# Synthesis and Inclusion Properties of a β-Cyclodextrin Heptaphosphoramidate

## TL;DR

This paper introduces a new water-soluble β-cyclodextrin derivative that can form stable drug complexes, potentially useful for drug delivery.

## Contribution

A novel β-cyclodextrin with seven phosphoramidate groups is synthesized and shown to form 2:1 drug inclusion complexes.

## Key findings

- Host 4 forms 2:1 inclusion complexes with various drug molecules.
- The inclusion process is primarily enthalpy driven due to phosphoramidate functionalities.
- A per-O2, O3-acetylated analog (6) has reduced inclusion capability despite high water solubility.

## Abstract

In this study, we report a novel per-6-substituted β-cyclodextrin (4) featuring seven phosphoramidate moieties as an innovative host for inclusion. This structurally well-defined host has remarkable water solubility and was isolated in pure form. Analytical techniques such as NMR and ITC were used to probe the molecular interactions with different drug molecules. Our investigations revealed that host 4 can form 2:1 inclusion complexes with various drugs. Further studies showed that the inclusions of drugs by β-CD host (4) are mostly enthalpy driven, highlighting the potential roles played by the phosphoramidate functionalities of the host. Comparatively, a per-O2, O3-acetylated analog (6) of compound 4 was also obtained, which also shows unusual water solubility but diminished inclusion capability.