa + Show 2 more

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https://doi.org/10.3390/ijms22063159

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Abstract

We investigate dissociative electron attachment to tirapazamine through a crossed electron–molecule beam experiment and quantum chemical calculations. After the electron is attached and the resulting anion reaches the first excited state, D1, we suggest a fast transition into the ground electronic state through a conical intersection with a distorted triazine ring that almost coincides with the minimum in the D1 state. Through analysis of all observed dissociative pathways producing heavier ions (90–161 u), we consider the predissociation of an OH radical with possible roaming mechanism to be the common first step. This destabilizes the triazine ring and leads to dissociation of highly stable nitrogen-containing species. The benzene ring is not altered during the process. Dissociation of small anionic fragments (NO2−, CN2−, CN−, NH2−, O−) cannot be conclusively linked to the OH predissociation mechanism; however, they again do not require dissociation of the benzene ring.

Highlights

Attempts to find innovative methods for applications in cancer radiotherapy and concomitant chemotherapy have been a focus of research for decades
We investigate dissociative electron attachment to tirapazamine through a crossed electron– molecule beam experiment and quantum chemical calculations
The incoming electron is captured by the parent molecule M yielding a transient negative ion (TNI), M*−, termed resonance, which subsequently dissociates into a neutral fragment (M–X) and a fragment anion X−

Summary

Introduction

Attempts to find innovative methods for applications in cancer radiotherapy and concomitant chemotherapy have been a focus of research for decades. The chemical agents, referred to as radiosensitizers, administered during cancer radiotherapy have the capability of differentially sensitizing hypoxic cells and enhancing radiation-induced DNA damage, especially in the local tumor regions [4,5]. Hypoxic cytotoxins are a kind of radiosensitizer designed to only activate under hypoxic conditions [7] Their ability to accumulate and retain their integrity in tumor cells under low oxygen content contributes greatly to their radiosensitization property. Such compounds can undergo a reduction process, converting them into reactive radicals, which are able to accumulate in hypoxic tumor cells and, subsequently, induce DNA damages [5]. All fragmentation pathways are attributed to the dissociation of the triazine moiety attached to the benzene ring

Results

Exp Theory

Conclusions