Adenine Dimerization vs Carboxylic Group Interactio - American

DOI: 10.1021/cg100470u

Contrasting Crystallographic Signatures of 9-Carboxypropyl Adeninium Cation: Adenine Dimerization vs Carboxylic Group Interaction

2010, Vol. 10 3555–3561

Jitendra Kumar, Shubhra Awasthi, and Sandeep Verma* Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur-208016 (UP), India Received April 9, 2010; Revised Manuscript Received May 13, 2010

Introduction Nucleobase protonation manifests into many crucial roles encompassing stability, structure, and mutagenic aspects of nucleic acid chemistry and biochemistry. The nitrogenous heterocyclic framework of purine and pyrimidine bases has been subjected to numerous studies related to acid-base equilibrium issues both in gas and condensed phases by the help of theoretical and experimental approaches.1 Of particular interest are the stability concerns where it has been shown that protonation of purine residues may lead to depurination, thus compromising the stability of nucleic acid sequences. Spontaneous DNA depurination could be considered as endogenous DNA damage that is mediated by the protonation of purine N-7 position, which is accelerated under low pH and high temperature regimes and by the presence of metal ions.2 Adenine protonation, leading to the possible formation of A-AHþ dimers, has been implicated for the emergence of double helical intermediates in polyriboadenylic acid, as recently demonstrated by vibrational circular dichroism studies.3 Such structures are believed to have relevance for the hierarchical organization of native and non-native singlestranded nucleic acid sequences. Crucial significance associated with protonated forms of nucleobases has spawned theoretical investigations where density functional computations were invoked to evaluate nucleobases for their proton affinities and gas-phase basicities. One such study suggests that protonation occurs preferentially at N7 in guanine, N1 in adenine, N3 in cytosine, and O4 in thymine.4 There are various literature reports showing homodimerization of protonated adenine (or adenosine) through the Hoogsteen faces (N6 being H-donor and N7 as H-acceptor),5 as protonation at N1 blocks the Watson-Crick site. Heterocyclic and exocyclic substituents in nucleobases are perfectly predisposed to form well-defined hydrogen bonded complementary base pairs, which hold key to nucleic acid structure and crucial biochemical processes such as replication and transcription. The possible role of hydrogen bonding, along with other electrostatic and nonelectrostatic forces, can also be extended to interactions between nucleobases and amino acid side chains found in transcription factors and protein enzymes.6 For example, carboxyl group side chain of aspartic and glutamic acid residues interact with adenine via hydrogen bonding, while asparagine and glutamine residues may interact through bidentate hydrogen bonds.7 Several low temperature NMR studies are reported to elucidate the issue of adenine-carboxylic acid interaction.8 Moreover, it was reported that aspartic acid preferentially binds to the WatsonCrick side of the adenine base through hydrogen bonding. *To whom correspondence should be addressed. E-mail: [email protected]. r 2010 American Chemical Society

We have been exploring coordination and catalytic aspects of adenine for the purpose of creating metal-organic frameworks as well as for the mimicry of prebiotic catalysis.9 In this paper, we have tried to merge the issue of adenine protonation and its interaction with carboxylic acid moiety by incorporating a carboxylic group at the N9 position of adenine in order to explore the possibility of dimer formation by the adeninium cation, via crystallographic studies. As carboxylic group may also afford dimers through self-association, there is a possibility of competition between self-dimerization either through the adeninium cation or carboxylic group or via the interaction of carboxylic group with adeninium cation. This paper reports the structure of five protonated 9(carboxypropyl)adenine (9-CA) adducts in the solid state with four different counteranions with different shapes such as chloride (spherical), nitrate (trigonal), trifluoro acetate, and perchlorate (tetrahedral). All the crystals exhibit an extensive hydrogen bonding network through the Hoogsteen face, carboxylic group, and counteranion (and in few cases water molecules). Experimental Section The synthesis of 9-(carboxypropyl)adenine is reported elsewhere.9b We have chosen water as our solvent of choice and a dilute solution of corresponding acid for protonation. The resulting solution was filtered and kept for slow evaporation. Colorless crystals suitable for X-ray crystallographic studies were obtained within a few weeks. In the case of 9-CA 3 HNO3, we obtained two isomorphic crystals: one in the same manner as discussed, whereas the other was obtained in the presence of metal salts such as cupric nitrate or uranyl nitrate in a 1:1 ratio with respect to ligand and the purity of the bulk phase has been checked by X-ray powder diffraction patterns.10 [9-CA 3 Hþ]2[Cl-]2[H2O]2: slow evaporation in the presence of 1 M hydrochloric acid. (2a) [9-CA 3 Hþ][NO3-]: slow evaporation in the presence of dil. HNO3 and one equivalent of metal salt. (2b) [9-CA 3 Hþ][NO3-]: slow evaporation in the presence of dil. HNO3 solution. (3) [9-CA 3 Hþ][CF3COO-] [CF3COOH]: slow evaporation in the presence of dil. trifluoroacetic acid. (4) [9-CA 3 Hþ][ClO4-][H2O]2: slow evaporation in the presence of dil. perchloric acid.

(1)

Crystal Structure Determination and Refinement. Crystals were coated with light hydrocarbon oil and mounted in the 100 K dinitrogen stream of a Bruker SMART APEX CCD diffractometer equipped with CRYO Industries low-temperature apparatus and intensity data were collected using graphite-monochromated Mo KR radiation. The data integration and reduction were processed with the SAINT software.11 An absorption correction was applied.12 Structures were solved by the direct method using SHELXS-97 and refined on F2 by a full-matrix least-squares technique using the SHELXL-97 program package.13 Non-hydrogen atoms were refined anisotropically. In the refinement, hydrogens were treated as Published on Web 06/08/2010

pubs.acs.org/crystal

3556

Crystal Growth & Design, Vol. 10, No. 8, 2010

Kumar et al.

Scheme 1. Molecular Structure of 9-Carboxypropyl Adeninium Cation with Atom Numbering and Three Possible Modes of Dimerization: Base-Base (I); Base-Carboxyl Group (II); Carboxyl-Carboxyl (III)

Figure 1. Asymmetric unit of 1 as ORTEP diagram with 35% ellipsoid probability.

riding atoms using the SHELXL default parameters. All water hydrogen and COOH hydrogen atoms were refined freely except in the case of 1 and 4 where constraints were applied to fix the O-H distance and angle (in the case of water molecules). In all cases, four to five crystals were randomly picked and checked for cell parameters. Crystal structure refinement data and various H-bonds are given as Table S1 and S2, Supporting Information, respectively. CCDC contains the supplementary crystallographic data for this paper with a deposition number of CCDC 719939 (4), 719940 (3), 719941 (2b), 719942 (1), and 757226 (2a). Copies of this information can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK. [Fax: þ44-1223/336-033; e-mail: [email protected]].

Results and Discussion Representative structure of protonated 9-(carboxypropyl) adeninium cation with a numbering scheme is shown in Scheme 1 and depending on the orientation and preference of hydrogen bonding interactions, at least three different pairing schemes can be invoked. (a) Homodimerization of the adeninium cation through the Hoogsteen site (type I). (b) Cross-dimerization where the carboxyl group interacts with the Hoogsteen face of the adeninium cation (type II). (c) Homodimerization of the carboxyl group (type III). Type I: Adduct 1 and 2a belongs to this category as they exhibit homodimerization through the Hoogsteen face. Crystal Analysis of 1. The crystal structure of 1 is depicted in Figure 1 which crystallizes in the orthorhombic system, space group Pn21a. Two protonated molecules of 9-CA, two Cl- ions, and two water molecules are present in the asymmetric unit (Figure 1). The ensuing cation is held by moderate hydrogen-bonding to Cl- counteranion, with participation from the carboxylic OH group, whereas a water molecule is found strongly hydrogen bonded to the protonated N1 nitrogen. In the crystal lattice of 1, 9-(carboxypropyl) adeninium cation exists as a dimeric species due to self-association through the Hoogsteen hydrogen bonding. Chloride anions are simultaneously hydrogen bonded to N6-H and hydroxyl OH of the carboxyl group (Figure 2). This interaction leads to the formation of two-dimensional polymeric structures extending along the a-axis. The crystal lattice can also be dissected to visualize an embedded helical structure where each turn is contributed by four 9-CA cations and two chloride anions with a pitch of 5.11 A˚.10

Figure 2. (a) Crystal lattice of 1 exhibiting self-association through the Hoogsteen face (view along the c-axis); (b) self-association of adeninium cations and position of water molecules; (c) schematic representation of the interaction (green spheres represent chloride anions).

The water molecules present in the lattice are also hydrogen bonded to protonated N1 and Cl- ions, thus reinforcing supramolecular organization in 1. However, it is interesting to note that carboxyl-carboxyl dimers are not observed in this particular case as chloride ions perhaps interfere with the proper alignment of the carboxyl groups from two dimeric species. Crystal Analysis of 2a. Two different types of isomorphic crystals were obtained in the case of the nitrate counteranion under slightly different conditions. The X-ray crystal structure of 2a and 2b are shown in Figure 3. The adduct 2a crystallized in the monoclinic system, space group P21/c, when 9-CA was allowed to stand in the acidic medium in the presence of one equivalent of copper nitrate (Figure 3a). Transient coordination of metal ion could be ascribed for the preference of type I crystal patterns as the eventual crystal structure lacked the presence of metal ions in the asymmetric unit and crystal lattice (Figure 3a,b). In the case of 2a, selfassociation of the cation dominates through the Hoogsteen face (Figure 4). The crystal lattice of 2a (Figure 4) offers similarity in many respects to the crystal lattice of 1 (Figure 2). For example, self-association of cations occurring through

Article

Crystal Growth & Design, Vol. 10, No. 8, 2010

3557

Figure 3. (a) Asymmetric units of 2a and (b) 2b as ORTEP diagrams drawn with 35% ellipsoid probability.

Figure 5. Crystal lattice of 2b shows linear polymeric chains (view along the b-axis), highlighted with green and yellow color, due to cross-dimerization (H-bonds are drawn as fragmented bonds).

Figure 4. Crystal lattice of 2a stabilized by H-bonding drawn as fragmented bonds (view along the b-axis) showing self-association of cation (highlighted as green bonds).

the Hoogsteen face and bridging of dimeric species through counteranion, can also be observed in 2a. The oxygen atoms of the nitrate anion in 2a act as acceptors in four different hydrogen bonding schemes with N1-H, N6-H, O1-H, and C2-H, respectively (Figure 4). The hydrogen atom at the C2 carbon is involved in weak hydrogen bonding with the nitrate oxygen, whereas another weak hydrogen bond between C8-H and carbonyl oxygen O2 also stabilizes the lattice. As in the previous example, formation of a helical structure with the participation of four 9-CA cations and two nitrate anions is observed with a pitch rise of
˚ .10 Thus, 1 and 2a fall under type I category by exhibit5.75 A ing adeninium cation homodimerization through the Hoogsteen face. Type II: Crystal structures 2b, 3, and 4 exhibit intermolecular cross-dimerization through the interaction of the Hoogsteen face of the adeninium cation with the carboxyl group. Crystal Analysis of 2b. Adduct 2b crystallized in the orthorhombic system, space group Pbcn. Interestingly, 2b exhibited cross-dimerization through the interaction of the adeninium cation (N6H and N7) and the carboxyl group (O1H and O2) leading to the formation of an infinite linear chain. The alternate linear polymeric chains were antiparallel in orientation and connected through hydrogen bonding involving N6-H and N1-H as hydrogen bond donors and nitrate oxygens as acceptors. The hydroxyl OH of the carboxylic group simultaneously acts as a donor for N7 and acceptor for

Figure 6. (a) Asymmetric units of 3 and (b) 4 with numbering schemes (ORTEP diagrams with 35% ellipsoid probability).

C2-H. C8-H exhibits bifurcated hydrogen bonding with two different oxygen atoms of the same nitrate group (Figure 5). Additional weak hydrogen bonding interactions involving C2 and C8 hydrogens hold the linear chains together resulting in a zigzag like arrangement of 2b crystal lattice. Crystal Structure Analysis of 3 and 4. 9-CA adducts 3 and 4, with trifluoroacetate and perchlorate counteranions, respectively, crystallized in the monoclinic system with space group P21 and P21/n, respectively. The asymmetric unit of 3 consists of one 9-CA cation, one trifluoroacetate counteranion, and a trifluoroacetic acid molecule as the solvent of crystallization, whereas the asymmetric unit of 4 consists of one 9-CA cation, one perchlorate counteranion, and two water molecules as the solvent of crystallization (Figure 6). The crystal lattice of both adducts show cross-dimerization where the carboxylic group interacts with the Hoogsteen face of adeninium cation forming an infinite linear chain similar to that of 2b. The crystal lattice of 3 is composed of polymeric chains running parallel to each other along the b-axis, and the space created in between these polymeric chains accommodates trifluoroacetate anions and trifluoroacetic acid molecules (Figure 7). Trifluoroacetic acid is hydrogen bonded to trifluoroacetate anion, which is simultaneously hydrogen bonded to

3558

Crystal Growth & Design, Vol. 10, No. 8, 2010

Figure 7. (a) Formation of linear polymeric chain in 3 (view along the a-axis) by cross- dimerization; (b) representation of polymeric chains.

Kumar et al.

Figure 9. Formation of a boxlike structure due to hydrogen bonding between water hydrogens and perchlorate oxygens and position of ligand around this rectangular box structure (N9-subtituent has been removed for clarity).

within this boxlike geometry shows that all O1W molecules interact with exocyclic N6-H, whereas O2W interacts with protonated N1-H (Figure 9). Type III: The last possibility of self-association of the carboxyl group to yield dimer formation was not encountered in any of the five crystal structures reported here. It suggests that the propensity of nucleobase-nucleobase and carboxyl-nucleobase interactions dominates compared to carboxyl-carboxyl interaction. Discussion

Figure 8. (a) Formation of an infinite linear chain by cross-dimerization in 4 running antiparallel to each other as shown with the use of two different colors (view along the a-axis); (b) representation of antiparallel polymeric chains.

N6-H and protonated N1-H (Figure 7). A weak interaction between F1 fluorine and C11-H (d = 2.43 A˚) can be envisaged as a connector of polymeric chains. The crystal lattice again form a ladderlike arrangement similar to 2b when viewed along the c-axis (see Table S2, Supporting Information). Adduct 4, with perchlorate counteranion, also exhibits similar cross-dimerization as 3, affording formation of antiparallel, linear polymeric chains owing to the interaction between the carboxylic group and the Hoogsteen face of the adeninium cation (Figure 8). The crystal lattice forms complex hydrogen bonding patterns because of the presence of two crystallographically unique water molecules, present as the solvent of crystallization. The water molecule O1W is involved in hydrogen bonding with O4 and O5 of perchlorate anion leading to the formation of an infinite chain-like structure (shown in green and aqua color) in Figure 9, and these polymeric chains are connected to each other with the help of hydrogen bonding involving the second water molecule O2W and O3 of perchlorate anion. Overall this pattern gives rise to a unique boxlike structure composed of six perchlorate anions and eight water molecules. The position of two protonated 9-CA cations

Earlier studies have used carboxyl group modified adenine as simple model systems to elucidate protein-nucleic acid interaction. More specifically, presence of a carboxyl group in adenine might be considered as mimicry of adenine-aspartic/glutamic acid interaction, whereas a carboxamide in adenine could be considered as mimicry of adenine-asparagine/glutamine interaction.14 Crystal lattice analysis of five adducts of protonated 9-(carboxypropyl)adenine provided an interesting preference of dimer formation and hydrogen bonding patterns. Type I pattern representing self-association of the adeninium cation was exhibited by two adducts, 1 and 2a, whereas the other three adducts, 2b, 3, and 4, displayed cross-dimerization by the interaction of adeninium cation with the carboxyl group, leading to the formation of infinite linear chains in the crystal lattice. We propose that the preference for type I or type II mode of interaction in protonated 9-CA ligand can be explained on the basis of the stabilization of its gauche or anti conformers (Figure 10). In solution, protonated 9-CA can equilibrate between two conformers by the rotation along its C10-C11 bond: the gauche conformer, where the dihedral angle between the adeninium moiety and carboxyl group is ∼60° and the other one as an anti conformer, where these two groups have a maximum separation at an angle of ∼180°. Notably, adduct 1 (dihedral angle along the C10-C11 bond is 176.1° and 175.9° for two molecules in asymmetric unit) and 2a (dihedral angle is 178.1°) are anti conformers and shows homodimerization of adeninium cation through the nucleobase part, whereas the other three adducts 2b, 3, and 4 (dihedral angles are 81.6°, 72.9°, and 78.1°, respectively) show

Article

Crystal Growth & Design, Vol. 10, No. 8, 2010

3559

Figure 10. Representation of protonated 9-CA ligand as a Newman projection along the C10-C11 bond. The anti conformer shows homodimerization (type I), while the gauche conformer shows crossdimerization (type II).

higher propensity for the gauche conformation and show cross-dimerization between the carboxyl group and the Hoogsteen site of the protonated adenine moiety. It is worth noticing that 1 and 2a, with a preference for the anti conformation, contain an embedded helical structure within their crystal lattice, whereas the other three lack helical features in their lattice but prefer an infinite polymeric chain structure. This scheme is generally applicable to all five adducts (Figure 10). Thus, it is clear that self-association or crossdimerization of ligand, to some extent, is dictated by the conformation of the ligand despite the presence of counteranions of various shapes. Interestingly, however, we did not observe any crystal structure belonging to type III, where the carboxylic group homodimerization dominates. To gain an insight into these different modes of interaction, namely, type I, type II, and type III, density functional calculations were performed on N1-protonated 9-CA cation for geometry optimization followed by frequency calculation using the Gaussian 03 program15 applying the B3LYP 6-31þþG (d,p) theoretical level. The hydrogen bond energies were determined according to the following equation: ΔE ¼ EðA 3 3 3 BÞ - ðEA þ EB Þ where E(A 3 3 3 B) is the H-bond energy (kcal/mol) of the dimer and EA and EB depict the energy of the individual monomer. The ΔE values were appraised by ZPE and BSSE correction methods. Hence, the corrected hydrogen bond energies, (ΔE C), were obtained according to the following equation. ΔE C ¼ ΔE - ðΔZPE þ BSSEÞ To further confirm the relative stabilities of the conformers, single-point energy calculations have been performed at the B3LYP/6-311þþG (2d, 2p) level of theory. In all the cases for energy calculation, we have removed solvent molecules and counteranions, although they are forming strong hydrogen bonding with the ligand, as we wish to check the relative stability gained by the dimerization utilizing all three different

Figure 11. Optimized geometry of the 9-carboxypropyl adeninium cation. (a) Base-base homodimerization (type I; anti confirmation), (b) base-carboxyl cross-dimerization (type II; gauche confirmation), (c) carboxyl-carboxyl homodimerization (type III).

modes of interaction. The optimized geometries of dimer formation for all three different modes of interaction is given in Figure 11. The optimized bond lengths and bond angles of all conformers of 9-carboxypropyl adeninium cation and crystal data are compared in Tables 1 and 2. The purpose of the current study is to investigate the stability of the basebase (anti confirmation), base-carboxyl (gauche confirmation), and carboxyl-carboxyl hydrogen bond dimers. The calculated intermolecular hydrogen bond distances between base-base interactions (type I), that is, N6H 3 3 3 N7 and N7 3 3 3 HN6, are found to be 2.010 and 2.012 A˚ which show shortening when compared to the starting geometry. The two adeninium moieties are nonplanar and inclined at an angle of 30° (in the crystal structure both rings are planar), whereas for the nucleobase-carboxylic group dimer (type II), that is, N7 3 3 3 HO1 (1.737 A˚) and O1 3 3 3 HN6 (1.805 A˚), hydrogen bonds are again shortened as compared to the starting geometry (Table 1). The dihedral angle along the C10-C11 bond is 70.9°, and both the adeninium rings are almost perpendicular to each other (in the crystal structure it is 79.3°). However, in the case of the COOH-COOH dimer (Type III) both hydrogen bonds have almost similar bond lengths (O-H 3 3 3 O) 1.675 A˚ and 1.678 A˚ and bond angle O-H 3 3 3 O of 178°. The effect of hydrogen bonding on other structural parameters of the molecule is not significant. Some recent articles setting up the energy borders for the weak, moderate, and strong H-bond report ranges from 0.2 to 40.0 kcal/mol in the crystals.16 Our calculation shows that the EH-bond of anti conformer (Type I) of 9-carboxypropyl adeninium cation is about 27.9 kcal/mol indicating strong hydrogen bonding, whereas for gauche confirmation (type II), it is 13.5 kcal/ mol which indicates the presence of moderate hydrogen bonding. Although we have not obtained any crystal structure

3560

Crystal Growth & Design, Vol. 10, No. 8, 2010

Kumar et al.

Table 1. Selected Bond Lengths (A˚) of Optimized Geometry for Arrangement of Type I and Type II of 9-Carboxypropyl Adeninium Cation and Comparison with Crystal Dataa Type I

Type II

Type III

distances

crystal data

DFT

d(N7 3 3 3 HN6) d(N6H 3 3 3 N7) d(N6-H) d(CdO2) d(C-O1) d(N6H 3 3 3 O2) d(N7 3 3 3 HO1) d(O1-H) d(CdO2) d(C-O1) d(O1H 3 3 3 O2) d(O2 3 3 3 HO1) d(O1-H) d(CdO2) d(C-O1)

2.062 2.062 0.860 1.205 1.330 1.952 1.745 0.968 1.218 1.318

2.010 2.012 1.029 1.212 1.341 1.805 1.737 1.008 1.235 1.315 1.675 1.678 1.003 1.232 1.317

a The crystal data for type I and type II has been taken for adduct 2a and adduct 4 respectively.

Table 2. Selected Bond Angles (°) of Optimized Geometry for Arrangement of Type I and Type II of 9-Carboxypropyl Adeninium Cation and Comparison with Crystal Datab Type I

Type II

Type III

bond angles

crystal data

DFT

C8-N7 3 3 3 H H 3 3 3 N7-C8 N6-H 3 3 3 N7 N7 3 3 3 H-N6 H-N6-H C8-N7 3 3 3 H N6-H 3 3 3 O2 O1-H 3 3 3 N7 CdO2 3 3 3 H C-O1-H O1-H 3 3 3 O2 O2 3 3 3 H-O1 O2dC-O1 C-O1-H

110.06 110.06 163.49 163.49 119.93 122.41 163.22 171.22 127.33 110.76

118.7 118.5 163.2 163.4 116.8 120.8 170.8 171.5 130.6 112.5 178.9 178.6 124.6 110.9

b The crystal data for type I and type II has been taken for adduct 2a and adduct 4 respectively.

belonging to the type III yet, we have considered this mode of dimerization for theoretical calculation to investigate the feasibility of its formation. Our calculations shows that the third conformer has only 3.0 kcal/mol of energy showing very weak hydrogen bonding (see Table 3). The strength of H-bond energy is the measure of the stability of the adduct which means that adduct of type I has the maximum stability followed by type II and type III has the least stability. In general, the most stable dimer will form only when the H-bond interactions take place between more negative proton acceptor and the more positive proton donor. Mulliken charge population shows that in the case of type I, the more positive charge is localized on H6B (0.638 and 0.657) and the more negative charge is localized on N7 (-0.402 and -0.420) explaining the dimerization through the Hoogsteen face, whereas, in the case of type II, the more positive charge is localized on H6B and H1A (0.593 and 0.690, respectively) and more negative charge is localized on O2 and N7 (-0.511 and -0.435) revealing the existence of cross-dimerization between Hoogsteen face of nucleobase and carboxyl group. In the case of type III, it was found that more positive charge is localized on H1A (0.691 and 0.689 respectively) and almost equal negative charge of the magnitude of -0.970 is localized on the oxygen atom of the carboxylic group.

Table 3. Calculated Absolute Energies (E in a.u.), Hydrogen Bond Energies (ΔE in kcal/mol), Corrected Hydrogen Bond Energies (ΔEC in kcal/mol), Relative Energies (kcal/mol) and Dipole Moment (debye) for Arrangement of Type I, II, and III of 9-CA Cation at B3LYP/6-31þþG(d,p) E ΔE ΔEC relative energies dipole moment

Type I

Type II

Type III

-1469.833311 28.9 27.9 0.0 4.7

-1469.865933 14.4 13.5 -20.1 12.8

-1469.871883 4.2 3.0 23.9 0.0

Similarly, Lippert and co-workers had also reported a crystallographic and ab initio calculation based study for mispaired protonated adenine and guanine (or hypoxanthine), AHþanti G/Hxsyn, that could associate in various ways to give mixed purine quartets.17a Garcia-Teran and co-workers reported crystal structures of compounds resulting from the reactions of adenine with water-soluble oxalato complexes at acidic pH. Density functional theory calculations were used to study the stability of the protonated nucleobase forms and their hydrogen-bonded adducts by the comparison of crystallographic and theoretical results.17b Conclusion We have reported change in dimerization pattern of adeninium cation having incorporated carboxylic group at N9 position because of the competition between homodimerization versus cross-dimerization. Our findings have suggested that the change in hydrogen bonding pattern can be partially attributed to the conformation adopted by the 9-carboxypropyl adeninium cation. When the conformation is found to be anti, self- dimerization of adeninium cation moiety through Hoogsteen face dominates, whereas, for the gauche conformation there is cross-dimerization between carboxylic group and Hoogsteen face of adeninium cation. DFT studies for geometry optimization revealed that the feasibility for self-dimerization through carboxylic group is much less and we also did not observe any crystal structure having this mode of dimerization. Acknowledgment. We thank Single Crystal CCD X-ray facility at IIT-Kanpur; CSIR, for S. P. Mukherjee Fellowship (J.K.); IFCPAR for funding (S.A.). This work is supported by IFCPAR, New Delhi, India (SV). Supporting Information Available: Additional pictures, crystal structure refinement parameters and hydrogen bond parameters as tables and X-ray crystallographic data in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org.

References (1) (a) Kampf, G.; Kapinos, L. E.; Griesser, R.; Lippert, B.; Sigel, H. J. Chem. Soc., Perkin Trans. 2 2002, 7, 1320–1327. (b) Lippert, B. Prog. Inorg. Chem. 2005, 54, 385–447. (2) (a) Amosova, O.; Coulter, R.; Fresco., J. R. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 4392–4397. (b) Bregadze, V. G.; Gelagutashvili, E. S.; Tsakadze, K. J.; Melikishvili, S. Z. Chem. Biodiversity 2008, 5, 1980–1989. (3) Petrovic A. G.; Polavarapu P. L. J. Phys. Chem. B 2005, 109, 2369823705; and references cited therein. (4) Russo, N.; Toscano, M.; Grand, A.; Jolibois, F. J. Comput. Chem. 1998, 19, 989–1000. (5) Cherouana, A.; Bousboua, R.; Bendjeddou, L.; Dahaoui, S.; Lecomte, C. Acta Crystallogr., Sect. E: Struct. Rep. Online 2009, E65, o2285–o2286. (6) (a) Norberg, J. Arch. Biochem. Biophys. 2003, 410, 48–68. (b) Nadassy, K.; Wodak, S. J.; Janin, J. Biochemistry 1999, 38, 1999–2017. (7) Luscombe, N. M.; Laskowski, R. A.; Thornton, J. M. Nucleic Acids Res. 2001, 29, 2860–2874.

Article (8) (a) Janke, E. M. B.; Weisz, K. J. Phys. Chem. A 2007, 111, 12136– 12140. (b) Schlund, S.; Mladenovic, M.; Janke, E. M. B.; Engels, B.; Weisz., K. J. Am. Chem. Soc. 2005, 127, 16151–16158. (c) Janke, E. M. B.; Limbach, H.-H.; Weisz, K. J. Am. Chem. Soc. 2004, 126, 2135–2141. (9) (a) Verma, S.; Mishra, A. K.; Kumar, J. Acc. Chem. Res. 2010, 43, 79–91. (b) Kumar, J.; Verma, S. Inorg. Chem. 2009, 48, 6350–6352. (c) Purohit, C. S.; Verma, S. J. Am. Chem. Soc. 2007, 129, 3488–3489. (d) Purohit, C. S.; Mishra, A. K.; Verma., S. Inorg. Chem. 2007, 46, 8493–8495. (e) Purohit, C. S.; Verma., S. J. Am. Chem. Soc. 2006, 128, 400–401. (f) Srivatsan, S. G.; Verma, S. Chem. Commun. 2000, 515– 516. (g) Srivatsan, S. G.; Verma, S. Chem.—Eur. J. 2001, 7, 828–833. (h) Srivatsan, S. G.; Parvez, M.; Verma, S. Chem.—Eur. J. 2002, 8, 5184–5191. (10) See Supporting Information. (11) SAINTþ, 6.02 ed.; Bruker AXS: Madison, WI, 1999. (12) Sheldrick, G. M. SADABS 2.0; University of G€ottingen: G€ottingen, Germany, 2000. (13) Sheldrick, G. M. SHELXL-97: Program for Crystal Structure Refinement; University of G€ottingen: G€ottingen, Germany, 1997. (14) Takimoto, M.; Takenaka, A.; Sasada, Y. Bull. Chem. Soc. Jpn. 1981, 54, 1635–1639. (15) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven,

Crystal Growth & Design, Vol. 10, No. 8, 2010

3561

T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision B.04; Gaussian, Inc.: Wallingford, CT, 2004. (16) (a) Parthasarathi, R.; Subramanian, V.; Sathyamurthy, N. J. Phys. Chem. A 2006, 110, 3349–3351. (b) Grabowski, S. J. Annu. Rep. Chem., Sect. C 2006, 102, 131–165. (17) (a) Amo-Ochoa, P.; Sanz Miguel, P. J.; Lax, P.; Alonso, I.; Roitzsch, M.; Zamora, F.; Lippert, B. Angew. Chem., Int. Ed. 2005, 44, 5670– 5674. (b) Garcia-Teran, J. P.; Castillo, O.; Luque, A.; Garcia-Couceiro, U.; Beobide, G.; Roman, P. Inorg. Chem. 2007, 46, 3593–3602.