Proton Collision on Deoxyribose Originating from Doubly Ionized

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Proton Collision on Deoxyribose Originating from Doubly Ionized Water Molecules Dissociation Marie-Anne Herve du Penhoat, Nely Rodriguez Moraga, Marie-Pierre Gaigeot, Rodolphe Vuilleumier, Ivano Tavernelli, and Marie-Francoise Politis J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.8b04787 • Publication Date (Web): 30 May 2018 Downloaded from http://pubs.acs.org on May 30, 2018

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The Journal of Physical Chemistry

Proton Collision on Deoxyribose Originating from Doubly Ionized Water Molecules Dissociation Marie-Anne Hervé du Penhoat,∗,† Nely Rodriguez Moraga,† Marie-Pierre Gaigeot,‡ Rodolphe Vuilleumier,¶ Ivano Tavernelli,§ and Marie-Fran¸coise Politis‡ †IMPMC, Sorbonne Université, UMR CNRS 7590, MNHN, IRD UMR 206, 75005 Paris, France ‡LAMBE UMR8587, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, Université d’Evry val d’Essonne, Université Paris-Saclay, CEA, CNRS, Blvd F. Mitterrand, 91025 Evry, France ¶PASTEUR, Département de chimie, École normale supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France §IBM Research - Zurich, Säumerstrasse 4, 8803 Rüschlikon, Switzerland E-mail: [email protected] Phone: +33 (1) 44 27 72 05. Fax: +33 (1)

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Abstract In this work, we studied the fragmentation dynamics of 2-deoxy-D-ribose (DR) in solution that arises from the double ionization of a water molecule in its primary hydration shell. This process was modeled in the framework of ab initio Molecular Dynamics. The charge unbalanced in the solvent molecules produces a Coulomb explosion with the consequent release of protons with kinetic energy in the few eV range, which collide with the surrounding molecules in solution inducing further chemical reactions. In particular, we observe proton collisions with the solute molecule DR, which lead to a complete ring opening. In DNA, damage to the DR moiety may lead to DNA strand breaking. This mechanism can be understood as a one of the possible step in the radiation induced fragmentation of DNA chains.

Introduction Ionizing radiations are commonly used in radio-diagnostic and cancer therapy. Energy deposition by ionizing radiations can lead to permanent molecular lesions in DNA, either through direct interaction at various DNA sites, such as sugars and bases, (direct effects) or indirectly through reactions with radicals produced in the surrounding free water (indirect effects). There are now substantial indications suggesting that clonogenic death and other biological endpoints may result from a class of complex DNA lesions induced by significant energy deposits on or near the DNA. 1,2 Indeed, low and high Linear Energy Transfer (LET) radiations induce about 1500 ionizations in the DNA of a mammalian cell per Gy, but only a few lethal events per cell are observed. 3 Goodhead and coworkers have suggested that clusters of ionizations on DNA (100 eV in 2nm-long DNA segments) could be responsible for cellular inactivation. For instance, 100 keV electrons produce 22 such clusters per Gy and per cell. Chetioui et al have shown that inner-shell ionizations in DNA constituent atoms could be partly responsible for cellular inactivation upon heavy ion 4 and γ-ray 5 irradiation, although such events are very rare, about ten core ionizations per Gy and per cell upon γ-ray 2


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irradiation. 5 In DNA light atoms, inner shell ionization events undergo Auger decay which leads to the double ionization of the molecule. The (2a1 )−2 state has been calculated to be one of the most probable final state, with equivalent probability as the (1b1 )−2 state. 6 Moreover, the nowadays growing use of hadrontherapy for the treatment of deep tumors has triggered fundamental research for the characterization of damages in biomolecules induced by multiple ionization events, highly probable in swift ions tracks before and in the Bragg peak. 7 For 10 MeV carbon ions, the double ionization cross section is about ten percent of the single ionization cross section. 8 Moreover, for high energy protons, collisions can lead to singly ionized states, which may decay to a doubly ionized state (autoionization). 9 In liquid water, experimental studies showing an enhanced production of HO2 radicals in swift ions tracks, such as those used in Carbon Therapies, were first undertaken in order to explain the oxygen effect in hypoxic tumors treatment. It has been shown in different works qualitatively and quantitatively that localized double ionizations induce such an enhancement of the HO2 yield. 10 When a double ionization is localized on a water molecule in the liquid phase, the water molecule explodes leading to the formation of one oxygen atom and two protons with an energy of few eV. 11 The calculated cross section of double ionization matches that of HO2 production, and all chemical kinetic Monte Carlo simulations show the necessity to produce isolated oxygen atoms in order to induce such a chemical event. 7,8,12 In liquid water, the fragmentation of doubly ionized water molecules is well known. However, the effect of such an event, when happening in the hydration shell of a biomolecule, is less understood. Even if relatively rare, these processes deserve a special study since damages to DNA are known to be the result of complex processes and not just a simple function of the amount of energy delivered to the system. Recently, we developed a theoretical method which allows to specifically investigate the early stages of the Coulomb explosion of a doubly ionized biomolecule, either isolated of embedded in liquid water. This method is based on nonadiabatic Time-Dependent Density Functional Theory (TDDFT) molecular dynamics (MD) simulations in which effective

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molecular orbitals are propagated in time. 11,13,14 The ionization process is obtained by removing two electrons from one selected molecular orbital of the sample. These simulations are completed by Car Parrinello (CP) or Born Oppenheimer (BO) molecular dynamics up to the picosecond timescale. Indeed, the multitude of doubly ionized states are expected to be close in energy leading to fast non-adiabatic switches, which can quickly drive the system to the ground state. The dissociation of doubly ionized water 11 and uracil 15 molecules solution as well as isolated uracil 16 have already been reported. In the present paper, we investigate the physico-chemical modifications of a deoxyribopyranose (DR) molecule embedded in liquid water, focusing on the effect of the double ionization of a water molecule bound to the sugar. Numerous studies have indeed suggested that ionization of the primary hydration layer of DNA results in damage to the DNA due to charge transfer, 17 a phenomenon called the quasi-direct effect. 18 Moreover, when a water molecule is doubly ionized, two protons are emitted with a few electronvolts kinetic energy. 11 If such an event takes place in the hydration layer of DR, a cascade of collisions of these protons on the sugar itself as well as on other water molecules occurs, as a billard game among molecules and atoms. These protons, in a condensed medium, often collide the molecules of the medium, the DR or water molecules, at low impact parameters. The two electrons were both removed either from the 1b1 or 2a1 molecular orbitals, which are the least (about 30 eV) and most (about 70 eV) energetical double ionization events, respectively. This allows us to probe the effect of the excess energy delivered to the system, which leads to the emission of protons in the range from 4 to 7 eV. In fact, the collision of few eV protons with matter is not exactly known, neither for charge exchange cross sections nor for the possible dissociation channels, and when studies exist, they deal with the gas phase. At energies lower than 1 keV per nucleon, the stopping power is even difficult to evaluate theoretically. 19 In this range of collision energies, the nuclear stopping power is evaluated to be of the same order of magnitude as the electronic stopping power (for a qualitative study see Ref. 20). Testing collisions in the eV energy range as a funtion of nuclear versus electronic stopping

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power remains an open challenge. Even single ionization processes induced by swift ions in liquid water can lead to the dissociation of a water molecule leading to few eV protons (see supporting information). These kinds of events are usually not considered in Monte Carlo simulations in water. The same is also true for the case of biomolecules embedded in water solution. As a prelimiary study we have checked the effect of the impact energy on the possible charge transfer and distorsion of an isolated water molecule in the gas phase at low impact parameter (see supporting information). Indeed in the collision we studied, the impact parameter is low since it is constrained by the hydrogen bond of the exploding water molecule to the sugar or to other water molecules. In order to disentangle the effect of the liquid environment, we have modeled the same collision in the gas and liquid phases, that is starting from the same atomic positions and velocities for the proton and the water molecule. We have also investigated the effect of the proton energy on the energy deposit in order to understand the specificity of low energy and low impact parameter collisions (see supporting information). In fact, methods of determination of charge exchange cross sections do not generally give the energy deposit and these are calculated averaging on all impact parameters. Moreover, in most applications, these cross sections are evaluated assuming frozen geometries during the charge migration process. As a matter of fact, the intramolecular energy transfer process that occurs upon collision may become an important descriptor of the molecular dissociation dynamics. To this end, molecular dynamics is the method of choice to gain atomistic understanding of these processes. In particular, TDDFT Ehrenfest dynamics 13,14 allows to study the on-the-fly evolution of a system during the collision and the possible dissociation of molecules, as shown in the case of 4 keV proton collisions on DNA base pairs 21 and in the case of sub-keV proton collisions on isolated organic molecules. 22–24 Nonetheless, all theoretical methods have been applied to investigate the effects of the collision of ions with isolated molecules. Only in a few cases a partial hydration shell of the solute molecule was considered. 25 Regarding deoxyribose, damage induced to this molecule in the gas phase

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upon collision with keV proton has been measured 26,27 and charge exchange and ensuing damage have been modeled. 28

Computational Methods The aim of this study is to understand the effect of slow (few electronvolts) protons colliding with a deoxyribose molecule embedded in liquid water. To produce these protons, we model the coulombic explosion of a doubly ionized water molecule, as described in details for the case of pure liquid water in a previous work. 11 The method is based on time dependent Density Functional Theory molecular dynamics in which effective molecular orbitals (MO) are propagated in time. These molecular orbitals are constructed at t=0 as a unitary transformation of the Kohn-Sham orbitals that achieves maximal localization in space (Wannier orbitals). 29,30 The ionization process is obtained by removing electrons from selected molecular orbitals. 11 This allows to localize the double charge on one specific molecule. Once specified this initial state, the electronic structure is propagated by Ehrenfest dynamics: It is not bound to any specific (ground or excited) state of the system (solute and liquid solvent) but instead is driven by a state-averaged potential (mean-field potential). The numerical solution of the corresponding time-dependent Kohn-Sham equations (TDKS) is obtained by direct integration in time: 31,32 It describes the time-dependent evolution of an initial non-stationary electronic state. In our calculations, the numerical integration of the TDKS equations was performed using an iterative Crank-Nicolson algorithm with a time step of ∆t = 0.00012 fs combined with a two-step Runge-Kutta scheme to maintain ∆t3 order accuracy. 33 The ions are propagated alongside the electrons in the Ehrenfest scheme, which is expected to be valid at these very short time scales. Because of the very small time step used in the real time propagation of electrons, the total simulation time is limited to 10-20 fs. To further investigate the early chemical reactions of the fragments within the sample, we switched to ground-state Car Parrinello MD with a

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time step of 0.006 fs for a total simulation length of 1.3 ps. 15 When switching from TDDFT to CP MD, the positions and the velocities of all the atoms are kept unchanged, while the electronic structure is optimized to reach the BO surface, leading to a slight redistribution of the electronic cloud. For aqueous deoxyribose, the periodic cubic box is composed of the sugar molecule (solute) surrounded by 58 water molecules in a cubic box of size L=12.43 Å. The sugar is in the pyranose conformation, which is the most probable conformation in the liquid phase. The long range electrostatic potential is computed using the standard Ewald-summation scheme and a compensating background is used in order to neutralize the total charge of the system. All simulations are performed with the plane wave Kohn-Sham (KS) based DFT code CPMD. 34 Core electrons are replaced by pseudopotentials of the standard Troullier-Martins form. 35 The Kleinman-Bylander 36 integration scheme is used for all types, and the plane wave basis set is truncated at an energy cutoff of 70 Ry and 90 Ry for the TDDFT and CP MD, respectively. The exchange correlation energy is calculated using the GGA functional BLYP, 37,38 and the TDDFT calculations are performed within the so-called adiabatic approximation. 39 The neutral system has been equilibrated at 310 K by running an about 10 ps CP MD during which a rescaling of velocities was applied and then a 4.1 ps CP MD during which no rescaling of velocities was applied. For the analysis, we considered two different initial configurations, labelled A and B, sampled from the tail of the CP MD trajectory and separated by a time interval of 970 fs. The average temperature of the ions during this laps of time was 300 K. The three DR hydroxyl groups generally form one or two hydrogen bonds (HB) with the surrounding water network, and the ring oxygen accepts one HB. Prior to launching the Ehrenfest MD, the effective Wannier moleculars orbitals of all molecules in the sample are assigned as follows: 27 effective MOs are localized on the DR molecule, and four effective MOs are ascribed to each water molecule of the sample, which can unambiguously be labeled 2A1, 1B2, 3A1 and 1B1 by similarity with the isolated water

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Figure 1: Initial configuration for the simulation of aqueous deoxyribose (configuration A). Left: Two electrons are initially removed from the 2a1 MO of a water molecule close to the DR molecule (black contour). Right: Six water molecules were selected. For the sake of clarity, the other water molecules are not presented. C cyan, O red, H white.

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molecular orbitals. 30 The initial non-stationary electronic state of the doubly charged sample is prepared by removing two electrons either from the 1b1 or from the 2a1 molecular orbital of one specific water molecule, as illustrated on Figure 1. This molecule is ionized into H2 O2+ , while all the other molecules of the sample remain strictly neutral. We have generated twelve Ehrenfest MD trajectories starting from the initial configuration A. The six water molecules selected for the initial ionization are shown in Figure 1: WAN56 donates an HB to the C1−OH group; WAN92 accepts an HB from the C4−OH group; WAN144 donates an HB to the C3−OH group, while WAN168 accepts an HB from the same hydroxyl group; WAN200 donates an HB to the ring oxygen of deoxyribose; and finally WAN164 does not form any HB with the DR molecule. When the two electrons were removed from the 1b1 MO, the six Ehrenfest MD were propagated for 16.4 fs, and CP MD were started at t=10.5 fs and at t=16.4 fs. When the two electrons were removed from the 2a1 MO, the Ehrenfest MD were propagated either for 10.5 fs (in the case of molecules WAN144, WAN164 and WAN168) or for 21.6 fs (in the case of molecules WAN56, WAN92 and WAN200). CP MD were started at t=10.5 fs and at t=21.6 fs. Three additional trajectories were generated starting from the initial configuration B. In this case, all selected water molecules were forming direct HB with the solute (WAN56, WAN92, WAN144). In this case, the Ehrenfest MD were initiated from an electronic configuration where two electrons were removed from the 2a1 MO, and propagated for 10.5 fs.

Results and discussion Protons collisions with water molecules: the first 10 fs Ehrenfest MD In this section, we will first describe the early dynamics induced by the removal of two electrons from the 2a1 molecular orbital of a series of water molecules (one for each simulation). All these H2 O2+ molecules are located in the primary hydration shell of a single solvated DR molecule (see Figure 1). As shown in a previous study, 11 the doubly ionized water molecules 9



dissociates according to the reaction H2 O2+ −→ 2 H+ + O, and both protons are emitted with a kinetic energy of a few eV. These protons then undergo collisions with the other molecules in solution, namely DR or other water molecules. In this way, the initial Coulomb explosion event can induce further bond breaking reactions with or without intermolecular charge migration. The nature of these processes in solution is in a way peculiar since the collisions occur in the kinetic energy range of only few eV and for relatively small impact parameters.

Figure 2: Electrons of the 2a1 MO of the water molecule WAN92 are removed to initiate the dynamics (black contour). After Coulomb explosion, two protons Ha and Hb move at high velocity towards the water molecules Oa Ha1 Ha2 and Ob Hb1 Hb2 , respectively. The trace of the most relevant atoms are shown. For the sake of clarity, only WAN92 and the molecules forming hydrogens bonds with it at t = 0 are shown. Color code: C cyan, O red, H white. Figure 2 shows a typical example of the ionization induced dynamics in the liquid phase. The double vacancy was initially localized on the molecule WAN92. At the time t = 0, this molecule is forming a HB directly with the DR. Its hydrogen atoms, Ha and Hb , also form hydrogen bonds with two neighboring water molecules, labeled Oa Ha1 Ha2 and Ob Hb1 Hb2 , respectively. After ionization, the two protons Ha and Hb dissociate and move at high velocity towards the water molecules Oa Ha1 Ha2 and Ob Hb1 Hb2 , respectively. Their trajectories follow 10


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a linear path until they collide with the oxygen atoms of the water molecules, which induces a deviation of the protons trajectories. In the case of Ha , the scattering angle amounts to θD = 168.8◦ meaning that it is deflected back to the original O* atom, where O* is the oxygen atom of the initially ionized WAN92 molecule. On the other hand, for Hb the scattering angle is only θD = 92◦ , implying that after collision the Hb moves further aways from its parent atom O* . As shown on Figure 2, the Oa Ha1 , Oa Ha2 , Ob Hb1 and Ob Hb2 bonds also elongate during the first 10 fs of dynamics following the ionization process.

Figure 3: Comparison of a proton/water collision in the liquid (dotted lines) and in the gas (solid lines) phases. Top left : Distance between the Ha proton and the oxygen atoms of the ionized water molecule (O* , black lines) and of the target water molecule (Oa , red lines). Bottom left : kinetic energy of the Ha proton (black lines) and of Oa (red lines). Top right : Oa Ha1 (black line) and Oa Ha2 (red line) distances. Bottom right : Ha1 (red lines) and Ha2 (black lines) kinetic energies. Figure 3 shows the time evolution of the O* Ha and Oa Ha distances (dotted lines). The O* Ha bond reaches dissociation within the time window of the Ehrenfest dynamics (10.5 fs).a As also shown on Figure 3, the kinetic energy of Ha increases rapidly with time after ionization, and reaches a maximum EM AX1 = 6.57 eV at tM AX1 = 3.07 fs. After this point, which corresponds to a distance between Ha and Oa of 0.99 Å, the Ha atom is slowing down as it a

CO and CC bonds are considered broken when the bond distance exceeds 2 Å. A criteria of 1.5 Å is used for OH and CH bonds

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starts interacting with the oxygen atom Oa . The distance Ha Oa reaches a minimum value of dM IN = 0.658 Å at tM IN = 4.41 fs, while the kinetic energy of Ha is also at its minimum value (0.041 eV) at a slightly later time t = 4.45 fs. At later times, the Ha atom continues its departure from Oa and its kinetic energy increases again to a new maximum value of EM AX2 = 5.25 eV at tM AX2 = 5.91 fs.b At this point, the Oa Ha distance reaches the value of 1.05 Å. Upon collision, the atom Oa gains kinetic energy, which increases by 1.49 eV between tM AX1 and tM AX2 ; during the same time interval the Ha atom looses instead 1.32 eV. The angle defined by the atoms Ha1 Oa Ha2 varies from 96◦ at t = 0 to 128◦ at t = 10.5 fs. In order to understand the role of the environment, we also simulated using BO and TDDFT MD the collision of Ha with molecule Oa Ha1 Ha2 in the gas phase (without the environment). To this end, the gas phase dynamics was started with the positions and velocities for the atoms Ha , Oa , Ha1 and Ha2 obtained from the liquid phase trajectory at t = 2.95 fs. Results are compared in Figure 3 (solid lines) and in Table 1. Interestingly, we found the same minimum distance from the scattering oxygen atom Oa (0.651 Å) occurring at the same time t = 4.43 fs as in solution. However, the scattering angle is slightly different. The angle Ha1 Oa Ha2 varies strongly from 104◦ at t = 2.95 fs to 137◦ at t = 10.3 fs, and it then returns to 104◦ at t = 17 fs. As shown on Table 1, the Ehrenfest and BO trajectories give very similar results, including the variation of the angle of the water molecule. However, contrary to the liquid phase simulation, in gas phase we do not notice any elongation of the Oa Ha1 and Oa Ha2 bonds of the target water molecule during the collision process. The charge of the incident hydrogen atom is +1e at t = 2.95 fs (starting point of the gas phase simulation) and becomes +0.56e at t = 10.5 fs (e is the electronic fundamental charge). To conclude, we find similar results in the liquid and gas phase during the interaction time (3 fs) when the initial conditions are similar and the impact parameter is small. At low impact parameters, the process in the condensed phase can be described as an "isolated" collision between a proton and a single water molecule, the environment doesn’t play an b

The deviation angle θD is estimated from the angle between the velocities of Ha at tM AX1 and tM AX2 .

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Table 1: Comparison liquid and isolated. Minimum distance (dM IN ) between the proton Ha+ et the oxygen atom Oa , deviation angle θD and kinetic energy difference between tM AX1 and tM AX2 of the proton Ha+ , the oxygen atom Oa and the two hydrogens Ha1 and Ha2 . See text for definition of tM AX1 , tM AX2 and tM IN . tM IN (fs) TDDFT 4.41 BO 4.43 TDDFT 4.43

Medium Method Liquid Isolated

dM IN (Å) 0.658 0.651 0.652

θD tM AX1 ◦ () (fs) 168.8 3.07 166.3 3.06 166.3 3.06

tM AX2 (fs) 5.91 5.79 5.79

Kinetic energy variation (eV) Ha Oa Ha1 Ha2 1.32 1.49 0.325 -0.030 1.52 1.67 0.116 -0.042 1.51 1.67 0.112 -0.045

important role during the collision time. The impact parameters are small because of the presence of hydrogen bonds, leading to small values of the minimum approach distance (dM IN ) between the proton and the oxygen atom to which it was initially hydrogen bonded. This distance was on average 0.74 and 0.76 Å for the first collision occuring after ionization from the 2a1 and 1b1 MO, respectively. The lowest value was 0.64 Å, with a deviation angle of 173.9◦ .

Early charge transfers and protons collisions with deoxyribose Several different collision events have been observed, depending on wether the DR molecule accepts or donates an HB to the nearby doubly ionized water molecule. They lead to differences in both charge transfer mechanisms and collisions patterns. When the ionized water molecule donates an HB to the DR molecule, an ultra fast electronic transfer occurs from the sugar to the oxygen of the water in about 0.2 fs, generating a singly ionized DR moiety (charge about + 0.5 e) well before a complete dissociation of the water molecule occurs (see Figure 4). More generally, this charge transfer involves the two molecules which initially accept an hydrogen bond from the doubly ionized water molecule. On the other hand, when the doubly ionized water molecule accepts an HB from the DR, the electronic transfer from the DR to the oxygen atom is slower (about 10 fs) and it takes place after the complete coulombic explosion of the water molecule. The collisions on the sugar are summarized on Tables 2 and 3. Two types of collisional

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Figure 4: TDDFT-MD trajectory initiated from an electronic configuration where two electrons were removed from the 2a1 MO of water molecule WAN56 (initial configuration A). Top. Difference between the electronic density of the neutral system at t = 0 fs and that of the doubly ionized system at t = 0 fs (left) and t = 0.24 fs (right). Positive (orange contour) and negative (yellow contour) isovalues correspond respectively to holes and electrons. Bottom. Charges on selected molecules along the TDDFT-MD trajectory: WAN56 (black line); DR (red line); the water molecule (blue line), which accepts an HB from WAN56; total charge of these three molecules (grey line).

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Table 2: Collisionnal events on the deoxyribose molecule (2a1 ). Two different initial configurations, A and B, were investigated. Charge of the DR molecule along the TDDFT MD, immediately before switching to the CP MD. Cases when the colliding proton charge is included (when the DR and the proton form a quasi-molecule) are marked by an asterix. The DR energies refer to the average kinetic energy of the DR atoms in the time interval between t=22 to t=50 fs, minus the initial value at t=0. H2 O2+ (config.)

Hydrogen bond with DR

WAN56 (B) WAN56 (A)

Donor to C1−OH Donor to C1−OH

Atom EM AX1 struck (eV)

WAN144 (A) Donor to C3−OH WAN144 (B) Donor to C3−OH

WAN200 (A) Donor to ring oxygen

WAN92 (A)

Acceptor from C4−OH

O1 O1 H1 O3 O3 C3 C2 H76 O5 H69

7.20 7.58

C3

6.13

7.14 6.28

6.54

C4 O4 WAN92 (B) Acceptor from C4−OH WAN168 (A) Acceptor from C3−OH

H4 O4 C4 C3 O3 O4 O3

6.00 7.21

WAN164 (A) None, next to C5 none a b TDDFT MD; CP MD initiated at t = 10.5f s;

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c

dM IN (Å)

tM IN (fs)

0.685a 1.16a 0.757a 0.642a 0.717a 1.565a 1.460a 1.267b 0.933a 0.828a 0.789b 1.367a 1.340b 1.532a 1.199b 0.953c 1.046b 1.200b 0.793b 1.191b 1.398b 0.846b 0.754b 0.871b 0.837b 0.857b

4.23 5.50 7.04 4.78 4.92 5.90 9.89 12.0 5.45 12.95 13.06 17.83 16.81 18.65 18.26 24.31 19.83 12.46 18.38 20.20 23.58 26.24 48.86 59.38 70.87 81.27

DR charge (e) 0.41b 0.46b 0.17c 0.36b 0.86*b

DR energy (eV) 0.8±0.3b 1.6±0.5b 1.5±0.5c 0.8±0.3b 1.7±0.5b

0.69b 0.42c

1.7±1.1b 0.6±0.4c

0.60b 0.74c

1.0±0.5b 0.9±0.6c

0.33b 0.16b

0.2±0.1b 0.5±0.4b

0.16b -0.2±0.1b CP MD initiated at t = 21.6f s.



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Table 3: Collisionnal events on the deoxyribose molecule (1b1 ). One initial configuration, A, was investigated. Charge of the DR molecule along the TDDFT MD, immediately before switching to the CP MD. Cases when the colliding proton charge is included (when the DR and the proton form a quasi-molecule) are marked by an asterix. The DR energies refer to the average kinetic energy of the DR atoms in the time interval between t=22 to t=50 fs, minus the initial value at t=0. H2 O2+ (config.)

Hydrogen bond with DR

Atom EM AX1 struck (eV)

dM IN (Å)

tM IN (fs)

DR DR charge energy (e) (eV) WAN56 (A) Donor to C1−OH H1 3.14 0.968a 8.97 0.91*b 1.0±0.4b O1 0.912a 9.01 0.82*c 1.2±0.4c WAN144 (A) Donor to C3−OH O3 2.51 0.769a 6.85 0.85*b 0.1±0.1b H3 1.357a 7.04 0.18c 0.3±0.1c WAN200 (A) Donor to ring oxygen O5 4.38 0.773a 6.39 0.41b 0.0±0.2b 0.707b 38.82 0.34c 0.1±0.2c c 0.730 42.09 0.861b 115.7 0.827c 104.0 WAN92 (A) Acceptor from C4−OH O4 3.08 0.821b 32.05 0.59b 0.1±0.2b 0.818c 31.81 0.44c 0.0±0.2c b WAN168 (A) Acceptor from C3−OH none 0.26 -0.3±0.1b 0.17c -0.3±0.1c WAN164 (A) None, next to C5 none 0.35b -0.2±0.1b 0.26c -0.2±0.1c a TDDFT MD; b CP MD initiated at t = 10.5 f s; c CP MD initiated at t = 16.4 f s.

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events take place. Direct collisional events on the DR occur when the ionized water molecule donates an HB to the DR. On the other hand, when the ionized water molecule accepts an HB from the DR, the protons are emitted towards other water molecules and may be retrodiffused towards the sugar, as illustrated in Figure 2. We also observe multiple collisions of this proton on the DR atoms, which gradually looses kinetic energy after each collision. This process gives rise to oscillations of the kinetic energy of the proton as a function of time (see Figure 5). As expected, the energy deposited in the sugar molecule is larger when the colliding proton originates from the most energetic initial electronic configuration (electrons removed from the 2a1 MO). Moreover, it reaches its minimal value in the case of the simulation involving molecule WAN164, where no proton collision with the sugar is observed. (In fact, this molecule does not form an hydrogen bond with the sugar.)

Figure 5: Trajectory initiated from an electronic configuration where two electrons were removed from the 2a1 MO of water molecule WAN168 (initial configuration A). Time evolution of the kinetic energy of the proton which is retrodiffused on a water molecule (labelled W), and then interacts with atoms O4, C4, C3 and O3 of DR. TDDFT-MD (solid red line); CP-MD (solid black line); time at which the distance between the proton and the indicated atoms presents a minimum (dotted black lines, see Table 2).

Sugar damage: the subsequent 1.3 ps CP MD At the end of the Ehrenfest dynamics, we observe different reactive transient species in solution, which result from the Coulombic explosion of the H2 O2+ molecule. When compared 17



to the inital geometry (t = 0) the conformation of the DR molecule can be considered substantially unchanged, but positively charged. The following chemical rearrangements are investigated in the framework of Car Parrinello MD, in which the systems wavefunction is set in its fundamental state. The electron distribution is thus slightly different from that at the end of the TDDFT MD. However, the difference observed in the density is mainly in the liquid water environment. As shown in Figure 6, the main change is localized on O∗ , which was taking part to the excited state at the end of the TDDFT MD.

Figure 6: Trajectory initiated from an electronic configuration where two electrons were removed from the 2a1 (left) and 1b1 (right) MO of water molecule WAN200 (initial configuration A). Difference between the electronic density of the TDDFT wavefunction and that of the fundamental state wavefuncion at t = 10.5 fs. Positive (orange contour) and negative (yellow contour) isovalues of 0.02. During the 1.3 ps CP MD dynamics, we observe different patterns of damages, which are summarized in Table 4 and detailed in the supporting information. The first fragmentation channel is illustrated in Figure 7. In this case, the doubly ionized water molecule is WAN56, which donates an HB to the C1 hydroxyl group of DR. As a result, one of the two protons emitted from the Coulomb explosion of WAN56 collides with the oxygen atom O1. The minimum distance is however quite large (1.16 Å) and the kinetic energy of O1 at the end of the Ehrenfest MD (after 10.5 fs) increases only to 0.2 eV. The proton then interacts with H1 with a distance of minimum approach of 0.76 Å, which gains about 1.1 eV kinetic energy at 10.5 fs. However, this kinetic energy transfer does not lead to the breakage of the C1-O1 and O1-H1 bonds; instead a rotation of H1 around the C1O1 18


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Table 4: Species formed at the end of a 1.3 ps Car Parrinello MD, after reaction with fragments originating from the Coulomb explosion of the water molecules located in its primary hydration shell. Damage to the DR molecule (C5 H10 O4 ) CHO−CH2 −CHOH−O−CH2 −CHO (C5 H8 O4 ) CHO−CH2 −CHOH−CHO + CH2 O (C4 H6 O3 + CH2 O) Cetone group on C4 (C5 H8 O4 ) Cetone group on C3 (C5 H8 O4 ) CHO−O−CH2 −CHOH−COH−CH2 (C5 H8 O4 ) C5 H11 O4+ None

Species formed in the medium 2H3 O+

occurence

2H3 O+

4/24

H2 + H2 O2 + 2H3 O+

1/24

2 H3 O+

1/24

2 H3 O+

1/24

H2 O2 + H3 O+ H2 O2 + 2 H3 O+

1/24 6/24

10/24

Figure 7: 10.5 fs Ehrenfest MD trajectory initiated from an electronic configuration where two electrons were removed from the 2a1 MO of water molecule WAN56 (black contour; left, t = 0, initial configuration A). This molecule donates an HB to the C1 −OH hydroxyl group of DR at t = 0. C cyan, O red, H white.

19



bond is observed. In fact, the charge of the DR molecule increases gradually from +0.4e at the end of the Ehrenfest MD to +1.1e when 110

Proton Collision on Deoxyribose Originating from Doubly Ionized

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