Probing non-adiabatic dynamics in radiosensitisers

Probing non-adiabatic dynamics in radiosensitisers


The goal of this research is to obtain a fundamental understanding of the non-adiabatic processes that occur during irradiation of radiosensitisers by ion and light sources. In particular, ionization and fragmentation of these molecules will be studied in the gas phase and in the presence of water. The overarching goal is to understand how the presence of an environment modifies the response and to obtain detailed information on the charged products that are produced.

We will study irradiation processes in two exemplar systems, namely nucleobases and 5-halouracils. The 5-halouracils are radiosensitisers that are widely used in cancer treatments. They are formed when a halogen atom, such as fluorine (5-FU) or bromine (5-BrU), replaces the C5 hydrogen in uracil and can be used to replace thymine in DNA. When exposed to radiation such as ions or photons, lethal damage to DNA containing these radiosensitisers is magnified and so they find therapeutic use in destroying cancerous cells. Ionization was found to increase mispairing of 5-FU and 5-BrU with guanine [1]. This mispairing is due to isomerization of the 5-halouracil to its enol form and so nuclear dynamics initiated by electronic processes is crucial to the mispairing process.

To date, a lot of research on non-adiabatic dynamics in uracil and 5-halouracils has focussed on fragmentation processes [234]. For instance, by studying the fragmentation products of 5-FU by high-frequency radiation pulses the electronic processes leading to the formation of particular ions was extracted [1]. Additionally, photoelectron spectra (PES) for uracil have been calculated using the multi-configurational time-dependent Hartree (MCTDH) method and the molecular dynamics of its radical cation studied [3]. However, all these studies have been in the gas phase. Understanding how dynamical processes in these molecules are altered by the presence of water is essential for realistic modelling of biological systems. To date, pioneering simulations of the interaction of low energy electrons with DNA bases in the presence of liquid water and amino acids have been carried out [5678]. However, these simulations have considered an adiabatic treatment of the dynamics.

In this project we will mainly use non-adiabatic quantum molecular dynamic (NA-QMD) methods, developed by Dr Dundas in QUB and Prof. Suraud in Toulouse, for studying fragmentation processes induced by irradiation. At the heart of the NA-QMD approach is a time-dependent density functional theory (TDDFT) treatment of the electronic dynamics together with a classical description of the nuclear dynamics. This approach is implemented in a parallel code called EDAMAME (Ehrenfest DynAMics on Adaptive MEshes) [9]. This code has been recently used to study ionization processes in benzene and acetylene [101112]. In addition, there will be an opportunity to use another state-of-the-art NA-QMD code (PW-TELEMAN) developed by Prof. Suraud and co-workers [13].

The following aspects will be considered.

  1. Calculation of electron energy spectra (EES) of DNA bases and 5-FU due to ionization by electrons and ions. This will provide crucial information on the production of secondary electrons. In addition, these spectra can be directly compared in the gas-phase to benchmark the accuracy of the theoretical approach.
  2. Study of fragmentation dynamics of DNA bases and radiosensitisers in the presence of several water molecules. This will provide important information on key questions such as fragmentation pathways and the production of radicals. These simulations will require work on several fronts including the implementation of new exchange-correlation functionals and the potential description of electron-nuclear dynamics beyond the Ehrenfest level.
  3. These non-adiabatic simulations can act as a useful benchmark of the adiabatic methods described above [78]. This is important as it will provide information about the validity of these computationally cheaper approaches.
  4. It should be noted that the methods we will employ are applicable to a wider range of molecules of direct relevance to physicists, biologists and pharamicists. One important example is cisplatin. Cisplatin is a radiosensitiser that is a member of the platinum-based antineoplastic family of chemotherapeutic drugs. It works by inhibiting the repair and production of DNA in cancerous cells. It is commonly used in conjunction with ionizing radiation in treatments [1415]. Initial simulations of the irradiation of this molecule will be considered as well. This will build upon initial work carried out at the adiabatic level [8].


[1]    H. Yu et al. J. Biol. Chem. 268 15935 (1993)

[2]    P. Çarçabal et al. Faraday Discuss. 194 407 (2016)

[3]    S. Matsika et al. J. Phys. Chem. A 117 12796 (2013)

[4]    A. Giussani et al. Topics Curr. Chem. 355 57 (2013)

[5]    M. McAllister et al. J Phys Chem Lett 6 3091 (2015)

[6]    P.-M. Dinh et al. In Nanoscale Insights into Ion-Beam Cancer Therapy, Solov’yov, A. V. (ed.) p.277 (2016)

[7]    J. Kohanoff et al. JPCM 29 383001 (2017)

[8]    M.P. McAllister Computational modelling of radiation damage to DNA, PhD thesis, QUB (2016)

[9]    D. Dundas, J. Chem. Phys. 136 194303 (2012)

[10]    A. Wardlow & D. Dundas, PRA 93 023428 (2015)

[11]    D. Dundas et al, PCCP 19 19619 (2017)

[12]    P. Mulholland & D. Dundas, Submitted to PRL (2017)

[13]    www.pw-teleman.org

[14]    H. J. Boeckman et al. Mo. Cancer Res. 3 277 (2005)

[15]    H.-Y. Chen et al PCCP 16 19290 (2014)

[16]    R. Pandey et al Euro Phys J D 71 190 (2017)





If you meet the eligibility criteria and wish to apply for any of these posts, you will need to complete an online application via the Queen's University Applications Portal:



You must include the code CAIRR18 on your application form to indicate that you wish to be considered for.

Applicants should choose the option “I wish to be considered for external funding” and then enter CAIRR18 in the free text box which follows.



  • All applicants must provide an up-to-date CV; this should be uploaded to the Admissions Portal as a separate document.
  • All applicants are required to provide a 100 - 400 word statement why they have applied for the project and what particular qualities they will bring to it.
  • Applicants must provide the name of an Academic Referee in support. Failure to provide a referee will result in the application being rejected.
  • Applications can be considered for multiple projects but they should make a separate application for each one they are interested in.
  • Please note, failure to include the reference CAIRR18 in the free text box may result in your application not being allocated or considered for funding.


The deadline for applications is 5.00 pm, Thursday 8 February 2018.