Synthesis, crystal structure and self-assembly of novel ninhydrin-derived isoquinoline compounds

Abstract

Isoquinoline skeletons are ubiquitous in natural products and pharmaceuticals with broad range of biological activity. In the present work, novel isoquinoline compounds are synthesized via the insertion of suitable nucleophile into the ninhydrin core. The reaction of ninhydrin with acetamide in refluxing AcOH afforded indanedione linked isoquinoline derivative 1. On the other hand, treatment of ninhydrin-4-methoxyphenol adduct 2 with ortho phenylenediamine in EtOH/AcOH led to the formation of isoquinoline fused benzimidazole scaffold 3. In DMSO‑d6 medium, compound 3 get oxidized to the corresponding isoquinolinone form 4. Single crystal X-ray diffraction study revealed that isoquinoline derivative 1 self-assembled to form zipper arrangement. Interestingly, fused isoquinoline scaffold 4 was found to display supramolecular helical arrangement in the crystalline state. The role of weak intermolecular interactions for development of supramolecular structure has been analysed and quatified using Hirshfeld surface analysis. The scanning electron microscopy (SEM) images of compound 1 show the formation of vesicular structure, whereas structurally analogous compounds 3 and 4 exhibit fibrilllar morphology.