Electric and magnetic properties of TiCo and related compositions

Abstract

In the present work, the interaction between HSA with three potential anti-trypanosomal drugs – (E)-2-benzylidene-hydrazine-carbothioamide (UTS); (E)-2-(3,4-difluoro-benzylidene)-hydrazine-carbothioamide (DFTS) and (E)-2-(2,3,4-trifluoro-benzylidene)-hydrazine-carbothioamide (TFTS) – was studied under physiological conditions by spectroscopic techniques (UV–vis, circular dichroism, steady state, time resolved and synchronous fluorescence) at 296 K, 303 K and 310 K, and theoretical calculations (molecular docking). The bimolecular quenching constant values (kq) were higher than 5.00 × 109 M−1 s−1, suggesting a ground state association between albumin and the ligands (static quenching mechanism). Time-resolved fluorescence measurements confirmed the static quenching mechanism, despite the high probability of Förster resonance energy transfer (FRET) (r ≈ 4.00 nm for TFTS and r ≈ 3.00 nm for UTS and DFTS). Modified Stern–Volmer binding constant values (Ka = 104 M−1), CD results and synchronous fluorescence (Δλ = 15 and 60 nm) indicated moderate association between HSA:UTS, HSA:DFTS and HSA:TFTS, with weak perturbation on the secondary structure of albumin, without perturbation on the microenvironment of the Trp and Tyr residues. The calculated thermodynamic parameters (ΔH°, ΔS° and ΔG°) are in agreement with a spontaneous binding process, both entropically and enthalpically driven with hydrogen bonding and hydrophobic interactions as the main binding forces. Competitive binding experiments indicated site I as the main binding site of the protein for all studied compounds and molecular docking results suggested the same intermolecular interactions indicated by the thermodynamic parameters.