Experimental and Computational Investigations of Carboplatin Supramolecular Complexes

[Image: see text] Supramolecular systems (macromolecules), such as calix[n]arenes (SCn), cyclodextrins (CDs), and cucurbiturils (CBs), are promising vehicles for anticancer drugs. In this work, guest–host complexes of carboplatin, a second-generation platinum-based anticancer drug, and p-4-sulfocalix[n]arenes (n = 4 and 6; PS4 and PS6, respectively) were prepared and studied using (1)H NMR, UV, Job’s plot analysis, HPLC, and density-functional theory calculations. The experimental and the computational studies suggest the formation of 1:1 complexes between carboplatin and each of PS4 and PS6. The stability constants of the formed complexes were estimated to be 5.3 × 10(4) M(–1) and 9.8 × 10(4) M(–1), which correspond to free energy of complexation of −6.40 and −6.81 kcal mol(–1), in the case of PS4 and PS6, respectively. The interaction free energy depends on the different inclusion modes of carboplatin in the host cavities. UV–vis findings and atoms in molecules analysis showed that hydrogen bond interactions stabilize the host–guest complexes without the full inclusion in the host cavity. The in vitro anticancer study revealed that both complexes exhibited stronger anticancer activities against breast adenocarcinoma cells (MCF-7) and lung cancer cells (A-549) compared to free carboplatin, preluding to their potential use in cancer therapy.