A one pot reaction involving sym 𝑁,𝑁'-diarylthiourea and the respective arylamine in the presence of aq. KOH in nitrobenzene at $≥ 105^\circ$C afforded sym 𝑁,𝑁',𝑁"-triarylguanidine in fair to good yield and the products have been characterized. Sym 𝑁,𝑁',𝑁"-tri(4-tolyl)guanidine possesses (7) anti-anti conformation, sym 𝑁,𝑁',𝑁"-tri(2-tolyl)guanidine (8) and sym 𝑁,𝑁',𝑁"-tris(2,4-xylyl)guanidine (11) each possess anti-anti $\alpha \beta \alpha$ conformation whereas sym 𝑁,𝑁',𝑁"-tris(2-anisyl)guanidine possesses (9) syn-anti $\alpha \beta \beta$ conformation as determined by single crystal X-ray diffraction data. The observed conformations appear to result from a subtle balance between steric factor associated with the aryl substituent and multiple electronic factors namely 𝑛-𝜋 conjugation/negative hyperconjugation and non-covalent interactions in the crystal lattice.

A new class of chiral phthalimides functionalized with aryl piperazines was designed anticipating their strong candidature for crystal engineering and technological applications. Five new phthalimides were synthesized, characterized and subjected to single crystal X-ray diffraction study that directed their noncentrosymmetric structures. Four phthalimides crystallized in 𝑃2₁ space group with monoclinic crystal system, however, one was found to possess 𝑃2₁2₁2₁ space group with orthorhombic system. The supramolecular architectures of phthalimide crystals were analysed by an approach based on consideration of energy of intermolecular interaction. The molecular hyperpolarizability (𝛽) calculation for all the listed phthalimides indicated their promising candidature for NLO materials. Further, the crystalline form of all phthalimides was evaluated for their second harmonic generation (SHG) response. A significant response of 16.4mV was measured for phthalimide possessing t-butyl substituent at the para position of 4-benzylpiperazine. This high SHG response may be attributed to the molecular chirality and helical supramolecular frameworks stabilized by C-H· · ·O hydrogen bonds in the solid state. The current study attests chiral phthalimides possessing arylpiperazines as effective nominees to the area of crystal engineering and nonlinear optics.

Understanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines aspotential apoptotic inducers. The listed twenty phthalimides were assessed for their in vitro apoptotic activity against testicular germ cells. All phthalimides showed a significant apoptotic response (∼39 to ∼68%). TUNEL assay and acridine orange fluorescence staining were carried out to investigate the molecular mechanismsresponsible for the cell death. Phthalimides exhibited substantial apoptotic induction following the intrinsic pathway mechanism. Studies advocated that the apoptotic induction was mediated through caspase-9, caspase-3, JNK MAP kinase and tumor suppressor p53, which was accompanied by DNA fragmentation and nuclearcondensation. Besides, the best five phthalimides regarding apoptotic action were evaluated for in vitro cytotoxic effects against CAL-72 and MCF-7 cancer cell lines. Compounds showed efficient killing of cancer cells. This discovery of functionalized phthalimides as apoptotic inducers would be highly valuable in understanding the mechanism of apoptosis at the molecular level and opens up new possibilities for therapeutic strategies.