# Zn–IMP 3D Coordination Polymers for Drug Delivery: Crystal Structure and Computational Studies

## TL;DR

This paper introduces two new 3D zinc-based coordination polymers for drug delivery, showing one is better at carrying and releasing hydroxyurea in a tumor-like environment.

## Contribution

The study introduces two novel Zn–IMP coordination polymers with distinct drug delivery properties based on structural and computational analysis.

## Key findings

- CP−1 exhibits stronger binding (ΔG = −10.87 kcal·mol−1) and higher stability for hydroxyurea compared to CP−2.
- CP−1 shows a more pronounced pH-responsive release profile, making it suitable for targeted drug delivery in acidic tumor environments.
- MD simulations reveal that CP−1 has a more compact and rigid cavity at physiological pH compared to CP−2.

## Abstract

Coordination polymers (CPs) are garnering attention in the field of medicine day by day. The goal is to develop a CP with biosafe and environment-friendly characteristics. Herein, we report two such novel 3D coordination polymers of zinc-inosine-5′-monophosphate (Zn-IMP) and bpe/azpy (as linkers) which were engineered as metal–organic frameworks that can be used as drug carriers for hydroxyurea (HU). We employed SCXRD, PXRD, solid-state CD, FTIR and TGA for crystal structure characterizations; the results achieved 3D coordination polymers which contain a P21 space group with chiral distorted tetrahedral geometry. Solution phase studies like UV–vis and CD were carried out to understand mechanistic pathways for interaction and chirality, respectively. We have also performed computational studies to evaluate the drug delivery capacity of both 3D CPs. Molecular docking and multi-pH molecular dynamics (MD) quantify that HU binds more strongly with CP−1 (ΔG =−10.87 ± 0.12) as compared to CP−2 (ΔG = −7.59 ± 0.26 kcal·mol−1), at normal and basic pH. MD simulation analysis indicated that a more compact and rigid cavity is observed by CP−1 as compared to CP−2 at physiological pH. Across acidic pH, for CP−1 the ligand RMSD increases markedly and U becomes slightly less negative, which indicated partial loss of contacts, thus releasing drugs in a tumor-like environment more easily. These result showed that CP−1 offers stronger binding, higher structural stability and a more pronounced pH-responsive release profile than CP−2, making CP-1 more promising candidate for targeted HU drug delivery, while CP−2 may serve as a weaker-binding, faster-release complement.