Screening, Manufacturing, Photoluminescence, and Molecular Recognition of Co-Crystals: Cytosine with Dicarboxylic Acids

A workflow for screening and manufacturing co-crystals was used to produce 4:1 co-crystal of cytosine−oxalic acid dihydrate, 2:1 co-crystal of cytosine−malonic acid, and 2:1 co-crystal of cytosine−succinic acid with melting points of 270.2, 219.2, and 249.5 °C, and K_sp values of 8.21 × 10⁻¹² m⁵, 4.90 × 10⁻⁵ m³, and 3.11 × 10⁻⁶ m³ in water at 25 °C, respectively. 4:1 co-crystal of cytosine−oxalic acid dihydrate crystallized in the P2₁/c space group. Both 2:1 co-crystal of cytosine−malonic acid and 2:1 co-crystal of cytosine−succinic acid crystallized in the P1̅ space group. Co-crystals of cytosine with dicarboxylic acids all possessed a self-assembled cyclic pattern of R₂²(12) forming by a pair of N−H···O hydrogen bonds within a dimeric motif of cytosine. The self-recognition pairing of cytosine here resembled the standard hydrogen bonding pattern in the Watson−Crick complementary base pairing of guanine and cytosine but without the middle N−H···N interaction. Both photoluminescence (PL) emission intensity and the solubility of co-crystals at a given temperature followed the same descending order of 2:1 co-crystal of cytosine−malonic acid > 2:1 co-crystal of cytosine−succinic acid > 4:1 co-crystal of cytosine−oxalic acid dihydrate. The weakening of the hydrogen bonding strength of 2:1 co-crystal of cytosine−malonic acid due to the angling of the interlayers might explain its lowest melting point of 219.2 °C, its highest solubility and its highest PL emission intensity.