Water Bridged Assembly and Dimer Formation in Co-Crystals of Caffeine or Theophylline with Polycarboxylic Acids

Caffeine (caf) forms co-crystals caf·dpa (1), caf·pzca (2) and 2caf·trimel (3) with dipicolinic acid (dpa), 3,5-pyrazole dicarboxylic acid (pzca), and trimellitic acid (trimel), respectively, whereas theophylline formed co-crystals theo·2dpa (4) and 2theo·2pzca (5) with the first two acids. These co-crystals are characterized by X-ray diffraction and conventional spectroscopic techniques. Co-crystal 1 forms a hydrogen-bonded assembly through one of the carboxylic acids with the imidazole moiety of caffeine, whereas the other carboxylic acid group is involved in strong hydrogen bonding with the crystallized water molecule. Thus, water-assisted assemblies are formed in which the water molecules are held by the nitrogen atom and also by the two carboxylic acid groups of dpa. In the case of co-crystal 2, pzca exhibits a hydrogen-bonded dimer through N−H···O and O−H···O interactions. A three component 2:1 co-crystal 3 of caffeine and trimellitic acid possesses acid-imidazole as well as O−H···OC interactions. Similar to 1, theophylline co-crystal with dpa, 4, also exhibits an aqua bridged assembly, whereas a 2:2 co-crystal with pzca, 5, resulted in a dimer through an R22(8) homosynthon in the presence of a heterosynthon.

咖啡因（Caffeine，caf）可分别与吡啶二羧酸（dipicolinic acid，dpa）、3,5-吡唑二甲酸（3,5-pyrazole dicarboxylic acid，pzca）以及偏苯三甲酸（trimellitic acid，trimel）形成共晶体caf·dpa（1）、caf·pzca（2）和2caf·trimel（3）；而茶碱（theophylline，theo）则可与前两种羧酸分别形成共晶体theo·2dpa（4）与2theo·2pzca（5）。上述所有共晶体均通过X射线衍射（X-ray diffraction）与常规光谱技术完成表征。共晶体1中，dpa的其中一个羧酸基团与咖啡因的咪唑基团形成氢键组装体，而另一个羧酸基团则与结晶水分子形成强氢键相互作用，由此构建出水辅助组装结构，其中水分子同时与dpa的氮原子以及两个羧酸基团相结合。对于共晶体2，pzca通过N−H···O与O−H···O相互作用形成氢键二聚体。咖啡因与偏苯三甲酸形成的三组分2:1共晶体3同时具备酸-咪唑以及O−H···O=C氢键相互作用。与共晶体1类似，茶碱与dpa形成的共晶体4同样呈现出水桥组装结构；而茶碱与pzca形成的2:2共晶体5则在异超分子合成子存在的条件下，通过R22(8)同超分子合成子形成二聚体。