Electron impact ionisation cross sections of fluoro-substituted nucleosides

Eur. Phys. J. D (2019) 73: 137 https://doi.org/10.1140/epjd/e2019-90708-9 THE EUROPEAN PHYSICAL JOURNAL D Regular Article Electron impact ionisation cross sections of fluoro-substituted nucleosides? Stefan E. Hubera and Andreas Mauracherb Institute of Ion Physics and Applied Physics, Leopold-Franzens-University Innsbruck, Technikerstr. 25/3, 6020 Innsbruck, Austria Received 30 December 2018 / Received in final form 25 March 2019 Published online 2 July 2019 c The Author(s) 2019. This article is published with open access at Springerlink.com Abstract. We report calculated electron-impact ionisation cross sections (EICSs) for 20 -deoxycytidine (Cyt), 20 -deoxy-5-fluorocytidine (fCyt) and 20 ,20 -difluorocytidine (gemcitabine, Gem) from threshold to 10 keV. We compare the Deutsch-Märk (DM) and the binary-encounter-Bethe (BEB) methods used to obtain these cross sections. The methods yield excellent agreement with each other, within 3−4% at the cross section maxima. In particular, the DM cross sections for Cyt, fCyt and Gem yield maxima of 29.88 Å2 at 79 eV, 28.96 Å2 at 82.2 eV and 29.51 Å2 at 83.4 eV, respectively, whereas the BEB cross sections yield maxima of 28.89 Å2 at 87.6 eV, 27.97 Å2 at 91.6 eV and 29.02 Å2 at 93.4 eV, respectively. In addition, we compute EICSs for small sequences built from the considered nucleosides, i.e. for the sequences Cyt-Cyt, fCyt-Cyt, Cyt-fCyt, Gem-Cyt and Cyt-Gem. We find that the resulting EICSs differ only slightly between different sequences of the same constituents. Moreover, they can be approximated with an accuracy within 6% by simply adding the EICSs of individual molecular subsystems. Finally, we find that alterations in the ionisation energy due to the presence of an aqueous solvent can be substantial and may hence also considerably affect the resulting EICSs especially at low energies close to the ionisation threshold. 1 Introduction Patients diagnosed with cancer often receive combinations of chemo- and radiotherapy in order to mutually enhance the effectiveness of the two treatments [1]. Besides cisplatin (cis-diamminedichloroplatinum(II)) and 5-fluorouracil, gemcitabine (20 ,20 -difluorocytidine; denoted simply as Gem for the remainder of this work) belongs to the pharmaceutical substances most widely applied in concomitant chemoradiotherapy [2]. Besides the biological effects of these compounds [3,4], cisplatin and halogenated uracil molecules are also known for their efficiency as radiosensitisers, i.e. they enhance DNA damage and tumour cell killing rates upon irradiation of the targeted cells [5–10]. In contrast, Gem has been widely applied in anticancer therapy rather due to its effectiveness towards a broad range of tumours by being highly efficient in inhibiting DNA synthesis and repair [3]. However, it has also been suggested that fluorination of nucleosides results in increased induction of DNA damage via fragmentation due to enhancement of the electron attachment process [11]. Fragmentation enhancement factors of 2.8–5.5 have been reported depending on the location of ? Contribution to the Topical Issue “Dynamics of Systems on the Nanoscale (2018)”, edited by Ilko Bald, Ilia A. Solov’yov, Nigel J. Mason and Andrey V. Solov’yov. a e-mail: b e-mail: fluorination in 20 -deoxycytidine (denoted simply as Cyt for the remainder of this work) suggesting Gem also as an efficient radiosensitiser [11]. Generally, when biological tissue is irradiated, products of ionising radiation such as electrons not only interact with the biomolecular environment but also with administered pharmaceuticals. Among others, such as electron attachment processes, electron impact ionisation processes constitute dominant processes for electron molecule scattering phenomena and play also a role in interatomic Coulombic decay (ICD) which is driven by energy transfer [12]. Upon ICD, an ionised compound relaxes via transferring its excess energy to a neighbouring molecule which then becomes also ionised, resulting finally in two positively charged products that repel each other and subsequently often break apart [13]. ICD represents one of the processes which need to be considered especially in the context of electron interaction with molecules in biological environments. Data on the probability distribution characterising the interaction of the ionising radiation with the cell as a function of impact energy are then required as input for modelling purposes using e.g. Monte-Carlo track structure simulations [14,15]. In general, these simulations also require, among other input, single and double differential cross sections (SDCSs and DDCSs) to properly describe the effects of secondary electrons in media. For total cross sections, which can sometimes be enough for some purposes, two widely established methods are the Deutsch-Märk (DM) method [16], see Section 2.1, as well Page 2 of 7 as the binary-encounter-Bethe (BEB) method [17,18], see Section 2.2. While the DM method does not offer a possibility to calculate differential cross sections, the BEB method allows in principle to derive SDCSs (energy distributions) although their shapes may not be realistic [17]. To arrive at more realistic SDCSs in the framework of inelastic electron scattering, the more sophisticated binary-encounter-dipole method can be employed. The modified Jain-Khare semi-empirical approach is the only method that can be used to calculate (partial) SDCSs and DDCSs for molecules in electron ionisation [19]. In the context of radiation damage of biological tissue, interaction of ionising particles with condensed matter is also of importance. For such systems, methods exist which combine a relative simplicity, accuracy and generality, which can provide both total and differential ionisation cross sections. Many of those are based on the dielectric formalism, which are applicable for ions [20–22] and electron impact [23–25]. Although it is important to note that many ingredients are typically necessary as input for the mentioned Monte-Carlo track simulations, we focus here on a subset of these, i.e. the total cross sections. In particular, we choose the above mentioned DM and BEB methods to compute (total) electron-impact ionisation cross sections (EICSs) due to the typical reliability, simplicity and generality of these models, see also below. Here, we assess calculated EICSs for the molecules Cyt, Gem and 20 -deoxy-5-fluorocytidine (fCyt for the reminder of this work), see Figure 1. These molecules also represent building blocks of larger (fluorinated) DNA sequences. In order to investigate effects due to different direct biomolecular environments on the resulting EICSs, we report and compare thus also the cross sections of the sequences CytCyt, fCyt-Cyt, Cyt-fCyt, Gem-Cyt and Cyt-Gem (written in a 30 -to-50 direction). These sequences are constructed as illustrated in Figure 1 for the case of Gem-Cyt. Moreover, we report also EICSs for the considered molecules wh (...truncated)