A new intermolecular mechanism to selectively drive photoinduced damages
Kirill Gokhberg, Premysl Kolorenc, Alexander I. Kuleff, Lorenz S. Cederbaum
aa r X i v : . [ phy s i c s . a t m - c l u s ] M a r A new intermolecular mechanism to selectively drivephotoinduced damages
Kirill Gokhberg , Pˇremysl Kolorenˇc , Alexander I. Kuleff , Lorenz S.Cederbaum Theoretische Chemie, Physikalisch-Chemisches Institut,Universit¨at Heidelberg, Im Neuenheimer Feld 229, D-69120 Heidelberg, Germany Institute of Theoretical Physics, Faculty of Mathematics and Physics,Charles University in Prague, V Holeˇsoviˇck´ach 2, 180 00, Prague, Czech Republic
Abstract:
Low-energy electrons (LEEs) are known to be effective in causing strandbreaks in DNA. Recent experiments show that an important direct source of LEEs is theintermolecular Coulombic decay (ICD) process. Here we propose a new cascade mechanisminitiated by core excitation and terminated by ICD and demonstrate its properties. Explicitcalculations show that the energies of the emitted ICD-electrons can be controlled byselecting the initial atomic excitation. The properties of the cascade may have interestingapplications in the fields of electron spectroscopy and radiation damage. Initiating sucha cascade by resonant X-ray absorption from a high-Z element embedded in a cancerouscell nucleus, ICD will deliver genotoxic particles locally at the absorption site, increasing inthat way the controllability of the induced damage.When embedded in a medium, electronically excited atoms and molecules efficiently de-cay radiationlessly by transferring their excess energy to the neighboring species in the en-vironment and ionizing them, creating in that way low-energy electrons (LEEs) and radicalcations. This process is known as intermolecular Coulombic decay (ICD) [1].Since its discovery in 1997 [1], the ICD has been successfully investigated in a variety ofsystems [2]. It usually proceeds on a femtosecond timescale and becomes faster the moreneighbors are present, dominating most of the competing relaxation processes. Experimentalinvestigation of ICD in water dimers [3] found the rate of this process to be so large asto completely suppress the proton transfer in the inner-valence ionized water molecules.As a result of ICD, two intact water cations are produced by the consecutive Coulomb1xplosion in addition to the slow ICD electrons. Another striking feature of this process isthat ICD remains effective for considerable interatomic distances. ICD was demonstratedexperimentally and theoretically for He dimer, which is the weakest bound system known innature, and found to be operative over distances of about 45 times the atomic radius [4, 5].These properties of ICD and the fact that it appeared to be ubiquitious in hydrogen-bonded systems [6–8] suggest its potential importance for radiation damage [9]. Low-energyelectrons (LEEs) [10, 11], as well as radical cations [12], the direct products of the ICD,are known to be effective in causing single- and double-strand breaks in DNA. Recent ex-periments even suggest that ICD electrons contribute up to about 50% of the single-strandbreaks (SSB) in DNA [13]. Moreover, these electrons possess energies at which much harderto repair double-strand breaks (DSB) occur [10, 14] and the energetic cations produced inCoulomb explosions may additionally damage the DNA.The excited electronic states undergoing ICD with the environment may be produceddirectly by photoabsorption, electron impact, or even by ion impact as demonstrated recently[15]. Alternatively, they may be formed as a result of multistage cascade processes. TheAuger decay process followed by ICD is one type of such cascades. It is initiated by coreionization of an atom, e.g., through X-ray absorption. This cascade, postulated theoretically[16], has since been studied in a series of experimental works [17–19]. Importantly, since theAuger-ICD cascade is initiated by core ionization, in a complex system one has little controlover the location where the Auger decay can be initiated and the follow-up ICD is going totake place. Indeed, in a polyatomic system, all atoms with core-ionization potentials belowthe energy of the impacting photon may become ionized and, therefore, undergo an Augertransition. Here we propose a different scheme to initiate a cascade ending by ICD in whichone has control not only over the location of the process, but also over the energies of theemitted ICD electrons.If the energy of the incoming photon lies just below the core-ionization threshold of aselected atom in a larger system, at a number of discrete energies the core electron willresonantly absorb the photon and be promoted to some bound unoccupied orbital. Theresulting highly energetic core-excited state may decay through the emission of an Augerelectron in the process known as resonant Auger (RA) decay [20–22]. Here, a valenceelectron fills the initial vacancy and another valence electron is ejected into the continuum,while the initially excited electron remains a spectator. This commonly termed spectator2A mechanism produces highly excited valence-ionized states (so-called photoionizationsatellite states). The alternative participator process, in which the initially excited electronparticipates in the decay, is usually the much less efficient de-excitation pathway followingcore excitations [23].Using modern high-resolution synchrotron-radiation sources one can selectively excitecore electrons not only on chemically different atoms but also on identical atoms occupyingnon-equivalent sites in the system. The latter stems from the different chemical shifts theatoms experience in a different chemical environment. This selectivity is used in the NearEdge X-ray Absorption Fine Structure spectroscopy (NEXAFS) [24] to study, for example,the bonding in biologically relevant organic molecules [25].The RA decay takes place on the initially excited species, and the excited ionic statesproduced usually have excess energies of a few tens of eV which they can transfer efficiently tothe environment by continuing to decay electronically via ICD. We illustrate schematicallythe resulting RA-ICD electronic cascade in Fig. 1. It bears decisive differences from theAuger-ICD cascade described above, allowing one to control the ICD process. First, theenergy of emitted ICD electrons in the same environment depends sensitively on the energiesand population of the states produced by RA. These parameters depend in turn on thenature of the parent core-excited state. Consequently, by varying the energy of the high-energy photon one can resonantly excite different parent states and change the appearance ofICD spectra in a controlled manner. Second, the initial parent core excitation can be placedselectively on an atom in a moiety of choice. And as the RA decay tends to proceed locallypopulating ionized-excited states with two holes localized predominantly on the atom bearingthe initial excitation, see e.g. Ref. [22], ICD will follow leading mostly to the ionization ofthe environment in the vicinity of the parent core-excitation (see Fig. 1b). In other words,the site where the damaging ICD electrons are produced can be selectively chosen.We illustrate the RA-ICD cascade on the example of ArKr. The relative simplicity of thissystem gives a transparent picture of the processes involved. This cascade can be initiatedby selectively producing a core-excited state localized on the Ar atom. Choosing a photonenergy of 246.51 eV one populates the 2 p − / s state of Ar [26]. This state lives only 5.5 fs[27] and decays locally by spectator Auger populating a band of excited states of Ar + (seethe Supplementary Materials). These states lie at energies between 17 and 22 eV above theground state of Ar + and can, therefore, undergo ICD with the neighboring Kr whose lowest3 +++ + X-ray excitationResonant Auger decayICD (a) (b)
FIG. 1: Schematic illustration of the resonant Auger-ICD cascade. (Panel a) The mechanism. Aparent core excited state embedded in the environment decays locally in the spectator resonantAuger process producing ionized-excited states. The latter continue decaying in the ICD processionizing the neighbors in the environment. The two cations produced by ICD repel each otherstrongly and undergo a Coulomb explosion (not shown). (Panel b) Selectivity property. Theparent state is produced selectively on a given atom of the embedded system. The ionized-excitedstates formed in the RA process tend to be localized close to the site of the initial excitation anddecay by ICD ionizing predominantly neighbors from the environment nearest to this site. ionization potential is 14 eV. To demonstrate that these states indeed further decay by ICD,we have determined the ICD rates employing extensive ab initio many-body calculations.We can estimate the spectra of the ICD electrons emitted in the cascade using the com-putational scheme presented in the Supplementary Materials. The corresponding electronspectrum is depicted in Fig. 2a. It exhibits two peaks: a pronounced peak between 0 and1 eV, and a weaker peak between 2 and 4 eV. Following the ICD, Ar + and Kr + will repeleach other resulting in the Coulomb explosion. At the end of this dissociative process, the4ons acquire ∼ . (b) (a) ICD-electron spectraafter 2p 4s excitation of Ar atomafter 2p 3d excitation of Ar atom I n t en s i t y ( a r b . un i t s ) Electron energy (eV)
FIG. 2: Spectra of the ICD electrons emitted in the RA-ICD cascades in ArKr: (a) followingcore-excitation of the Ar(2 p − / s ) parent state at 246.51 eV, and (b) following the core-excitationof the Ar(2 p − / d ) parent state at 246.93 eV. One sees that two different core-excitations of thesame atom lead to totally different energy distributions of the ICD electrons. The possibility tocontrol the energies of the ICD electrons becomes apparent. For more details, see text and theSupplementary Materials. Increasing the energy of the X-ray photon by just 0.4 eV to 246.93 eV one excites the2 p − / d parent state of Ar. The RA decay of this core excitation populates a totally differentband of excited states of Ar + . All these states can further decay via ICD emitting electronswhose spectrum is shown in Fig. 2b. It consists again of two peaks: one between 3 and 5 eVand another between 6 and 8 eV. One sees that two different core-excitations of the sameatom lead to totally different energy distributions of the ICD electrons. The possibility tocontrol the energies of the ICD electrons becomes apparent.While details may differ, the mechanism of RA-ICD cascade in other systems will besimilar to the case of ArKr. Very recently, the RA-ICD cascade was demonstrated experi-mentally in molecular dimers [28]. The selectivity property of the cascade and the ability tocontrol the energies of ICD electrons by tuning to the different parent state make RA-ICDcascade a foundation for a promising analytical technique. For example, in a larger molecule5mbedded in a solvent one may create a core excitation localized on a selected moiety. Augerdecay is an intra-molecular process and by observing the Auger electrons one studies theelectronic structure of the molecule at the excitation site. ICD is an intermolecular processand involves the neighbors, and the observation of ICD electrons allows one to probe thelocal environment (see Fig. 1b). X - R ay A u g e r I C D K - s he ll e xc i t a t i on P r i m a r y X - r a y p h o t o n FIG. 3: Schematic illustration of the proposed biomedical application of the RA-ICD cascade. Amonochromatic high-energy X-ray photon is resonantly absorbed by a K-shell electron to producea core-excited parent state of a high-Z compound brought to the vicinity of the DNA of the cellto be damaged. Due to the high energy, these X-rays have a large penetration depth in thetissue. The use of high-Z compounds in combination with the resonant core-excitation also hasthe advantages of improving the contrast between the healthy and cancerous tissue enabling touse lower concentrations of such — often toxic — compounds, and lower intensity of the X-rayscompared to the case where less specific core-ionization is employed. The parent state decaysin a local multistage cascade of X-ray emission and resonant Auger processes emitting secondaryphotons and energetic Auger electrons, and producing thereby ionized-excited, doubly ionized-excited, etc. states of the moiety containing the high-Z element. These states continue to decayintermolecularly by ICD releasing genotoxic low-energy electrons and causing additional mechanicaldamage to DNA by Coulomb explosions.
Let us elaborate on another possible practical application of the high selectivity and6ontrollability of RA-ICD and related cascades (for brevity we will call them all RA-ICD).The properties of these cascades and the fact that they can be initiated by high-energyX-rays makes them potentially useful in controlling the radiation damage of living cells.Embedding a high-Z element in the nucleus of a cancerous cell, a high-energy photon tunedresonantly to a particular core-excited state of this element will be predominantly absorbedby this element and trigger a RA-ICD cascade (see Fig. 3). In contrast to the cascade in thelow-Z ArKr system, where one Auger and one ICD electron are emitted, a K-shell excitationof a high-Z element will usually initiate a complex multistage process. Its first steps willbe dominated by fluorescence [29]. The later steps will proceed radiationlessly by emittingeither Auger electrons or ICD electrons in the so-called core-ICD process [30, 31] (see alsothe Supplementary Materials). The final states of the decay will still be ionized-excitedstates which will continue decaying by ICD with the water shell surrounding the DNA orwith the DNA itself.We note that radiotherapeutic techniques based on DNA-incorporated high-Z Auger-electron emitters (radionuclides [32] or photon activated ones [33]) have already been sug-gested. For instance, platinum-containing or iodinated compounds such as iodo-deoxyuridinehas been extensively investigated. The damage is thought to arise primarily from twosources. The Auger cascade initiated in the high-Z element either spontaneously (in ra-dionuclides) or by absorbing an X-ray photon leads to the emission of genotoxic Augerelectrons with energies below 500 eV [34]. Following this cascade, electron transfer to thehighly charged high-Z ion from the environment may also result in a Coulomb explosioncausing further damage [35]. In the proposed RA-ICD cascade, in addition to the Augerand the above mentioned core-ICD electrons, highly damaging low-energy ICD electronswith controllable energies are emitted. For example, SSBs in DNA are produced favorablyby electrons with energies between 0 and 4 eV [36], while DSBs are mostly induced by elec-trons with energies above 6 eV [11]. We note that only for electrons with energies below15 eV the microscopic mechanisms for strand breakage have been investigated [10, 11, 37–39](for brief discussion on higher energy electrons, see Supplementary Materials). In all theICD processes during the cascade two or more neighboring ions are produced directly leadingto damaging Coulomb explosion [3, 40]. The damage to DNA through the ICD electrons andthe Coulomb explosion following RA-ICD cascades will happen in the immediate vicinity ofthe site where the energy was initially deposited.7dditional benefits of the proposed scheme is that the RA-ICD cascade is triggered byresonant photon absorption which is more efficient than the traditional photon activatedtechniques where the Auger cascade is initiated by K-shell ionization. As we saw in theArKr example, the RA-ICD cascade provides the opportunity to tune the energies of theslow electrons by using the site and energy selectivity of the resonant core-excitations processwhich, in turn, may be useful to increase the damage of unwanted cells. Very importantly,in each ICD process, including the core-ICD ones which may take place at each step of thecascade, a genotoxic electron and a radical cation are simultaneously produced. The latterare also known to be extremely effective in causing DNA lesions [12].Understanding the microscopic mechanisms of DNA lesions would enable us to find therelevant parameters needed to increase the control over the induced damage and to maximizeit, paving the way for efficient cancer therapies. [1] L. S. Cederbaum, J. Zobeley, F. Tarantelli,
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The research leading to these results has received funding from the Eu-ropean Research Council under the European Community’s Seventh Framework Programme(FP7/2007-2013) / ERC Advanced Investigator Grant n ◦ upplementary Materials Materials and MethodsSupplemantary TextFigures S1 to S3References (XX–XX)