Exploring the role of neutral/ionized TPI hydrogen bonds and OPI halogen bonds for multifacial recognition in 5-halouracils/aminoazine cocrystals

Ten new heterodimers were synthesized in different stoichiometry to explore the role exerted by potential proton-transfer reactions in the supramolecular structures of A-B cocrystals formed by 5-haloderivatives of uracil (halogen = F, Cl, Br, I; coformer A) coupled with aminoazines as 2-aminoadenine simulants (melamine, 2,4,6-triaminopyrimidine, 2,6-diaminopyridine; coformer B) for pyrimidine nucleobase recognition. The crystallographic analysis showed that in all binary cocrystals the expected three-point hydrogen bonds (TPI), charged or uncharged depending on the acid/base properties of the components, were used for WC interfacial recognition. Moreover, the general ability of pyrimidine nucleobases to provide electron donating groups to halogen bonding has been confirmed in six of eight cocrystals containing the 5-bromo or 5-Iododerivatives coupled with 2,4,6-triaminopyrimidine or 2,6-diaminopyridine. “Lateral” one-point halogen bonds cooperate with hydrogen bonds in directing the overall crystal structures. Considerations of the relative acidities of coformers A and of the relative basicities of coformers B allowed us to design and characterize by single-crystal X-ray diffraction the first ternary pyrimidine nucleobase-containing cocrystal based on the JANUS-WEDGE concept [1]: the (1:1:1) triad showing a 2,4,6-triaminopyrimidine molecule wedged via neutral and ionized TPI between the 5-fluorouracil/1-methyluracil pair in reverse WC fashion (Fig. 1).