A study on the physicochemical properties and cytotoxic activity of p-sulfocalix[4]arene-nedaplatin complex

Abstract

Macromolecules including macrocyclic species have been reported to have the potential to encapsulate biologically active compounds such as drugs through host-guest complexation to increase their solubility, stability and bioavailability. Here we investigate the complexation between nedaplatin, a second generation antineoplastic drug, and p-4-sulfocalix[4]arene, a macromolecule possessing a bipolar amphiphilic structure with good biocompatibility and relatively low haemolytic toxicity for potential use as a drug delivery system. Data from 1H NMR, UV-Vis spectroscopy, Job’s plot analysis, HPLC, DSC and DFT calculations are detailed and suggest the formation of a 1:1 complex. The stability constant of the complex was experimentally estimated to be 3.6 × 104 M−1 and 2.1 × 104 M−1 which correspond to values of −6.2 and −5.9 kcal mol−1, respectively for the free energy of complexation while the interaction free energy is calculated to be −4.9 kcal mol−1. The formed species is shown to be stabilised in solution through hydrogen bonding between the host and the guest. The complex displayed enhanced antitumor activity against MDA-MB-231 cells compared to nedaplatin which may allow for its application in cancer therapy.