photoelectron spectroscopic and density functional theoretical

Photoelectron spectroscopic and density functional theoretical studies ofthe 2prime-deoxycytidine homodimer radical anionPiotr Storoniak Janusz Rak Yeon Jae Ko Haopeng Wang and Kit H Bowen Citation J Chem Phys 139 075101 (2013) doi 10106314817779 View online httpdxdoiorg10106314817779 View Table of Contents httpjcpaiporgresource1JCPSA6v139i7 Published by the AIP Publishing LLC Additional information on J Chem PhysJournal Homepage httpjcpaiporg Journal Information httpjcpaiporgaboutabout_the_journal Top downloads httpjcpaiporgfeaturesmost_downloaded Information for Authors httpjcpaiporgauthors

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THE JOURNAL OF CHEMICAL PHYSICS 139 075101 (2013)

Photoelectron spectroscopic and density functional theoretical studiesof the 2prime-deoxycytidine homodimer radical anion

Piotr Storoniak1a) Janusz Rak1 Yeon Jae Ko2 Haopeng Wang2 and Kit H Bowen2a)

1Department of Chemistry University of Gdansk Wita Stwosza 63 80-952 Gdansk Poland2Department of Chemistry Johns Hopkins University Baltimore Maryland 21218 USA

(Received 11 May 2013 accepted 24 July 2013 published online 15 August 2013)

The intact (parent) 2prime-deoxycytidine homodimer anion (dC)2bullminus was generated in the gas phase

(in vacuo) using an infrared desorptionphotoemission source and its photoelectron spectrum wasrecorded using a pulsed magnetic bottle photoelectron spectrometer The photoelectron spectrum(PES) revealed a broad peak with the maximum at an electron binding energy between 16 and19 eV and with a threshold at sim12 eV The relative energies and vertical detachment energies ofpossible anion radicals were calculated at the B3LYP6-31++Glowastlowast level of theory The most stableanion radicals are the complexes involving combinations of the sugar middot middot middot base and base middot middot middot baseinteractions The calculated adiabatic electron affinities and vertical detachment energies of the moststable (dC)2

bullminus anions agree with the experimental values In contrast with previous experimental-computational studies on the anionic complexes involving nucleobases with various proton-donorsthe electron-induced proton transferred structures of (dC)2

bullminus are not responsible for the shape ofPES copy 2013 AIP Publishing LLC [httpdxdoiorg10106314817779]

I INTRODUCTION

The interaction of ionizing radiation with biological sys-tems results in secondary low energy electrons (LEEs) of en-ergies in the range from 0 to 15 eV1 Because LEEs are shownto be capable of inducing strand breaks in dry DNA2 electronattachment to sub-units of DNA has been studied extensivelyin recent years3ndash16 Pyrimidines possess the highest electronaffinities among the DNA constituents17 which suggests thatboth thymine and cytosine are plausible targets for thermal-ized electrons Indeed the gas phase adiabatic electron affini-ties (AEAs) of individual nucleobases predicted by differentdensity functionals with different basis sets support the exis-tence of valence bound (VB) anions of uracil thymine andpossibly cytosine but question the stability of the VB an-ions of purines18ndash20 Solvation increases the stability of theVB anions of nucleobases as indicated by the PES experi-ments of Hendricks et al21 and Schiedt et al22 the former ofwhich demonstrated the existence of gas phase VB anions ofcanonical uracil solvated by a single atom of rare gas or wa-ter molecule Analogous molecular anionic clusters were ob-served using the crossed beam RET (Rydberg Electron Trans-fer) technique against uracil and thymine anions solvatedby rare gas atom23 Finally the gas phase hydrogen-bondedcomplexes of nucleobases with various inorganic24 and or-ganic (alcohols acids amino acids)25 proton donors werestudied within joint PES-DFT studies where an electron at-tachment induced barrier-free proton transfer was frequentlyobserved

The Watson-Crick AT26ndash30 and GC28 30ndash35 base pairs werealso shown to form stable VB anions in the gas phase Theexcess electron is localized on T or C in these complexes and

a)Authors to whom correspondence should be addressed Electronicaddresses pondroschemunivgdapl and kbowenjhuedu

the presence of a complementary purine base increases theAEA value of a pyrimidine

Moving from the Watson-Crick AT and GC base pairsto the dAdT and dGdC nucleoside pairs a significant in-crease in the electron affinity is observed According to theB3LYPDZP++ calculations the gas phase AEAs for thedAdT and dGdC nucleoside pairs are 06 eV and 083 eVrespectively36 37

The B3LYPDZP++ approach was also used to studyelectron attachment to more complex DNA fragments likesingle-strand (dCpdG dGpdC dTpdA dApdT dGpdGdGpdCpdG)38ndash41 and double-strand nucleotide oligomers(dGpdC)2)42 Based on the theoretical estimates all these sys-tems easily accept the excess electron and form adiabaticallystable radical anions

The B3LYPDZP++ calculations pertaining to 2prime-deoxyribonucleosides predicted positive gas phase electronaffinities for all of them The theoretical AEA values ofpurine nucleosides are negligible (006 and 009 eV for dAand dG respectively) compared to pyrimidine nucleosides(033 and 044 eV for dC and dT respectively) Howeverthe vertical detachment energy (VDE) value of 091 eV fordA (which is of similar magnitude to VDEs predicted fordC and dT) speaks in favor of the existence of the VB of2prime-deoxyadenosine anion radical in the gas phase43 IndeedStokes et al44 employing a combination of infrared desorp-tion electron photoemission and gas jet expansion recordedthe anion photoelectron spectra of the nucleoside parentanions of 2prime-deoxythymidinebullminus (dTbullminus) 2prime-deoxycytidinebullminus

(dCbullminus) 2prime-deoxyadenosinebullminus (dAbullminus) uridinebullminus (rUbullminus)cytidinebullminus (rCbullminus) adenosinebullminus (rAbullminus) and guanosinebullminus

(rGbullminus) Their measurements proved the appearance of the sta-ble valence radical anions of nucleosides in the gas phase Theexperimental VDEs and AEAs of dT dC and dA match wellwith those calculated by Richardson et al43 and by Li et al45

0021-96062013139(7)0751019$3000 copy 2013 AIP Publishing LLC139 075101-1


075101-2 Storoniak et al J Chem Phys 139 075101 (2013)

In the current work we employ infrared desorptionelectron photoemission and a gas jet expansion to gener-ate intact (parent anion) stable radical anionic species (2prime-deoxycytidine)2

bullminus in the gas phase in order to record its pho-toelectron spectrum In parallel the B3LYP6-31++Glowastlowast cal-culations were carried out to elucidate the structure of thespecies responsible for the measured spectrum The compu-tational approach allowed us to identify the most stable rad-ical anionic homodimers The calculated VDEs for thermo-dynamically most favorable structures are in good agreementwith the experimental values We demonstrate that electron-induced barrier-free proton transfer does not occur in the VB(dC)2

bullminus anions which is in accord with our previous resultsfor the nucleoside dimers (rU)2

bullminus46 and (dT)2bullminus47

II METHODS

A Experimental details

2prime-deoxycytidine radical dimer anions were generated us-ing a novel pulsed infrared desorption-pulsed visible photoe-mission anion source which has been described previously44

Anion photoelectron spectroscopy (PES) is conducted bycrossing beams of mass-selected negative ions and fixed fre-quency photons followed by energy-analysis of the resultingphotodetached electrons This technique is governed by theenergy conserving relationship hν = EBE + EKE where hν

is the photon energy EBE is the electron-binding energy andEKE is the measured electron kinetic energy

Low-power infrared laser pulses (117 eVphoton) froma NdYAG laser were used to desorb neutral 2prime-deoxycytidinefrom a slowly translating graphite rod which was thinlycoated with the sample Simultaneously electrons were gen-erated by visible laser pulses (another NdYAG laser operatedat 532 nm 233 eVphoton) striking a rotating yttrium oxidedisk Since yttrium oxidersquos work function of sim2 eV is slightlybelow the photon energy of the visible laser low energy elec-trons were produced and this process is critical to the forma-tion of intact (parent) biomolecular anions At the same timea pulsed valve provided a collisionally cooled jet of heliumto carry away excess energy and stabilize the resulting parentradical anions The photoelectron spectrum of the intact 2prime-deoxycytidine dimer radical anions was recorded by crossinga mass-selected beam of (dC)2

bullminus parent anions with a fixed-frequency photon beam (a third NdYAG laser operated at355 nm 349 eVphoton) The photodetached electrons wereenergy-analyzed using a magnetic bottle energy analyzer witha resolution of 35 meV at EKE = 1 eV Photoelectron spectrawere calibrated against the well-known photoelectron spec-trum of Cuminus48

B Computational details

Quantum chemical calculations were carried out by us-ing density functional theory with Beckersquos three-parameterhybrid functional (B3LYP)49ndash51 and the 6-31++G basisset52 53 The usefulness of the B3LYP6-31++G methodto describe intra- and intermolecular hydrogen bonds hasbeen demonstrated through comparison with the second orderMoslashller-Plesset (MP2) predictions for uracil middot middot middot water com-

plexes which were treated at the MP2 level by van Mouriket al54 and at the B3LYP level by Haranczyk et al24(a) Im-portantly calculations at the B3LYP6-31++G level ofHaranczyk et al for the VB (uracil middot middot middot water)minus clusters re-produced very well the VDE value extracted from the photo-electron spectrum registered by Hendricks et al21 For thesesystems the B3LYP6-31++G results appeared as goodas those calculated at the MP26-31++G(2df2p)MP26-311++G level55

Geometrical features of the 2prime-deoxyribonucleosides ob-tained at the DFT level (torsional angles bond lengths va-lence angles as well as intramolecular hydrogen bonds) wereshown to correlate well with those obtained at the MP2level56 Application of DFT and MP2 approaches also re-sulted in the identical energy order of the different conformersinvestigated in above reports

The ability of the B3LYP method to predict excess elec-tron binding energies was reviewed and the results were foundto be satisfactory for valence-type molecular anions57

All geometries presented here have been fully optimizedwithout geometrical constraints and the analysis of harmonicfrequencies proved that all of them are also geometrically sta-ble (all force constants were positive) The relative energiesE and Gibbs free energies G of the neutral and anioniccomplexes are defined with respect to the energy of the moststable neutral or anionic configuration The stabilization freeenergies Gstab of neutral complexes are calculated as a dif-ference between the energy of the complex and the sum of theenergies of fully optimized isolated monomers In the case ofanion radical complexes Gstab are calculated by subtractingenergies of the fully optimized anionic and neutral monomersfrom the energy of the given anion radical complex The freeenergies of the neutral and anionic species result from correct-ing the relevant values of electronic energies for zero-pointvibration terms thermal contributions to energy the pV termand the entropy terms These terms were calculated in therigid rotor-harmonic oscillator approximation at T = 298 Kand p = 1 atm

The adiabatic electron affinity AEA is defined as the dif-ference between the electronic energy corrected for zero-pointenergy of the neutral and the anion at their fully relaxed ge-ometries The vertical detachment energy VDE which is adirect observable in photoelectron spectroscopy experimentis defined as the energy of neutral dimer minus the energy ofthe anionic dimer at the geometry of the fully relaxed anionThe vertical electron affinity VEA is the energy of the neu-tral minus the energy of the anion both at the fully relaxedneutral geometry

All quantum chemical calculations have been carried outwith the GAUSSIAN 0358 and GAUSSIAN 0959 codes The pic-tures of molecules and molecular orbitals were plotted usingthe GaussView 41 program60

III RESULTS

A Experimental results

Photoelectron spectrum of the 2prime-deoxycytidine dimerradical anion is presented in Figure 1 A typical mass



FIG 1 Photoelectron spectrum of (2prime-deoxycytidine)2bullminus recorded with

349 eV photons

spectrum showing both the monomeric and dimeric anions of2prime-deoxycytidine is shown in the supplementary material asFigure S161 The broad peak indicative of a valence boundanion results from the vertical photodetachment of the ex-cess electron from a ground vibronic state of mass-selectednucleoside dimer radical anions to the ground vibronic stateof the resulting neutrals The maximal photoelectron inten-sities correspond to the optimal Franck-Condon overlaps ofthe vibrational wave functions between anion and neutralground states The photoelectron spectrum of (dC)2

bullminus ex-hibits a broad peak covering the range of sim12ndash25 eV Themaximum intensity of the signal which occurs between 16and 19 eV corresponds to the experimental VDE value Theelectron affinity (AEA) is more difficult to determine explic-itly Since there may be vibrational hot bands present in spec-

TABLE I Values of relative electronic energy free energy (E and G) forthe conformations of the neutral and anion radical 2prime-deoxycytidine verticaldetachment energies (VDEs) and adiabatic electron affinities (AEAs) of an-ion radical 2prime-deoxycytidine calculated at the B3LYP6-31++G level EG are given in kcalmol and VEA AEA and VDE are given in eV

Neutrals Anions

Conformation E G VEA E G AEA VDE

C2prime-endoanti minus 041 001 minus 015 014 175 025 114C3prime-endoanti 0 0 minus 016 0 0 030 075

tra such as these the threshold EBE energy is not necessarilyequivalent to the value of AEA As a reasonable approxima-tion however one can estimate the AEA value as that cor-responding to the EBE at sim10 of the rising photoelectronintensity Therefore from the onset of the photoelectron spec-trum AEA for (dC)2

bullminus can be estimated to be sim12 eV

B Computational results

The search through the dimer potential energy surfacewas preceded by the optimization of the neutral monomerThe starting nucleoside geometry was adopted after 2prime-deoxycytidine nucleotide gas-phase PBEaug-TZVP-GTHstructure published by Smyth and Kohanoff62 Similar stabil-ity of the C3prime-endo and C2prime-endo sugar conformations56 mo-tivated us to take under consideration both neutral dC confor-mations C2prime-endoanti and C3prime-endoanti Figure 2 presentstheir B3LYP6-31++Glowastlowast optimized geometries The C2prime-endo monomer is more stable than C3prime-endo by 041 kcalmolbut this difference vanishes when the Gibbs free energies arecompared (see Table I and Figure 2)

Both neutral conformations are characterized by al-most identical negative vertical electron affinities (minus015 andminus016 eV) However as indicated by the positive AEA val-ues shown in Table I the anion radicals should be stableonce they are formed The relative stability order of anions

FIG 2 Conformations of neutral and anion radical 2prime-deoxycytidine monomers optimized at the B3LYP6-31++G level



is reversed in comparison with the neutrals The B3LYP6-31++G AEA values 025 and 03 eV agree with the com-putational value of 033 eV reported by Richardson et al43

and Li et al45 as well as with the experimental value sim05 eVmeasured by Stokes et al44 There is a small difference in sta-bility of the monomeric anion radicals compared to a signifi-cant difference of sim04 eV in their VDE values (see Table I)As shown in Figure 2 the C2prime-endo anion radical involvesthe intramolecular 5primeOndashH middot middot middot C6 bond This hydrogen bondpresumably allows for better stabilization of the excess elec-tron The VDE calculated for the C3prime-endo monomer matchesperfectly its theoretical value of 072 eV calculated by

Richardson et al43 and agrees well with the experimentalVDE of 087 eV from the PES experiment44

1 Structures and energetics of the neutralhomodimers

The geometries of the neutral 2prime-deoxycitidine homod-imers optimized at B3LYP6-31++G level are shown inFigure 3 All 18 geometries were assembled from the opti-mized C3prime-endo monomers discussed in the preceding sec-tion Combination of the proton-donating centers (N8-H1N8-H2 C5-H O3prime-H O5prime-H) with proton-accepting centers

FIG 3 Structures of neutral 2prime-deoxycytidine homodimers optimized at the B3LYP6-31++G level



TABLE II Values of relative electronic energy and free energy (E andG) with respect to the most stable neutral 2prime-deoxycytidine homodimer andstabilization free energies (Gstab) of the neutral 2prime-deoxycytidine dimers cal-culated at the B3LYP6-31++G level All values given in kcalmol VEAis given in eV

Complex E G Gstab VEA

N8ndashH middot middot middot N3 familyn1 928 743 226 030n2 909 794 277 024n3 000 000 minus 517 019

N8ndashH middot middot middot N8 familyn4 1548 1339 822 035n5 1093 1167 650 027

N8ndashH middot middot middot O7 familyn6 844 628 111 028n7 769 774 257 011n8 893 1099 582 031n9 623 837 320 016

3primeOndashH middot middot middot N8 familyn10 995 1178 661 031n11 1094 1394 877 033n12 573 871 354 020

3primeOndashH middot middot middot N3 familyn13 630 585 068 029n14 599 603 086 022

3primeOndashH middot middot middot O7 familyn15 621 756 239 021n16 258 451 minus 066 027n17 253 399 minus 118 026n18 102 313 minus 204 013

(N8 O7 N3 O5prime O4prime) leads to the structures stabilizedthrough one or two hydrogen bonds In Table II and Figure 3the neutral (dC)2 structures are organized according to theirstructural cognation

As far as the relative orientation of the monomers is con-sidered the complexes can be divided into two main groupsA common feature of the complexes belonging to the firstgroup (structures n1-n9) is the presence of a hydrogen bondinvolving the proton-donating N8-H site of one nucleobaseand the proton accepting N3 N8 or O7 site of the sec-ond nucleobase Within this family there are dimers whereapart from the conventional hydrogen bonding solely amongnucleobases that is N8-H middot middot middot N3 (structures n1-n3) N8-H middot middot middot N8 (n4) or N8-H middot middot middot O7 (n6) interactions among thesugar and base (n7-n9) are also present as well as the com-plex n5 in which the nucleosides are attracted to each otherwith base middot middot middot base N8-H middot middot middot N8 and sugar middot middot middot sugar O5prime-H middot middot middot O5prime interactions

In the second group of structures the complexes are sta-bilized by sugar middot middot middot base hydrogen bonds that is through in-teractions between the sugarrsquos O3prime-H proton donating site andthe proton accepting atom of the cytosine moiety There arecomplexes belonging to this family where nucleosides in-teract via one or two hydrogen bonds one of which beingO3prime-H middot middot middot N8 (homodimers n10-n12) O3prime-H middot middot middot N3 (n13n14) or O3prime-H middot middot middot O7 (n15-n18) As in the first groupapart from common (sugar)O3prime-H middot middot middot base bonding in sev-

eral complexes an additional hydrogen bond between sugarand base is formed (n11 n12 n16-n18)

The relative energies and Gibbs free energies (Es andGs) VEAs as well as the stabilization free energies (Gstabs)calculated for each of the 18 neutral 2prime-deoxycytidine homod-imers are given in Table II Their electronic energies and freeenergies span a wide range of values The energy and free en-ergy difference between the most (n3) and least (n4) stablestructures is 155 and 134 kcalmol respectively

The most stable are four homodimers n3 n18 n17 andn16 The n3 geometry belongs to the first group of struc-tures while the three remaining belong to the second one Allthese dimers are characterized by the negative Gstab values ofminus52 minus20 minus12 and minus07 kcalmol (see Table II) suggest-ing their occurrence in the gaseous dC From the comparisonof VEAs calculated for monomers and dimers it can be notedthat homodimers should attach the excess electron more spon-taneously than monomers as indicated by the positive VEAvalues in Table II that span the range of 011 to 035 eV

2 Structures and energetics of the anionradical homodimers

Our B3LYP6-31++G calculations ended up with 27anion radical homodimers All anionic structures are shown inFigure S2 in the supplementary material61 and the most stableanion radicals are depicted in Figure 4 The thermodynamiccharacteristics of (dC)2

bullminus complexes are gathered in Table IIIThe names of the anion radicals correspond to the names ofthe respective neutrals for example the anion radical denotedas a1 originates from the geometry optimization of anion rad-ical starting from the neutral n1 geometry This rule was ap-plied to all geometries but the a_N8H-O7C5H-N3_intraa_3primeOH-N8 and a_3primeOH-O7_intra structures where geom-etry optimization converged to the structures being far fromthe starting point Therefore the names of these three anionswere supplemented with information on the intermolecularhydrogen bonds stabilizing the complex rather than on theneutral geometry they originated from The suffix ldquointrardquo in-dicates structures where an intramolecular O5primeH middot middot middot C6 hy-drogen bond is formed Finally the attachment of an electronto a given neutral (dC)2 triggers in some cases intermolec-ular electron-induced proton transfer which is labeled by theldquoPTrdquo suffix

The most stable anionic complexes a13 a13_intraa16_intra and a8 are displayed in Figure 4 the first three ge-ometries differ no more than 07 kcalmol in electronic energywhile the last one is less stable by sim12 kcalmol than a13The estimated adiabatic stability (AEA) for the most stablestructures spans the range of sim08ndash11 eV and for the struc-ture a13 which is expected to dominate in the gas phase AEAequals to 101 eV Comparing the previously measured adia-batic affinities for 2prime-deoxycytidine which is sim05 eV44 withthe calculated value of 03 eV one can assume that a +02 eVincrement is necessary to convert the calculated value into ameasured one It is worth noting that the corrected AEA val-ues for a13 and for the remaining low energy dimeric anionsmatch reasonably well with the experimental AEA of sim12 eVmeasured for (dC)2

bullminus in the present study (see Figure 1)



TABLE III Values of relative electronic energy and free energy (E and G) with respect to the most stable 2prime-deoxycytidine homodimer radical anion stabilization free energies (Gstab) vertical detachment energies (VDEs)and adiabatic electron affinities (AEAs) of anion radical 2prime-deoxycytidine homodimers calculated at the B3LYP6-31++G level E G and Gstab are given in kcalmol AEA and VDE are given in eV

Family Complex E G Gstab AEA VDE

3primeOndashH middot middot middot N3 a13 000 000 minus 1477 101 1603primeOndashH middot middot middot N3 a13_intra 067 305 minus 1172 094 1953primeOndashH middot middot middot O7 a16_intra 068 384 minus 1093 079 179N8ndashH middot middot middot O7 a8 117 301 minus 1177 108 1603primeOndashH middot middot middot O7 a15 232 231 minus 1246 092 1523primeOndashH middot middot middot O7 a16 252 309 minus 1169 075 1353primeOndashH middot middot middot O7 a15_intra 277 348 minus 1129 087 1883primeOndashH middot middot middot O7 a17_intra 293 605 minus 873 068 165N8ndashH middot middot middot O7 a_N8H-O7C5H-N3_intra 358 384 minus 1094 1863primeOndashH middot middot middot N8 a10_intra 385 654 minus 824 097 188N8ndashH middot middot middot N3 a1_intra 392 480 minus 997 093 187N8ndashH middot middot middot N3 a1 407 281 minus 1197 096 1503primeOndashH middot middot middot O7 a18 420 572 minus 905 060 088N8ndashH middot middot middot O7 a6 420 220 minus 1257 092 145N8ndashH middot middot middot N3 a3_PT 461 538 minus 940 056 192N8ndashH middot middot middot N8 a5_intra 466 793 minus 685 097 194N8ndashH middot middot middot N3 a3_intra_PT 525 612 minus 865 051 2203primeOndashH middot middot middot N8 a12 538 709 minus 769 077 138N8ndashH middot middot middot N3 a2 555 627 minus 850 086 1833primeOndashH middot middot middot O7 a_3primeOH-O7_intra 557 499 minus 978 1423primeOndashH middot middot middot N8 a11 598 921 minus 556 095 136N8ndashH middot middot middot N3 a3 653 417 minus 1061 052 060N8ndashH middot middot middot N3 a3_intra 759 792 minus 685 043 140N8ndashH middot middot middot O7 a6_intra 773 861 minus 616 075 188N8ndashH middot middot middot N3 a2_intra_PT 801 688 minus 790 076 2753primeOndashH middot middot middot N8 a_3primeOH-N8 1150 857 minus 621 112N8ndashH middot middot middot N8 a4_intra 1352 1278 minus 200 080 166

The theoretical VDEs calculated for the structures ofFigure 4 correlate perfectly with the maximum EBE16ndash19 eV displayed on the photoelectron spectrum (seeFigure 1) The highest VDE values among the most stable

structures 195 and 179 eV are attributed to the a13_intraand a16_intra geometries where one of the monomersfeatures an intramolecular H-bond As shown in Table Ithe formation of the intramolecular O5prime-H middot middot middot C6 bond in

FIG 4 Structures of the most stable anion radical 2prime-deoxycytidine homodimers optimized at the B3LYP6-31++G level with corresponding VDE valuesand their singly occupied molecular orbitals plotted with a contour value of 005 bohrminus32



2prime-deoxycytidine monomer stabilizes the excess charge andshifts its VDE to higher values by 039 eV as compared to thenucleoside without an internal H-bond

IV DISCUSSION

The photoelectron spectrum recorded for (dC)2bullminus is ex-

perimental evidence of 2prime-deoxycytidinersquos ability to exist inthe gas phase as an adiabatically stable valence anion rad-ical The broad photoelectron spectral signal suggests that(dC)2

bullminus may occur under our experimental conditions in sev-eral forms these having various VDEs This observation isin agreement with our results of quantum chemical mod-eling which indicates that the four most stable structurespossess almost identical energetic stability (Figure 4) Thesedimeric geometries are stabilized by two hydrogen bonds in-volving both sugarsrsquo and cytosinesrsquo sites The H-bond pat-tern is identical in the two most stable anionic structures(a13 and a13_intra) The only difference lies in the confor-mation of one of the nucleosides Thus a13 and a13_intraare held together by the sugar middot middot middot base O3prime-H middot middot middot N3 andbase middot middot middot base C6-H middot middot middot O7 interactions In the third most sta-ble complex a16_intra one of the nucleosides utilizes twoof the sugarrsquos hydroxyl groups (its O3prime-H serves as a pro-ton donor and O5prime as a proton acceptor) to bind to the nu-cleobase of the second nucleoside The least stable structurea8 employs deoxyribosersquos 5prime-end hydroxyl group as a protondonor to form a H-bond with the N8 of cytosine in the sec-ond nucleoside The finding that the strongest stabilization ofthe anionic nucleoside dimer structures arises from the O3prime-H middot middot middot N3 sugar middot middot middot base interaction agrees with our previousstudies on the uridine and thymidine homodimer anions46 47

Basically two types of H-bonds that keep together themonomers in the studied dimers are discussed in the currentpaper as well as in Refs 46 and 47 Namely the H-bonds be-tween nucleobases involves a proton acceptor site of one baseand a proton donor site of another one This type of com-plex forms the global minimum n3 which is stabilized bytwo N8-H middot middot middot N3 such hydrogen bonds To the another pos-sible type of (dC)2 belong the species which are stabilized byhydrogen bonds between the C3prime-OH of one monomer anda proton acceptor site of cytosine in the second monomerThe most stable structure of this type is the n18 dimer thatis only 1 kcalmol (E) less stable than the n3 one Inter-estingly the neutral global minimum does not support themost stable anion Surprisingly the favorable anionic struc-ture is stabilized by only one hydrogen bond involving theC3prime-OH proton donor site of one monomer At the very firstglance this finding is unintuitive Electrostatic interactions be-tween the charged and neutral monomer rather than hydro-gen bonds may be responsible for the observed stability or-der of dimers Probably dipole middot middot middot monopole interactions ac-count for the observed effect The direction of dipole momentin the dC molecule is shown in the supplementary material(see Figure S3)61 Hence the positive pole of dipole momentpoints to the region of negative charge in the a13 and remain-ing anionic structures of the highest stability The oppositearrangement is observed in the cytosine middot middot middot cytosine geome-tries As a consequence attractive dipole middot middot middot monopole inter-

actions are present in a13 while repulsive ones are presentin the cytosine middot middot middot cytosine families which may explain theobserved stability order Similarly in the least stable of an-ionic geometry a4_intra where monomers interact by sin-gle N8-H middot middot middot N8 bond between cytosinesrsquo repulsive interac-tions between dipole and monopole are observed An unfa-vorable dipole middot middot middot dipole interaction between neutral nucleo-sides may already be noted in the neutral parent n4 of the an-ionic homodimer a4_intra which is the most unstable neutralhomodimer among the considered geometries

The VDE of 16 eV calculated for two of the fourmost stable anion radical complexes a13 and a8 shown inFigure 4 agrees with the lower limit of the EBE of the sig-nal intensity maximum Additionally the remaining two com-plexes a13_intra and a16_intra may be responsible for theupper limit of the photoelectron signal at EBE of 19 eV

Note that the thermodynamically most stable neutralcomplex n3 stabilized by two N8-H middot middot middot N3 H-bonds doesnot form the most stable anion radical (see a3 in Table II)However since electron induced proton transfer was shownto be an important stabilizing factor for anionic complexes in-volving nucleobases24 25 we also modeled intermolecular pro-ton transfer from N8H amine group to the N3 atom withinanionic dimers originating from the most stable n3 and thesecond most stable in the N8-H middot middot middot N3 family n2 geome-try (see Table II) Three such anions a2_intra_PT a3_PTand a3_intra_PT have been identified and their characteris-tics as well as structures are gathered in Table III and Fig-ure S261 respectively Despite favorable Gstab and AEA wefound these complexes to be relatively unstable in comparisonto the lowest energy a13 anion radical (see Table III) More-over the calculated VDEs 275 and 22 for dimers involvingone monomer with intramolecular H-bond a2_intra_PT anda3_intra_PT respectively are well above the measured verti-cal detachment energy (cf Figure 1) Only a VDE of 192 eVobtained for the a3_intra complex consisting of monomerswithout intramolecular H-bond is close to the higher en-ergy limit of maximum on the photoelectron spectrum (atsim19 eV) Nevertheless structure a3_PT similar to remain-ing proton-transferred geometries that is a2_intra_PT anda3_intra_PT is not expected to occur in the experiment dueto its low stability

The fact that thermodynamically most favorable neutralhomodimers do not directly form the most stable anion radi-cals suggests that the formation of gaseous anionic dimer doesnot necessarily involve an electron attachment to the neutraldimer In particular it cannot be ruled out that the processleading to the formation of (dC)2

bullminus starts from the attachmentof electron to a monomeric nucleoside Then the adiabaticallystable (see Table I) dCbullminus anion could interact with a neutraldeoxycytidine molecule forming the anionic dimers observedin the photoelectron experiment

Finally we note that the maximum of photoelectronsignal for the (dC)2

bullminus anion is significantly shifted towardhigher values of electron binding energy with respect tothose of both the anionic cytosine dimer (cytosine)2

bullminus63

and 2prime-deoxycytidine (dC)bullminus44 (see Figure 5) The verticalstability of 2prime-deoxycytidine homodimer anion results fromintermolecular interactions between the negatively charged



FIG 5 Comparison of the anion photoelectron spectra of (2prime-deoxycytidine)bullminus from Ref 44 (cytosine)2

bullminus from Ref 63 and(2prime-deoxycytidine)2

bullminus from the current study recorded with 349 eVphotons

monomer and the neutral dC as well as from the presence ofthe sugar moiety in the anionic nucleoside Hence by com-paring the vertical stability of (cytosine)2

bullminus with that of theisolated cytosine anion radical (cytosine)bullminus one can estimatethe effect of dimerization while the comparison between thestability of (dC)bullminus and (cytosine)bullminus approximates the influ-ence of the sugar moiety The most accurate VDE for the cy-tosine valence anion amounts to 04 eV and originates from abinitio calculations carried out at the CCSD(T)aug-cc-pVDZlevel64 If one subtracts the computed VDE of 04 eV fromthe experimental VDE of 14 eV (see Figure 5) measured forcytosine homodimer (cytosine)2

bullminus one may draw the con-clusion that intermolecular interactions present in the dimershifts its VDE value by sim1 eV toward higher EBEs Com-paring in turn the VDE of (cytosine)bullminus to that of (dC)bullminuswhich amounts to 09 eV (see Figure 5) one can estimate thatthe substitution of the N1 position of cytosine with the 2prime-deoxyribose residue shifts the VDE value by sim05 eV On the

premise that both effects are additive supplementing VDE ofisolated cytosine (04 eV) by the VDE shift of 1 eV (resultingfrom dimerization) and by 05 eV (the effect of the substitu-tion of the N1 position of cytosine) one could estimate thatthe maximum of the photoelectron signal for (dC)2

bullminus shouldbe observed at EBE of sim19 eV The latter value matches rel-atively well the maximum of photoelectron spectrum reportedherein

V CONCLUSION

The 2prime-deoxycytidine homodimer anion (dC)2bullminus was in-

vestigated using a combination of anion photoelectron spec-troscopy and computational approaches The spectrum of theintact (dC)2

bullminus exhibits a broad signal with a maximum lo-cated between EBE sim 16 and 19 eV and a threshold at EBEsim 12 eV The value of the vertical detachment energy indi-cates strong stabilization of the nucleoside complexes Thesignificant width of the photoelectron spectral band suggeststhat more than one adiabatically stable valence bound anionmay be populated under the experimental conditions Takinginto account possible configurations we analyzed a numberof homodimers involving the proton donor and acceptor cen-ters of cytosine and sugar The computational data obtainedat the DFT level confirmed the existence of the stable valenceanions of 2prime-deoxycytidine dimers in the gas phase and gaveinsight into their structural and thermodynamic features

We note that only a few of the considered neutral homod-imer (dC)2 configurations are thermodynamically viable butall the considered configurations should readily accept the in-coming electron (as indicated by their positive VEAs)

Due to a large number of dimer arrangements resultingfrom the possible combinations of proton donor and accep-tor centers of the monomers as well as due to the confor-mational flexibility of the nucleoside itself we were able tostudy only a limited set of possible conformations Neverthe-less our approach allowed us to interpret the photoelectronspectrum The calculated VDEs indicate that we did identifythe most important structures responsible for the experimen-tally observed picture

The most stable anion radical homodimer a3 turnedout to be the complex where the nucleosides are connectedby (sugar)O3prime-H middot middot middot N3(cytosine) and (cytosine)O7 middot middot middot H-C6(cytosine) interactions The second most stable conformeris stabilized by the same interactions as observed in a3and additionally possesses the internal hydrogen bond 5primeO-H middot middot middot C6 within the anionic monomer

ACKNOWLEDGMENTS

The experimental results reported here are based uponwork supported by the National Science Foundation (NSF)under Grant No CHE-1111693 (KHB) This work wasalso supported by the Polish Ministry of Science andHigher Education (MNiSW) Grant No DS530-8221-D186-13 (JR) The calculations have been carried out atthe Wrocław Center for Networking and Supercomputing(httpwwwwcsswrocpl) under Grant No 196 and at theAcademic Computer Center in Gdansk (TASK)



1S M Pimblott J A LaVerne and A Mozumder J Phys Chem 100 8595(1996)

2B Boudaiumlffa P Cloutier D Hunting M A Huels and L Sanche Science287 1658 (2000)

3B Boudaiumlffa P Cloutier D Hunting M A Huels and L Sanche RadiatRes 157 227 (2002)

4M A Huels B Boudaiumlffa P Cloutier D Hunting M A Huels and LSanche J Am Chem Soc 125 4467 (2003)

5F Martin P D Burrow Z Cai P Cloutier D Hunting and L SanchePhys Rev Lett 93 068101 (2004)

6Y Zheng P Cloutier D J Hunting L Sanche and J R Wagner J AmChem Soc 127 16592 (2005)

7Z Cai P Cloutier D Hunting and L Sanche J Phys Chem B 109 4796(2005)

8R Panajotovic F Martin P Cloutier D Hunting and L Sanche RadiatRes 165 452 (2006)

9Y Zheng P Cloutier D J Hunting J R Wagner and L Sanche J ChemPhys 124 064710 (2006)

10Y Zheng J R Wagner and L Sanche Phys Rev Lett 96 208101 (2006)11Z Li Y Zheng P Cloutier L Sanche and J R Wagner J Am Chem

Soc 130 5612 (2008)12H Abdoul-Carime and L Sanche Int J Radiat Biol 78 89 (2002)13L Sanche Mass Spectrom Rev 21 349 (2002)14X Pan P Cloutier D Hunting and L Sanche Phys Rev Lett 90 208102

(2003)15X Pan and L Sanche Phys Rev Lett 94 198104 (2005)16J Rak K Mazurkiewicz M Kobyłecka P Storoniak M Haranczyk I

Dabkowska R A Bachorz M Gutowski D Radisic S T Stokes S NEustis D Wang X Li Y J Ko and K H Bowen ldquoStable valence an-ions of nucleic acid bases and DNA strand breaks induced by low energyelectronsrdquo in Radiation Induced Molecular Phenomena in Nucleic AcidA Comprehensive Theoretical and Experimental Analysis (Challenges andAdvances in Computational Chemistry and Physics) edited by M Shuklaand J Leszczynski (Springer 2008) pp 619ndash667

17M Yan D Becker S Summerfield P Renke and M D Sevilla J PhysChem 96 1983 (1992)

18S Wetmore R Boyd and L Eriksson Chem Phys Lett 322 129(2000)

19N Russo M Toscano and A Grand J Comput Chem 21 1243(2000)

20S Wesolowski M Leininger P Pentchev and H Schaefer J Am ChemSoc 123 4023 (2001)

21J H Hendricks S A Lyapustina H L de Clercq and K H Bowen JChem Phys 108 8 (1998)

22J Schiedt R Weinkauf D Neumark and E Schlag Chem Phys 239 511(1998)

23C Desfranccedilois V Periquet Y Bouteiller and J P Schermann J PhysChem A 102 1274 (1998)

24(a) M Haranczyk R Bachorz J Rak M Gutowski D Radisic S TStokes J M Nilles and K H Bowen J Phys Chem B 107 7889 (2003)(b) Isr J Chem 44 157 (2004)

25M Haranczyk J Rak M Gutowski D Radisic S T Stokes and K HBowen J Phys Chem B 109 13383 (2005) M Haranczyk I DabkowskaJ Rak M Gutowski J M Nilles S T Stokes D Radisic and K HBowen ibid 108 6919 (2004) K Mazurkiewicz M Haranczyk MGutowski J Rak D Radisic S N Eustis D Wang and K H BowenJ Am Chem Soc 129 1216 (2007) K Mazurkiewicz M Haranczyk PStoroniak M Gutowski J Rak D Radisic S N Eustis D Wang andK H Bowen Chem Phys 342 215 (2007) M Gutowski I DabkowskaJ Rak S Xu J M Nilles D Radisic and K H Bowen Eur Phys J D20 431 (2002) I Dabkowska J Rak M Gutowski J M Nilles D Ra-disic and K H Bowen J Chem Phys 120 6064 (2004) I Dabkowska JRak M Gutowski D Radisic S T Stokes J M Nilles and K H BowenPhys Chem Chem Phys 6 4351 (2004)

26N A Richardson S S Wesolowski and H F Schaefer J Phys Chem B107 848 (2003)

27I Al-Jihad J Smets and L Adamowicz J Phys Chem A 104 2994(2000)

28A Kumar M Knapp-Mohammady P C Mishra and S Suhai J ComputChem 25 1047 (2004)

29D Radisic K H Bowen I Dabkowska P Storoniak J Rak and MGutowski J Am Chem Soc 127 6443 (2005)

30A-O Colson B Besler D M Close and M D Sevilla J Phys Chem96 661 (1992)

31J Smets A F Jalbout and L Adamowicz Chem Phys Lett 342 342(2001)

32N A Richardson S S Wesolowski and H F Schaefer III J Am ChemSoc 124 10163 (2002)

33X Li Z Cai and M D Sevilla J Phys Chem B 105 10115 (2001)34A Szyperska J Rak J Leszczynski X Li Y J Ko H Wang and K H

Bowen J Am Chem Soc 131 2663 (2009)35A Szyperska J Rak J Leszczynski X Li Y J Ko H Wang and K H

Bowen Chem Phys Chem 11 880 (2010)36J Gu Y Xie and H F Schaefer J Phys Chem B 109 13067 (2005)37J Gu Y Xie and H F Schaefer J Chem Phys 127 155107 (2007)38J Gu Y Xie and H F Schaefer Chem Eur J 16 5089 (2010)39J Gu Y Xie and H F Schaefer Chem Phys Lett 473 213 (2009)40J Gu Y Xie and H F Schaefer Chem Eur J 18 5232 (2012)41J Gu J Wang and J Leszczynski J Phys Chem B 116 1458 (2012)42J Gu N-B Wong Y Xie and H F Schaefer Chem Eur J 16 13155

(2010)43N A Richardson J Gu S Wang Y Xie and H F Schaefer J Am Chem

Soc 126 4404 (2004)44S T Stokes X Li A Grubisic Y J Ko and K H Bowen J Chem Phys

127 084321 (2007)45X Li L Sanche and M D Sevilla Radiat Res 165 721 (2006)46Y J Ko P Storoniak H Wang K H Bowen and J Rak J Chem Phys

137 205101 (2012)47P Storoniak J Rak Y Ko H Wang and K H Bowen J Phys Chem B

116 13975 (2012)48J Ho K M Ervin and W C Lineberger J Chem Phys 93 6987 (1990)49A D Becke Phys Rev A 38 3098 (1988)50A D Becke J Chem Phys 98 5648 (1993)51C Lee W Yang and R G Parr Phys Rev B 37 785 (1988)52R Ditchfield W J Hehre and J A Pople J Chem Phys 54 724 (1971)53W J Hehre R Ditchfield and J A Pople J Chem Phys 56 2257 (1972)54T van Mourik S L Price and D C Clary J Phys Chem A 103 1611

(1999)55O Dolgounitcheva V Zakrzewski and J Ortiz J Phys Chem A 103

7912 (1999)56N Foloppe and A D MacKerell Biophys J 76 3206 (1999) A Hocquet

N Leulliot and M Ghomi J Phys Chem B 104 4560 (2000)57J C Rienstra-Kiracofe G S Tschumper and H F Schaefer Chem Rev

102 231 (2002)58M J Frisch G W Trucks H B Schlegel et al GAUSSIAN 03 Revision

B05 Gaussian Inc Pittsburgh PA 200359M J Frisch G W Trucks H B Schlegel et al GAUSSIAN 09 Revision

B01 Gaussian Inc Pittsburgh PA 201060R Dennington II T Keith J Millam K Eppinnett W Lee Hovell and R

Gilliland GAUSSVIEW Version 309 Semichem Inc Shawnee MissionKS 2003

61See supplementary material at httpdxdoiorg10106314817779 formass spectrum showing both the monomeric and dimeric anions of2prime-deoxycytidine complete anion radical homodimeric structures (listedin Table III) and the direction of dipole moment in the neutral 2prime-deoxycytidine

62M Smyth and J Kohanoff J Am Chem Soc 134 9122 (2012)63Y J Ko H Wang R Cao D Radisic S N Eustis S T Stokes S Lya-

pustina S X Tian and K H Bowen Phys Chem Chem Phys 12 3535(2010)

64X Li K H Bowen M Haranczyk R A Bachorz K Mazurkiewicz JRak and M Gutowski J Chem Phys 127 174309 (2007)


THE JOURNAL OF CHEMICAL PHYSICS 139 075101 (2013)

Photoelectron spectroscopic and density functional theoretical studiesof the 2prime-deoxycytidine homodimer radical anion

Piotr Storoniak1a) Janusz Rak1 Yeon Jae Ko2 Haopeng Wang2 and Kit H Bowen2a)

1Department of Chemistry University of Gdansk Wita Stwosza 63 80-952 Gdansk Poland2Department of Chemistry Johns Hopkins University Baltimore Maryland 21218 USA

(Received 11 May 2013 accepted 24 July 2013 published online 15 August 2013)

The intact (parent) 2prime-deoxycytidine homodimer anion (dC)2bullminus was generated in the gas phase

(in vacuo) using an infrared desorptionphotoemission source and its photoelectron spectrum wasrecorded using a pulsed magnetic bottle photoelectron spectrometer The photoelectron spectrum(PES) revealed a broad peak with the maximum at an electron binding energy between 16 and19 eV and with a threshold at sim12 eV The relative energies and vertical detachment energies ofpossible anion radicals were calculated at the B3LYP6-31++Glowastlowast level of theory The most stableanion radicals are the complexes involving combinations of the sugar middot middot middot base and base middot middot middot baseinteractions The calculated adiabatic electron affinities and vertical detachment energies of the moststable (dC)2

bullminus anions agree with the experimental values In contrast with previous experimental-computational studies on the anionic complexes involving nucleobases with various proton-donorsthe electron-induced proton transferred structures of (dC)2

bullminus are not responsible for the shape ofPES copy 2013 AIP Publishing LLC [httpdxdoiorg10106314817779]

I INTRODUCTION

The interaction of ionizing radiation with biological sys-tems results in secondary low energy electrons (LEEs) of en-ergies in the range from 0 to 15 eV1 Because LEEs are shownto be capable of inducing strand breaks in dry DNA2 electronattachment to sub-units of DNA has been studied extensivelyin recent years3ndash16 Pyrimidines possess the highest electronaffinities among the DNA constituents17 which suggests thatboth thymine and cytosine are plausible targets for thermal-ized electrons Indeed the gas phase adiabatic electron affini-ties (AEAs) of individual nucleobases predicted by differentdensity functionals with different basis sets support the exis-tence of valence bound (VB) anions of uracil thymine andpossibly cytosine but question the stability of the VB an-ions of purines18ndash20 Solvation increases the stability of theVB anions of nucleobases as indicated by the PES experi-ments of Hendricks et al21 and Schiedt et al22 the former ofwhich demonstrated the existence of gas phase VB anions ofcanonical uracil solvated by a single atom of rare gas or wa-ter molecule Analogous molecular anionic clusters were ob-served using the crossed beam RET (Rydberg Electron Trans-fer) technique against uracil and thymine anions solvatedby rare gas atom23 Finally the gas phase hydrogen-bondedcomplexes of nucleobases with various inorganic24 and or-ganic (alcohols acids amino acids)25 proton donors werestudied within joint PES-DFT studies where an electron at-tachment induced barrier-free proton transfer was frequentlyobserved

The Watson-Crick AT26ndash30 and GC28 30ndash35 base pairs werealso shown to form stable VB anions in the gas phase Theexcess electron is localized on T or C in these complexes and

a)Authors to whom correspondence should be addressed Electronicaddresses pondroschemunivgdapl and kbowenjhuedu

the presence of a complementary purine base increases theAEA value of a pyrimidine

Moving from the Watson-Crick AT and GC base pairsto the dAdT and dGdC nucleoside pairs a significant in-crease in the electron affinity is observed According to theB3LYPDZP++ calculations the gas phase AEAs for thedAdT and dGdC nucleoside pairs are 06 eV and 083 eVrespectively36 37

The B3LYPDZP++ approach was also used to studyelectron attachment to more complex DNA fragments likesingle-strand (dCpdG dGpdC dTpdA dApdT dGpdGdGpdCpdG)38ndash41 and double-strand nucleotide oligomers(dGpdC)2)42 Based on the theoretical estimates all these sys-tems easily accept the excess electron and form adiabaticallystable radical anions

The B3LYPDZP++ calculations pertaining to 2prime-deoxyribonucleosides predicted positive gas phase electronaffinities for all of them The theoretical AEA values ofpurine nucleosides are negligible (006 and 009 eV for dAand dG respectively) compared to pyrimidine nucleosides(033 and 044 eV for dC and dT respectively) Howeverthe vertical detachment energy (VDE) value of 091 eV fordA (which is of similar magnitude to VDEs predicted fordC and dT) speaks in favor of the existence of the VB of2prime-deoxyadenosine anion radical in the gas phase43 IndeedStokes et al44 employing a combination of infrared desorp-tion electron photoemission and gas jet expansion recordedthe anion photoelectron spectra of the nucleoside parentanions of 2prime-deoxythymidinebullminus (dTbullminus) 2prime-deoxycytidinebullminus

(dCbullminus) 2prime-deoxyadenosinebullminus (dAbullminus) uridinebullminus (rUbullminus)cytidinebullminus (rCbullminus) adenosinebullminus (rAbullminus) and guanosinebullminus

(rGbullminus) Their measurements proved the appearance of the sta-ble valence radical anions of nucleosides in the gas phase Theexperimental VDEs and AEAs of dT dC and dA match wellwith those calculated by Richardson et al43 and by Li et al45

0021-96062013139(7)0751019$3000 copy 2013 AIP Publishing LLC139 075101-1







II METHODS















III RESULTS






349 eV photons




Neutrals Anions

















































IV DISCUSSION












bullminus63












V CONCLUSION







ACKNOWLEDGMENTS


























































II METHODS















III RESULTS






349 eV photons




Neutrals Anions

















































IV DISCUSSION












bullminus63












V CONCLUSION







ACKNOWLEDGMENTS























































349 eV photons




Neutrals Anions

















































IV DISCUSSION












bullminus63












V CONCLUSION







ACKNOWLEDGMENTS




























































































IV DISCUSSION












bullminus63












V CONCLUSION







ACKNOWLEDGMENTS






























































V CONCLUSION







ACKNOWLEDGMENTS





















































photoelectron spectroscopic and density functional theoretical

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