Electron scattering from molecules and molecular aggregates of biological relevance

TLDR: The methods and techniques used in the investigation of low energy electron collisions with biologically relevant molecules and molecular clusters are described and the results obtained so far for DNA constituents and their model compounds, amino acids, peptides and other biomolecules are summarized.

Abstract: In this Topical Review we survey the current state of the art in the study of low energy electron collisions with biologically relevant molecules and molecular clusters. We briefly describe the methods and techniques used in the investigation of these processes and summarise the results obtained so far for DNA constituents and their model compounds, amino acids, peptides and other biomolecules. The applications of the data obtained is briefly described as well as future required developments.

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Electron scattering from molecules and molecular
aggregates of biological relevance
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How to cite:
Gorfinkiel, Jimena D. and Ptasinska, Sylwia (2017). Electron scattering from molecules and molecular aggregates of
biological relevance. Journal of Physics B: Atomic, Molecular and Optical Physics, 50(18) p. 182001.
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Electron scattering from molecules and molecular
aggregates of biological relevance
Jimena D. Gorfinkiel
School of Physical Sciences, The Open University, Walton Hall, Milton Keynes,
United Kingdom
E-mail: Jimena.Gorfinkiel@open.ac.uk
Sylwia Ptasinska
Radiation Laboratory and Department of Physics, University of Notre Dame, Notre
Dame, Indiana 46556, USA
E-mail: sptasins@nd.edu
Abstract.
In this Topical Review we survey the current state of the art in the study of low
energy electron collisions with biologically relevant molecules and molecular clusters.
We briefly describe the methods and techniques used in the investigation of these
processes and summarise the results obtained so far for DNA constituents and their
model compounds, amino acids, peptide and other biomolecules. The applications of
the data obtained is briefly described as well as future required developments.
PACS numbers: 34.80.-i, 36.40.Qv, 87.14.ef, 87.14.gf, 87.53.-j
Keywords: Submitted to: J. Phys. B: At. Mol. Phys.
1. Introduction
One of the main challenges of the XXI century is to respond to the medical needs of
a growing and ageing population. Over 20 million new cancers are predicted for 2030
(Ferlay et al. 2013). The improvement and development of current and new cancer
treatments is therefore a major scientific concern. Radiation therapy, that is, the
use of highly energetic, ionising radiation, is employed to treat around 50% of cancer
patients (Baskar & Itahana 2017). Its relative low cost compared to other treatments
makes it particularly appropriate for use in developing countries, where cancer-survival
rates require improvement. In addition, radiation is also used for medical imaging
and understanding of its interaction with biological material is important for radiation
protection (not only on Earth but also during space missions).

Electron scattering from biological targets 2
The first medical use of radiation was in imaging (X-rays) and the treatment of skin
conditions (UV light). By the 1930’s protocols for the use of radiation to treat some
cancers had been developed. These days, treatments are highly sophisticated, using
several types of ionisation radiation (photons, alpha particles, ions, etc.) and a variety
of methods to ensure dose is maximized for the cancer cells while protecting healthy
tissue. Overall, radiotherapy developments have been based on experimental knowledge
and empirical methods. Nowadays, however, efforts are being made to develop a deeper
understanding of the underlying molecular processes in order to design models and
software to aid these developments.
Any type of ionising radiation interacting with a medium will produce large
number of secondary electrons, the product of enough energy being transferred between
projectile and target to ionise the latter. Around 10
4
electrons with energies below 30 eV
are generated per MeV of deposited radiation (Pimblott & LaVerne 2007, Alizadeh &
Sanche 2012). The experiments of Bouda¨ıffa et al. (2000) confirmed that subionisation
electrons can produce single and double-strand breaks (SSBs and DSBs, respectively)
in DNA via the process known as dissociative electron attachment (DEA). This work
marked the beginning of intense experimental and theoretical interest in electron
interactions with biologically relevant molecules, particularly DNA components, as
well as DNA strands. The aim of this research is to provide an understanding of the
mechanisms of electron induced damage, as well as quantitative data to be used in its
modelling. A lot of the work has been performed in the gas phase (or, the computational
equivalent, isolated molecules). Researchers recognise, however, that radiation damage
in the cell occurs in a condensed medium and that the environment (fundamentally, the
water that surrounds cell constituents) will modify the electron-molecule interaction and
its outcome. For this reason, studies in the condensed phase (mostly films) and, more
recently, in pure and hydrated clusters have been performed.
It should be pointed out that an understanding of radiation effects at the molecular
level is only a small part of the knowledge needed to accurately describe (and predict)
biological radiation damage. A number of other effects (dose deposition, repair
mechanisms, indirect mechanisms like the bystander effect, etc.) contribute to the
complex biological process and must be taken into account (Hall & Giaccia 2012). We
should also mention that many exciting developments in the field of cancer treatment are
currently taking place (from the concurrent use of radio and chemotherapy to genetics-
based approaches) not all of which involve the use of radiation. It is the case however,
that radiation will remain a highly used tool both for treatment and imaging.
The aim of this Topical Review is to provide an overview of the research performed
so far on electron collisions with biological targets, summarising the main finds and
how this information is relevant, both from an applied perspective and a fundamental
one. A prior review (Baccarelli et al. 2011) described the work performed up to 2011,
particularly on resonance formation and DEA. We also refer the reader to two recent
reviews of DEA (Fabrikant et al. 2017) and DEA to biomolecules (Bald et al. 2017)
for more details regarding this process. In this Topical Review, we will concentrate on

Electron scattering from biological targets 3
more recent work and include all electron-induced processes as well as widen the range
of targets including aggregates. Results from aggregates can bridge our understanding
of electron-induced processes in the gas and condensed biomolecules, including DNA
and its constituents. A comparison of results from different states of matter has
already revealed the basics mechanisms initiated by electron scattering and how they are
modified under conditions more related to those in the cell (Alizadeh & Sanche 2012).
These mechanisms can assist in a better interpretation of the role of secondary electrons
in radiation-induced damage as well as in potential applications to radiotherapy
(Sanche 2016). We will also describe some electron-biomolecule interactions not related
to biological radiation damage.
1.1. Targets and processes of interest
The work described in this Topical Review corresponds to low-energy collisions. We
define these as collisions happening below ≈20 eV (i.e., not much above the ionisation
threshold). Low energy electrons (LEEs) can scatter elastically or lead to the excita-
tion (rotational, vibrational and/or electronic) of the target molecule. This excitation
can lead to (neutral) dissociation. In addition, DEA can take place. This is a reso-
nant process that involves electron capture by a molecule, AB, to produce a temporary
molecular anion (also called a transient negative ion, TNI, or resonance), (AB)
∗−
that
can then dissociate into an anion, A
−
, and a neutral radical or radicals, B·, according
to the following reaction:
e + AB −→ (AB)
∗
−→ A + B·
where A and B· are atoms and/or molecular fragments. DEA can lead to both simple,
single bond cleavage or a more complex decomposition into a number of fragments;
it is also extremely effective at selectively breaking specific molecular bonds. The
experiments of Bouda¨ıffa et al. (2000) demonstrated clearly the presence of resonant
features in the occurrence of SSBs and DSBs as a function of electron kinetic energy;
that is, they showed that DEA played a major role in DNA damage.
Resonances are classified according to whether they involve fundamentally the
electronic states of the target or they involve nuclear (vibrational) degrees of freedom.
The electronic resonances are classified into shape, when the electron attaches to the
molecule in its ground state (the ground state is then described as the parent state of the
resonance) and core-excited, when the electron attaches to the molecule an electronic
excited state (Schulz 1973a, Schulz 1973b). In shape resonances the incoming electron
is trapped by the potential resulting from a combination of short-range attractive and
long-range repulsive forces (the latter are caused by the angular-momentum barrier of
the incoming electron). These resonances can be seen as the incoming electron being
trapped in one of the unoccupied orbitals of the molecule. In core-excited resonances
the incoming electron can be seen as electronically exciting the target molecule to a

Electron scattering from biological targets 4
state (the parent state) and then being trapped into one of the empty spin-orbitals.
Core-excited resonances are further classified as Feshbach (also known as Type I) or
core-excited-shape (known as Type II) . In the latter the resonance is energetically
above its parent state and can therefore decay (via autoionisation) to it and in the
former it lies below (Herbert 2015)‡. Feshbach resonances have lifetimes much larger
than shape or core-excited shape resonances and, consequently, very narrow widths.
Vibrational Feshbach resonances (VFR) involve nuclear motion and usually occur at
very low energies when the electron is trapped into a diffuse (dipole-bound) state and its
energy transferred to the molecular vibrations (since the anion state is weakly bound,
it tends to lie slightly below the ground state of the neutral target and therefore its
vibrational levels are very close, but slightly below the corresponding vibrational states
of the neutral target). VFRs are likely to occur in molecules with large polarizability
and/or a very large dipole moment that leads to a long-range attractive interaction
(large dipole moments can also lead to the very-low energy formation of scattering-type
dipole states that might lead to anion stabilization as an alternative route to DEA
(Carelli & Gianturco 2016)). VFRs are found just below the thresholds for vibrational
excitation of the target molecule.
At higher energies (≈10 eV for most of the molecules discussed here) ionisation
becomes energetically possible and so does ion pair formation/dipolar dissociation. Data
(cross sections) for a broad energy range are needed for the description of radiation
interaction with matter, for example using Monte Carlo-based techniques. In addition,
the computational description of DEA requires information on the temporary anions
formed (energy and lifetime). In this Topical Review, we will summarise work available
on most of the relevant low-energy cross sections (neutral dissociation and rotational
excitation are excluded because of the very little available data) as well as theoretical
work on resonance characteristics.
In principle, all biological molecules present in the cell are of potential relevance
to understanding the effects of radiation. In addition, electron scattering data for some
inorganic molecules is also highly relevant. The most significant of all is water, the main
constituent of most living organisms. Other molecules used in track structure modelling
(see Section 5.1.1 for more details) are N
2
, CH
4
and CO
2
(these are employed to produce
tissue equivalent gas). We will not review work on these inorganic targets here, so we
refer the reader to earlier reviews: Itikawa & Mason (2005) for water, Anzai et al. (2012)
for water and CO
2
, etc..
DNA (and RNA) constituents have been the focus of a lot of the experimental
work: not only the bases and sugar, but also nucleosides and nucleotides as well as
as short DNA strands. Collisions with substituted DNA bases (in particular halo-
substituted) have been studied as these substitutions can render the molecules more
prone to radiation-induced break-up, in other words, these molecules have the potential
‡ We note that this classification is somewhat over-simplifying: resonances that have a mixed shape
and core-excited character have been identified (e.g. Nenner & Schulz 1975, Winstead & McKoy 2007)
as well as other resonances that have more than one parent state.

Frequently asked questions

Q1. What are the contributions in "Electron scattering from molecules and molecular aggregates of biological relevance" ?

In this Topical Review the authors survey the current state of the art in the study of low energy electron collisions with biologically relevant molecules and molecular clusters. The authors briefly describe the methods and techniques used in the investigation of these processes and summarise the results obtained so far for DNA constituents and their model compounds, amino acids, peptide and other biomolecules. 

Q2. What is the widely studied process in electron-biomolecule scattering?

Dissociative electron attachment (DEA) is experimentally one of the most widely studied processes in electron-biomolecule scattering due to its centrality to radiation damage. 

Q3. Why are absolute DEA cross sections still challenging?

due to the low precision of pressure measurements of the effusive molecularbeam, particularly in the case of powder samples, absolute DEA cross sections for most biomolecules still remain challenging. 

Q4. What is the probability of a biomolecule decomposing during heating?

Since most biomolecules (e.g., nucleobases, amino acids, and peptides) exist as solids at room temperature, there is a probability that they will decompose during heating, as was reported for thymidine (Ptasinska et al. 2006). 

Q5. What is the main reason for the improvement of the computational description of the effects of the laser?

The provision of accurate photoionisation data (that involves determining similar quantities to those needed in electron scattering studies and therefore can be done using the same software) is an essential step to improve the computational description of the effects induced by the laser field. 

Q6. What are the sources of uncertainty in low energy calculations of electron-molecule collisions?

There are three sources of uncertainty in low-energy calculations of electron-molecule collisions: the description of the (non-interacting target (i.e. the model that is used to describe its internal states), the approximation used to describe the scattering processes (e.g. how the continuum is modelled, whether polarization is included) and the theoretical method (and the computational implementation) used to perform the scattering calculations. 

Q7. What is the common technique used to study electron scattering from gas-phase targets?

One of the earliest experimental techniques used to study electron scattering from gas-phase targets is Electron Transmission Spectroscopy (ETS). 

Q8. What is the main difficulty in evaluating elastic cross sections for biologically relevant molecules?

The main difficulty in evaluating elastic cross sections for most biologically relevantmolecules arises from their permanent dipole moment. 

Q9. What is the peculiar observation in the resonance formation of dehydrogenated amino acids?

Another peculiar observation in the resonance formation of dehydrogenated amino acids is that the ion yield alters significantly depending on the position of the amino group in the molecule, as was shown by comparing DEA processes to α- and β-isomers alanine (Vizcaino et al. 2011). 

Q10. How was the breakage of the N-C bond in the tripeptide proposed?

This peptide breakage was proposed to be energetically possible only via a complex reaction, including a subsequent proton transfer, as was also suggested for dipeptides (Muftakhov & Shchukin 2011a). 

Q11. What is the simplest way to study the motion of a nuclear wave packet?

The 2D spectra provide both state-to-state information and insight into the dynamics of nuclear motion in resonances: information about the motion of a nuclear wave packet on a resonant potential surface is possible since this wave packet (of the resonant state) follows one of two competing pathways: molecular dissociation (DEA) or electron detachment. 

Q12. What type of molecules are considered as the elementary prototype of deoxyribose?

Targets of these type are, for example, tetrahydrofuran (THF) a five-membered heterocyclic compound which may be considered a hydrogenated form of furan and is regarded as the elementary prototype of deoxyribose, and pyrimidine. 

Q13. Why are the positions of the shape resonances higher than those determined experimentally?

The calculated positions tend to be higher than those determined experimentally (Aflatooni et al. 1998) for well known reasons: in general, the polarization effects are not fully described, or (particularly for the third resonance) the character of the resonance is partially core-excited so elastic calculations do not describe it very well. 

Q14. Why is it important to compare experimental TCS with calculated elastic integral cross sections?

Results for TCS are mentioned in Section 3.1, because at low energies it is sometimes customary to compare experimental TCS with calculated elastic integral cross sections as the inelastic contribution to the TCS can be,in this energy range, significantly smaller. 

Q15. What are the types of cross sections that are provided for a specific energy?

The latter, in the energy range of interest to this Topical Review, are normally angular differential cross section that are provided for a specific scattering energy as a function of the scattering angle (these cross sections can also be provided for a specific scattering angle as a function of scattering energy; these are normally referred to as excitation functions). 

Q16. What is the main reason for the push towards better computational description of electron-biomolecule interactions?

It is worth mentioning that another push towards better computational descriptionof electron-biomolecule interactions comes from the study of molecular processes induced by ultrashort laser pulses (e.g., high-harmonic generation in biomolecules (Marangos 2016), charge migration (Calegari et al. 2016)). 

Q17. Why is the phosphate group in the gas phase not investigated?

due to experimental difficulties, the phosphate group in the gas phase has not been investigated but several compounds involving phosphoric acid derivatives, e.g., dibutylphosphate and triethylphosphate (König et al. 2006), have been examined.