pubs.acs.org/crystal Published on Web 06/08/2010 r 2010 American Chemical Society DOI: 10.1021/cg100470u 2010, Vol. 10 3555–3561 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 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 parti- cular 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 endo- genous 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-AH þ 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 single- stranded nucleic acid sequences. Crucial significance associ- ated with protonated forms of nucleobases has spawned theo- retical investigations where density functional computations were invoked to evaluate nucleobases for their proton affi- nities 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 pro- tonated 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 Watson- Crick side of the adenine base through hydrogen bonding. We have been exploring coordination and catalytic aspects of adenine for the purpose of creating metal-organic frame- works 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 incorporat- ing 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 possi- bility of competition between self-dimerization either through the 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 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 HNO 3 , 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 (1) [9-CA 3 H þ ] 2 [Cl - ] 2 [H 2 O] 2 : slow evaporation in the presence of 1 M hydrochloric acid. (2a) [9-CA 3 H þ ][NO 3 - ]: slow evaporation in the presence of dil. HNO 3 and one equivalent of metal salt. (2b) [9-CA 3 H þ ][NO 3 - ]: slow evaporation in the presence of dil. HNO 3 solution. (3) [9-CA 3 H þ ][CF 3 COO - ] [CF 3 COOH]: slow evaporation in the presence of dil. trifluoroacetic acid. (4) [9-CA 3 H þ ][ClO 4 - ][H 2 O] 2 : slow evaporation in the presence of dil. perchloric acid. 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 F 2 by a full-matrix least-squares technique using the SHELXL-97 program package. 13 Non-hydrogen atoms were refi- ned anisotropically. In the refinement, hydrogens were treated as *To whom correspondence should be addressed. E-mail: sverma@iitk.ac.in.