可逆配体结合驱动的小分子化学趋向:微流控分析与统计热力学模型OA

Here,we systematically investigate and model the chemotactic behavior of zinc and iron porphyrin complexes under concentration gradients of small nitrogen-donor ligands in aqueous solution,including monodentate and bidentate derivatives of imidazole and pyridine.The results demonstrate that ligand binding can drive the directional migration of porphyrin receptors,while fluorescence correlation spectroscopy measurements show that the binding process does not significantly increase their intrinsic diffusion coefficients.In a three-inlet microfluidic channel,controlled ligand concentration gradients enable suppression of lateral spreading,spatial focusing or broadening,and directional displacement of the porphyrin molecules.Furthermore,fitting the chemotactic displacement as a function of ligand concentration enables determination of the equilibrium dissociation constant,KD,for the binding process.For a given ligand or porphyrin system,the displacement magnitude is closely related to the number of binding sites.Ligands containing two coordination sites can couple the motion of two porphyrin molecules,there by producing larger displacements.When the central metal is changed from zinc to iron,the same porphyrin macrocycle undergoes stepwise binding of two ligand molecules,and the KD values for the two binding steps can be separately extracted from the displacement isotherm.Based on these experimental observations,we develop a statistical thermodynamic model that links changes in binding free-energy to directional molecular migration.The model predictions are in good agreement with the experimental results.These findings demonstrate that the free-energy difference associated with reversible ligand-receptor interactions is an important driving force for molecular chemotaxis.