Quantum Chemical Investigations on the Nonradiative Deactivation

Article pubs.acs.org/JPCA

Quantum Chemical Investigations on the Nonradiative Deactivation Pathways of Cytosine Derivatives Akira Nakayama,*,† Shohei Yamazaki,‡ and Tetsuya Taketsugu§ †

Catalysis Research Center, Hokkaido University, Sapporo 001-0021, Japan Department of Frontier Materials Chemistry, Graduate School of Science and Technology, Hirosaki University, Hirosaki 036-8561, Japan § Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan ‡

S Supporting Information *

ABSTRACT: The nonradiative deactivation pathways of cytosine derivatives (cytosine, 5-fluorocytosine, 5-methylcytosine, and 1-methycytosine) and their tautomers are investigated by quantum chemical calculations, and the substituent effects on the deactivation process are examined. The MSCASPT2 method is employed in the excited-state geometry optimization and also in the search for conical intersection points, and the potential energy profiles connecting the Franck−Condon point, excited-state minimum energy structures, and the conical intersection points are investigated. Our calculated vertical and adiabatic excitation energies are in quite good agreement with the experimental results, and the relative barrier heights leading to the conical intersections are correlated with the experimentally observed excite-state lifetimes, where the calculated barrier heights are in the order of cytosine < 5-methylcytosine < 5-fluorocytosine.

1. INTRODUCTION There have been numerous efforts on the molecular-level elucidation of the nonradiative deactivation mechanisms of DNA/RNA bases. These nucleic acid bases, which are the molecular building blocks of life, naturally possess an efficient nonreactive deactivation pathway after UV irradiation, and this photophysical property provides intrinsic photostability in DNA/RNA. The lifetimes of this deactivation process are reported to be on the order of subpicoseconds or picoseconds,1,2 and the existence of conical intersection (CI) points along the deactivation pathway is almost conclusively accepted as a funnel for efficiently dissipating the energy attained by photoexcitation.3 Cytosine is one of the well-studied DNA bases, and numerous experimental4−9 and theoretical10−28 works have been conducted in order to gain insight into the nonradiative decay mechanisms. In our previous work,27 we have investigated the nonradiative deactivation process of cytosine tautomers (amino−keto, imino−keto, and amino−enol forms) by quantum chemical calculations and also by excited-state molecular dynamics simulations and successfully explained the recent experimental data obtained by the femtosecond pump− probe photoionization spectroscopy.7,8 We have demonstrated that the amino−keto (keto) and amino−enol (enol) forms deactivate predominantly through the ethylene-like CI involving the twisting of the C−C double bond in the pyrimidine ring and that the enol form has a slightly higher barrier leading to CI than the keto form. Also, the imino−keto (imino) form exhibits a remarkably efficient deactivation © 2014 American Chemical Society

pathway involving the twisting of the imino group. These observations are consistent with the experimental findings,7,8 where the three tautomers are involved in the photophysics of isolated cytosine and each tautomer exhibits a different excitedstate lifetime. Very recently, Leutwyler and co-workers have investigated the excited-state structures, vibrations, and nonradiative relaxation dynamics of cytosine (Cyt),9 5-methylcytosine (5MeCyt),29 and 5-fluorocytosine (5FCyt)30 using two-color resonant two-photon ionization (R2PI) spectroscopy. The 1 ππ* state lifetimes of their keto tautomers (canonical forms) were determined by the Lorentzian line broadening of the bands, and in particular, the 000 band lifetimes were reported as 45 ps for Cyt, 30−60 ps for 5MeCyt, and 75 ps for 5FCyt. Moreover, from the positions of the break-off of the gas-phase vibration spectra, the barrier heights leading to the ethylene-like CI were estimated to be 350 (0.043), 500 (0.062), and 1200 cm−1 (0.15 eV) for Cyt, 5MeCyt, and 5FCyt, respectively. These observations are seemingly inconsistent with the previous experimental findings, where the excited-state lifetime of isolated cytosine is in the subpicosecond range4−8 and also the substitution of hydrogen by fluorine at the C5 position (5FCyt) increases the excited-state lifetime by 2 orders of magnitude,15,31 but the authors nicely illustrated the consistency between these experiments by analyzing correlation Received: July 7, 2014 Revised: September 2, 2014 Published: September 2, 2014 9429

dx.doi.org/10.1021/jp506740r | J. Phys. Chem. A 2014, 118, 9429−9437

The Journal of Physical Chemistry A

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symmetry constraints are imposed during the geometry optimization. After the geometry optimization, single-point energy calculations are carried out at the MS-CASPT2 level with a larger active space in order to provide improved energetic for given geometries. A level shift with a value of 0.2 is applied for the MS-CASPT2 calculations.32 The Sapporo-DZP basis set33 (denoted as DZP hereafter) is employed throughout this study, and all quantum chemical calculations are performed by the MOLPRO2008.1 package.34 The MECI geometries are located by the penalty function approach,35 where the following function is minimized:

between the excess vibrational energy and excited-state lifetime.9,30 Our previous calculations predicted that the barrier height from the 1ππ* minimum energy structure to the ethylene-like CI is ∼0.08 eV for keto-Cyt and this value is in semiquantitatively good agreement with the experimental estimate by R2PI spectroscopy.9 These recent experimental studies have inspired us to perform a comparative study on the deactivation processes of cytosine derivatives. This Paper is a follow-up of the previous study and focuses on the cytosine derivatives Cyt, 5MeCyt, 5FCyt, and 1-methycytosine (1MeCyt) for understanding the substituent effects on the ultrafast deactivation processes (see Figure 1 for molecular structure). In the

Fij(R; σ , α) =

Ei(R) + Ej(R) 2

+σ

(Ei(R) − Ej(R))2 Ei(R) − Ej(R) + α (2.1)

Here, Ei(R) (Ej(R)) is the energy of the i-th (j-th) adiabatic electronic state at the molecular coordinate R. The parameters are employed as α = 0.02 hartree and σ = 3.5 by following the previous works.27,35,36 The potential energy profiles along the pathways connecting the excited-state minimum to MECIs provide an important information on the efficiency of nonradiative transition, and the barrier heights between these structures are often used to estimate the excited-state lifetimes. In this context, the linearly interpolated internal coordinate (LIIC) is widely employed to connect these two structures. In general, the global MECI geometry exhibits a highly deformed structure, and therefore, the straight-line pathway by LIIC sometimes results in a serious overestimation of the potential energy barrier, because it cuts through a ridge of the surfaces rather than following the valley. To ameliorate this aspect of the problem, we also perform a distance-constrained MECI (cMECI) search, where the geometrical constrains are added to the above function as shown below:

Figure 1. Molecular structure of cytosine derivatives.

experimental conditions, the possibility of existence of tautomers cannot be excluded,7,8 at least, in the gas phase, and therefore, in addition to the canonical keto form of these derivatives, their enol tautomers are also examined in a similar manner. The imino form, which is relatively stable in the electronic ground state, is also considered but only for 5MeCyt, because it has been shown that the imino-Cyt possesses quite efficient barrierless pathway and similar mechanisms would be easily expected for other derivatives. There are a few previous reports on the deactivation pathways of 5FCyt in the canonical keto form,14,15 but to our knowledge, there is no literature examining the potential energy profiles of the above-mentioned cytosine derivatives and their tautomers on equal footing. This Paper is organized as follows. After presenting the computational details, the vertical and adiabatic excitation energies are examined for the cytosine derivatives and their tautomers. Then, the deactivation pathways in the 1ππ* state are investigated by exploring the excited-state potential energy surfaces from the Franck−Condon (FC) point to the minimal energy conical intersection (MECI) points. The relative energies of the MECI points and the barrier heights along the pathways from the 1ππ* minimum energy structures to the MECI points are compared in detail for these derivatives. Finally, conclusions are given in Section 4.

Fijconst ,d0 (R ; k , σ , α) =

Ei(R) + Ej(R) 1 k(d − d0)2 + 2 2 2 (Ei(R) − Ej(R)) +σ Ei(R) − Ej(R) + α (2.2)

In the above equation, d is the mass-weighted distance between R and a reference geometry Rref, which is set to the 1ππ* minimum energy structure and is written as N

d=

∑ mi |R(i) − R (refi) |2 (2.3)

i=1 (i)

where N represents the number of atoms and R is the coordinates of i-th atom. The spring constant k is fixed during the optimization, and we use k = 1.0 hartree/(bohr2·amu) throughout this study. The constrained MECI geometry optimizations are performed at several values of d0, which yields the MECI geometries at fixed distances from the 1ππ* minimum energy structure. The potential energy profiles are calculated from the 1ππ* minimum energy structure to these cMECI points using LIIC, and the minimum barrier height from these potential energy profiles is taken as a good estimate of the barrier height of the minimum energy pathway. It is noted in passing that the penalty function approach35,37 is useful for locating the MECI points when the nonadiabatic coupling vectors are not available, in particular, for highly correlated electronic structure calculations such as MS-

2. COMPUTATIONAL DETAILS The ground-state equilibrium geometry is determined by the Møller−Plesset second-order perturbation (MP2) method while the geometry optimization in the singlet excited states is performed by the multistate complete active space secondorder perturbation theory (MS-CASPT2) method. The MECI geometries are also located by the MS-CASPT2 approach. No 9430



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CASPT2(12, 9) calculations, where the S0, two lowest-lying ππ*, and lowest-lying 1nπ* states are averaged with equal weights in the reference SA(4)-CASSCF(12, 9) wave functions.

CASPT2. The so-called branching plane, which is spanned by the nonadiabatic coupling vectors and energy difference gradient vectors, possesses important characteristics of CI,38 and it is of course desirable to obtain these vectors. Unfortunately, the penalty function approach is unable to obtain the branching plane, and a certain energy gap is seen even if the optimization process is completed; therefore, it does not provide information whether the optimized geometry corresponds to a true conical intersection or a weakly avoided crossing. However, it has been stated by Truhlar and Mead that the small energy gap region is much more likely to be associated with the neighborhood of a true conical intersection than with an avoid crossing.39 In MS-CASPT2 calculations, the notation of MS(l)CASPT2(m, n) is occasionally used, in which case the active space for a reference state-averaged complete active space selfconsistent field (SA-CASSCF) wave function is composed of m electrons and n orbitals (SA-CASSCF(m, n)) and the lowest l states are averaged with equal weights in SA-CASSCF calculations. Subsequently, the corresponding l states are mixed in the perturbation calculations. For keto tautomers of cytosine derivatives, the minimum energy structure in the 1ππ* state is located by the MS(2)-CASPT2(8, 7) method, where the active space is composed of only π orbitals. The π orbital on the N8 atom is excluded from the active space (see Figure 1 for atomic numbering). The cMECI search between the 1ππ* and S0 states is performed at the MS(3)-CASPT2(2, 2) level, where only the π*/π orbitals that are localized around C5−C6 double bonds are included in the active space, in order to reduce the computation effort. The MECI search without a distance constraint is also carried out by the MS(2)-CASPT2(8, 7) method only for Cyt in order to ascertain the accuracy of the MS(3)-CASPT2(2, 2) approach. After the above-mentioned geometry optimizations, the single-point MS(4)-CASPT2(12, 9) energy calculations are performed for obtaining the potential energy profiles, where the S0, lowest-lying 1ππ*, and two lowest-lying 1nπ* states are averaged with equal weights in the reference SA(4)-CASSCF(12, 9) wave functions. Here, the active space is composed of seven π orbitals (four of them are doubly occupied in the closed-shell configuration) and two lone-pair orbitals on the N3 and O7 atoms. This choice of the active space is the same as that used in our previous work on keto-Cyt.27 The active orbitals of 5MeCyt in each tautomeric form at the S0 equilibrium structure are given in the Supporting Information. For enol tautomers, the geometry optimizations in the 1ππ* state are performed by the MS(2)-CASPT2(8, 7) method, where the π orbitals in the pyrimidine ring and one of the nonbonding orbitals are included in the active space, as employed in our previous work. The MS(3)-CASPT2(2, 2) calculations are also carried out for the cMECI optimization. The potential energy profiles are recalculated at the MS(3)CASPT2(10, 8) level, where the other nonbonding orbital is added in the active space, and the S0 and lowest-lying 1ππ* and lowest-lying 1nπ* states are averaged with equal weights in the reference SA(3)-CASSCF(10, 8) wave functions. For an imino tautomer of 5MeCyt, the MECI geometry is determined at the MS(2)-CASPT2(6, 5) level, where the active space is composed of four π orbitals (two occupied and two unoccupied) plus one lone-pair orbital belonging to the N8 atom. This active space is the same as that employed in the previous work on imino-Cyt. The potential energy profiles from the FC region to MECI are obtained by the MS(4)-

1

3. RESULTS AND DISCUSSION 3.1. Relative Stability of Tautomers. Before discussing the photophysical properties, the relative stability of tautomers in the electronic ground state is examined for each cytosine derivative. Table 1 shows the relative energies of imino and Table 1. Relative Energy (in eV) of Tautomers with Respect to the Keto Form Cyta 5MeCyt 5FCyt 1MeCyt a

imino

enol

+0.027 −0.003 +0.015 +0.075

−0.074 −0.099 −0.153 ―

From ref 27.

enol tautomers with respect to the keto one. The lower-energy rotamers of the imino and enol tautomers are only considered in this work, and the imino rotamer directing the NH bond in the imino group to the C5 side and the enol rotamer directing the OH bond in the hydroxyl group to the N1 side are found to be lower in energy for all cytosine derivatives (see Figure 2 for equilibrium structures of 5MeCyt; equilibrium structures of higher-energy rotamers are given in the Supporting Information). It is also noted that the enol form does not exist for 1MeCyt. Cartesian coordinates of equilibrium structures of all derivatives are provided in the Supporting Information. As seen in the table, the enol form is the most stable for all cytosine derivatives. The imino form is less stable than the keto form except for 5MeCyt. For 5MeCyt, the imino form is only slightly lower in energy than the keto form, and the energetic order of enol < imino < keto is consistent with other studies by CCSD/cc-pVTZ40 and also by spin component scaled (SCS) MP2/aug-cc-pVTZ29 calculations, although the DFT calculations predict that the keto form is more stable than the imino form.41 For Cyt and 5FCyt, the energetic order of enol < keto < imino is also consistent with other theoretical studies; see refs 8, 9, 42−48 and refs 8 and 30 for Cyt and 5FCyt, respectively. It is interesting to note that the enol form of 5FCyt is much more stable than its keto and imino forms, and it would be expected that the enol form strongly dominates in the 5FCyt vapor. 3.2. Vertical and Adiabatic Excitation Energy. The vertical excitation energies at the S0 equilibrium structure (denoted as (S0)min heareafter) are tabulated in Table 2, along with the recent literature values by RI-CC2/aug-cc-pVTZ. There are many theoretical and experimental reports for vertical excitation energies for Cyt, and these values are summarized in our previous paper.27 In each tautomeric form, it is found that the excitation energies of the derivatives to the lowest 1ππ* state are very close to each other. The 1nπ* states lie slightly higher than the 1 ππ* state in all derivatives. For the keto form, the order of the 1 ππ* excitation energies (Cyt > 5MeCyt > 5FCyt) are in accord with experiments and also with the RI-CC2/aug-cc-pVTZ calculations. The minimum energy structures in the 1ππ* state are determined both in the keto and enol forms by the MS(2)9431



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Figure 2. Equilibrium structures, (S0)min, of (a) keto-5MeCyt, (b) enol-5MeCyt, and (c) imino-5MeCyt. Bond lengths are given in units of Å.

Table 2. Vertical Excitation Energies (in eV) for Low-Lying Singlet Excited States of Cytosine Derivatives Calculated by MS(4)CASPT2(12, 9) for Keto and Imino Tautomers and by MS(3)-CASPT2(10, 8) for Enol Tautomers keto

enol

ππ*

1

Cyt

5MeCyt 5FCyt

1MeCyt a

MS-CASPT2/DZP RI-CC2/aug-cc-pVTZa exptb MS-CASPT2/DZP RI-CC2/aug-cc-pVTZc MS-CASPT2/DZP RI-CC2/aug-cc-pVTZd expte MS-CASPT2/DZP

4.48 4.61 4.65 4.41 4.48 4.39 4.42 4.51 4.40

1

ππ*

imino 1

4.74, 5.26 4.83

4.78

4.91

4.67, 5.75

5.59

4.71, 5.22 4.77 4.74, 5.16 4.78

4.72

4.88

4.62, 5.77

5.61

4.66

4.80

4.67, 5.83

5.59

4.79, 5.27

―

―

4.46, 5.66

5.60

nπ*

1

ππ*

1

nπ*

1

nπ*

From ref 9. bFrom ref 49. cFrom ref 29. dFrom ref 30. eFrom ref 50.

CASPT2(8, 7) method, and they are labeled as (1ππ*)min hereafter. The frequency analysis is also performed for keto-Cyt and enol-Cyt at the same level of MS-CASPT2, and it is confirmed that the optimized structures are true minima in the 1 ππ* state. The zero-point energy at (1ππ*)min amounts to 2.55 and 2.60 eV for keto-Cyt and enol-Cyt, respectively (vibrational frequencies and corresponding normal modes are given in the Supporting Information). The frequency analysis for other derivatives is not performed due to the high computational cost, but the optimized structures are very similar between the derivatives, and it is almost certain that these structures are the minimum energy ones in the 1ππ* state. Figure 3 shows the (1ππ*)min structures of keto-5MeCyt and enol-5MeCyt. As seen in the figure, for the keto form, the molecule maintains planarity in the pyrimidine ring, and the notable changes from the (S0)min structure involve bond inversion of the ring. For the enol form, the C5−C6 bond elongation is seen as in the keto form, and also, a deformation of the ring with a puckering of C6 atom is observed. Cartesian coordinates of (1ππ*)min structures of the other derivatives are given in the Supporting Information. Table 3 shows the adiabatic excitation energies, along with the experimental and other calculated values. As seen clearly, our calculated values are in quite good agreement with the R2PI experiments with a difference of only ∼0.1 eV for all derivatives. The relative values between the derivatives are also

Figure 3. Minimum energy structures, (1ππ*)min, of (a) keto-5MeCyt and (b) enol-5MeCyt. Bond lengths are given in units of Å.

in accord with the experiments. For example, our calculated relative shift of the adiabatic excitation energy from keto-Cyt to keto-5FCyt is −0.11 eV, and it is in good agreement with the experimental shift of the 000 band origin (−1192 cm−1 = −0.148 eV). The previous CASPT2 calculation15 predicted a shift of −807 cm−1 (−0.10 eV), which is also in good agreement with our results. 9432



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Table 3. Adiabatic Excitation Energies (in eV) for the Lowest 1ππ* States of Cytosine Derivatives Calculated by MS(4)-CASPT2(12, 9) for Keto Tautomers and by MS(3)CASPT2(10, 8) for Enol Tautomers Cyt

5MeCyt

5FCyt

1MeCyt

MS-CASPT2/DZP RI-CC2/aug-cc-pVTZ9 expta MS-CASPT2/DZP RI-CC2/aug-cc-pVTZ29 expta MS-CASPT2/DZP RI-CC2/aug-cc-pVTZ30 expta MS-CASPT2/DZP expta

keto

enol

3.98 (3.84)b 3.77 3.95c, 3.95d 3.97 3.71 3.88e, 3.88d 3.87 3.61 3.80f 3.98 3.96d

4.30 (4.19)b

4.28 (4.46)d 4.24

―

a

Experimental values are given as the positions of the 000 band origin. The italic numbers in parentheses are the zero-point energy corrected values where the MP2 and MS(8)-CASPT2(8, 7) methods are used to obtain vibrational frequencies for S0 and 1ππ* states, respectively. c From ref 9. dFrom ref 51. eFrom ref 29. fFrom ref 30. b

The adiabatic excitation energies of the enol form are ∼0.3 eV higher than the corresponding values of the keto form. This is also consistent with the experimental observations for 5MeCyt, where the second vibrational bands in the R2PI spectrum appear around 36 000 cm−1 (4.46 eV). This second vibrational bands were assigned to the enol form, which was 0.58 eV above the 000 band origin.51,52 3.3. Potential Energy Profiles of Keto Tautomers. The potential energy profiles from (S0)min to (1ππ*)min using the LIIC geometries are shown in Figure 4a for keto-5MeCyt. As expected from our previous study of keto-Cyt, the 1ππ* state exhibits a smooth downhill potential toward (1ππ*)min. The energy profiles of the other derivatives are very similar to those of keto-5MeCyt. It is also confirmed that the minimum energy path (MEP) approach starting from (S0)min leads to (1ππ*)min, and therefore, the molecule is expected to initially relax toward (1ππ*)min after photoexcitation to the 1ππ* state. Next, the deactivation pathways from (1ππ*)min to CI between the 1ππ* and S0 states are explored. Three types of CIs have been reported as possible deactivation channels for cytosine, and in this study, we focus only on the ethylene-like CI that involves the twisting of the C5−C6 double bond, because the other two types of CIs are expected to play a minor role, as demonstrated in our previous study.27 The ethylene-like MECI structure of keto-5MeCy is given in Figure 5a, where one can observe a twisting of the C5−C6 double bond with a strong puckering of the C6 atom. The MS(4)-CASPT2(12, 9) potential energy profiles from (1ππ*)min to several cMECI points using the LIIC geometries are shown in Figure 6 for all derivatives. In this work, the mass of substituents (−CH3 or −F) is set to that of a hydrogen atom in order to compare energetics using a similar reaction coordinate. As seen in the figure, the 1ππ* energies of the cMECI points are gradually decreasing as the distance from (1ππ*)min is increased and the 1ππ* energies approach to the converged values. For keto-Cyt, the MECI optimization by MS(2)-CASPT2(8, 7) without a distance constraint leads to a 1 geometry that has a distance of 5.76 bohr·amu /2 from (1ππ*)min. The potential energies at this point are given as 3.81 and 3.74 eV for the 1ππ* and S0 states, respectively, which

Figure 4. Potential energy profiles from (S0)min to (1ππ*)min for lowlying electronic states of (a) keto-5MeCyt and (b) enol-5MeCyt using LIIC points calculated by MS(4)-CASPT2(12, 9) and MS(3)CASPT2(10, 8), respectively.

Figure 5. cMECI structures of (a) keto-5MeCyt and (b) enol-5MeCyt 1

at d0 = 6.0 bohr·amu /2. Bond lengths are given in units of Å.

indicates that the cMECI optimization by MS(3)-CASPT2(2, 2) performs very well. The minimum barrier height along the pathways from (1ππ*)min to cMECI points derived from these profiles is given as ∼0.20 eV for keto-Cyt, which is in good agreement with previous theoretical results of 0.1−0.14 eV.11,14,18,19,27,53 Note that, in our previous work, we estimated this barrier height as 9433



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Figure 6. MS(4)-CASPT2(12, 9) potential energy profiles for low-lying electronic states of (a) keto-Cyt, (b) keto-5MeCyt, (c) keto-5FCyt, and (d) 1

keto-1MeCyt from (1ππ*)min to cMECIs using LIIC points. cMECIs are located at d0 = 3.5, 4.0, 5.0, 6.0 bohr·amu /2 for keto-Cyt and d0 = 4.0, 5.0, 6.0 1

bohr·amu /2 for keto-5MeCyt, keto-5FCyt, and keto-1MeCy (shown as solid squares). The 1ππ* energies at (1ππ*)min and cMECIs are included. The cross marks indicate the MECI point optimized by MS(2)-CASPT2(8, 7).

Figure 7. MS(3)-CASPT2(10, 8) potential energy profiles for low-lying electronic states of (a) enol-Cyt, (b) enol-5MeCyt, and (c) enol-5FCyt from 1

(1ππ*)min to cMECIs using LIIC points. cMECIs are located at d0 = 4.0, 5.0, 6.0 bohr·amu /2 (shown as solid squares). The 1ππ* energies at (1ππ*)min and cMECIs are included. The cross marks indicate the MECI point optimized by MS(2)-CASPT2(8, 7).

∼0.08 eV, and this descrepancy is caused by a different way to define pathways between the (1ππ*)min and MECI points. For keto-5MeCyt and keto-5FCyt, the 1ππ* energies of the cMECI points relative to (1ππ*)min are higher than those of Cyt, and the minimum barrier heights are ∼0.26 and ∼0.40 eV for keto5MeCyt and keto-5FCyt, respectively. The barrier heights estimated by the R2PI experiments are 0.043, 0.062, and 0.15 eV for keto-Cyt,9 keto-5MeCyt,29 and keto-5FCyt,30 respectively. Our calculated values are higher than the experimental values, but the order of these barrier heights is consistent. It should be

noted here that the reaction pathways along the LIIC coordinates are not the optimal deactivation pathways and therefore the barrier height estimated from these profiles can be viewed as an upper bound for that of the minimum energy pathway. Previous calculations by Blancafort et al.15 showed that the barrier heights of keto-Cyt and keto-5FCyt were 6.6 (0.286) and 6.5 kcal/mol (0.282 eV), respectively, and in our calculations, we observed appreciable difference in the barrier heights between keto-Cyt and keto-5FCyt. This difference may be due to the different methodogies employed in optimizing 9434



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the MECI geometries and also calculating the potential energy profiles. Here, it is interesting to note that very similar charasteristics have been observed for the deactivation process of uracil derivatives (uracil, thymine, and 5-fluorouracil), which also involves the twisting of the C5−C6 double bond.54 The calculations predicted that methyl substitution does not affect the barrier height leading to CI, but the substition by fluorine increases the barrier height, which would result in the elongation of the excited-state lifetime. For 1MeCyt, the potential energy profiles are very similar to those of keto-Cyt, and the barrier height from (1ππ*)min to cMECI points is estimated as ∼0.20 eV, indicating that the N1 substitution with a methyl group plays a very minor role in the relaxation process. This is in line with the experiments by Ho et al.8 and Keane et al.,55 where similar relaxation dynamics were observed for keto-Cyt and keto-1MeCyt. 3.4. Potential Energy Profiles of Enol Tautomers. Figure 4b shows the potential energy profiles of enol-5MeCyt from (S0)min to (1ππ*)min using the LIIC geometries. As expected from our previous study on enol-Cyt, the 1ππ* state exhibits a smooth downhill potential toward (1ππ*)min. The computation of MEP starting from (S0)min was performed for enol-Cyt in the previous study, and it was confirmed that the MEP leads to (1ππ*)min. Therefore, relaxation to (1ππ*)min is also expected for the other derivatives in the early dynamics after photoexcitation. Figure 7 shows the MS(3)-CASPT2(10, 8) potential energy profiles from (1ππ*)min to several cMECI points for enol tautomers of the derivatives. As seen in the figure, the 1ππ* and S0 state energies by the MS(3)-CASPT2(10, 8) calculations at these cMECI points are separated by an appreciable value, in particular, at small distances from (1ππ*)min. This is mainly because the active space is not large enough. For enol-Cyt, the MECI optimization by MS(2)-CASPT2(8, 7) predicted a

Figure 8. (a) MECI structure of imino-5MeCyt determined by MS(2)CASPT2(6, 5). Bond lengths are given in units of Å. (b) MS(4)CASPT2(12, 9) potential energy profiles for low-lying electronic states of imino-5MeCyt from (S0)min to MECI using LIIC points. The 1ππ* energies at (S0)min and MECI are included.

structural changes from (S0)min involve bond elongation of C4− N8 from 1.294 to 1.474 Å and also bond shrinking of C4−C5 from 1.470 to 1.382 Å. The excitation character at this MECI involves a single excitation from a lone-pair orbital on the N8 atom to a π* orbital in the ring. Since this lone-pair orbital corresponds to a π orbital on the N8 atom at (S0)min, this MECI was denoted by (1πN8π*/S0)CI in our previous study.27 Figure 8b shows the MS(4)-CASPT2(12, 9) potential energy profiles from (S0)min to MECI using the LIIC geometries. As seen clearly, the efficient barrierless deactivation pathway exists for imino-5MeCyt, and in fact, the excited-state molecular dynamics simulations of imino-Cyt revealed the decay time of only ∼100 fs;27 a similar time scale is expected for imino5MeCyt and also for other imino derivatives.

1

geometry that has a distance of 6.82 bohr·amu /2 from (1ππ*)min, and at this point, the MS(3)-CASPT2(10, 8) potential energies of the 1ππ* and S0 state are very close (4.15 and 4.09 eV; see Figure 7a). The minimum barrier height is estimated to be ∼0.25 eV for enol-Cyt, which is higher than that of the keto form. These results were already confimed by the previous calculations.27 Similar profiles are observed for enol-5MeCyt and enol-5FCyt, and the barrier heights are estimated to be ∼0.32 and ∼0.4 eV for enol-5MeCyt and enol5FCyt, respectively. When comparing these barrier heights of enol tautomers with those of corresponding keto tautomers, it is observed that the barrier heights are quite similar, which may indicate that the keto and enol tautomers deactivate in a similar time scale. However, it should be noted that the 1ππ* energies of the MECI points relative to (1ππ*)min of enol tautomers are higher than those of the corresponding keto forms. This implies that there would be a wider energy range of intersection seems accessible with a given amount of energy for keto tautomers, and the higher efficiency of the deactivation will be expected for the keto tautomers. 3.5. Potential Energy Profiles of Imino Tautomers. As demonstrated in the previous work,27 imino-Cyt possesses an extremely efficient deactivation pathway involving the twisting of the imino group, and therefore, a similar mechanism would be certainly expected for other derivatives. Figure 8a shows the MECI structure of imino-5MeCyt determined by the MS(2)CASPT2(6, 5) method, and it is seen that the significant

4. CONCLUSIONS AND FUTURE DIRECTIONS In this work, we have performed a comparative investigation on the nonradiative deactivation process of cytosine derivatives (Cyt, 5MeCyt, 5FCyt, and 1MeCyt) and their tautomers, based on the MS-CASPT2 method. The calculated vertical and adiabatic excitation energies are in quite good agreement with experimental results, and the shifts of excitation energy by substitution are well reproduced. For keto tautomers, the relative energy of MECI with respect to the (1ππ*)min structure and also barrier heights from (1ππ*)min to MECI are in the order of Cyt < 1MeCyt < 5MeCyt < 5FCyt. These observations are in line with the recent R2PI experiments. For enol tautomers, similar behavior has been observed, where the barrier heights are in the order of Cyt < 5MeCyt < 5FCyt. These barrier heights are only slightly larger than those of the corresponding keto forms, and the efficient deactivation is also expected for the enol tautomers. The imino tautomer exhibits quite efficient deactivation pathways involving the twisting of the imino group while maintaining the planarity of the ring; thus, the lifetimes of the tautomers are expected to be in the order of imino < keto < enol for all derivatives. Of course, our findings in the present study should be complemented by dynamics simulations to provide more comprehensive picture of the relaxation dynamics. In addition to the difference in the underlying excited-state potential energy surfaces of derivatives, the dynamics of the substituents (i.e., methyl group or fluorine) versus hydrogen are expected to 9435



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State Is Nonplanar and Its Radiationless Decay Is Not Ultrafast. J. Phys. Chem. B 2013, 117, 6106−6115. (10) Ismail, N.; Blancafort, L.; Olivucci, M.; Kohler, B.; Robb, M. A. Ultrafast Decay of Electronically Excited Singlet Cytosine via a π,π* to no,π* State Switch. J. Am. Chem. Soc. 2002, 124, 6818−6819. (11) Merchán, M.; Serrano-Andrés, L. Ultrafast Internal Conversion of Excited Cytosine via the Lowest ππ* Electronic Singlet State. J. Am. Chem. Soc. 2003, 125, 8108−8109. (12) Blancafort, L.; Robb, M. A. Key Role of a Threefold State Crossing in the Ultrafast Decay of Electronically Excited Cytosine. J. Phys. Chem. A 2004, 108, 10609−10614. (13) Zgierski, M. Z.; Patchkovskii, S.; Fujiwara, T.; Lim, E. C. On the Origin of the Ultrafast Internal Conversion of Electronically Excited Pyrimidine Bases. J. Phys. Chem. A 2005, 109, 9384−9387. (14) Zgierski, M. Z.; Patchkovskii, S.; Lim, E. C. Ab Initio Study of a Biradical Radiationless Decay Channel of the Lowest Excited Electronic State of Cytosine and Its Derivatives. J. Chem. Phys. 2005, 123, 081101. (15) Blancafort, L.; Cohen, B.; Hare, P. M.; Kohler, B.; Robb, M. A. Singlet Excited-State Dynamics of 5-Fluorocytosine and Cytosine: An Experimental and Computational Study. J. Phys. Chem. A 2005, 109, 4431−4436. (16) Tomić, K.; Tatchen, J.; Marian, C. M. Quantum Chemical Investigation of the Electronic Spectra of the Keto, Enol, and Keto− Imine Tautomers of Cytosine. J. Phys. Chem. A 2005, 109, 8410−8418. (17) Merchán, M.; González-Luque, R.; Climent, T.; Serrano-Andrés, L.; Rodríguez, E.; Reguero, M.; Peláez, D. Unified Model for the Ultrafast Decay of Pyrimidine Nucleobases. J. Phys. Chem. B 2006, 110, 26471−26476. (18) Kistler, K. A.; Matsika, S. Radiationless Decay Mechanism of Cytosine: An ab Initio Study with Comparisons to the Fluorescent Analogue 5-Methyl-2-Pyrimidinone. J. Phys. Chem. A 2007, 111, 2650−2661. (19) Blancafort, L. Energetics of Cytosine Singlet Excited-State Decay PathsA Difficult Case for CASSCF and CASPT2. Photochem. Photobiol. 2007, 83, 603−610. (20) Kistler, K. A.; Matsika, S. Three-State Conical Intersections in Cytosine and Pyrimidinone Bases. J. Chem. Phys. 2008, 128, 215102. (21) González-Luque, R.; Climent, T.; González-Ramírez, I.; Merchán, M.; Serrano-Andrés, L. Singlet−Triplet States Interaction Regions in DNA/RNA Nucleobase Hypersurfaces. J. Chem. Theory Comput. 2010, 6, 2103−2114. (22) Hudock, H. R.; Martínez, T. J. Excited-State Dynamics of Cytosine Reveal Multiple Intrinsic Subpicosecond Pathways. ChemPhysChem 2008, 9, 2486−2490. (23) Lan, Z.; Fabiano, E.; Thiel, W. Photoinduced Nonadiabatic Dynamics of Pyrimidine Nucleobases: On-the-Fly Surface-Hopping Study with Semiempirical Methods. J. Phys. Chem. B 2009, 113, 3548− 3555. (24) González-Vázquez, J.; González, L. A Time-Dependent Picture of the Ultrafast Deactivation of Keto-Cytosine Including Three-State Conical Intersections. ChemPhysChem 2010, 11, 3617−3624. (25) Alexandrova, A. N.; Tully, J. C.; Granucci, G. Photochemistry of DNA Fragments via Semiclassical Nonadiabatic Dynamics. J. Phys. Chem. B 2010, 114, 12116−12128. (26) Barbatti, M.; Aquino, A. J. A.; Szymczak, J. J.; Nachtigallova, D.; Lischka, H. Photodynamical Simulations of Cytosine: Characterization of the Ultrafast Bi-Exponential UV Deactivation. Phys. Chem. Chem. Phys. 2011, 13, 6145−6155. (27) Nakayama, A.; Harabuchi, Y.; Yamazaki, S.; Taketsugu, T. Photophysics of Cytosine Tautomers: New Insights into the Nonradiative Decay Mechanisms from MS-CASPT2 Potential Energy Calculations and Excited-State Molecular Dynamics Simulations. Phys. Chem. Chem. Phys. 2013, 15, 12322−12339. (28) Triandafillou, C. G.; Matsika, S. Excited-State Tautomerization of Gas-Phase Cytosine. J. Phys. Chem. A 2013, 117, 12165−12174. (29) Trachsel, M. A.; Lobsiger, S.; Leutwyler, S. Out-of-Plane LowFrequency Vibrations and Nonradiative Decay in the 1ππ* State of JetCooled 5-Methylcytosine. J. Phys. Chem. B 2012, 116, 11081−11091.

be different due to the difference in the mass of the substituents. In this context, the on-the-fly excited-state molecular dynamics simulations are powerful tool to investigate the intricate relaxation dynamics of DNA bases.27,36 Admittedly, the electronic structure calculations at each time step of molecular dynamics simulations are computationally demanding especially for highly correlated ab initio methods such as MS-CASPT2, and one needs to find a good compromise between accuracy and efficiency. Even so, the excited-state molecular dynamics simulation with nonadiabatic coupling vectors computed by the MS-CASPT2 method has recently appeared in the study of the photodynamics of ethylene.56 Given the rapid increase in computational power, the complex dynamics of DNA bases will be unraveled in the near future.

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ASSOCIATED CONTENT

S Supporting Information *

Active orbitals of 5MeCyt at (S0)min, Cartesian coordinates of cytosine derivatives at (S0)min and (1ππ*)min, equilibrium structures of higher-energy rotamers of 5MeCyt, and normal modes of Cyt at (1ππ*)min. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors acknowledge the financial support by KAKENHI (Grant-in-Aid for Scientific Research). Part of the calculations was performed on supercomputers at Research Center for Computational Science, Okazaki, Japan.

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REFERENCES

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Quantum Chemical Investigations on the Nonradiative Deactivation

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