Computational Design and Pharmacokinetic Profiling of Novel Fe(II)-Peptide Complex
DOI:
https://doi.org/10.51574/hayyan.v3i1.5302Keywords:
Fe(II)-peptide, proline-arginine, metal coordination, pharmacokinetics, drug-like propertiesAbstract
Metal-peptide complexes represent a promising avenue in medicinal chemistry due to their unique coordination and biological properties. This study aimed to design and evaluate a Fe(II)-proline-arginine-dipeptide complex as a potential therapeutic agent. Computational modeling constructed the ligand and optimized the coordination geometry with Fe(II) and two chloride ligands, forming a stable distorted tetrahedral structure. 1H- and 13C-NMR spectra confirmed preservation of the dipeptide framework. Physicochemical assessment revealed a molecular weight of 396.056 g/mol, low LogP of 0.21947, balanced hydrogen-bond donors and acceptors, and a polar surface area of 139.047 Ų, supporting oral drug-likeness. ADMET analysis predicted moderate intestinal absorption (38.444%), low CNS penetration, minimal CYP enzyme interaction, and moderate clearance (1.11 log mL/min/kg). Toxicity prediction indicated no AMES mutagenicity, hepatotoxicity, or hERG inhibition, with an oral rat LD50 of 2.174 mol/kg. These results demonstrate that the Fe(II)-proline-arginine-dipeptide complex possesses structural stability, favorable pharmacokinetic behavior, and a broad safety profile, highlighting its potential as a therapeutic candidate. The study provides a framework for integrating peptide ligand design with metal coordination and in silico pharmacokinetic evaluation, suggesting avenues for experimental validation and future drug development.
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