Selective Fe3+ sensing probes with transport-Mimetic behaviour: DFT studies and molecular docking insights into transferrin receptor interactions

Abstract

In this study, we present the design, synthesis, and characterization of two coumarin-based fluorescent chemosensors, C1 (4-((4-((Benzo[d]oxazol-2-ylthio)methyl)1H-1,2,3-triazol-1-yl)methyl)-7-methoxy-2H-chromen-2-one) and C2 (4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-6-(tert-butyl)-2H-chromen-2-one), synthesized via click chemistry. The absorptive and emissive properties of probes were investigated with various metal ions, revealing an excellent luminescent sensing response to key micronutrients, specifically Fe³⁺ ions. Thermodynamic fluorescence studies demonstrated that the quenching of the probes by Fe³⁺ is dynamic, involving photo-induced electron transfer (PET) that reduces fluorescence intensity. The detection limit for Fe³⁺ was determined to be 1.88 μM for C1 and 2.06 μM for C2, indicating high sensitivity. Binding sites and interactions between the probes and metal ions were elucidated through density functional theory (DFT) calculations, supported by Fourier transmission infrared (FT-IR) and mass spectrometry. Additionally, molecular docking studies were performed with the human transferrin receptor, demonstrating strong binding affinities of −10.2 kcal/mol for C1 and -9.6 kcal/mol for C2 with key amino acid residues, suggesting their potential role as Fe³⁺ transporters, which may be useful in managing transferrin imbalances and related disorders. These findings highlight the potential of C1 and C2 as effective sensors for Fe³⁺ ions, with promising applications in biomedicine and molecular diagnostics.