Coordination Polymer Carrying Antimicrobial Peptide for Enhanced Anti-Infective Therapy

Antimicrobial peptides (AMPs) offer a promising avenue for combating drug-resistant bacterial infections, but their clinical utility is often limited by poor bioavailability and stability. This study presents the design and synthesis of a novel, enantiomerically pure 2D-coordination polymer, {[Cu(dUMP)(dpp)₂]·3(H₂O)·(NO₃)]}_n (CP-1), derived from Cu(II) ions, deoxy-uridine monophosphate, and 1,3-di(4-pyridyl)propane (dpp), as a potential delivery system for AMPs. Single-crystal X-ray diffraction reveals a 2D double helical structure with square pyramidal Cu(II) coordination. Spectroscopic characterization (IR, UV–vis, thermogravimetric analysis, X-ray diffraction, circular dichroism) confirms the successful synthesis and reveals chirality transfer to the achiral dpp ligand. Molecular docking studies identify DGL 13K as the AMP exhibiting the strongest binding affinity to CP-1 (ΔG = −13.03 kcal mol⁻¹). Critically, molecular dynamics simulations provide detailed insights into the mechanism of action of the CP-1–DGL 13K complex against a Gram-negative bacterial membrane. The simulations demonstrate that DGL 13K, stabilized by CP-1, undergoes conformational changes, penetrating the membrane and disrupting its integrity through pore formation. These findings highlight the potential of CP-1 as an effective carrier for AMPs, enhancing their stability and facilitating membrane disruption, offering a promising strategy for developing novel antimicrobial therapies to combat drug resistance.