Experimental and theoretical investigation of novel ferrocene-based sulfisoxazole derivatives and their palladium(II) complex: Synthesis, spectroscopic characterization, DFT analysis, molecular docking, and in silico evaluation

Bilkan Ç., Alyar S., Bilkan M. T., Alyar H., ÖZDEMİR ÖZMEN Ü., ERDEM K.

Journal of Molecular Structure, cilt.1353, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1353
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.molstruc.2025.144849
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Density functional theory, FT-IR spectroscopy, In silico predictions, Molecular docking, Sulfonamide derivatives
  • Gazi Üniversitesi Adresli: Evet

Özet

In this study, two novel ferrocene-based sulfonamide ligands (S1 and S2) and their palladium(II) complexes were synthesized and thoroughly characterized using spectroscopic and computational methods. Density Functional Theory (DFT) calculations provided insights into the electronic structure and stability changes induced by metal coordination. Molecular docking analyses demonstrated enhanced binding affinities of the Pd(II) complexes towards key oncogenic targets, including topoisomerase IIα, EGFR, and VEGFR, compared to the free ligands and conventional chemotherapeutics such as doxorubicin and cisplatin. Pharmacokinetic properties predicted via in silico ADME modeling revealed improved blood–brain barrier permeability, intestinal absorption, and P-glycoprotein inhibition for the complexes, suggesting potential for increased bioavailability and overcoming multidrug resistance. Toxicity profiling indicated lower acute toxicity and reduced mutagenic and cardiotoxic risks relative to reference drugs. These findings highlight the promising multifunctional nature of ferrocene-Pd(II) hybrids as candidates for therapeutic development, integrating favorable electronic, biological, and pharmacokinetic attributes.