DFT Investigation of the Interaction of Gold Nanoclusters with Nucleic

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DFT Investigation of the Interaction of Gold Nanoclusters with Nucleic Acid Base Guanine and the Watson-Crick Guanine-Cytosine Base Pair Manoj K. Shukla,† Madan Dubey,‡ Eugene Zakar,‡ and Jerzy Leszczynski*,† NSF CREST Interdisciplinary Nanotoxicity Center, Department of Chemistry, Jackson State UniVersity, Jackson, Mississippi 39217, and U.S. Army Research Laboratory, Sensors and Electron DeVices Directorate, AMSRD-ARL-SE-RL, Adelphi, Maryland 20783 ReceiVed: September 29, 2008; ReVised Manuscript ReceiVed: January 8, 2009

The interaction of gold nanoclusters (Aun, n ) 2, 4, 6, 8, 10, 12) with nucleic acid purine base guanine (G) and the Watson-Crick guanine-cytosine (GC) base pair through the major groove site (N7 site of guanine) of DNA was investigated theoretically. Geometries of complexes were optimized at the density functional theory (DFT) level employing the hybrid B3LYP functional. The 6-31G(d) basis set was used for all atoms except gold, for which the LANL2DZ effective core potential (ECP) was used. Natural population analysis was performed to determine NBO charges. The vertical first ionization potential and electron affinity of guanine and the guanine-cytosine base pair and their complexes with gold nanoclusters were also analyzed. It was revealed that gold clusters interact more strongly with the GC base pair than with isolated guanine. It was found that consequent to the binding of gold nanoclusters a substantial amount of electronic charge was transferred from guanine (or the guanine-cytosine base pair) to the gold clusters. Furthermore, the amount of the electronic charge transferred to the gold cluster was found to be larger for GC-Aun complexes than that in the G-Aun complexes. The vertical ionization potential, electron affinity, and biological significance of the interaction of gold nanoclusters with nucleic acid building blocks have also been discussed. Introduction Particles in the nanoscale range have physical and chemical properties that are significantly different from those of the corresponding bulk structure. The existence of size-specific physicochemical characteristics of nanomaterials offers novel applications in different fields such as electronic devices, drug delivery systems, space applications, and many more. For example, the tetrahedral form of a gold cluster involving 20 atoms (Au20) possesses a significantly larger HOMO-LUMO energy gap (∼1.82 eV) whereas the other forms of the same cluster have significantly smaller energy gaps ranging from 0 to 0.7 eV.1,2 Smalley and co-workers,3 on the basis of the photoelectron spectra, have shown that the Au20 cluster, with some exceptions (Au2 and Au6), has the largest HOMO-LUMO energy gap among coinage metal clusters. Gold is an important substance not only representing socio-economic prosperity but also possessing various useful applications. It is very stable and oxidation-resistant4 and therefore is used in different aspects of human life, including many centuries of glass staining,5 applications as a component of ornaments, and more recently in many electronics devices. Gold binds selectively with DNA6 and is used as a catalyst for hydrogen production.7 Liu et al.7 have shown that in the water-gas shift reaction on Au-ceria catalysts for the production of hydrogen gas that the gold in active sites of the catalyst are in the form of only ultrasmall Au clusters. The presence of single gold atoms or noticeable sizes of gold particles was not detected. The existence of unique optical properties of different shapes and sizes of gold nanoparticles such as spheres, rods, and prisms have been extensively researched in the area of biosensors, photocatalysts, diagnostics, * Corresponding author. E-mail: [email protected]. † Jackson State University. ‡ U.S. Army Research Laboratory.

and medicinal applications.8–11 For example, the existence of the near-infrared region absorption band in gold nanorods and the fact that tissues generally do not absorb in this region have opened the possibility to apply gold nanorods in different biochemical applications.12 Pyykko has performed seminal work on different aspects of gold, the rigorous and lucid analysis of which can be found in his series of review articles.13 Although impressive from the remarkable physicochemical point of view, the novelty of nanomaterials has been also a cause for potential concern regarding environmental hazards.14 It has been speculated that nanoparticles upon significant and prolonged exposure may cause allergic reactions and could lead to a disease similar to asbestosis.14 For example, gold nanorods have significant absorption in the near-infrared region, which can potentially be exploited for different biochemical applications, but hexadecyltrimethylammonium bromide (CTAB), which is needed for the preparation of gold nanorods, is very toxic.12,15,16 Chithrani et al.9 have shown that the intracellular uptake and kinetics of gold nanoparticles significantly depend on their physical dimensions. Recent results suggest that longer multiwalled carbon nanotubes (MWCN) have toxic effects similar to those from asbestos.17 Furthermore, it was concluded that the shape and size of nanoparticles play a paramount role compared to their chemistry in relation to their toxicity.18 Several investigations have suggested the complexity of interactions involving DNA fragments with gold surfaces, and such interactions have been suggested to be very sequencedependent.19–21 Demers et al.19 have studied the interaction of nucleic acid bases and nucleosides with gold surfaces using the temperature-programmed desorption (TDP) and reflection absorption Fourier transform infrared (RAIR) spectroscopic techniques. It was revealed that desorption from the gold surface takes place at lower temperature for pyrimidine bases (thymine and cytosine) than for purine bases (guanine and adenine).

10.1021/jp808622y CCC: $40.75  2009 American Chemical Society Published on Web 02/17/2009

Nanocluster Interaction with Guanine/Guanine-Cytosine Consequently, the measured desorption was revealed in the order thymine < cytosine < adenine < guanine. It was suggested that the presence of the sugar moiety in nucleosides provides steric hindrance for the most suitable orientation of bases to bond with the gold surface. Therefore, it was revealed that the desorption of nucleosides from the gold surface takes place at lower temperature than for the corresponding bases. KimuraSuda et al.20 studied the adsorption of homonucleotides on polycrystalline gold films using the Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopic methods including the competitive adsorption between pairs of unmodified oligomers. It was found that oligo(dA) has the strongest whereas oligo(dT) possesses the lowest adsorption affinity for the Au surface. Furthermore, the (dA) · (dT) duplexes were found to be denatured by the stronger interaction of oligo(dA) with the Au surface. Kryachko and Remacle22,23 have investigated the interaction of small gold clusters (up to six gold atoms) with nucleic acid bases and base pairs at the density functional theory (DFT) level. In these investigations, the interaction energies of small gold clusters with different sites of bases and base pairs, proton affinity, and deprotonation affinity were evaluated, and thus the most probable site for binding with gold clusters was determined. It was found that gold interacts with oxygen and nitrogen centers and the presence of NH...Au hydrogen bonding was also revealed. Kumar et al.24 have studied the interaction of four and eight atomic gold clusters with the guanine-cytosine (GC) and adenine-thymine (AT) base pairs and the electron affinity of bases in the presence of gold clusters at the DFT level of theory. In this investigation, the different binding sites of bases were also considered, but maximum cluster size was limited to four gold atoms. For example, in order to model the interaction with eight gold atoms, two clusters with four gold atoms each were considered around two sites of base pairs. It was found that the binding of gold clusters is significantly modified in the anionic complexes. Furthermore, a significant amount of electronic charge was transferred from base pairs to the gold clusters in the neutral complexes. However, in the anionic complexes, the excess electronic charge was found to be localized at the gold cluster. Recent investigations suggest that gold nanoparticles or nanorods usually form gold aggregates inside the cells.11,12,25 In nucleic acids, the N7 of purine bases is the major groove site. It is expected that gold clusters would interact with purine bases via the major groove site. Furthermore, guanine has the lowest ionization potential among DNA bases; therefore, it is the most frequent site of oxidative damage.26 It would be necessary to determine how the binding of gold nanoclusters (Aun) will affect the physicochemical properties of nucleic acid bases and the Watson-Crick base pairs. Therefore, in the present work we have considered the interaction of even sizes of selected Aun clusters (n ) 2, 4, 6, 8, 10, 12) with guanine (G) and the Watson-Crick guanine-cytosine (GC) base pair through the N7 site of guanine. We performed detailed analysis of structures, interactions, electron affinity, ionization potential, and charge distributions of G-Aun and GC-Aun complexes to shed light on the influence of gold nanoparticles on physicochemical properties of nucleic acids. Computational Details Geometries of complexes were optimized at the density functional theory (DFT) level using the Becke’s27 threeparameter nonlocal hybrid exchange potential with the nonlocal correlation functional of Lee, Yang, and Parr (B3LYP)28 without any symmetry restriction. The standard 6-31G(d) basis set was

J. Phys. Chem. C, Vol. 113, No. 10, 2009 3961 used for all atoms except for gold, for which the LANL2DZ effective core potential (ECP) was used. The combined basis set hereafter will be called 6-31G(d)∪LANL2DZ. It is well known that the computation of interaction energy with finite basis sets introduces error known as basis set superposition error (BSSE). Because interaction energy is defined as the energy difference between the complex and that of the energies of constituent monomers, the BSSE error arises because of the fact that a different number of basis functions is used to describe the complex and that of monomers for the same basis set. Because of the larger number of basis functions, the complex has comparatively lower energy than does the sum of its components. The BSSE corrected interaction energy was computed using the Boys-Bernardi counterpoise correction scheme.29 Interaction energies of complexes were computed using eq 1

Eint ) EAB-EA(AB)-EB(AB)

(1)

where Eint represents the interaction energy, EAB is the total energy of the complex, EA(AB) represents the total energy of the guanine or the GC base pair of the respective complex with ghost atoms in place of gold atoms, and EB(AB) represents the total energy of the gold cluster of the complex with ghost atoms for the rest of the system. The vertical ionization potentials (IPv) and vertical electron affinities (EAv) were computed using eqs 2 and 3, respectively,

IPv ) ERC-Etot

(2)

EAv ) Etot-ERA

(3)

where Etot is the total energy of the complex, ERC is the total energy of the one-electron oxidized form of the complex (radical cation), and ERA is the one-electron reduced form of the complex (radical anion) at the respective neutral geometry. All calculations were performed using the Gaussian 03 suite of programs,30 and molecular orbitals were visualized using the Molekel program.31 Results and Discussion The B3LYP/6-31G(d)∪LANL2DZ level ground-state optimized geometries of the guanine-gold (G-Aun) and guaninecytosine-gold (GC-Aun) complexes, where gold clusters are coordinated at the N7 site of guanine, are shown in Figure 1. The NBO charges at selected atomic sites and atomic numbering schemes are also shown in the same Figure. In the present study, we have considered the closed-shell configuration of the complexes; therefore, only even numbers of gold atoms (n ) 2, 4, 6, 8, 10, 12) were taken into account. Kumar et al.24 have optimized the geometry of the GC-Au4 complex also in the triplet state at the B3LYP/6-31+G(d, p)∪LANL2DZ level. The singlet state was found to be about 2.4 eV more stable than the triplet state. Therefore, in the present study we have optimized geometries of complexes only in the ground singlet state. The Au1-N7 bond distance or the anchor distance, where Au1 represents the gold atom involved in direct interaction with the N7 site of guanine, of the studied complexes and the hydrogen bond distances of the GC base pair are presented in Table 1. The BSSE-corrected and -uncorrected interaction energies of G-Aun and GC-Aun complexes (here the interaction is between the G base or GC base pair and the gold clusters) and the dipole moments are shown in Table 2. It is evident from Table 1 that the Au1-N7 distance in all complexes is generally in the range of 2.16-2.26 Å. However, careful analysis suggests that with increasing size of the cluster the

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Figure 1. Optimized structures and atomic numbering schemes of G-Aun and GC-Aun complexes. NBO charges for selected atoms are given in green color while selected gold atoms and base distances are in Å.

TABLE 1: Hydrogen Bond and Corresponding Heavy Atom Distances (Å) in the GC and GC-Aun Complexes and the N7-Au1 Distance in the G-Aun and GC-Aun Complexes Obtained at the B3LYP Level Using the 6-31G(d)∪LanL2DZ Basis Seta hydrogen bond distance complex

O6(G)...NH2(C)/O6(G)...N4′(C)

N1H(G)...N3′(C)/N1(G)...N3′(C)

NH2(G)...O2′(C)/N2(G)...O2′(C)

N7...Au1

GC GC-Au2 GC-Au4 GC-Au6 GC-Au8 GC-Au10 GC-Au12 GC-Au12-1

1.782/2.818 1.818/2.849 1.816/2.842 1.864/2.887 1.826/2.856 1.847/2.863 1.903/2.922 1.824/2.854

1.918/2.950 1.888/2.925 1.858/2.900 1.857/2.899 1.886/2.924 1.873/2.913 1.902/2.943 1.887/2.924

1.913/2.937 1.861/2.887 1.842/2.871 1.816/2.846 1.858/2.885 1.842/2.870 1.810/2.839 1.859/2.885

2.161(2.162) 2.151(2.141) 2.130(2.222) 2.217(2.228) 2.201(2.218) 2.258(2.288) 2.252(2.267)

a

The N7...Au1 parameter for G-Aun is shown in parentheses.

N7-Au1 distance is generally increased for both the G-Aun and GC-Aun complexes, except for smaller clusters where this anchor distance was found to be initially slightly decreased. The largest distance was found for the G-Au12 and GC-Au12 complexes. Hydrogen bond distances of the GC base pair and the GC-Aun complexes along with the corresponding distances between heavy atoms are also shown in Table 1. It is evident

from this Table that with increasing size of the gold cluster the O6(G)...NH2(C) (and O6(G)...N4′(C)) hydrogen bond distance is substantially increased whereas the N1H(G)...N3′(C) and NH2(G)...O2′(C) (and corresponding N1(G)...N3′(C) and N2(G)...O2′(C)) hydrogen bond distances are significantly decreased. Furthermore, in a given complex the predicted decrease in hydrogen bond distance is more pronounced for

Nanocluster Interaction with Guanine/Guanine-Cytosine TABLE 2: BSSE-Corrected and -Uncorrected (in Parenthesis) Interaction Energy (Eint, kcal/mol), Dipole Moment (µ, D), Vertical First Ionization Potential (IPv, eV), and Vertical Electron Affinity (EAv, eV) of the G-Aun and GC-Aun Complexes X ) guanine complex X X-Au2 X-Au4 X-Au6 X-Au8 X-Au10 X-Au12 X-Au12-1

Eint

µ

-24.2 (-28.9) -33.3 (-38.5) -19.3 (-25.1) -18.7 (-24.0) -24.3 (-29.7) -25.4 (-32.8) -15.7 (-20.9)

6.5 13.7 13.7 15.7 15.4 18.9 21.8 15.7

IPv EAv

X ) GC base pair EInt

µ

IPv EAv

7.7 -1.8 6.1 6.9 -0.8 7.5 -0.3 -27.3 (-32.3) 12.0 7.1 0.1 7.4 0.9 -35.9 (-42.1) 9.5 7.1 1.0 6.9 1.4 -43.9 (-51.2) 9.5 7.1 1.5 6.9 1.5 -21.8 (-27.4) 15.2 6.8 1.4 6.6 1.4 -28.6 (-35.4) 14.4 6.6 1.5 6.6 1.5 -30.1 (-38.5) 19.4 6.5 1.6 6.6 2.1 -18.8 (-24.3) 15.3 6.5 2.0

NH2(G)...O2′(C) than for N1H(G)...N3′(C). Among the studied complexes, the maximum change in O6(G)...NH2(C) and NH2(G)...O2′(C) hydrogen bond distances is revealed for the GC-Au12 complex, where these distances are increased and decreased by about 6.8 and 5.4%, respectively. The maximum change in the N1H(G)...N3′(C) hydrogen bond distance is predicted for the GC-Au6 complex (decreased by about 3.2%) with respect to the corresponding hydrogen bond distances in the isolated GC base pair (Table 1). Furthermore, in the GCAu12 complex the Au12 atom of the gold cluster also forms a bond with the O6 site of guanine (Figure 1). The lack of significant change in the N1H(G)...N3′(C) hydrogen bond distance in the GC-Au12 complex with respect to the GC base pair is due to the geometry of the GC base pair in the complex, which was predicted to be nonplanar. It is clear that consequent to the interaction with the gold cluster the O6(G)...NH2(C) hydrogen bond distance is increased while the NH2(G)...O2′(C) hydrogen bond distance is decreased compared to that in the isolated GC base pair (Table 1). Thus, it appears that for interactions with gold clusters at the major groove site of DNA the GC base pairing may facilitate a slight opening of the hydrogen bond from the O6(G)...NH2(C) hydrogen bonding site. However, the effect of larger gold clusters, which will be able to form several bonds at different base and base pair sites, needs to be further investigated. In an earlier investigation, Kumar et al.24 studied the GC-Aun complexes at the B3LYP/6-31+G(d,p)∪LANL2DZ level and found the O6(G)...N4′(C), N1(G)...N3′(C), and N2(G)...O2′(C) hydrogen distances to be 2.846, 2.900, and 2.820 Å, respectively, in the GC-Au4 complex and 2.824, 2.860, and 2.790 Å, respectively, in the GC-Au8 complex. Our corresponding computed values for the GC-Au4 complex are found to be 2.842, 2.900, and 2.871 Å whereas for the GC-Au8 complexes the predicted values are 2.856, 2.924, and 2.885 Å (Table 1). Thus, it appears that our results are significantly different from those reported earlier.24 However, in an earlier investigation24 for the GC-Au4 complex the two gold atoms were bonded to the N7 site of guanine and the other two gold atoms were bonded to the N3 site of guanine. Similarly, in the GC-Au8 complex the four gold atoms were bonded to the N7 site, and the other four atoms were bonded to the N3 site of guanine. However, in the present investigation gold clusters are bonded only to the N7 site of guanine (Figure 1). Thus, the computed difference between our results and those obtained earlier24 is mainly due to the different modes of interaction of the gold clusters in these two investigations. The NBO atomic charge distribution in the form of varying atomic colors (red being the most negative and green being the most positive electronic charge) of the neutral and ionic forms

J. Phys. Chem. C, Vol. 113, No. 10, 2009 3963 of the G-Aun and GC-Aun complexes are shown in Figures S1 and S2, respectively, and the amount of electronic charge at each atomic site is shown in Tables S1 and S2 of the Supporting Information. The total amount of NBO charge on each monomer (gold cluster, guanine, and cytosine) of the studied complexes in the neutral and ionic forms is shown in Table 3. It is evident that in the case of the neutral complexes there is a significant amount of electronic charge transferred from the guanine or the GC base pair to the gold cluster. Furthermore, the amount of electronic charge transferred to the gold cluster is larger for the GC-Aun complexes than for the G-Aun complexes. In another investigation, electronic charge transfer from the GC base pair to the gold cluster was also obtained.24 Interestingly, in the case of C60-Aun complexes, a significant amount of electronic charge was also transferred from C60 to the gold clusters.32 Although Kumar et al.24 have reported larger amounts of electronic charge transfer from the GC pair to the gold clusters, they have reported that the Mulliken charges and the mode of interaction of gold clusters were quite different than those considered here by us. Furthermore, it is evident (Figures 1, S1, and S2 and Tables S1 and S2) that the Au1 atom, which interacts directly with the N7 site of guanine in both complexes, is generally electrondeficient (positive charge). Thus, in the microscopic region near the interaction site there is charge transfer from the Au1 atom to guanine (or the GC base pair) and preferably to the N7 site and to other gold atoms. The phenomenon of charge transfer to the N7 site is also evident from the comparison of NBO charges between the isolated guanine and the G-Aun complexes and that between the isolated GC base pair and the GC-Aun complexes. Thus, at the microscopic level there is charge transfer from Au1 to the rest of the system, whereas at the macroscopic level (complex as a whole) there is electronic charge transfer from the base and the base pair to gold clusters. Similar results were also obtained in the theoretical study of nanocontacts involving the Aun-C60-Aun system.32 In the experimental investigation of the metal-C60 contact region, the transfer of electronic charge from the gold surface to C60 was revealed.33,34 Compared to the isolated guanine and the GC base pair, the dipole moments of complexes are significantly larger (Table 2), which is due to the significant amount of charge transfer from the base and base pair to the complexes. In the case of the radical anionic form of complexes, the gold clusters have slightly more than one unit of electronic charge, and guanine and cytosine possess slightly positive charges. The exceptions include the G-Au2 complex, where guanine has about -0.239e and the gold cluster has -0.761e unit of electronic charge, and the GC-Au2 complex, where cytosine has about -0.424e and the gold cluster has -0.583e unit of electronic charge (Table 2). The presence of electronic charge at the cytosine site is due to the fact that cytosine has higher electron affinity than guanine.35 It is also evident that although gold clusters have generally more than one unit of electronic charge the Au1 atom in all complexes generally has positive electronic charge (except G-Au2). However, the amount of charge is smaller than that in the neutral complexes. In the case of the one-electron oxidized form of complexes, NBO charge analysis suggests that gold clusters generally have more positive charge than the corresponding guanine and cytosine monomers (Table 3). Furthermore, in general all gold atoms have positive (or close to zero) electronic charge in the vertical radical cationic complexes. The Au1 atom generally has more positive charge than that in the neutral form of the corresponding complexes. A detailed discussion of the electron

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TABLE 3: Total NBO Charges on Each Monomer of the Neutral (N), Radical Cation (RC), and Radical Anion (RA) of G-Aun and GC-Aun Complexesa X ) guanine complex X X-Au2 X-Au4 X-Au6 X-Au8 X-Au10 X-Au12 X-Au12-1 a

N

RC

Au

Au

G

-0.135 -0.158 -0.131 -0.127 -0.137 -0.164 -0.117

0.530 (0.689) 0.693 (0.875) 0.802 (0.975) 0.787 (0.941) 0.825 (1.002) 0.777 (0.975) 0.802 (0.939)

0.470 0.307 0.198 0.213 0.175 0.223 0.198

X ) GC base pair RA Au

N G

Au

-0.761 -0.239 -0.148 -1.102 0.102 -0.166 -1.077 0.077 -0.163 -1.089 0.089 -0.141 -1.051 0.051 -0.156 -1.013 0.013 -0.191 -1.085 0.085 -0.131

RC G -0.029 0.097 0.110 0.111 0.088 0.094 0.115 0.078

C 0.029 0.051 0.056 0.052 0.053 0.062 0.076 0.053

Au 0.363 (0.511) 0.493 (0.662) 0.519 (0.677) 0.646 (0.799) 0.794 (0.994) 0.731 (0.962) 0.761 (0.911)

RA G 0.899 0.542 0.424 0.401 0.285 0.137 0.183 0.176

C 0.101 0.095 0.083 0.080 0.069 0.069 0.086 0.063

Au -0.583 -1.086 -1.098 -1.027 -1.086 -1.060 -1.097

G C -0.194 -0.806 0.008 -0.424 0.048 0.038 0.057 0.041 0.055 -0.028 0.037 0.049 0.033 0.027 0.050 0.047

The Mulliken spin density on gold clusters for radical cations is shown in parentheses.

affinity, ionization potential, and localization of the unpaired spin will be provided later. A comparison of the geometries of complexes generally shows significant differences among the structure of gold clusters and also their modes of interaction with guanine and the GC base pair (Figure 1). For example, in the G-Au4 complex the gold cluster forms a triangle where the Au4 atom with negative electronic charge forms a weak bond with the C8H site of guanine. However, in the GC-Au4 complex the orientation of the gold cluster is changed toward the amino group of cytosine, which is hydrogen bonded to the carbonyl group of guanine. In this complex, the terminal Au4 atom has negative electronic charge. Thus, the electrostatic repulsion between the negatively charged Au4 gold atom and the O6 site of guanine in the G-Au4 complex is responsible for the orientation of gold atoms toward the C8H site. However, the attraction between the negatively charged Au4 atom and the positively charged amino hydrogens of cytosine is responsible for the comparatively different orientation of the gold cluster in the GC-Au4 complex. In the case of G-Au6 and GC-Au6 complexes, it is evident that the shape of the gold cluster is significantly modified in the latter complex compared to that in the former one. Although a considerable deformation in the shape of gold clusters between the G-Aun and GC-Aun (n ) 2, 8 and 10) complexes is not revealed, a noticeable change (particularly in the GC-Au10 complex where Au2 and Au3 atoms are weakly bonded to the carbonyl group of guanine and the amino hydrogen of cytosine, respectively, compared to the bonding in the G-Au10 complex) is evident (Figure 1). We have considered two different configurations of the complexes of guanine and the GC base pair with 12 gold atoms. The G-Au12 and GC-Au12 complexes were found to be about 10.9 and 12.4 kcal/mol more stable than the respective G-Au12-1 and GC-Au12-1 complexes. In the G-Au12 and GC-Au12 complexes, the gold cluster is doubly anchored to guanine where the Au1 atom is bonded to the N7 site and the Au12 atom is bonded to the O6 site of guanine. Therefore, in these complexes the Au1...N7 distance was found to be the largest among all complexes (Table 1). However, in the G-Au12-1 and GC-Au12-1 complexes only the Au1 atom of the gold clusters is in direct contact (interaction) with guanine through the N7 site (Figure 1). Thus, the existence of double interactions is responsible for the larger stability of G-Au12 and GC-Au12 complexes compared to that of the respective complex of the other configuration. The BSSE-corrected interaction energies between the gold clusters and guanine and that between the gold clusters and the GC base pair are presented in Table 2. It is evident that gold clusters form stable complexes via the N7 site of guanine. The interaction energy for the G-Aun complexes is in the range of

-16.0 to -33.0 kcal/mol, whereas that for the GC-Aun complexes it is in the range of -19.0 to -44.0 kcal/mol. Thus, gold clusters interact more strongly with the GC base pair than with the isolated guanine. Furthermore, a clear trend relating the interaction energy of complexes to the size of gold clusters is not revealed. However, it is not unexpected (i) because the stability of the complex will depend upon the structure of the gold clusters and (ii) the gold cluster will form a number of contacts with guanine and the GC base pair. For example, the GC-Au6 complex has the largest interaction energy, and this interaction stems from the structure of the gold cluster, which also favors strong interaction between the Au6 of the gold cluster and the amino hydrogen of cytosine. Similarly, the gold cluster in X-Au12 (X ) guanine or GC base pair) interacts significantly more strongly with guanine or the GC base pair than with that in the X-Au12-1 complex. The stability of the X-Au12 complex over X-Au12-1 arises from the fact that Au1 and Au12 gold atoms are involved in direct interaction with the N7 and O6 sites, respectively, of guanine in the former complex whereas only the Au1 atom is involved in binding with the N7 site of guanine in the latter complex (Figure 1). Demers et al.19 have reported that the heat of desorption of guanine on the gold surface would be around 35 kcal/mol whereas that for 2′deoxyguanosine is reported to be around 29 kcal/mol. Thus, it appears that substitution at the N9 site of guanine changes the orientation of guanine involved in the interaction with the gold surface and reduces the binding energy. Our computed interaction energy can also be compared with the desorption energy of guanine on the gold surface as discussed earlier. It is expected that the larger size of gold clusters, which are expected to form more interacting sites with guanine, will enhance the agreement between the computed interaction energy and the desorption energy. This argument is also validated by the fact that the interaction energy of GC-Aun complexes is generally larger in magnitude than that of the corresponding G-Aun complexes. It is well known that nucleic acid purine bases generally have a negative electron affinity whereas pyrimidine bases have nearly zero electron affinity in the gas phase.35 It has been revealed that hydrogen bonding (base pairing) slightly increases the electron affinity of the bases.35 Nucleic acid bases have a vertical ionization potential in the range of 8.2-9.5 eV in which guanine has the lowest and uracil has the highest value and base pairing decreases the ionization potential value.36–38 Gold and gold clusters, however, have electron affinity and ionization potential values13,39 that are significantly larger than for the guanine and the GC base pair.35–38 The electron- and hole-transfer phenomena of different systems can be understood by the investigation of the electron affinity and ionization potential of molecules.35–41 The computed vertical electron affinity (EAv) and vertical

Nanocluster Interaction with Guanine/Guanine-Cytosine ionization potential (IPv) of guanine, the GC base pair, and G-Aun and GC-Aun complexes are shown in Table 2. It is evident from the data shown in this Table that guanine and the GC base pair have negative electron affinities, although it is less negative for the GC base pair than for guanine. These results are in agreement with the earlier computed results.35 It is also apparent that the respective EAv and IPv values of the G-Aun and GC-Aun complexes are generally similar. Furthermore, consequent to interaction with the gold clusters, the electron affinity is found to be increased (Table 2). However, EAv values remain around 1.5 eV for complexes where 6-12 gold atoms were used in the interaction, except for the G-Au12-1 and GCAu12-1 complexes for which they were computed to be around 2.0 eV (Table 2). The IPv values shown in Table 2 suggest that with increase in the size of the gold clusters in the G-Aun complexes the ionization potential values are decreased slightly and become stable at about 6.9 eV for complexes with more than four gold atoms. However, for the GC-Aun complexes, the ionization potential increases slightly and then starts to decrease, attaining a value of about 6.5 eV for complexes where more than eight gold atoms are involved in the interaction. To explain the electron affinity and the ionization processes, information about the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) of neutral complexes, singly occupied molecular orbital (SOMO), singly unoccupied molecular orbital (SUMO), and spin density distribution of radical complexes is needed. The plots corresponding to the isodensity surfaces of the HOMO, LUMO, SOMO, SUMO, and electronic spin density maps are shown in Figures S3-S10 of the Supporting Information. It was found that for the GC base pair the HOMO is localized on the guanine whereas the LUMO is localized on the cytosine. Therefore, it is expected that ionization of the GC base pair would involve the removal of an electron from guanine whereas electron attachment would take place at cytosine. This is also in agreement with the fact that guanine has a lower ionization potential and electron affinity than cytosine.26,35–38 It is also supported by the isodensity spin map, which is localized on guanine for the radical cationic and on cytosine for the radical anionic form of the GC base pair. In the G-Aun and GC-Aun complexes, HOMO and LUMO are mainly localized on gold clusters, except for the GC-Au2 complex where LUMO is localized on cytosine. Similar results were also found in other investigation.24 However, from spin density maps and SOMO of radical anionic species of complexes, it is evident that the unpaired spin is mainly localized on the gold cluster, except for complexes with two gold atoms where some localization on guanine of the G-Au2 complex and on cytosine of the GC-Au2 complex was also revealed. From the NBO charges given in Table 3, it is evident that for the radical anionic forms of G-Au2 and GC-Au2 complexes the gold complexes have electronic charges of only -0.761e and -0.583e, respectively. For all other complexes, the gold clusters have more than one unit of electronic charge, suggesting some amount of electronic charge transfer from guanine and cytosine. Thus, electronic attachment in G-Aun and GC-Aun complexes will take place at the gold clusters of these complexes, and some electronic charges will also be transferred from the bases or base pair to the gold clusters. The isodensity SUMO and spin density maps of radical cationic species of the studied complexes were found to be slightly complicated where density is also delocalized on the guanine in complexes with smaller numbers of gold atoms. This complexity is also evident from the NBO charges of radical cationic species of the complexes shown in Table 3. It is evident from this Table that for complexes with smaller numbers of gold atoms (G-Au2, GC-Au2, GC-Au4, and GC-Au6) the NBO

J. Phys. Chem. C, Vol. 113, No. 10, 2009 3965 charges (positive) on bases (mainly guanine) are comparable to or larger than that on gold clusters whereas for other complexes they are significantly larger on gold clusters. Thus, the positive charges on gold clusters in the studied complexes are increased with the number of gold atoms in the cluster. However, such an increase is more pronounced in the G-Aun complexes than in the GC-Aun complexes, and this result is in agreement with the fact that the ionization potential of the GC base pair is smaller than that for isolated guanine.35 However, as discussed earlier, the HOMO of complexes are localized on gold clusters, suggesting that electronic ionization will take place from the gold cluster fragments. It was found that although the SUMO and spin density are mainly localized on the gold cluster, for smaller complexes some localization on guanine is also revealed. Such delocalization decreases with the increase in the size of the gold cluster. The total Mulliken spin density on gold clusters for the radical cationic form is also given in Table 3. It is clear from this Table that the electronic spin is mainly localized on gold clusters for larger complexes. However, for smaller complexes some localization on the rest of the system is also evident. Thus, it appears that electronic ionization will take place mainly from the gold cluster. However, consequent to the oxidation of the gold cluster, some electronic charge transfer will take place from guanine (mainly) to the gold cluster. Such charge transfer will be larger for smaller complexes and will decrease with the increase in size of the gold cluster in both the G-Aun- and GC-Aun-type complexes. Conclusions Gold nanoclusters form stable complexes with nucleic acid base guanine and the Watson-Crick guanine-cytosine base pair. It has also been predicted that gold nanoclusters would form more stable complexes with the GC base pair than with the guanine base alone. In addition, it was revealed that consequent to the interaction with gold nanoclusters the GC base pair may slightly open the hydrogen bond (O6(G)...(NH2(C)) belonging to the major groove site of DNA. Following gold binding, a substantial amount of electronic charge is transferred from the guanine and guanine-cytosine base pair to the gold cluster. Furthermore, the amount of electronic charge transferred to the gold nanocluster is more for the GC-Aun than for the G-Aun complex. The electron attachment as well as ionization processes in the complexes will take place at the gold cluster. In addition, these processes are also supplemented by the charge transfer from the guanine and the GC base pair, especially in the smaller complexes. Thus, it appears that neutral gold clusters will oxidize guanine and the GC base pair and such oxidation will be more pronounced for the GC base pair than for the isolated guanine. However, because electron attachment takes place at the gold cluster site, in the medium of excess free electrons the gold cluster may protect DNA. However, more rigorous investigations are necessary to explore the role of gold clusters in protecting DNA against direct interaction with free electrons. The one-electron oxidation of G-Aun and GC-Aun complexes may trigger the oxidation of DNA bases and the base pair through the π back-donation of electronic charges to the gold clusters. Acknowledgment. M.K.S. and J.L. are thankful for financial support from the Army Research Laboratory (BAA no. DAAD1903-R-0017, section no. 2.41, contract no. W911QX-07-C-0100), NSF-CREST (grant no. HRD-0833178), and ONR (grant no. N00014-08-1-0324). We are also grateful to the Mississippi Center for Supercomputing Research (MCSR) for generous access to the computational facility.

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