Design and synthesis of water-soluble alkynylplatinum(II) complexes with 2,6-BIS(benzimidazol-2'-yl)pyridine as tridentate N-donor ligand : from supramolecular self-assembly to biosensing applications

Abstract

A number of anionic and cationic water-soluble alkynylplatinum(II) complexes with 2,6-bis(benzimidazol-2'-yl)pyridine (bzimpy) as tridentate N-donor ligand have been designed and synthesized. Their spectroscopic, luminescence, and supramolecular self-assembly properties have been examined. More importantly, their spectral changes due to an alteration in Pt(II)···Pt(II) and pi-pi stacking interactions upon addition of biological substrates have offered a new strategy for the design of luminescence probes in biomedical applications. Water-soluble anionic alkynylplatinum(II) bzimpy complexes have been strategically designed and synthesized to show supramolecular self-assembly with cationic arginine-rich peptides through unique noncovalent Pt(II)···Pt(II) and pi-pi stacking interactions. In the presence of trypsin, the arginine-rich peptides could be hydrolyzed into small fragments and deaggregation of the platinum(II) complex molecules was observed. The aggregation-deaggregation process has been probed by UV-vis absorption, emission, and resonance light scattering (RLS) studies. These platinum(II) complexes have been employed for developing a new continuous and label-free luminescence assay for trypsin and inhibitor screening, and have been successfully applied to detect trypsin in diluted serum samples. In addition, a new approach towards acetylcholinesterase (AChE) detection has been demonstrated based on the electrostatic interactions between anionic complexes and cationic coordination polymer, as well as the spectroscopic and luminescence properties of the complexes upon supramolecular self-assembly. This process involved a strengthening of unique noncovalent Pt(II)···Pt(II) and pi-pi stacking interactions. This method has been applied to AChE inhibitor screening, which was important as the demand for AChE inhibitor assays arose along with the drug development for Alzheimer’s disease. A luminescence assay for hyaluronidase (HAase) detection has been developed based on the supramolecular self-assembly of water-soluble cationic alkynylplatinum(II) bzimpy complexes. Based on the electrostatic assembly of cationic complex molecules onto anionic hyaluronic acid (HA), the complexes exhibited aggregation processes through noncovalent Pt(II)···Pt(II) and pi-pi stacking interactions, which could be analyzed by UV-vis absorption, emission, and RLS studies. After the ensemble was exposed to HAase, HA was degraded, leading to deaggregation of the complexes. The potential applicability of this assay in real biological environment has been assessed. At the same time, cationic alkynylplatinum(II) bzimpy complexes have been employed in the luminescence assay for RNA and nucleolus imaging. These complexes showed a high affinity towards RNA through electrostatic interactions and hydrogen bonding. As a result of the formation of noncovalent Pt(II)···Pt(II) and pi-pi stacking interactions, the resultant luminescence enhancement allowed the staining of RNA-rich nucleolus in cells. The low-energy red emission could afford a satisfactory signal-to-background autofluorescence ratio. More importantly, when the cells were incubated with the complexes at a concentration used in the staining process for 24 hours, no appreciable cytotoxic response was observed. In addition, amyloid detection was key to understanding a number of neurodegenerative disorders. Herein, water-soluble platinum(II) bzimpy complexes have been adopted for the tracking of insulin amyloid fibrillation, which was found to be strongly luminescent only after binding to insulin amyloid fibrils. It was anticipated that the conformational changes of insulin could lead to the supramolecular self-assembly of the complexes via noncovalent Pt(II)···Pt(II) and pi-pi stacking interactions.