Ionization-Induced Tautomerization in Cytosine and Effect of Solvation

Article pubs.acs.org/JPCA

Ionization-Induced Tautomerization in Cytosine and Effect of Solvation Tamal Das and Debashree Ghosh* Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune 411008, India S Supporting Information *

ABSTRACT: The recent observation of excitation-induced tautomerization in gas-phase cytosine motivated us to investigate the possibility of facile tautomerization in ionized cytosine and the effect of solvation on the tautomerization barriers. The tautomerization mechanisms were characterized at the density functional theory (DFT)/ωB97X-D and coupled-cluster singles and doubles (CCSD) levels of theory. Vertical and adiabatic ionization energies (VIEs and AIEs, respectively) of the tautomers of cytosine and the microsolvated species were calculated with the equation-of-motion ionization-potential coupled-cluster (EOM-IP-CCSD) method. We observed that, in microsolvated cytosine, the solvatochromic shifts of the VIEs can be both blue- and red-shifted depending on the tautomers. This is explained by the analysis of the charge−dipole interactions between the cytosine and water molecules. We noticed that, upon ionization, gas-phase tautomerization barriers are reduced by 0−4 kcal/mol, whereas microsolvated (with one water) tautomerization barriers are reduced by 4−5 kcal/mol. We also investigated the tautomerization process in solvation using a continuum model with one active water molecule in the quantum mechanical region. We noticed that, even though bulk solvation has a significant effect on ionization energies, its effect on the ionizationinduced tautomerization barrier is minimal. cesses.21,45−47 However, the effects of specific solvent interactions on the tautomerization process are still largely unexplored. In this work, we investigate the effects of both microsolvation and bulk solvation on tautomerization equilibria and use natural bond orbital (NBO) analysis and dipole moments of the species to understand the relative stabilities of the tautomers. The second aim of this study is to understand the kinetics of the tautomerization pathways, namely, the barriers in the gas phase, microsolvation, and bulk solvation. Although some of these studies have already been carried out in the ground state, relatively few efforts have been made to understand excited-state and especially ionized-state pathways for tautomerization.10,11,17,21,48−51 In the past few years, some studies have been performed on the ionization potentials of the NABs,9,14,17,18,52−60 as well as the proton transfer (PT) processes from NABs to water47,61,62 or between base pairs.32,46,63,64 In the case of cytosine, because there are several low-energy tautomers,33 ionization can alternatively lead to facile tautomerization by hydrogen atom transfer (HAT) or PT intramolecularly. We study the tautomerization of cytosine by ionization-induced pathways as well as the effect of solvation on these pathways. Understanding these pathways is especially crucial because, upon radiationinduced ionization, tautomerization can become energetically

1. INTRODUCTION Nucleic acid bases (NABs) are the basic building blocks of DNA, and therefore, understanding their properties is crucial. Over the past two decades, there have been extensive studies, both experimental1−11 and theoretical,1−3,12−24 on the excited and ionized states of NABs in the condensed and gas phases.21 One of the main aims of these studies has been to understand the mechanism of radiation-induced DNA damage25−32 and possible routes of photoprotection. Among the four NABs, adenine and thymine are each known to have a single lowenergy tautomer, whereas cytosine and guanine have a few possible low-energy tautomers.9,33−38 There is significant amount of debate in the literature about the exact percentages of different tautomers in gas-phase cytosine. Experiments and theoretical predictions show different percentages of tautomers depending on the experimental methods and theoretical levels employed.33,37 The most recent theoretical studies suggested that the enol tautomer of gas-phase cytosine is the most abundant at room temperature.39,40 Microwave jet-cooled experiments predicted a 1:1 ratio of keto to enol tautomers in the gas phase,38 whereas Fourier transform infrared (FTIR) spectroscopy experiments on cytosine in an argon matrix provided a ratio of 1:2 favoring the enol population.41 Computationally, coupled-cluster-based methods predict a keto population of about 20−30%, whereas density-functional-theory- (DFT-) based approaches show that the keto form has an occurrence of ∼40% in the gas phase.41−44 Solvation has pronounced effects on tautomerization equilibria, as well as the rates of tautomerization pro© 2014 American Chemical Society

Received: April 23, 2014 Revised: June 19, 2014 Published: June 23, 2014 5323

dx.doi.org/10.1021/jp503947d | J. Phys. Chem. A 2014, 118, 5323−5332

The Journal of Physical Chemistry A

Article

does not have spin-contamination, artificial symmetry-breaking, or self-interaction errors that plague many of the other methods. The EOM-IP-CCSD method treats the states with different numbers of electrons (neutral and cation) on an equal footing and includes both dynamic and nondynamic correlations. The CCSD wave function of the ground state is given by

favorable and, therefore, will have important ramifications in DNA damage as well as repair mechanisms. The tautomerization barriers for gas-phase cytosine are predicted to be about 41.83 kcal/mol (keto−enol) and 46.74 kcal/mol (keto−ketoimine) with the coupled-cluster singles and doubles (CCSD) level of theory.39 However, upon microsolvation, these barriers are significantly reduced to 11.6 kcal/mol (keto−enol) and 15.2 kcal/mol (keto−ketoimine) (calculated at the DFT level).65 This is because the water molecule is actively involved in the tautomerization reaction. A very recent study of the excited-state pathway of tautomerization predicted that tautomerization barriers through the S1 (n → π*) excited state are 35.28 kcal/mol (keto−enol) and 23.89 kcal/mol (keto−ketoimine) in the gas phase.39 The S2 (π → π*) excited-state pathway changes the barriers to 59.50 kcal/ mol (keto−enol) and 60.88 kcal/mol (keto−ketoimine). In their study, they considered both the photoinduced dissociation association mechanism (possibility of S0−S1 crossing) and excited-state intramolecular PT. They showed that both of these mechanisms have very high barriers when compared to the competing ultrafast decay channels. They finally probed a keto twist pathway that they found to be barrierless on the excited-state potential energy surface. Thus, some efforts have been made to study photoinduced tautomerization by excited states as a proposed competitive pathway to ultrafast excitedstate decay in DNA, but relatively little is known about the ionization-induced processes. Excited-state proton transfer (ESPT) is also abundant in nature and is one of the major pathways of photoprotection.50,66 Earlier work showed that ionization and excitation exhibit similar increase in the acidity of the NABs and, therefore, facilitate PT.62 There have been theoretical and experimental studies on ESPT as well as ionization-induced PT between model DNA base pairs and the 7-azaindole dimer.67−69 Excited-state and ionization-induced PT is also observed in 8-hydroxyquinoline.70 In the case of uracil, Krylov and co-workers found that PT from water to uracil is a very uphill (endothermic) process, with a barrier of about 59.96 kcal/mol, whereas in one of the higher ionized states, this process can indeed become barrierless. This is, in fact, not surprising because the ionized state in question has electron detachment entirely from the water molecule and the PT occurs from the positive water (H2O+) to uracil. They also showed that PT between base pairs (uracil dimers) is severely hindered in the presence of water because PT between water and NABs is the more favorable pathway. However, in the case of cytosine, the processes are further complicated by the presence of low-energy tautomers. Thus, the occurrence of two simultaneous/subsequent PT or HAT steps leading to tautomerization is a very viable competitive pathway. Therefore, we investigate the possibility of PT or HAT processes in the DNA base cytosine. Further, water is expected to take an active part in this process, as it is already known that the ground-state cytosine tautomerization barrier reduces by 3−4 times when a single water molecule is involved.65 Similar watercatalyzed processes are also quite abundant in nature.71−73 This work presents accurate CCSD calculations of the populations of tautomers in the gas phase, microsolvated, and bulk solvated (with polarizable-continuum-model) cytosine. We also present calculations of vertical and adiabatic ionization energies (VIEs and AIEs, respectively) with the equation-ofmotion ionization-potential coupled-cluster (EOM-IP-CCSD) method. EOM-IP-CCSD is the method of choice because it

ΨCC = exp(T ) Ψ0

(1)

where Ψ0 is the uncorrelated Hartree−Fock wave function and T = T1 + T2 is the CCSD amplitude. The ionized states are calculated by the EOM R operator given by R=

∑ R iai + ∑ R ijkai†ajak i

ijk

(2)

where a† and a represent the creation and annihilation operators, respectively. This article is organized as follows: Section 2 provides details of the computational methods used, section 3 discusses the results, and conclusions are presented in section 4.

2. COMPUTATIONAL DETAILS The gas-phase cytosine tautomers were optimized at the RIMP2/cc-pVTZ and dispersion-corrected ωB97X-D/ccpVTZ levels of theory. ωB97X-D/cc-pVTZ was used for all other optimizations of both microsolvated and all ionized species. Unrestricted MP2 (UMP2) is not a method of choice for the cations because it suffers from severe spin-contamination and overestimation of charge localization. The singlepoint CCSD/cc-pVTZ energies and entropies calculated at the ωB97X-D/cc-pVTZ level using the rigid-rotor harmonicoscillator (RRHO) approximation were used to calculate the relative populations of the tautomers (gas-phase and microsolvated). In the following sections, where optimizations and energy (or difference energy) calculations are carried out at different levels of theory, we denote the protocol by level 1/ basis 1//level 2/basis 2, where the optimizations were done with level 1/basis 1 and energy calculations were done with level 2/basis 2. The extrapolation to the complete-basis-set (CBS) limit was done using the two-point extrapolation method E(X) = E(CBS) + AX −3

(3)

where E(X) and E(CBS) are the energies at the cc-pVXZ and CBS levels, respectively, and A is a constant. The VIEs and AIEs were calculated with EOM-IP-CCSD/ccpVTZ. Transition states (TSs) were optimized with ωB97X-D/ cc-pVTZ. Unless mentioned otherwise, all final energies used for barrier calculations or relative populations were obtained with CCSD/cc-pVTZ (restricted for neutral moieties and unrestricted for cationic species) and with zero-point-energy (ZPE) corrections at the ωB97X-D/cc-pVTZ level. For the calculation of tautomerization barriers through waterionized states (higher ionized states), we optimized the TS-like geometries with constrained DFT74 (positive charge on water). The constrained geometry optimizations were carried out with the significant bond lengths (those that are broken and formed in the tautomerization process) constrained at the first-ionizedstate TS geometry. These structures were further used for estimating barriers at the EOM-IP-CCSD/cc-pVTZ level of theory. 5324



Article

Figure 1. Keto, enol, and ketoimine tautomers of cytosine. The bond lengths (of the gas-phase tautomers) calculated by RIMP2/cc-pVTZ (within parentheses) and ωB97X-D/cc-pVTZ are included in the figure. The red and green circles denote the positions of the two most stable positions of water in their respective monohydrated species.

were calculated by CCSD/6-31+G(d,p)/SM8 single-point calculations.

The calculations for the gas-phase and microsolvated structures were performed with the quantum chemistry package Q-Chem.75,76 The effect of bulk solvation was qualitatively probed with the continuum model SM8.77,78 The reactants, products, and TSs were optimized with ωB97X-D/6-31+G(d,p)/SM8. The QM/ SM8 optimizations were done in Gaussian 09.79 The barriers

3. RESULTS AND DISCUSSION 3.1. Relative Stabilities of Tautomers. Figure 1 shows the structures of the different tautomers of cytosine: keto, enols, and ketoimines. The Supporting Information (SI) contains the Cartesian coordinates of all of the tautomers 5325



Article

Figure 2. Pictorial representation of the water-mediated (a) keto−enol and (b) keto−ketoimine tautomerization mechanisms.

Table 1. Relative Stabilities (kcal/mol) and Boltzmann Populations,a as Well as ZPE-Corrected Energies, of the Tautomers of Cytosine, Obtained using RIMP2/cc-pVTZ//CCSD/cc-pVTZ, ωB97x-D/cc-pVTZ//CCSD/cc-pVTZ , and with ωB97x-D ZPE Correction Methods ωB97X-D/CCSD

RIMP2/CCSD

b

ωB97X-D ZPE

expt Pop (%)

species

relative energy

population (%)

relative energy

population (%)

relative energy

population (%)

IRb

MWc

C1 C2a C2b C3a C3b

1.240 0.705 0.000 1.154 2.799

12.50 16.65 65.71 4.85 0.29

1.159 0.672 0.000 0.924 2.566

13.62 16.73 62.45 6.79 0.41

1.144 0.684 0.000 1.547 3.276

14.66 17.20 65.52 2.49 0.13

22 26 44 8 0

44 − 44 11 −

Taken from ref 41. cTaken from ref 38. aPopulations calculated with RRHO-approximated entropies at 300 K.

Table 2. Relative Stabilities (kcal/mol) and Boltzmann Populations of the Monohydrated Tautomers of Cytosine Computed by ωB97X-D/cc-pVTZ//CCSD/cc-pVTZ and the Complete-Basis-Set (CBS) Limit cc-pVTZ

CBS

CBS + ZPE

species

relative energy

population (%)

relative energy

population (%)

relative energy

population (%)

C11 C12 C2a1 C2a2 C2b1 C2b2 C3a1 C3a2 C3b1 C3b2

0.000 0.542 2.140 3.215 0.302 0.712 0.965 1.588 2.847 3.342

35.77 28.92 0.71 0.23 9.75 18.16 4.66 1.44 0.23 0.15

0.000 0.543 2.660 3.444 0.770 0.954 1.409 2.050 3.298 3.796

42.26 34.12 0.35 0.19 5.23 14.27 2.60 0.78 0.13 0.08

0.000 0.528 2.512 3.426 0.928 0.950 1.853 2.718 3.593 3.911

43.17 35.74 0.45 0.20 4.09 14.67 1.26 0.26 0.08 0.07

optimized by the RIMP2 and ωB97X-D methods (sections S1 and S2). Figure 2 presents the keto−enol and keto−ketoimine tautomerization mechanisms. The optimized structures of gas-phase and microsolvated (monohydrated) cytosine tautomers were used to calculate the CCSD/cc-pVTZ energies and the relative stabilities of the tautomers. Although extensive work has been performed on the NABs, the relative stabilities and Boltzmann populations of different tautomers are still not completely known. In DNA, it is quite well-established that the keto form is the most predominant tautomer. Although most of the experimental evidence points toward the greater stability of the enol form in the gas phase, the keto/enol/ketoimine ratio varies between 1:1:0.2538 and 0.5:1.0:0.18.41,80,83 Table 1 lists the relative energies and populations of the gas-phase cytosine calculated with different methods. From our CCSD calculations (with ZPE correction), we find evidence that the enol form is more stable by 1.144 kcal/mol (0.05 eV). It should also be noted that

the populations for C2b and C3a with ZPE corrections are changed significantly (when compared to those without ZPE corrections). This cannot be explained by the differences in localized stretching and bending modes of the NH and OH bonds in the two moieties, but is rather the effect of all of the coupled modes together. The frequencies are listed in the SI (section S9). There is reasonable agreement between the experimental and theoretical populations, given the accuracy of CCSD and the added harmonic approximation used to compute the entropic contributions. The shortcomings of the experimental studies are explained quite succinctly in ref 41. They suggest that the microwave study might have mixed up the tautomers C3a and C2b. They also showed that there have been various other IR studies in which the ranges of populations predicted were 20− 30% for C1 and 40−67% of C2b, with detection but not quantification of C3a and small percentages of C3b. The possible sources of error in the experiments might be in the fitting of the 5326



Article

predict a lowering (−0.1 eV) of the VIE due to microsolvation.59 The amount of lowering is also well understood as a balance between the electron-donating H-bond between CO and water and the electron-accepting H-bond between NH and water.60 The NBO charges (see SI, section S11) for the neutral and first ionized states (vertical) were used to calculate the charge− dipole interactions between the water molecule (dipole) and the cytosine tautomers (charge) as shown in ref 59. As expected, the ΔVIEs (solvatochromic shifts of the VIEs) are directly proportional to the difference in charge−dipole interaction in the cationic versus neutral species. This is because the difference in the charge−dipole interactions is the major component of the preferential stabilization of the cation. A plot elucidating this effect is given in the SI (Figure S5). Figure 3 shows the leading molecular orbitals (MOs) for the lowest five ionizations (with the VIEs listed), for all the microsolvated tautomers of cytosine. We notice that as expected the first two ionizations are predominantly from cytosine (90−95%). The third and higher ionizations are from both cytosine and water. Unlike in the case of thymine (where the partial water ionizations start from 11 eV and higher),59 in the case of cytosine, the partial water ionizations start from ∼10 eV. In the case of microsolvated C2b, we notice that all of the higher ionizations (up to fifth) are mixed water−cytosine ionizations, unlike in the cases of C1, C3a, and thymine, where we notice at least one ionization predominantly from water. We also notice that the ionizations occur predominantly from π, π, σ + water, σ + water, and water in the cases of the first five ionization states of microsolvated C1 tautomer. The predominant components in the case of C2b come from π, σ + water, π, σ + water and π, and σ + water, respectively. It is important to note that the fifth ionized state originates from annihilation operators from two significant MOs. The predominant components in the case of C3a come from π, π, σ, σ + water, and water, respectively. Here, π and σ refers to the orbitals that are largely localized on cytosine tautomers. 3.3. Effect of Ionization on Gas-Phase Tautomerization. The next aim of this work is to understand the tautomerization mechanism and whether ionization-assisted tautomerization is a preferred pathway in gas-phase cytosine. The relative energies of the ionized tautomers show that the keto−ketoimine tautomerization barrier is virtually unchanged by ionization. The keto−enol tautomerization barrier is reduced by 4 kcal/mol. Thus, the effect of ionization is quite different from that of excitation on the tautomerization process. Matsika and coworkers39 showed that n → π* excitation reduces the keto− ketoimine barrier significantly (by 23.89 kcal/mol). The keto− enol barrier reductions through both ionization and n → π* excitation are similar. Figure 4 shows the barriers of the tautomerization processes in the ground and ionized states. The imaginary frequencies in the neutral and cationic TSs are very similar to each other in both tautomerization processes (see SI, section S10). This observation is again quite different from that for the firstexcited-state tautomerization (n → π*).39 We also tried to find higher ionization pathways and possible low-barrier tautomerization processes. The barriers to tautomerization by the higher ionized states are 57.40, 49.26, 58.41, 39.07, and 38.43 kcal/mol, respectively, for the keto−enol tautomerization and 63.28, 39.77, 72.04, 58.08, and 40.19 kcal/mol, respectively, for the keto−ketoimine tautomerization. Therefore, we did not

line shapes and, therefore, the ratios of the integrated areas of the overlapping spectral lines. There could also be small environmental effects on the experimentally predicted populations. Analyzing the optimized geometries with RIMP2/cc-pVTZ and ωB97X-D/cc-pVTZ show that the differences between the optimized structures are minimal (absolute average difference of 0.0036 Å in the bond lengths). Previous works have also shown that geometries optimized with ωB97X-D are very close to the RIMP2- and CCSD-optimized structures.40,81,82 The relative stabilities and Boltzmann populations of the monohydrated tautomers are listed in Table 2. We already notice that the most stable species is now a monohydrated keto tautomer. The keto tautomer is always more stable in the microsolvated or condensed phase because of stronger hydrogen bonds. The dipole moment of the keto tautomer (C1) in the gas phase is 6.55 D, whereas for the enol tautomers (C2a and C2b), they are 4.64 and 3.24 D, respectively. When the tautomers are hydrated, the more polar C1 is preferentially stabilized, thus making it the most energetically favorable species. We see the signature of this even in monohydrated C1. Another important observation is the role of entropy in affecting the relative populations between C2b1 and C2b2. Table 2 shows that, according to the relative energies, the population of C2b1 should have been higher than that of C2b2, but according to the free energies, the opposite was true. This is due to strongly coupled vibrational modes of water and cytosine OH in C2b1 as opposed to the weakly coupled modes of water and NH in C2b2. We notice evidence of coupling from visualization of the modes, as well as enhanced intensities (141.1, 553.89, and 1291.79 in C2b1 vs 210.331, 63.87, and 633.674, respectively, in C2b2). The frequencies are listed in the SI with the intensities and corresponding modes (section S9). 3.2. Ionization Energies of Gas-Phase and Microsolvated Cytosine Tautomers. Previous works have theoretically and experimentally determined the gas-phase VIEs and AIEs of the major tautomers of cytosine.82 Table 3 Table 3. Lowest VIEs and AIEs (in eV) of the Most Stable Monohydrated Tautomers of Cytosine species C1 C11 C12 C2b C2b1 C2b2 C3a C3a1 C3a2

VIEa,b (eV) 8.80 8.84 8.92 8.88 8.81 8.74 8.92 8.86 9.04

(+0.04) (+0.12) (−0.07) (−0.14) (−0.06) (+0.12)

AIEa (eV)

ΔZPE-corrected AIEc (eV)

8.65 8.41 8.61 8.53 8.28 8.32 8.71 8.40 8.51

8.61 8.33 8.53 8.53 8.21 8.27 8.67 8.32 8.42

a

VIEs and AIEs calculated by EOM-IP-CCSD/cc-pVTZ. bValues in parentheses denote the solvatochromic shifts (ΔVIEs) due to microsolvation. cZPE corrections to the AIE calculated by ωB97xD/cc-pVTZ.

shows the effect of monohydration on the VIEs and AIEs of the different tautomers calculated with EOM-IP-CCSD/cc-pVTZ. As expected, monohydration changes the IEs significantly from the gas-phase values. However, surprisingly, for cytosine, monohydration causes both increases and decreases in the VIEs. This is in contrast to the observation in thymine (which is also a pyrimidine base), where both experiment and theory 5327



Article

Figure 3. Most important molecular orbitals involved in the lowest five ionized states of gas-phase and microsolvated cytosine tautomers: (a) C1, (b) C2b, and (c) C3a. The coefficients of the Koopmans-like annihilation operators are given in parentheses. In C2b1, the contributions from two MOs in the fifth ionized state are almost the same, as shown in panel b.

observe any significantly low-barrier tautomerization pathways through several ionized states in gas-phase cytosine. These barriers were calculated for the ionized states with the optimized geometries of the ground-state TSs. 3.4. Effect of Solvation on Tautomerization Pathway. Because we noticed a very strong effect of solvation on the VIEs and AIEs of the tautomers, it is reasonable to expect that solvation will have a significant effect on the tautomerization pathway especially in the ionized state. Previous theoretical work (DFT level) already showed that, for ground-state (neutral) tautomerization of monohydrated species, the barrier reduces to 11.6 kcal/mol for keto−enol tautomerization and to 15.2 kcal/mol for keto−ketoimine tautomerization.65 We computed these barriers using CCSD/cc-pVTZ with ZPE correction (ωB97X-D/cc-pVTZ). Our computed barriers are 13.36 and 17.01 kcal/mol for keto−enol and keto−ketoimine tautomerizations, respectively. This lowering of the barrier is quite expected because the one active water molecule actually participates in the tautomerization process, thus stabilizing the TSs considerably. Figures 5 and 6 show the effect of microsolvation (monohydration) and bulk solvation on the ionized-state

Figure 4. Energetic barriers for ground-state tautomerization and adiabatic energy barriers for first-ionized-state tautomerization of gasphase cytosine calculated at the CCSD/cc-pVTZ level with ZPE correction at the ωB97X-D/cc-pVTZ level.

5328



Article

dipole interactions and it is, of course, the delicate balance of electron-donating and -withdrawing H-bonds that causes all of these effects. The imaginary frequencies of the TSs of the neutral species (1581 and 1621 cm−1) are very different from those of the cationic species (303 and 637 cm−1), signifying that, along the reaction coordinate, the neutral TSs are steeper than the cationic ones. It is also noticed that the normal modes corresponding to these frequencies are very different between the neutral and cationic TSs. The neutral normal modes are mostly localized near the H-bonds, whereas the cationic normal modes are spread out along the full molecule. We also examined the differences in the structures of the TSs at the lowest ionized state versus the ground neutral state. As expected, we noticed from the TS structures that bond formation starts before the bond-breaking process. This can be seen from the case of ionized-state keto−enol tautomerization: The bond length of the CO−Hw H-bond is 3.06 and 1.60 Å in the reactant and TS, respectively, and the O−H bond length in the product is 1.01 Å O−H (enol), whereas the N−H bond length is 1.05 and 1.49 Å in the reactant and TS, respectively, and the N−Hw H-bond length in the product is 3.20 Å. The same trend was noticed in all of the tautomerizations. To understand the effect of higher ionized states on the tautomerization barriers, we carried out EOM-IP-CCSD/ccpVTZ computations (with the ground-state geometries of the reactant, product, and TS). For the higher (second through fifth) ionized states, the computed tautomerization barriers are 21.17, 19.26, 21.85, and 1.03 kcal/mol for keto−enol tautomerization. Similar barriers for the keto−ketoimine tautomerization are 22.15, 24.51, 21.28, and −2.01 kcal/mol. We observe that for the fifth ionized state gives rise to very lowenergy barriers because this ionization predominantly takes place from water. It should be noted that similar observations of low-barrier or barrierless PT were made for uracil−water by Krylov and co-workers.62 In their work, they also noticed that the threshold energy for PT closely resembled that in experiment. However, one consideration regarding the higher ionized states is the adiabatic barriers in those states. Because we used the ground-state (neutral) structures, one can think of relaxation along the ionized states to get correct barriers in those states. Therefore, we recomputed optimized geometries using constrained DFT (with positive charge localized on water) with the significant bond lengths (as described in section 2) constrained at the first-ionized-state TS geometry. These TS-like structures were further used to compute ionized states (with EOM-IP-CCSD) and ionizations from water starting from the first ionized state (in these TS-like structures). Comparison of these ionized-state energies with similar ionizations from the reactants (C11 and C12) showed that we obtained low or negative barriers (4.77 and −5.59 kcal/mol), respectively, in the case of C12−C3a2 tautomerization and −10.93 kcal/mol in the case of C11−C2b1. The details of the reactants, TS-like geometries (constrained), and products, along with their significant MOs, are shown with the calculated barriers in the SI (section S7). We tried to qualitatively estimate the effect of bulk solvation on the tautomerization process using a continuum model. The barriers for tautomerizations through the neutral (ground) state in bulk solvation were found to be 14.63 kcal/mol (keto−enol) and 16.26 kcal/mol (keto−ketoimine). The barriers through

Figure 5. Energetic barriers for ground-state tautomerization and adiabatic energies for first-ionized-state tautomerization of microsolvated cytosine calculated at the CCSD/cc-pVTZ level with ZPE correction at the ωB97X-D/cc-pVTZ level.

Figure 6. Energetic barriers for ground-state tautomerization and adiabatic energies for first-ionized-state tautomerization of bulksolvated cytosine calculated at the CCSD/SM8/6-31+G(d,p) level. A single water molecule that participates in the tautomerization is explicitly included in the calculation.

tautomerizations. In the case of microsolvation, the tautomerization barrier through the first ionized state decreases to 9.53 kcal/mol for keto−enol tautomerization and 12.46 kcal/mol for keto−ketoimine tautomerization. The barriers are low enough for the tautomerizations through the first ionized states to be feasible. To understand the underlying reasons for the reduction of the barriers through the ionized state, we carried out analysis of the charge−dipole components of the interaction energies (from the NBO charges). The charge− dipole interaction energies were found to be more negative (more stable) in the ionized state than the neutral state for both the reactant and the TS. However, the extent of stabilization was greater in the TS than the reactant (−0.372 vs −0.275 au in keto−enol and −0.357 vs −0.150 au in keto−ketoimine). It is this preferential stabilization of the charge−dipole interactions that causes the barrier to be lower in the ionized state. We noticed that the trends are consistent with the charge−dipole interactions (in barrier lowering or solvatochromic shifts) because the major component in H-bonding is the charge− 5329


The Journal of Physical Chemistry A the first ionized state in bulk solvation are 9.82 kcal/mol (keto−enol) and 12.07 kcal/mol (keto−ketoimine). Thus, we notice that there is no significant change in barriers on going from microsolvation to bulk and the predominant effect is that of the water molecule that is actually taking part in the tautomerization process. In other words, the effect of the polarizing field of the bulk water does not change the tautomerization barriers significantly. This is, in fact, very surprising. However, the bulk solvation effect has only been characterized at a qualitative level because the specific interactions between cytosine and water (except for one active water) are not considered. Although the effect of bulk solvation on the tautomerization barriers is rather small (with respect to monohydration), the effect on the AIEs is ∼2 eV (red shift). The AIEs in the solvated cytosine (with CCSD/SM8 approach) are 6.13 (C11), 6.44 (C12), 5.91 (C2b1), and 5.92 (C3a2) eV.

■

REFERENCES

(1) Trofimov, A. B.; Schirmer, J.; Kobychev, V. B.; Potts, A. W.; Holland, D. M. P.; Karlsson, L. Photoelectron spectra of the nucleobases cytosine, thymine and adenine. J. Phys. B 2006, 39, 305−330. (2) Satzger, H.; Townsend, D.; Stolow, A. Reassignment of the low lying cationic states in gas phase adenine and 9-methyl adenine. Chem. Phys. Lett. 2006, 430, 144−148. (3) Zaytseva, I. L.; Trofimov, A. B.; Schirmer, J.; Plekan, O.; Feyer, V.; Richter, R.; Coreno, M.; Prince, K. C. Theoretical and Experimental Study of Valence-Shell Ionization Spectra of Guanine. J. Phys. Chem. A 2009, 113, 15142−15149. (4) Lin, J.; Yu, C.; Peng, S.; Akiyama, I.; Li, K.; Lee, L. K.; LeBreton, P. R. Ultraviolet photoelectron studies of the ground-state electronic structure and gas-phase tautomerism of hypoxanthine and guanine. J. Phys. Chem. 1980, 84, 1006−1012. (5) Urano, S.; Yang, X.; LeBreton, P. R. UV photoelectron and quantum mechanical characterization of DNA and RNA bases: Valence electronic structures of adenine, 1,9-dimethyl-guanine, 1methylcytosine, thymine and uracil. J. Mol. Struct. 1989, 214, 315. (6) Dougherty, D.; Wittel, K.; Meeks, J.; McGlynn, S. P. Photoelectron spectroscopy of carbonyls. Ureas, uracils, and thymine. J. Am. Chem. Soc. 1976, 98, 3815−3820. (7) Hush, N. S.; Cheung, A. S. Ionization potentials and donor properties of nucleic acid bases and related compounds. Chem. Phys. Lett. 1975, 34, 11−13. (8) Zavilopulo, A. N.; Shepnik, O. B.; Agafonova, A. S. Electron impact ionization of gas-phase guanine near the threshold. J. Phys. B 2009, 42, 025101. (9) Zhou, J.; Kostko, O.; Nicolas, C.; Tang, X.; Belau, L.; de Vries, M. S.; Ahmed, M. Experimental Observation of Guanine Tautomers with VUV Photoionization. J. Phys. Chem. A 2009, 113, 4829−4832. (10) Saigusa, H. Excited-state dynamics of isolated nucleic acid bases and their clusters. Photochem. Photobiol. 2006, 7, 197−210. (11) Crespo-Hernández, C. E.; Kohen, B.; Kohler, B. Base stacking controls excited-state dynamics in A·T DNA. Nature 2005, 436, 1141− 1144. (12) Dolgounitcheva, O.; Zakrzewski, V. G.; Ortiz, J. V. Vertical Ionization Energies of Adenine and 9-Methyl Adenine. J. Phys. Chem. A 2009, 113, 14630−14635. (13) Dolgounitcheva, O.; Zakrzewski, V. G.; Ortiz, J. V. Electron Propagator Theory of Guanine and Its Cations: Tautomerism and Photoelectron Spectra. J. Am. Chem. Soc. 2000, 122, 12304−12309. (14) Dolgounitcheva, O.; Zakrzewski, V. G.; Ortiz, J. V. Ionization Energies and Dyson Orbitals of Thymine and Other Methylated Uracils. J. Phys. Chem. A 2002, 106, 8411−8416. (15) Dolgounitcheva, O.; Zakrzewski, V. G.; Ortiz, J. V. Ionization Energies and Dyson Orbitals of Cytosine and 1-Methylcytosine. J. Phys. Chem. A 2003, 107, 822−828. (16) Roca-Sanjuán, D.; Rubio, M.; Merchán, M.; Serrano-Andrés, L. Ab initio determination of ionization potential of DNA and RNA nucleobases. J. Chem. Phys. 2006, 125, 084302. (17) Cauët, E.; Dehareng, D.; Lievin, J. Ab Initio Study of the Ionization of the DNA Bases: Ionization Potentials and Excited States of the Cations. J. Phys. Chem. A 2006, 110, 9200−9211. (18) Orlov, V. M.; Smirnov, A. N.; Varshavsky, Ya. M. Ionization potentials and electron-donor ability of nucleic acid bases and their analogues. Tetrahedron Lett. 1976, 17, 4377−4378.

ASSOCIATED CONTENT

* Supporting Information S

Cartesian geometries and energies of all species (gas-phase, microsolvated, and bulk-solvated), neutral and ionized; frequencies of all relevant species; charge−dipole interaction versus solvatochromic shift; and NBO charges. This material is available free of charge via the Internet at http://pubs.acs.org.

■

ACKNOWLEDGMENTS

We acknowledge a grant from the CSIR XIIth five-year plan project on Multi-Scale Simulations of Material and facilities of the Centre of Excellence in Scientific Computing at NCL. Support from CSIR-National Chemical Laboratory in the form of a startup grant is gratefully acknowledged. We also thank Ms. Purvi Gupta from IIT Roorkee for her help.

4. CONCLUSIONS In this work, we have calculated the relative stabilities of the stable tautomers of cytosine in the gas phase and under microsolvation. In the gas phase, the enol tautomer was found to be most stable (which is also seen in recent experiments). However, upon monohydration, the stabilities of the tautomers change dramatically, and the keto tautomer, which has a higher dipole, becomes more stable. We computed the VIEs and AIEs of the microsolvated tautomers and noticed that the solvatochromic shifts are consistent with the amount of differential charge−dipole interactions between the cation and neutral states. Unlike in the case of thymine, we noticed both red and blue solvatochromic shifts. We probed the various ionization channels for keto−enol and keto−ketoimine tautomerizations. We notice that the first ionized state provides a lower-barrier tautomerization except in the case of gas-phase keto−ketoimine tautomerization. The effect of ionization on the tautomerization in the microsolvated structures was further probed by charge−dipole interactions, and the changes in barriers were found to be consistent with the amount of charge−dipole interactions. However, we noticed that, in the case of bulk solvation the barriers, did not change significantly from the microsolvated state. This points to the rather low importance of the water polarization on the barrier, which is surprising. Because we studied this with continuum solvation only, this effect should be further probed with hybrid quantum mechanics/molcular mechanics (QM/MM) treatments to understand the specific interactions between the various water molecules and the cytosine and the balance of interactions at play. Work is in progress in this direction.

■

■

Article

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest. 5330



Article

(19) Peng, S.; Padva, A.; LeBreton, P. R. Ultraviolet photoelectron studies of biological purines: The valence electronic structure of adenine. Proc. Natl. Acad. Sci. U.S.A. 1976, 73, 2966−2968. (20) Lange, A. W.; Herbert, J. M. Both Intra- and Interstrand ChargeTransfer Excited States in Aqueous B-DNA Are Present at Energies Comparable To, or Just Above, the 1ππ* Excitonic Bright States. J. Am. Chem. Soc. 2009, 131, 3913−3922. (21) Zhang, X. ; Herbert, J. M. Excited-State Deactivation Pathways in Uracil versus Hydrated Uracil: Solvatochromatic Shift in the n → π* State is the Key J. Phys. Chem. B 2014. (22) Jurečka, P.; Šponer, J.; Č erný, J.; Hobza, P. Benchmark database of accurate (MP2 and CCSD(T) complete basis set limit) interaction energies of small model complexes, DNA base pairs, and amino acid pairs. Phys. Chem. Chem. Phys. 2006, 8, 1985−1993. (23) Hanus, M.; Kabelác,̧ M.; Rejnek, J.; Ryjék, F.; Hobza, P. Correlated ab Initio Study of Nucleic Acid Bases and Their Tautomers in the Gas Phase, in a Microhydrated Environment, and in Aqueous Solution. Part 3. Adenine. J. Phys. Chem. B 2004, 208, 2087−2097. (24) Rejnek, J.; Hanus, M.; Kabelác,̧ M.; Ryjék, F.; Hobza, P. Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment and in aqueous solution. Part 4. Uracil and thymine. Phys. Chem. Chem. Phys. 2005, 7, 2006−2017. (25) Colson, A. O.; Sevilla, M. D. Elucidation of primary radiation damage in DNA through application of ab initio molecular orbital theory. Int. J. Rad. Biol. 1995, 67, 627−645. (26) Kumar, A. ; Sevilla, M. D. Theoretical modeling of radiationinduced DNA damage. In Radical and Radical Ion Reactivity in Nucleic Acid Chemistry; Greenberg, M. D., Ed.; John Wiley and Sons: New York, 2009; pp 1−40. (27) Turecek, F. Computational Studies of Radicals Relevant to Nucleic Acid Damage. Adv. Quantum Chem. 2007, 52, 89−120. (28) Shukla, M. K.; Leszczynski, J. Radiation induced molecular phenomena in nucleic acids: A brief introduction. In Radiation-Induced Molecular Phenomena in Nucleic Acids; Shukla, M. K., Leszczynski, J., Eds.; Springer: Berlin, 2008; Chapter 1, pp 1−14. (29) Crespo-Hernández, C. E.; Cohen, B.; Hare, P. M.; Kohler, B. Ultrafast excited-state dynamics in nucleic acids. Chem. Rev. 2004, 104, 1977−2019. (30) Kanvah, S.; Joseph, J.; amd R.N. Barnett, G. B.; Schuster; Cleveland, C. L.; Landman, U. Oxidation of DNA: Damage to nucleobases. Acc. Chem. Res. 2010, 43, 280−287. (31) Friedberg, E. C. DNA damage and repair. Nature 2003, 421, 436−440. (32) Bertran, J. ; Blancafort, L. ; Noguera, M. Proton transfer in DNA base pairs: Potential mutagenic processes. In Computational Studies of DNA and RNA; Sponer, P., Lankas, F., Eds.; Springer: New York, 2006; Chapter 16, pp 411−432. (33) Choi, M. Y.; Dong, F.; Miller, R. E. Multiple tautomers of cytosine identifed and characterized by infrared laser spectroscopy in helium nanodroplets: Probing structure using vibrational transition moment angles. Philos. Trans. R. Soc. A 2005, 363, 393−413. (34) Sambrano, J. R.; de Souza, A. R.; Queralt, J. J.; Andrés, J. A theoretical study on cytosine tautomers in aqueous media by using continuum models. Chem. Phys. Lett. 2000, 317, 437−443. (35) Brown, R. D.; Godfrey, P. D.; McNaughton, D.; Pierlot, A. P. A study of the major gas-phase tautomer of adenine by microwave spectroscopy. Chem. Phys. Lett. 1989, 156, 61−63. (36) Plützer, Chr.; Kleinermanns, K. Tautomers and electronic states of jet-cooled adenine investigated by double resonance spectroscopy. Phys. Chem. Chem. Phys. 2002, 4, 4877−4882. (37) Piacenza, M.; Grimme, S. Systematic quantum chemical study of DNA-base tautomers. J. Comput. Chem. 2004, 25, 83−99. (38) Brown, R. D.; Godfrey, P. D.; McNaughton, D.; Pierlot, A. P. Tautomers of cytosine by microwave spectroscopy. J. Am. Chem. Soc. 1989, 111, 2308−2310. (39) Triandafillou, C. G.; Matsika, S. Excited-State Tautomerization of Gas-Phase Cytosine. J. Phys. Chem. A 2013, 117, 12165−12174.

(40) Bravaya, K. B.; Kostko, O.; Dolgikh, S.; Landau, A.; Ahmed, M.; Krylov, A. I. Electronic Structure and Spectroscopy of Nucleic Acid Bases: Ionization Energies, Ionization-Induced Structural Changes, and Photoelectron Spectra. J. Phys. Chem. A 2010, 114, 12305−12317. (41) Bazsó, G.; Tarczay, G.; Fogarasi, G.; Szalay, P. G. Tautomers of cytosine and their excited electronic states: A matrix isolation spectroscopic and quantum chemical study. Phys. Chem. Chem. Phys. 2011, 13, 6799−6807. (42) Fogarasi, G. Relative Stabilities of Three Low-Energy Tautomers of Cytosine: A Coupled Cluster Electron Correlation Study. J. Phys. Chem. A 2002, 106, 1381−1390. (43) Yang, Z.; Rodgers, M. T. Theoretical studies of the unimolecular and bimolecular tautomerization of cytosine. Phys. Chem. Chem. Phys. 2004, 6, 2749−2757. (44) Trygubenko, S. A.; Bogdan, T. V.; Rueda, M.; Orozco, M.; Luque, F. J.; Šponer, J.; Slaviček, P.; Hobza, P. Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment and in aqueous solution: Part 1. Cytosine. Phys. Chem. Chem. Phys. 2002, 4, 4192−4203. (45) Mennucci, B.; Toniolo, A.; Tomasi, J. Theoretical Study of the Photophysics of Adenine in Solution: Tautomerism, Deactivation Mechanisms, and Comparison with the 2-Aminopurine Fluorescent Isomer. J. Phys. Chem. A 2001, 105, 4749−4757. (46) Colominas, C.; Luque, F. J.; Orozco, M. Tautomerism and Protonation of Guanine and Cytosine. Implications in the Formation of Hydrogen-Bonded Complexes. J. Am. Chem. Soc. 1996, 118, 6811− 6821. (47) Park, H. S.; Nam, S. H.; Song, J. K.; Park, S. M.; Ryu, S. Density Functional Study of Intradimer Proton Transfers in Hydrated Adenine Dimer Ions, A2+(H2O)n (n = 0−2). J. Phys. Chem. A 2008, 112, 9023− 9030. (48) Sobolewski, A. L.; Domcke, W.; Dedonder-Lardeuxc, C.; Jouvet, C. Excited-state hydrogen detachment and hydrogen transfer driven by repulsive 1ππ* states: A new paradigm for nonradiative decay in aromatic biomolecules. Phys. Chem. Chem. Phys. 2002, 4, 1093−1100. (49) Guallar, V.; Douhal, A.; Moreno, M.; Lluch, J. M. DNA Mutations Induced by Proton and Charge Transfer in the Low-Lying Excited Singlet Electronic States of the DNA Base Pairs: A Theoretical Insight. J. Phys. Chem. A 1999, 103, 6251−6256. (50) Schultz, T.; Samoylova, E.; Radloff, W.; Hertel, I. V.; Sobolewski, A. L.; Domcke, W. Efficient Deactivation of a Model Base Pair via Excited-State Hydrogen Transfer. Science 2004, 306, 1765−1768. (51) Kozak, C. R.; Kistler, K. A.; Lu, Z.; Matsika, S. Excited-State Energies and Electronic Couplings of DNA Base Dimers. J. Phys. Chem. B 2010, 114, 1674−1683. (52) Guerra, C. F.; Bickelhaupt, F. M.; Saha, S.; Wang, F. Adenine Tautomers: Relative Stabilities, Ionization Energies, and Mismatch with Cytosine. J. Phys. Chem. A 2006, 110, 4012−4020. (53) Choi, K.-W.; Lee, J.-H.; Kim, S. K. Ionization Spectroscopy of a DNA Base: Vacuum-Ultraviolet Mass-Analyzed Threshold Ionization Spectroscopy of Jet-Cooled Thymine. J. Am. Chem. Soc. 2005, 127, 15674−15675. (54) Slavíček, P.; Winter, B.; Faubel, M.; Bradforth, S. E.; Jungwirth, P. Ionization Energies of Aqueous Nucleic Acids: Photoelectron Spectroscopy of Pyrimidine Nucleosides and ab Initio Calculations. J. Am. Chem. Soc. 2009, 131, 6460−6467. (55) Dolgounitcheva, O.; Zakrzewski, V. G.; Ortiz, J. V. Electron propagator calculations on uracil and adenine ionization energies. Int. J. Quantum Chem. 2000, 80, 831−835. (56) Wolken, J. K.; Yao, C. Y.; Turečeka, F.; Polce, M. J.; Wesdemiotis, C. Cytosine neutral molecules and cation-radicals in the gas phase: Structures, energetics, ion chemistry, and neutralizationreionization mass spectrometry. Int. J. Mass. Spectrom 2007, 267, 30− 42. (57) Colson, A.-O.; Besler, B.; Sevilla, M. D. Ab initio molecular orbital calculations on DNA base pair radical ions: Effect of base pairing on proton-transfer energies, electron affinities, and ionization potentials. J. Phys. Chem. 1992, 96, 9787−9794. 5331



Article

(58) Colson, A.-O.; Besler, B.; Sevilla, M. D. Ab initio molecular orbital calculations on DNA radical ions. 4. Effect of hydration on electron affinities and ionization potentials of base pairs. J. Phys. Chem. 1993, 97, 13852−13859. (59) Khistyaev, K.; Bravaya, K. B.; Kamarchik, E.; Kostko, O.; Ahmed, M.; Krylov, A. I. The effect of microhydration on ionization energies of thymine. Faraday Discuss. 2011, 150, 313−330. (60) Ghosh, D.; Isayev, O.; Slipchenko, L. V.; Krylov, A. I. Effect of Solvation on the Vertical Ionization Energy of Thymine: From Microhydration to Bulk. J. Phys. Chem. A 2011, 115, 6028−6038. (61) Ghosh, A. K.; Schuster, G. B. Role of the Guanine N1 Imino Proton in the Migration and Reaction of Radical Cations in DNA Oligomers. J. Am. Chem. Soc. 2006, 128, 4172−4173. (62) Khistyaev, K.; Golan, A.; Bravaya, K. B.; Orms, N.; Krylov, A. I.; Ahmed, M. Proton Transfer in Nucleobases is Mediated by Water. J. Phys. Chem. A 2013, 117, 6789−6797. (63) Kumar, A.; Sevilla, M. D. Influence of Hydration on Proton Transfer in the Guanine−Cytosine Radical Cation (G•+−C) Base Pair: A Density Functional Theory Study. J. Phys. Chem. B 2009, 113, 11359−11361. (64) Bertran, J.; Oliva, A.; Rodríguez-Santiago, L.; Sodupe, M. Single versus Double Proton-Transfer Reactions in Watson−Crick Base Pair Radical Cations. A Theoretical Study. J. Am. Chem. Soc. 1998, 120, 8159−8167. (65) Mazzuca, D.; Marino, T.; Russo, N.; Toscano, M. A theoretical study on tautomerization processes of dehydrated and monohydrated cytosine. J. Mol. Struct. (THEOCHEM) 2007, 811, 161−167. (66) Kobayashi, K.; Tagawa, S. Direct Observation of Guanine Radical Cation Deprotonation in Duplex DNA Using Pulse Radiolysis. J. Am. Chem. Soc. 2003, 125, 10213−10218. (67) Catalán, J.; Pérez, P.; del Valle, J. C.; de Paz, J. L. G.; Kasha, M. The answer to concerted versus step-wise controversy for the double proton transfer mechanism of 7-azaindole dimer in solution. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 419. (68) Mukherjee, M.; Karmakar, S.; Chakraborty, T. Excited State Tautomerization of 7-Azaindole in a 1:1 Complex with δValerolactam: A Comparative Study with the Homodimer. J. Phys. Chem. A 2012, 116, 9888−9896. (69) Chen, H.-Y.; Chao, I. Ionization-Induced Proton Transfer in Model DNA Base Pairs: A Theoretical Study of the Radical Ions of the 7-Azaindole Dimer. ChemPhysChem 2004, 5, 1855−1863. (70) Bardez, E.; Devol, I.; Larrey, B.; Valeur, B. Excited-State Processes in 8-Hydroxyquinoline: Photoinduced Tautomerization and Solvation Effects. J. Phys. Chem. B 1997, 101, 7786−7793. (71) Bensaude, O.; Chevrier, M.; Dubois, J.-E. Lactim/lactam tautomeric interconversion mechanism in water/polar aprotic solvent water systems. 2. Hydration of 2-hydroxypyridines. Evidence for a bifunctional water-catalyzed proton transfer. J. Am. Chem. Soc. 1979, 101, 2423−2429. (72) Chao, P.-T.; Yu, W.-S.; Wei, C.-Y.; Cheng, Y.-M.; Yang, C.-Y. Water-Catalyzed Excited-State Double Proton Transfer in 3-Cyano-7azaindole: The Resolution of the Proton-Transfer Mechanism for 7Azaindoles in Pure Water. J. Am. Chem. Soc. 2001, 123, 3599−3600. (73) Matsuda, Y.; Yamada, A.; Hanaue, K.-i.; Mikami, N.; Fujii, A. Catalytic Action of a Single Water Molecule in a Proton-Migration Reaction. Angew. Chem., Int. Ed. 2010, 49, 4898. (74) Kaduk, B.; Kowalczyk, T.; Van Voorhis, T. Constrained Density Functional Theory. Chem. Rev. 2012, 112 (1), 321−370. (75) Shao, Y.; Fusti-Molnar, L.; Jung, Y.; Kussmann, J.; Ochsenfeld, C.; Brown, S.; Gilbert, A. T. B.; Slipchenko, L. V.; Levchenko, S. V.; O’Neill, D. P.; et al. Advances in methods and algorithms in a modern quantum chemistry program package. Phys. Chem. Chem. Phys. 2006, 8, 3172−3191. (76) Krylov, A. I.; Gill, P. M. W. Q-Chem: An engine for innovation. WIREs Comput. Mol. Sci. 2013, 3, 317−326, DOI: 10.1002/ wcms.1122. (77) Cramer, C. J.; Truhlar, D. G. A universal approach to solvation modeling. Acc. Chem. Res. 2008, 41, 760−768.

(78) Kelley, C. P.; Cramer, C. J.; Truhlar, D. G. SM6: A Density Functional Theory Continuum Solvation Model for Calculating Aqueous Solvation Free Energies of Neutrals, Ions, and SoluteWater Clusters. J. Chem. Theory Comput. 2005, 1, 1133−1152. (79) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision D.01; Gaussian Inc.: Wallingford, CT, 2009. (80) Szczesniak, M.; Szczepaniak, K.; Kwiatkowski, J. S.; KuBulat, K.; Person, W. B. Matrix isolation infrared studies of nucleic acid constituents. 5. Experimental matrix-isolation and theoretical ab initio SCF molecular orbital studies of the infrared spectra of cytosine monomers. J. Am. Chem. Soc. 1988, 110, 8319−8330. (81) Bravaya, K. B.; Kostko, O.; Ahmed, M.; Krylov, A. I. The effect of π-stacking, H-bonding, and electrostatic interactions on the ionization energies of nucleic acid bases: Adenine−adenine, thymine−thymine and adenine−thymine dimers. Phys. Chem. Chem. Phys. 2010, 12, 2292−2307. (82) Kostko, O.; Bravaya, K. B.; Krylov, A. I.; Ahmed, M. Ionization of cytosine monomer and dimer studied by VUV photoionization and electronic structure calculation. Phys. Chem. Chem. Phys. 2010, 12, 2860−2872. (83) Lapinski, L.; Reva, I.; Nowak, M. J.; Fausto, R. Five isomers of monomeric cytosine and their interconversions induced by tunable UV laser light. Phys. Chem. Chem. Phys. 2011, 13, 9676−9684.

5332


Ionization-Induced Tautomerization in Cytosine and Effect of Solvation

Recommend Documents