# Applying a Tripodal Hexaurea Receptor for Binding to an Antitumor Drug, Combretastatin-A4 Phosphate

## TL;DR

Researchers developed a new molecule that can bind to a phosphate-based anticancer drug, improving its potential for drug delivery.

## Contribution

A tripodal hexaurea receptor with high binding affinity for CA4P was developed for potential drug delivery applications.

## Key findings

- The tripodal hexaurea receptor (L1) binds CA4P with a binding constant exceeding 10⁴ M⁻¹ in DMSO/water.
- L1 shows superior binding selectivity for CA4P over other anions and exhibits low cytotoxicity.
- The receptor is a promising candidate for enhancing the delivery of phosphate-based drugs.

## Abstract

Phosphates play a crucial role in drug design, but their negative charge and high polarity make the transmembrane transport of phosphate species challenging. This leads to poor bioavailability of phosphate drugs. Combretastatin-A4 phosphate (CA4P) is such an anticancer monoester phosphate compound, but its absorption and clinical applicability are greatly limited. Therefore, developing carrier systems to effectively deliver phosphate drugs like CA4P is essential. Anion receptors have been found to facilitate the transmembrane transport of anions through hydrogen bonding. In this study, we developed a tripodal hexaurea anion receptor (L1) capable of binding anionic CA4P through hydrogen bonding, with a binding constant larger than 104 M−1 in a DMSO/water mixed solvent. L1 demonstrated superior binding ability compared to other common anions, and exhibited negligible cell cytotoxicity, making it a promising candidate for future use as a carrier for drug delivery.