J. Phys. Chem. C 2007, 111, 7207-7210
7207
How to Switch the Direction of Photoinduced Charge Injection into DNA? Alexander A. Voityuk Institucio´ Catalana de Recerca i Estudis AVanc¸ ats (ICREA), Institute of Computational Chemistry, UniVersitat de Girona, Spain ReceiVed: January 11, 2007; In Final Form: March 14, 2007
Photoinduced hole injection by an acridine derivative X+ within the complex 5′-TG-2TX+TG2T-3′ has been studied using quantum chemical calculations. The probability of charge shift from the excited state of the intercalated chromophore, (X+)*, to the guanine acceptors, G-2 and G2, is computed for 24 different conformations of the complex generated by rotation of the chromophore about the DNA axis. Because the free energies and the reorganization energies for the charge shift in both direction are very similar, the probability of G-2 or G2 oxidation is determined by the ratio of squared electronic couplings between (X+)* and the diabatic states with a hole on the guanine bases. To estimate the electronic couplings we employ the multistate generalized Mulliken-Hush method and electronic adiabatic states of the system calculated within the multiconfigurational INDO/S approach. We show that the rate of the charge shift reaction critically depends on the chromophore position and that there are well-separated regions in the conformational space, where the hole charge is mainly injected either into G-2 or into G2 or is unlikely. Thus, the direction of the hole injection can be switched by rotation of the intercalated chromophore and the photocleavage efficiency of the acridine derivative and related species can be modulated by the conformational changes.
Introduction Most of the experimental data on charge transfer (CT) in DNA have been obtained in photochemical experiments.1 By photoexcitation of an intercalated chromophore, the positive or negative charge is injected into DNA and may be propagated over long distances within the π stack.2-5 The photoinduced CT is closely related to photocleavage of nucleic acids, and therefore, understanding the factors that modulate the charge injection probability of the intercalated chromophore may be important to design new DNA photocleavage agents.6 Recently, using quantum chemical calculations Beljonne et al. addressed the dependence of charge injection in model hairpin conjugates on the structure of an organic chromophore connecting two complementary oligonucleotides.7 They demonstrated that the nature of the charge injector has a significant influence on the distance dependence of the charge separation rate and emphasized that both the injection energy and the chromophore-bridge coupling should be accounted for when estimating CT rates through DNA stacks. Beljonne et al. also noted that the arrangement of the chromophore within a π stack can influence the CT kinetics.7 In recent years, both experimental and computational studies revealed the importance of the base pair conformational changes on HT in DNA. For instance, Wan et al.8 and O’Neill et al.9 experimentally demonstrated the importance of conformational dynamics for electron-transfer processes in DNA. The effects of conformational changes on the hole transfer have been treated using theoretical and computational approaches.10-16 On the basis of these results, one might expect that also the probability of charge injection into DNA should depend on the arrangement of the chromophore in the complex. However, to our knowledge there have been neither experimental nor theoretical studies that estimate this effect. In this study, we employ a computational approach to explore how the probability of charge injection is affected by confor-
mational changes within a chromophore-DNA complex. We consider the DNA duplex 5′-T-3G-2T-1X+T1G2T3-3′, where the intercalated hole injector X+ is 9-amino-6-chloro-2-methoxyacridine. The acridine derivatives exhibit relatively efficient DNA-damaging properties,6,17 and several DNA complexes with X+ have been experimentally studied.18-21 Binding of X+ to DNA occurs via intercalation where the planar chromophore slides between the bases. The photoexcited chromophore is used as a hole donor and guanine bases as a hole acceptor. Thus, by photoexcitation of the complex the positive charge is shifted from X+ to G-2 or G2. The oxidation potential of nucleobases in DNA depends on the nature of adjacent pairs.22,23 Since the guanine sites G-2 and G2 have identical nearest neighbors (thymine nucleobases), the free energies for HT in both directions should be very similar. Also, the reorganization energies are expected to be almost identical because of similar distances X+-G-2 and X+-G2. Consequently the ratio of the CT probabilities is exclusively determined by the electronic coupling of initial and final diabatic states.24,25 In our case, the ratio R of the charge injection rates into G-2 and G2 is controlled by the couplings between the excited state of the chromophore (X+)* and the diabatic states with the hole localized on the guanine bases R ) [(V(X+* - G-2+))/(V(X+* - G2+))]2. By analyzing the structural dependence of the couplings one can identify conformations of the complex in which the charge shift occurs largely in one direction, in both directions, or becomes ineffective. Computational Details Model. The chemical structure of the chromophore X+ (protonated 9-amino-6-chloro-2-methoxyacridine) is shown in Chart 1. Its geometry was optimized using DFT calculations (the B3LYP/6-31G* scheme). The calculated structure was employed
10.1021/jp070228+ CCC: $37.00 © 2007 American Chemical Society Published on Web 04/25/2007
7208 J. Phys. Chem. C, Vol. 111, No. 19, 2007 to generate 24 of conformations of the DNA complex with the intercalated acridine derivative
Voityuk CHART 1
5′-T-3G-2T-1T1 G2T3-3′ X+ A-3C-2A-1 A1C2A3 First, we generated a B-DNA duplex 5′-T-3G-2T-1T0T1G2T33′ of ideal structure and then replaced the base pair T0:A0 by the chromophore X+ centered on the helical axis perpendicular to the DNA axis. Rotation of X+ along the DNA axis is defined by the twist angle between the local y-axis of the chromophore (shown in Chart 1) and the y-axis of the T-1:A-1 base pair (the axis connects C6 of T with and C8 of A). We generated 24 conformations of the complex in which the twist angle ranges from 0° to 360° with an increment of 15°. The distance between X+ and neighboring pairs as well as the distance between adjacent base pairs was set to 3.38 Å. The algorithm to generate π stacks is described by Lu et al.26 Quantum Mechanical Calculations. For each of the 24 conformations, we computed the ground and excited states of the system using the CIS INDO/S approach.27 Configurational interaction of 400 singly excited states within the active space consisting of 20 HOMOs and 20 LUMOs was accounted for. We note that unlike the standard semiempirical schemes based on the NDDO approximation (MNDO, AM1, and PM3), the INDO/S method provides surprisingly good results for electronic couplings in π stacks.28 Because the calculations have been performed for the entire complex, the model explicitly accounts for the electrostatic interactions between nucleobases and X+. Note that the use of a many-electron picture allows for including at once the contributions from all possible pathways for the photoinduced CT.7 Estimation of Electronic Couplings. To obtain electronic couplings from relevant adiabatic states, we employed a multistate generalized Mulliken-Hush (GMH) approach.29,30 A two-state GMH model, commonly used for estimating electronic couplings, cannot provide accurate Vda values for the DNA π stacks because of the multistate effects.31 The dependence of the calculated couplings on the number of adiabatic states treated simultaneously within the GMH approach has been analyzed for hole transfer in π stacks.32 In particular, it has been shown that reliable estimates of the donor-acceptor coupling can be obtained if two states for each bridging base pair are accounted for. In our case, seven adiabatic states (S1 state of the chromophore X+*, two final states G-2+ and G2+, two states with the hole on the T-1:A-1 base pair, and two states for the bridge T1:A1) were included in the GMH scheme. The adiabatic energies and dipole moment differences as well as the corresponding transition dipole moments between the electronic states were computed using the multiconfiguration INDO/S scheme. Results and Discussion Excited-State Properties of the Chromophore. The INDO/S calculation of vertical excitations in the isolated chromophore predicts a strong electronic transition at 417 nm (∆E ) 2.98 eV), with the oscillator strength (f) of 0.22. This transition energy is in excellent agreement with the experimental spectrum which exhibits an intensive absorption band in the region of 380-430 nm peaking ∼408 nm.33 This excitation corresponds to the HOMO f LUMO transition and leads to an essential increase of the dipole moment (|∆µ| ) 7.9 D). Intercalation of
the chromophore into the π stack leads to moderate changes in the transition energy and the oscillator strength. The π-π interaction of X+ with the neighboring base pairs results in a blue shift of the transition (∆E ) 3.19 eV) in agreement with the experimental absorption spectrum.18,21 In the reference conformation (twist ) 0°), a small increase of the oscillator strength is found (f ) 0.25). The excitation energy of the intercalated chromophore depends on its position within the DNA stack, i.e., on the twist angle. Depending on the conformation of the complex, the transition energy changes within 0.2 eV ranging from 3.10 to 3.34 eV, while oscillator strength varies between 0.18 and 0.27. It should be noted that by the X+ f (X+)* excitation of the intercalated chromophore, a small portion (0.10-0.20) of the excess charge residing on the chromophore is transferred to the neighboring bases. Charge-Transfer Excited States. The excited-state properties of the complex 5′-T-3G-2T-1X+T1G2T3-3′ were calculated for 24 conformations with the twist angle 0°, 15°, ..., 345°. Let us consider in detail the calculation results for twist ) 0°. In excited states 1 and 2, the excess positive charge is shifted to the guanine nucleobases. The energy gaps between the ground state and the charge-transferred states G2+ and G-2+ are found to be 2.63 and 2.69 eV, respectively. This small difference in energy (0.06 eV) is due to the fact that although both guanines have the same nearest neighbors, the position of more distant X+ is not equivalent (G2 has it at the 5′-end, whereas with G-2 it is at the 3′-end). In the CT states, the hole is almost completely (99%) localized on the guanine acceptors. The oscillator strength of the transition from the ground state to the CT states is negligibly small (f ∼ 10-5), and therefore, these states cannot be populated directly by light absorption. The excited states 3 and 4 correspond to the CT states with the hole localized on the adenine sites A1 and A-1; their energies are calculated to be 2.87 and 3.05 eV. The energy difference is mainly due to electrostatic interaction with neighboring fragments. As was documented earlier, the energies of 5′-YA+Z-3′ and 5′-ZA+Y-3′, where Y and Z are base pairs, may differ by 0.2 eV. The oscillator strength for these transitions (f ∼ 0.007) is at least 30 times smaller as compared to f ) 0.25 for excitation of the chromophore X+ f (X+)*. The excited state 5 corresponds to the first excited state of the chromophore (X+)* and has been already considered. The CT states with a hole localized on flanking adenine A3 and A-3 (their energies are 3.31 and 3.39 eV) are not involved in mediating the coupling between the chromophore and the guanine acceptors. As recently shown,7,32 the virtual hole states localized on pyrimidine bases in a bridge between donor and acceptor may essentially contribute to the donor-acceptor coupling, and consequently, they must be accounted for when estimating the coupling. The CT states localized on T1 and T-1 (with energies of 4.05 and 4.31 eV) lie ∼1.2 eV higher than the states with a hole on the complementary adenine site A1 and A-1. Conformational Dependence of the Injection Probability. Seven adiabatic states, excited state of the chromophore X+*, two states with a hole on the acceptors G-2+, and G2+, and four states with the hole on the nucleobases of the bridging AT
Photoinduced Charge Injection into DNA
Figure 1. Model system 5′-TG-2TXTG2T-3′.
Figure 2. Conformational dependence of the probability (the coupling matrix element squared in meV2) of hole injection into G-2 and G2 in the complex TG-2TX+TG2T. The twist (in deg) determines rotation of the intercalated chromophore about the DNA axis.
base pairs, have been treated at once within the multistate GMH model to estimate the electronic couplings. In the system, both guanines are at the distance of 6.76 Å from the chromophore. The donor-acceptor coupling is mediated by single TA base pair (see Figure 1). The couplings V(X+* - G-2+) and V(X+* - G2+) remarkably depend on the twist angle as depicted in Figure 2. Their values are, in general, essentially different. For example, in the reference conformation (twist ) 0°), the coupling related to G2 is by a factor of 3 larger than the matrix element between (X+)* and G-2. Depending on the twist angle, the ratio of these matrix elements changes considerably. For instance, rotation of the chromophore by 15°
J. Phys. Chem. C, Vol. 111, No. 19, 2007 7209 (twist ) 15°) in one direction leads to the coupling ratio of ∼5, whereas the rotation in the opposite direction (twist ) 345°) results in the inverse ratio of 0.23. Thus, the donor-acceptor couplings are quite sensitive to the rotation angle of the intercalated chromophore. In the system under study, the free energies of CT to G-2 and G2 are calculated to be almost equal (they differ by 0.06 eV) and the reorganization energies are expected to be very similar because of the structure of the complex. Since the donor-acceptor distances do not change significantly with the twist angle, the reorganization energy should remain almost unchanged. Because of that, the dependence of the charge injection rates on the rotation angle is exclusively controlled by the square of the electronic couplings. Figure 2 shows how the matrix elements squared vary with the twist angle. When twist ranges from 0° to 60°, the hole will be mainly injected into G2, whereas G-2 will be predominantly oxidized when the twist is in the range of 240-300°. The injection rates are calculated to be small for “inactive” conformations with the twist angle ranging from 90° to 225°. The strong conformational dependence of the electronic coupling is mainly due to changes in the overlap of the initial diabatic state (X+)* with the diabatic bridge states. Unfortunately, a simple qualitative description of tunneling pathways (as usually used within the superexchange model25) is rather limited within the multistate model because several adiabatic states are included in the relevant diabatic states. However, it is worth noting that in the “inactive” conformations (twist ) 195°) the pathways via adenine and thymine bridges interfere destructively leading to small values of both V(X+* - G-2+) and V(X+* - G2+), 0.66 and 0.27 meV, respectively. By increasing the twist angle to 255°, the coupling between (X+)* with T-1+ becomes larger, whereas the coupling of the chromophore and the diabatic state A-1+ decreases. As a result, the matrix element V(X+* - G-2+) increases by a factor of about 15 and becomes 10.3 meV. While V(X+* - G2+) increases as well, its value remains relatively small (1.77 meV). In the conformation with twist ) 30° one finds opposite changes: the coupling V(X+* - G2+) becomes considerably stronger (10.1 meV), whereas V(X+* - G-2+) remains weak (0.94 meV). The conformational changes do not affect considerably the energy gap between the diabatic states. For instance, the gap between G2+ and A1+ is found to be 0.32, 0.34, and 0.39 eV for twist ) 195°, 30°, 255°. It should be noted that the arrangement of an intercalated chromophore in DNA is determined by six parameters (three translations and three rotations). Based on the results obtained for nucleic base pairs10,13 we expect that the electronic couplings for charge injection will also be sensitive to other parameters. Obviously, the effects of structural fluctuation increase with the temperature and may essentially influence the injection probability. Therefore, the conformational dependence of hole injection clearly observed at low temperature may be washed out at elevated temperatures. Concluding Remarks Based on the quantum chemical calculations of the DNA complex with the intercalated chromophore X+ (acridine derivative), 5′-TG-2TX+TGRT-3′, we estimated the effects of the chromophore arrangement on the probability of photoinduced hole injection into G-2 and G2. The donor-acceptor electronic couplings of the excited state of the chromophore (X+)* and the hole states localized on G-2 and G2 are computed for 24 different conformations of the complex generated by varying
7210 J. Phys. Chem. C, Vol. 111, No. 19, 2007 the twist angle. The rate of charge injection critically depends on the rotation angle of the chromophore. We have identified conformations in which the excess charge is preferentially transferred only in one direction, either to G-2 or to G2. Thus, the direction of the charge injection in DNA can be switched by rotation of the chromophore. Also, CT “inactive” conformations have been found. Such conformations are of interest when the intense fluorescence of the intercalated chromophore is a target function of the molecular design. The results suggest that the photocleavage efficiency of the acridine derivative X+ and related chromophores can modulated by changing the twist angle. With the use of different linkers or/and side groups one can vary the arrangement of the intercalated chromophore and thereby modulate the activity of the DNA photocleavers. We expect that the charge injection activity of other intercalated chromophores also depends on their conformation within the DNA complex. However, the interrelation between the orientation of the chromophore and its photoactivity is difficult to explore without quantum chemical calculations. The computational approach employed in the study can be very helpful (especially in combination with molecular dynamics simulations) to design new charge injectors and nucleic acid photocleavage agents. Acknowledgment. Stimulating discussions with Professor M. E. Michel-Beyerle are gratefully acknowledged. This work has been financially supported by the Spanish Ministerio de Educacio´n y Ciencia, Project No. CTQ2005-04563. References and Notes (1) Long-Range Charge Transfer in DNA. Topics in Current Chemistry; Shuster, G. B., Ed.; Springer: Berlin, 2004; Vols. 236 and 237. (2) Kelley, S. O.; Barton, J. K. Science 1999, 283, 375. (3) Schuster, G. B. Acc. Chem. Res. 2000, 33, 253. (4) Giese, B. Acc. Chem. Res. 2001, 34, 159. (5) Lewis, F. D.; Letsinger, R. L.; Wasielewski, M. R. Acc. Chem. Res. 2001, 34, 159.
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