Combined theoretical and experimental investigation of a DNA interactive poly-hydroxyl enamine tautomer exhibiting “turn on” sensing for Zn2+ in pseudo-aqueous medium

Abstract

Crystallographically established (solid state structure at 150 K temperature) enamine ligand 2-((1,3-dihydroxy-2-(hydroxymethyl)propan-2-ylamino)methyl)-4-bromo-6-methoxyphenol (H₄L) was prepared, which showed interconvertible equilibrium (ΔE = 7.37 kcal) of its tautomers and also found to exhibit DNA binding activity at the minor groove of double-stranded (ds) DNA. Spectroscopic and calorimetric methods were employed to explore the interaction of H₄L with DNA. Further, the competitive Hoechst 33258 displacement assay indicated the specific binding site of H₄L to be at the minor grooves of DNA. Thermodynamic evaluation from isothermal titration calorimetry (ITC) experiments suggested the association of H₄L with DNA to be an enthalpy driven process with an equilibrium binding affinity (K) of (2.50 ± 0.11) × 10⁴ M⁻¹. Molecular docking studies were found to be in good agreement with the experimental results of the DNA interaction of the probe in groove binding mode. The poor emission of H₄L in the excited state was due to excited state induced proton transfer (ESIPT), but in the presence of Zn²⁺, the ESIPT was blocked an chelation-enhanced fluorescence (CHEF) was initiated to exhibit ‘turn on’ fluorescence upon the coordination of Zn²⁺. The H₄L probe was found to detect Zn²⁺ selectively among various metal ions and the LOD was calculated to be ∼1.13 μM. The coordination of the Zn(II) bound complex and the relative stability of the tautomers of H₄L were investigated in detail via spectroscopic and computational studies.