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Tautomer‐Specific Resonant Photoelectron Imaging Of Angewandte Zuschriften Chemie Deutsche Ausgabe:DOI:10.1002/ange.201903444 Photoelectron Spectroscopy Internationale Ausgabe:DOI:10.1002/anie.201903444 Tautomer-Specific Resonant Photoelectron Imaging of Deprotonated Cytosine Anions Guo-Zhu Zhu, Chen-Hui Qian, and Lai-Sheng Wang* Abstract: Tautomers of the nucleobases play fundamental equilibrium in aqueous solution.[15] Additionally,various roles in spontaneous mutations of DNA. Tautomers of neutral tautomeric forms of the radical anion and cation of cytosine cytosine have been studied in the gas phase,but muchless is as well as the protonated cytosine have been studied.[16–20] knownabout charged species.Here,wereport the observation However,relatively little is known of the deprotonated [21–23] and characterization of three tautomers of deprotonated cytosine anion ([Cy H]À), despite its potential role in À cytosine anions,[trans-keto-amino-N3H-H8b] DNAdamage.The ionization of DNAbases by low-energy (tKAN3H8bÀ), [cis-keto-amino-N3H-H8a] (cKAN3H8aÀ) electrons is acrucial process for DNAdamage after [24] and [keto-amino-H] (KAN1À), produced by electrospray radiation. Dissociative-electron-attachment experiments ionization. Excited dipole-bound states (DBSs) are uncovered have shown that [Cy H]À is the most abundant anion À for the three anions by photodetachment spectroscopy. Exci- fragment[25] and it can pair with guanine to form anionic [26] tations to selected DBS vibrational levels of cKAN3H8aÀ and complexes. Thecytosine tautomers can be deprotonated at tKAN3H8bÀ yield tautomer-specific resonant photoelectron different sites to produce aplethora of negative ions spectra. The current study provides further insight into (Scheme S2). Luo et al.[21] calculated the structures of five tautomerism of cytosine and suggests anew method to study different [Cy H]À anions generated by deprotonation of the À the tautomers of nucleobases using electrosprayionization and canonical KAN1H tautomer and computed the electron anion spectroscopy. affinities (EAs) of the corresponding neutral [Cy H] radi- À cals.Considering the deprotonation of other rare tautomers Asfundamental building blocks of DNAand RNA, nucleic and searching for 95 initial structures,Vµzquez et al.[22] found acid bases are involved in the transmission and encoding of that the six most stable [Cy H]À anions were,inthe order À genetic information. Tautomerism is crucial to the structure of stability,tKAN3H8bÀ > cKAN3H8aÀ > KAN1À > and proper function of DNAbecause the formation of rare cEAOH8aÀ > cKAN1H8aÀ > tEAOH8aÀ (Table S1). tautomers can cause mismatches in base pairing, resulting in Forthe current study,werecalculated the structures and spontaneous mutagenesis.[1,2] Thetautomers of cytosine,one relative energies of these six anions and aseventh anion of the pyrimidine bases,have been studied in different tKAN1H8bÀ (Scheme 1) generated by deprotonation of environments.Theoretical calculations have shown that the KAN1H. Thecomputed EAs and dipole moments of their isolated neutral cytosine molecule can adopt six tautomers,as corresponding radicals are presented in Table S1. Thethree shown in Scheme S1 (Supporting Information), where their most stable [Cy H]À anions are similar to those described by À relative stabilities in aqueous solution[3] and gas phase[4] are Vµzquez et al.[22] It is interesting that the most stable anion also given. Thecanonical tautomer of keto-amino-N1H tKAN3H8bÀ is not stemming from the deprotonation of the (KAN1H) predominantly exists under physiological condi- canonical KAN1H cytosine (Scheme S2). Parsons et al.[23] tions and it is the tautomer that forms the Watson–Crick pair reported alow-resolution photoelectron imaging (PEI) [1] with guanine via hydrogen bonding. Other rare tautomers study on the [Cy H]À anion produced by apulsed discharge À have also been observed by various spectroscopic tech- method. Acongested broad band was observed and the niques.[5–11] Additionally,the effect of water molecules on the structural dynamics and tautomerism of cytosine have been investigated,[12,13] showing that water can facilitate tautomerization from the canonical form to the rare tauto- mers by lowering the activation barriers of the prototropic process.The high stability of the keto–amino tautomers in solution is derived from their large dipole moments.[3,14] Early thermodynamic and kinetic studies showed that the major KAN1H and minor KAN3H forms (Scheme S1a) are in [*] G. Z. Zhu, C. H. Qian, Prof. Dr.L.S.Wang Department of Chemistry,Brown University Providence, RI 02912 (USA) E-mail:[email protected] Supportinginformation and the ORCID identification number(s) for Scheme 1. The seven most stable tautomers of deprotonated cytosine the author(s) of this article can be found under: anions in the gas phase. Relative energies (below the structures) are 1 https://doi.org/10.1002/anie.201903444. given in kcalmolÀ . 7938 2019 Wiley-VCH Verlag GmbH &Co. KGaA,Weinheim Angew.Chem. 2019, 131,7938 –7942 Angewandte Zuschriften Chemie spectrum was assigned to the KAN1À anion with ameasured energies are due to photodetachment from tKAN3H8bÀ, EA of 3.037(15) eV for the neutral KAN1 radical, compared which is the most stable tautomeric anion according to our with the theoretical values of 3.00 eV by Lou et al.[21] and calculations (Table S1) and the previous study by Vµzquez 3.37 eV by Vµzquez et al.[22] However,noother tautomeric et al.[22] Thepeak labeled T0defines the EA of the neutral forms of the [Cy H]À anion have been disclosed. tKAN3H8b radical, which is more accurately measured to be À Anions with dipolar neutral cores (m > 2.5 D) can 3.0870(5) eV in the near-threshold resonant photoelectron support dipole-bound states (DBSs) near the electron-detach- spectra (see below). Themeasured EA is in perfect agree- ment thresholds,[27,28] which have been observed as resonances ment with our computed value for tKAN3H8b,which also in photodetachment spectra of anions[29] and studied by represents the largest EA among the first seven tautomers [30–32] 1 1 rotational autodetachment. We have investigated auto- (Table S1). Peaks Cand D, shiftes by 373 cmÀ and 575 cmÀ detachment from the vibrational levels of DBS more recently from peak T0, represent the most Franck–Condon-active T 1 T 1 for cryogenically cooled anions and obtained highly non- vibrational modes n21 (376 cmÀ )and n18 (583 cmÀ )of Franck–Condon resonant photoelectron spectra.[33–35] The tKAN3H8b (Table S2), respectively.Both modes involve in- corresponding radicals of the seven anions in Scheme 1all plane H-atom vibrations (Figure S2b). Thepeak labeled C0at have dipole moments larger than 2.5 Dexcept for the alower binding energy should come from another tautomer, cEAOH8a radical (Table S1). Hence,excited DBSs are most likely the second most stable cKAN3H8aÀ species (see expected to be observed, allowing tautomer-specific resonant below). TheEAofthe cKAN3H8a radical defined by peak C0 PEI to be performed.[36,37] was measured to be 3.0471(5) eV,which agrees well with our Here,wereport ahigh-resolution PEI and photodetach- computed value (Table S1). ment spectroscopy study of [Cy H]À .The experiment is done ThecKAN3H8a and tKAN3H8b radicals are calculated À on an electrospray–PEI apparatus,[38] which is equipped with to have dipole moments of 3.35 Dand 5.55 D(Table S1), an electrospray ionization (ESI) source,acryogenically respectively,which are large enough to support excited DBSs cooled ion trap,[39] and ahigh-resolution PEI system.[40] for the corresponding anions.Weperformed photodetach- More experimental details are provided in the Methods ment spectroscopy by monitoring the total electron yield section (Supporting Information). Three tautomeric depro- while scanning the laser wavelength across the detachment C tonated cytosine anions,tKAN3H8aÀ ,cKAN3H8bÀ ,and thresholds,asshown in Figure 2. Thearrow ( EA) at 1 T 1 KAN1À ,were observed. Thephotodetachment spectrum 24577 cmÀ and the arrow ( EA) at 24898 cmÀ indicate the shows strong DBS resonances due to autodetachment from detachment thresholds of cKAN3H8aÀ and tKAN3H8bÀ, vibrational levels of the excited DBSs of the tKAN3H8aÀ and respectively,which are consistent with the measured EAs cKAN3H8bÀ anions.Several weak resonant peaks were from the photoelectron spectra (Figures 1and 3). Around 1 C T tentatively assigned to athird deprotonated anion KAN1À, 24300 cmÀ ,the peaks labeled 0’ and 0’ represent the which is expected to have aweak ion abundance due to its low ground vibrational levels of the DBSs of cKAN3H8aÀ and stability. tKAN3H8bÀ ,respectively.These peaks are below the respec- Figure 1shows the non-resonant photoelectron image and spectrum of [Cy H]À at 354.7 nm. Thecomplexity of the À vibrational structures suggests the possible presence of differ- ent tautomeric anions.Toassist the spectral assignments,we performed Franck–Condon simulations for all the seven low- lying anions using the FC-LabII program[41] and compared them with the spectrum. Figure 1shows that the simulated spectrum of tKAN3H8bÀ is in good agreement with the spectral features at higher binding energies (above the peak T0), while the simulated spectra of the other anions are not (Figure S1). This means that the peaks at higher binding Figure 2. Photodetachment spectrum of [Cy H]À .The spectrum was À obtained by measuringthe total electron yield as afunction of the photon energy across the detachmentthresholds of cKAN3H8aÀ and C T tKAN3H8bÀ ,indicated by the arrows below EA and EA, respectively. 1 The intensity below 24900 cmÀ is multiplied by afactor of 10. Peaks C T 0’ and 0’ represent the ground DBS vibrationallevels of cKAN3H8aÀ C C and tKAN3H8bÀ ,respectively.Peaks 1– 3are due to autodetachment T T from vibrational levels of the DBS of cKAN3H8aÀ ,while peaks 1– 7 Figure 1. Non-resonant photoelectronimage and spectrum of [Cy H]À are from tKAN3H8bÀ .Peaks a, b,and g at lower photon energies are C À at 354.7 nm. The peak 0isdue to detachmentfrom cKAN3H8aÀ , assigned to DBS levels of KAN1À .The outermost ring in the inset T while the peaks above 0are from tKAN3H8bÀ .The Franck–Condon shows the PE image obtained with aphoton energy corresponding to T (FC) simulation data of tKAN3H8bÀ are presented as dots.
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