pubs.acs.org/crystalPublished on Web 06/08/2010r 2010 American Chemical Society

DOI: 10.1021/cg100470u

2010, Vol. 103555–3561

Contrasting Crystallographic Signatures of 9-Carboxypropyl Adeninium

Cation: Adenine Dimerization vs Carboxylic Group Interaction

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 rolesencompassing stability, structure, and mutagenic aspects ofnucleic acid chemistry and biochemistry. The nitrogenousheterocyclic framework of purine and pyrimidine bases hasbeen subjected to numerous studies related to acid-baseequilibrium issues both in gas and condensed phases by thehelp of theoretical and experimental approaches.1 Of parti-cular interest are the stability concerns where it has been shownthat protonation of purine residues may lead to depurination,thus compromising the stability of nucleic acid sequences.Spontaneous DNA depurination could be considered as endo-genous DNA damage that is mediated by the protonation ofpurine N-7 position, which is accelerated under low pH andhigh temperature regimes and by the presence of metal ions.2

Adenine protonation, leading to the possible formationof A-AHþ dimers, has been implicated for the emergenceof double helical intermediates in polyriboadenylic acid, asrecently demonstrated by vibrational circular dichroismstudies.3 Such structures are believed to have relevance forthe hierarchical organization of native and non-native single-stranded nucleic acid sequences. Crucial significance associ-ated with protonated forms of nucleobases has spawned theo-retical investigations where density functional computationswere invoked to evaluate nucleobases for their proton affi-nities and gas-phase basicities. One such study suggests thatprotonation occurs preferentially at N7 in guanine, N1 inadenine, N3 in cytosine, and O4 in thymine.4 There arevarious literature reports showing homodimerization of pro-tonated adenine (or adenosine) through the Hoogsteen faces(N6 beingH-donor andN7asH-acceptor),5 as protonation atN1 blocks the Watson-Crick site.

Heterocyclic and exocyclic substituents in nucleobases areperfectly predisposed to form well-defined hydrogen bondedcomplementary base pairs, which hold key to nucleic acidstructure andcrucial biochemical processes suchas replicationand transcription. The possible role of hydrogen bonding,along with other electrostatic and nonelectrostatic forces, canalso be extended to interactions between nucleobases andamino acid side chains found in transcription factors andprotein enzymes.6 For example, carboxyl group side chain ofaspartic and glutamic acid residues interact with adenine viahydrogen bonding, while asparagine and glutamine residuesmay interact through bidentate hydrogen bonds.7 Several lowtemperature NMR studies are reported to elucidate the issueof adenine-carboxylic acid interaction.8 Moreover, it wasreported that aspartic acid preferentially binds to theWatson-Crick side of the adenine base through hydrogen bonding.

We have been exploring coordination and catalytic aspectsof adenine for the purpose of creating metal-organic frame-works as well as for the mimicry of prebiotic catalysis.9 In thispaper, we have tried tomerge the issue of adenine protonationand its interaction with carboxylic acid moiety by incorporat-ing a carboxylic group at the N9 position of adenine in orderto explore the possibility of dimer formation by the adeniniumcation, via crystallographic studies. As carboxylic group mayalso afford dimers through self-association, there is a possi-bility of competition between self-dimerization either throughthe adeninium cation or carboxylic group or via the interac-tion of carboxylic group with adeninium cation.

This paper reports the structure of five protonated 9-(carboxypropyl)adenine (9-CA) adducts in the solid statewith four different counteranions with different shapessuch as chloride (spherical), nitrate (trigonal), trifluoroacetate, and perchlorate (tetrahedral). All the crystalsexhibit an extensive hydrogen bonding network throughthe Hoogsteen face, carboxylic group, and counteranion(and in few cases water molecules).

Experimental Section

The synthesis of 9-(carboxypropyl)adenine is reported elsewhere.9b

Wehave chosenwater as our solvent of choice and a dilute solutionofcorresponding acid for protonation. The resulting solutionwas filteredand kept for slow evaporation. Colorless crystals suitable for X-raycrystallographic studies were obtainedwithin a fewweeks. In the caseof 9-CA 3HNO3, we obtained two isomorphic crystals: one in thesame manner as discussed, whereas the other was obtained in thepresence of metal salts such as cupric nitrate or uranyl nitrate in a 1:1ratio with respect to ligand and the purity of the bulk phase has beenchecked by X-ray powder diffraction patterns.10

(1) [9-CA 3Hþ]2[Cl

-]2[H2O]2: slow evaporation in the presenceof 1 M hydrochloric acid.

(2a) [9-CA 3Hþ][NO3

-]: slow evaporation in the presence of dil.HNO3 and one equivalent of metal salt.

(2b) [9-CA 3Hþ][NO3

-]: slow evaporation in the presence of dil.HNO3 solution.

(3) [9-CA 3Hþ][CF3COO-] [CF3COOH]: slow evaporation in

the presence of dil. trifluoroacetic acid.(4) [9-CA 3H

þ][ClO4-][H2O]2: slow evaporation in the presence

of dil. perchloric acid.

Crystal Structure Determination and Refinement. Crystals werecoated with light hydrocarbon oil and mounted in the 100 Kdinitrogen stream of a Bruker SMARTAPEXCCD diffractometerequipped with CRYO Industries low-temperature apparatus andintensity data were collected using graphite-monochromated MoKR radiation. The data integration and reduction were processedwith the SAINT software.11 An absorption correction was applied.12

Structures were solved by the direct method using SHELXS-97 andrefined on F2 by a full-matrix least-squares technique using theSHELXL-97 program package.13 Non-hydrogen atoms were refi-ned anisotropically. In the refinement, hydrogens were treated as*Towhom correspondence should be addressed. E-mail: sverma@iitk.ac.in.

3556 Crystal Growth & Design, Vol. 10, No. 8, 2010 Kumar et al.

riding atoms using the SHELXL default parameters. All waterhydrogen and COOH hydrogen atoms were refined freely exceptin the case of 1 and 4where constraints were applied to fix the O-Hdistance and angle (in the case of water molecules). In all cases, fourto five crystals were randomly picked and checked for cell parameters.Crystal structure refinement data and various H-bonds are given asTable S1 and S2, Supporting Information, respectively.

CCDC contains the supplementary crystallographic data for thispaper with a deposition number of CCDC 719939 (4), 719940 (3),719941 (2b), 719942 (1), and 757226 (2a). Copies of this informationcan be obtained free of charge on application to CCDC, 12 UnionRoad, Cambridge CB21EZ, UK. [Fax: þ44-1223/336-033; e-mail:deposit@ccdc.cam.ac.uk].

Results and Discussion

Representative structure of protonated 9-(carboxypropyl)adeninium cation with a numbering scheme is shown inScheme 1 and depending on the orientation and preferenceof hydrogen bonding interactions, at least three differentpairing schemes can be invoked.

(a) Homodimerization of the adeninium cation throughthe Hoogsteen site (type I).

(b) Cross-dimerization where the carboxyl group inter-acts 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 theyexhibit homodimerization through the Hoogsteen face.

Crystal Analysis of 1. The crystal structure of 1 is depictedin Figure 1 which crystallizes in the orthorhombic system,space groupPn21a. Two protonatedmolecules of 9-CA, twoCl- ions, and two water molecules are present in the asym-metric unit (Figure 1). The ensuing cation is held bymoderatehydrogen-bonding to Cl- counteranion, with participationfrom the carboxylic OH group, whereas a water moleculeis found strongly hydrogen bonded to the protonated N1nitrogen.

In the crystal lattice of 1, 9-(carboxypropyl) adeniniumcation exists as a dimeric species due to self-associationthrough the Hoogsteen hydrogen bonding. Chloride anionsare simultaneously hydrogen bonded to N6-H and hydro-xyl OH of the carboxyl group (Figure 2). This interactionleads to the formation of two-dimensional polymeric struc-tures extending along the a-axis. The crystal lattice can alsobe dissected to visualize an embedded helical structure whereeach turn is contributed by four 9-CA cations and twochloride anions with a pitch of 5.11 A.10

The water molecules present in the lattice are also hydro-gen bonded to protonated N1 and Cl- ions, thus reinforcingsupramolecular organization in 1. However, it is interestingto note that carboxyl-carboxyl dimers are not observed inthis particular case as chloride ions perhaps interfere with theproper alignment of the carboxyl groups from two dimericspecies.

Crystal Analysis of 2a. Two different types of isomorphiccrystals were obtained in the case of the nitrate counteranionunder slightly different conditions. The X-ray crystal struc-ture of 2a and 2b are shown in Figure 3. The adduct 2acrystallized in the monoclinic system, space group P21/c,when 9-CA was allowed to stand in the acidic medium in thepresence of one equivalent of copper nitrate (Figure 3a).Transient coordination ofmetal ion could be ascribed for thepreference of type I crystal patterns as the eventual crystalstructure lacked the presence of metal ions in the asymmetricunit and crystal lattice (Figure 3a,b). In the case of 2a, self-association of the cation dominates through the Hoogsteenface (Figure 4). The crystal lattice of 2a (Figure 4) offerssimilarity in many respects to the crystal lattice of 1 (Figure 2).For example, self-association of cations occurring through

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 diagramwith 35% ellip-soid probability.

Figure 2. (a) Crystal lattice of 1 exhibiting self-association throughthe Hoogsteen face (view along the c-axis); (b) self-association ofadeninium cations and position of water molecules; (c) schematicrepresentation of the interaction (green spheres represent chlorideanions).

Article Crystal Growth & Design, Vol. 10, No. 8, 2010 3557

the Hoogsteen face and bridging of dimeric species throughcounteranion, can also be observed in 2a.

The oxygen atoms of the nitrate anion in 2a act as accep-tors in four different hydrogen bonding schemes with N1-H,N6-H, O1-H, and C2-H, respectively (Figure 4). Thehydrogen atom at the C2 carbon is involved in weak hydro-gen bonding with the nitrate oxygen, whereas another weakhydrogen bond betweenC8-Hand carbonyl oxygenO2 alsostabilizes the lattice. As in the previous example, formationof a helical structure with the participation of four 9-CAcations and two nitrate anions is observed with a pitch rise of5.75 A�.10 Thus, 1 and 2a fall under type I category by exhibit-ing adeninium cation homodimerization through theHoogsteenface.

Type II:Crystal structures2b,3, and4 exhibit intermolecularcross-dimerization through the interaction of the Hoogsteenface of the adeninium cation with the carboxyl group.

Crystal Analysis of 2b.Adduct 2b crystallized in the ortho-rhombic system, space group Pbcn. Interestingly, 2b exhibi-ted cross-dimerization through the interaction of the adeni-nium cation (N6H and N7) and the carboxyl group (O1Hand O2) leading to the formation of an infinite linear chain.The alternate linear polymeric chains were antiparallel inorientation and connected through hydrogen bonding invol-vingN6-HandN1-Has hydrogen bonddonors and nitrateoxygens as acceptors. The hydroxyl OH of the carboxylicgroup simultaneously acts as a donor forN7 andacceptor for

C2-H. C8-H exhibits bifurcated hydrogen bonding withtwo different oxygen atoms of the same nitrate group (Figure 5).Additional weak hydrogen bonding interactions involvingC2 and C8 hydrogens hold the linear chains together result-ing in a zigzag like arrangement of 2b crystal lattice.

Crystal Structure Analysis of 3 and 4. 9-CA adducts 3 and4, with trifluoroacetate and perchlorate counteranions, res-pectively, crystallized in the monoclinic system with spacegroup P21 and P21/n, respectively. The asymmetric unit of 3consists of one 9-CA cation, one trifluoroacetate counteranion,and a trifluoroacetic acid molecule as the solvent of crystal-lization, whereas the asymmetric unit of 4 consists of one 9-CAcation, one perchlorate counteranion, and twowatermoleculesas the solvent of crystallization (Figure 6). The crystal lattice ofboth adducts show cross-dimerization where the carboxylicgroup interacts with the Hoogsteen face of adeninium cationforming an infinite linear chain similar to that of 2b.

The crystal lattice of 3 is composed of polymeric chainsrunning parallel to each other along the b-axis, and the spacecreated in between these polymeric chains accommodatestrifluoroacetate anions and trifluoroacetic acid molecules(Figure 7). Trifluoroacetic acid is hydrogenbonded to trifluoro-acetate anion, which is simultaneously hydrogen bonded to

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

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

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

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

3558 Crystal Growth & Design, Vol. 10, No. 8, 2010 Kumar et al.

N6-H and protonated N1-H (Figure 7). A weak inter-action between F1 fluorine and C11-H (d=2.43 A) can beenvisagedas a connector of polymeric chains.The crystal latticeagain form a ladderlike arrangement similar to 2bwhen viewedalong the c-axis (see Table S2, Supporting Information).

Adduct 4, with perchlorate counteranion, also exhibitssimilar cross-dimerization as 3, affording formation of anti-parallel, linear polymeric chains owing to the interactionbetween the carboxylic group and the Hoogsteen face of theadeninium cation (Figure 8). The crystal lattice forms com-plex hydrogen bonding patterns because of the presence oftwo crystallographically unique water molecules, present asthe solvent of crystallization.

The water molecule O1W is involved in hydrogen bondingwith O4 and O5 of perchlorate anion leading to the forma-tion of an infinite chain-like structure (shown in green andaqua color) in Figure 9, and these polymeric chains areconnected to each other with the help of hydrogen bondinginvolving the second water molecule O2W and O3 of per-chlorate anion.Overall this pattern gives rise to auniqueboxlikestructure composed of six perchlorate anions and eight watermolecules. The position of two protonated 9-CA cations

within this boxlike geometry shows that all O1W moleculesinteract with exocyclic N6-H, whereas O2W interacts withprotonated N1-H (Figure 9).

Type III: The last possibility of self-association of thecarboxyl group to yield dimer formation was not encoun-tered in any of the five crystal structures reported here. Itsuggests that the propensity of nucleobase-nucleobase andcarboxyl-nucleobase interactions dominates compared tocarboxyl-carboxyl interaction.

Discussion

Earlier studies have used carboxyl group modified adenineas simplemodel systems to elucidate protein-nucleic acid inter-action.More specifically, presenceof a carboxyl group in adeninemight be considered asmimicryof adenine-aspartic/glutamicacid interaction, whereas a carboxamide in adenine couldbe considered as mimicry of adenine-asparagine/glutamineinteraction.14

Crystal lattice analysis of five adducts of protonated 9-(carb-oxypropyl)adenine provided an interesting preference of dimerformation and hydrogen bonding patterns. Type I patternrepresenting self-association of the adeninium cation wasexhibited by two adducts, 1 and 2a, whereas the other threeadducts, 2b, 3, and 4, displayed cross-dimerization by theinteraction of adeninium cation with the carboxyl group,leading to the formation of infinite linear chains in the crystallattice.

We propose that the preference for type I or type IImode ofinteraction in protonated 9-CA ligand can be explained on thebasis of the stabilization of its gauche or anti conformers(Figure 10). In solution, protonated 9-CA can equilibratebetween two conformers by the rotation along its C10-C11bond: the gauche conformer,where thedihedral angle betweenthe adeninium moiety and carboxyl group is ∼60� and theother one as an anti conformer, where these two groups have amaximum separation at an angle of ∼180�.

Notably, adduct 1 (dihedral angle along the C10-C11bond is 176.1� and 175.9� for two molecules in asymmetricunit) and 2a (dihedral angle is 178.1�) are anti conformers andshows homodimerization of adeninium cation through thenucleobase part, whereas the other three adducts 2b, 3, and 4

(dihedral angles are 81.6�, 72.9�, and 78.1�, respectively) show

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

Figure 9. Formation of a boxlike structure due to hydrogen bond-ing between water hydrogens and perchlorate oxygens and positionof ligand around this rectangular box structure (N9-subtituent hasbeen removed for clarity).

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

Article Crystal Growth & Design, Vol. 10, No. 8, 2010 3559

higher propensity for the gauche conformation and showcross-dimerization between the carboxyl group and theHoogsteen site of the protonated adenine moiety. It is worthnoticing that 1 and 2a, with a preference for the anti con-formation, contain an embedded helical structure within theircrystal lattice, whereas the other three lack helical featuresin their lattice but prefer an infinite polymeric chain struc-ture. This scheme is generally applicable to all five adducts(Figure 10). Thus, it is clear that self-association or cross-dimerization of ligand, to some extent, is dictated by theconformation of the ligand despite the presence of counter-anions of various shapes. Interestingly, however, we did notobserve any crystal structure belonging to type III, where thecarboxylic group homodimerization dominates.

To gain an insight into these differentmodes of interaction,namely, type I, type II, and type III, density functionalcalculations were performed on N1-protonated 9-CA cationfor geometry optimization followed by frequency calculationusing the Gaussian 03 program15 applying the B3LYP6-31þþG (d,p) theoretical level. The hydrogen bond energieswere determined according to the following equation:

ΔE ¼ EðA 3 3 3BÞ - ðEA þ EBÞwhere E(A 3 3 3B) is the H-bond energy (kcal/mol) of the dimerand EA and EB depict the energy of the individual monomer.The ΔE values were appraised by ZPE and BSSE correctionmethods. Hence, the corrected hydrogen bond energies,(ΔEC), were obtained according to the following equation.

ΔEC ¼ ΔE - ðΔZPE þ BSSEÞTo further confirm the relative stabilities of the conformers,

single-point energy calculations have been performed at theB3LYP/6-311þþG (2d, 2p) level of theory. In all the cases forenergy calculation, we have removed solvent molecules andcounteranions, although they are forming strong hydrogenbonding with the ligand, as we wish to check the relativestability gained by the dimerization utilizing all three different

modes of interaction. The optimized geometries of dimerformation for all three different modes of interaction is givenin Figure 11. The optimized bond lengths and bond angles ofall conformers of 9-carboxypropyl adeninium cation andcrystal data are compared in Tables 1 and 2. The purpose ofthe current study is to investigate the stability of the base-base (anti confirmation), base-carboxyl (gauche confirmation),and carboxyl-carboxyl hydrogen bond dimers.

The calculated intermolecular hydrogen bond distancesbetween base-base interactions (type I), that is, N6H 3 3 3N7and N7 3 3 3HN6, are found to be 2.010 and 2.012 A whichshow shortening when compared to the starting geometry.The two adeniniummoieties are nonplanar and inclined at anangle of 30� (in the crystal structure both rings are planar),whereas for the nucleobase-carboxylic group dimer (type II),that is, N7 3 3 3HO1 (1.737 A) and O1 3 3 3HN6 (1.805 A),hydrogen bonds are again shortened as compared to thestarting geometry (Table 1). The dihedral angle along theC10-C11 bond is 70.9�, and both the adeninium rings arealmost perpendicular to eachother (in the crystal structure it is79.3�). However, in the case of the COOH-COOH dimer(Type III) both hydrogen bonds have almost similar bondlengths (O-H 3 3 3O) 1.675 A and 1.678 A and bond angleO-H 3 3 3O of 178�. The effect of hydrogen bonding on otherstructural parameters of the molecule is not significant.

Some recent articles setting up the energy borders for theweak,moderate, and strongH-bond report ranges from0.2 to40.0 kcal/mol in the crystals.16 Our calculation shows that theEH-bond of anti conformer (Type I) of 9-carboxypropyl adeni-niumcation is about 27.9 kcal/mol indicating stronghydrogenbonding,whereas forgauche confirmation (typeII), it is 13.5kcal/mol which indicates the presence of moderate hydrogenbonding.Althoughwehave not obtained any crystal structure

Figure 10. Representation of protonated 9-CA ligand as a Newmanprojection along the C10-C11 bond. The anti conformer showshomodimerization (type I), while the gauche conformer shows cross-dimerization (type II).

Figure 11. Optimized geometry of the 9-carboxypropyl adeniniumcation. (a) Base-base homodimerization (type I; anti confir-mation), (b) base-carboxyl cross-dimerization (type II; gauche con-firmation), (c) carboxyl-carboxyl homodimerization (type III).

3560 Crystal Growth & Design, Vol. 10, No. 8, 2010 Kumar et al.

belonging to the type III yet, we have considered this modeof dimerization for theoretical calculation to investigate thefeasibility of its formation. Our calculations shows that thethird conformer has only 3.0 kcal/mol of energy showing veryweakhydrogenbonding (seeTable 3).The strengthofH-bondenergy is the measure of the stability of the adduct whichmeans that adduct of type I has the maximum stability follo-wed by type II and type III has the least stability.

In general, the most stable dimer will form only when theH-bond interactions take place betweenmore negative protonacceptor and the more positive proton donor.Mulliken chargepopulation shows that in the case of type I, the more positivecharge is localized on H6B (0.638 and 0.657) and the morenegative charge is localized onN7 (-0.402 and-0.420) expla-ining the dimerization through the Hoogsteen face, whereas,in the case of type II, the more positive charge is localized onH6B andH1A (0.593 and 0.690, respectively) and more nega-tive charge is localized on O2 and N7 (-0.511 and -0.435)revealing the existence of cross-dimerization betweenHoogsteenface 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 chargeof themagnitude of-0.970 is localized on the oxygen atomofthe carboxylic group.

Similarly, Lippert and co-workers had also reported acrystallographic and ab initio calculation based study for mis-paired protonated adenine and guanine (or hypoxanthine),AHþ

anti G/Hxsyn, that could associate in various ways to givemixed purine quartets.17a Garcia-Teran and co-workers repor-ted crystal structures of compounds resulting from the reac-tions of adenine with water-soluble oxalato complexes atacidic pH. Density functional theory calculations were usedto study the stability of the protonated nucleobase forms andtheir hydrogen-bonded adducts by the comparison of crystal-lographic and theoretical results.17b

Conclusion

We have reported change in dimerization pattern of adeni-nium cation having incorporated carboxylic group at N9position because of the competition between homodimeriza-tion versus cross-dimerization. Our findings have suggestedthat the change in hydrogen bonding pattern can be partiallyattributed to the conformationadoptedby the9-carboxypropyladeninium cation.When the conformation is found to be anti,self-dimerizationofadeniniumcationmoiety throughHoogsteenface dominates, whereas, for the gauche conformation there iscross-dimerization between carboxylic group and Hoogsteenface of adeniniumcation.DFT studies for geometry optimiza-tion revealed that the feasibility for self-dimerization throughcarboxylic group is much less and we also did not observe anycrystal structure having this mode of dimerization.

Acknowledgment. We thank Single Crystal CCD X-rayfacility at IIT-Kanpur; CSIR, for S. P.Mukherjee Fellowship(J.K.); IFCPARfor funding (S.A.). Thiswork is supported byIFCPAR, New Delhi, India (SV).

Supporting Information Available: Additional pictures, crystalstructure refinement parameters and hydrogen bond parameters astables and X-ray crystallographic data in CIF format. This materialis 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) PetrovicA.G.; PolavarapuP. L. J. Phys.Chem.B 2005, 109, 23698-23705; 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. NucleicAcids Res. 2001, 29, 2860–2874.

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

distances crystal data DFT

Type I d(N7 3 3 3HN6) 2.062 2.010d(N6H 3 3 3N7) 2.062 2.012d(N6-H) 0.860 1.029d(CdO2) 1.205 1.212d(C-O1) 1.330 1.341

Type II d(N6H 3 3 3O2) 1.952 1.805d(N7 3 3 3HO1) 1.745 1.737d(O1-H) 0.968 1.008d(CdO2) 1.218 1.235d(C-O1) 1.318 1.315

Type III d(O1H 3 3 3O2) 1.675d(O2 3 3 3HO1) 1.678d(O1-H) 1.003d(CdO2) 1.232d(C-O1) 1.317

aThe crystal data for type I and type II has been taken for adduct 2aand 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

bond angles crystal data DFT

Type I C8-N7 3 3 3H 110.06 118.7H 3 3 3N7-C8 110.06 118.5N6-H 3 3 3N7 163.49 163.2N7 3 3 3H-N6 163.49 163.4H-N6-H 119.93 116.8

Type II C8-N7 3 3 3H 122.41 120.8N6-H 3 3 3O2 163.22 170.8O1-H 3 3 3N7 171.22 171.5CdO2 3 3 3H 127.33 130.6C-O1-H 110.76 112.5

Type III O1-H 3 3 3O2 178.9O2 3 3 3H-O1 178.6O2dC-O1 124.6C-O1-H 110.9

bThe crystal data for type I and type II has been taken for adduct 2aand adduct 4 respectively.

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)

Type I Type II Type III

E -1469.833311 -1469.865933 -1469.871883ΔE 28.9 14.4 4.2ΔEC 27.9 13.5 3.0relative energies 0.0 -20.1 23.9dipole moment 4.7 12.8 0.0

Article Crystal Growth & Design, Vol. 10, No. 8, 2010 3561

(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,

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.; SanzMiguel, 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.