Competition between the two-point and three-point synthon in cytosine-carboxylic acid complexes

The analysis of Cambridge Structural Database (CSD) on cytosine-acid complexes indicated a strong competition between a two-point 2-aminopyridinium-carboxylate synthon and a three-point cytosinium-cytosine synthon. Statistics surprisingly showed a higher probability for the two-point synthon rather than the highly robust three-point synthon (66% vs. 33%). The exact reasons contributing to this unusual synthon preference are elucidated in the present study with the structural analyses of four cytosine complexes with aromatic carboxylic acids viz., 2,5-dihydroxybenzoic acid (1), 3,5-dinitrobenzoic acid (2), 4-hydroxyphenylacetic acid (3) and para-aminobenzoic acid (4) along with 44 cytosine-acid complexes extracted from the CSD. Structures 1 and 2 crystallized in a stoichiometric ratio of 1 : 1 and form a two-point 2-aminopyridinium-carboxylate synthon, whereas structures 3 and 4 crystallized in 2 : 1 ratio and exhibit the three-point cytosinium-cytosine synthon. The water molecules in structures 2, 3 and 4 play a vital role in forming the supramolecular hydrogen-bonded networks. From this study it is concluded that the choice of synthon in a particular crystal structure is highly dependent on the strength of the acid coformer used and on its stoichiometry with it.