New 8-hydroxy quinoline-polycyclic aromatic hydrocarbon (PAH) conjugates and their sulfonated derivatives: effects of sulfonation and PAH size on their structural, supramolecular and cytotoxic properties

Abstract

Inter-molecular π–π stacking interactions of aromatic systems play crucial roles in functional nanomaterials and therapeutics. Herein, we developed a series of novel 8-hydroxyquinoline-polycyclic aromatic hydrocarbon (PAH) conjugates (PH1–PH3) by coupling 8-hydroxyquinoline with a series of PAHs such as naphthalene, anthracene, and pyrene. A second series of quinoline-PAH derivatives (PD1–PD3) has also been developed by sulfonating the quinoline –OH of the first series. Crystallographic analyses of these compounds revealed exciting structural and supramolecular features. Supramolecular analyses of PH series compounds revealed that the crystal packing interactions in these compounds are dominated by intermolecular C–H⋯O and C–H⋯π interactions, in which the C–H⋯O interactions lead to the formation of zig-zag 1D chains in the crystal lattice, which are interconnected to a 3D network by various intermolecular C–H⋯π interactions. Compared to the PH series, the supramolecular interactions in the PD series are dominated by π–π and C–H⋯π interactions. In these compounds, two adjacent V-shaped molecules are arranged in a dimeric fashion such that one arm of the V-shaped molecule is packed within the cleft formed by the arms of the other. In the crystal lattice of PD series compounds, such dimers are interconnected through π–π interactions into 1D chains/2D sheets, which are further interconnected into 2D/3D networks through additional C–H⋯π/π–π stacking interactions. The preliminary cytotoxicity properties of PH and PD series compounds were evaluated using human hepatocellular carcinoma cells (HepG2 cells). It was observed that the presence/absence of –OH group on the quinoline ring and the size of the PAH ring play significant roles in determining the cytotoxicity of these compounds. The PH series compounds with an –OH substituent on the quinoline ring exhibited comparatively better cytotoxicity (IC₅₀ values in the range 8.03–11.72 μM) than the PD series compounds (IC₅₀ values in the range 9.48–38.16 μM) with sulfonated quinoline moiety. The compound bearing pyrene PAH and –OH substituent on the quinoline ring exhibited the best cytotoxicity (IC₅₀ = 8.03 μM) among all the compounds tested. The present study, therefore, shows that the quinoline-PAH conjugates can exhibit interesting structural and supramolecular properties along with appreciable cytotoxic effects. Further, these properties could be fine-tuned by changing the size of the PAH ring and the substituent on the quinoline ring.