Relevance and Assessment of Molecular Diffusion Coefficients in Liquid Chromatography

Molecular diffusion plays an important role in high-performance liquid chromatography, especially in fundamental column performance studies. An accurate knowledge of the molecular diffusion coefficients (D _m) of compounds selected for column evaluation is therefore crucial. In this review, a general overview is presented of the advantages and drawbacks of correlation-based and experimental methods that can be employed to determine molecular diffusion coefficients. The former include the Wilke–Chang, Scheibel, Reddy–Doraiswamy, Lusis–Ratcliff and Hayduk–Laudie equations, and other empirical correlations based on the Wilke–Chang equation. It is discussed how the association factor (ψ) that is required in several of these correlations can be obtained from the solubility parameter (δ). Frequently used experimental methods include the light scattering, nuclear magnetic resonance, peak parking and Taylor–Aris method, and methods employing microfluidic devices. The principles of these experimental methods are elucidated in detail. Moreover, the influence of several parameters, such as solute characteristics, solvent viscosity, temperature and pressure on the molecular diffusion coefficient is described.