Perspectives in Hydrophobic Interaction Temperature- Responsive Liquid Chromatography (TRLC)

Temperature-responsive liquid chromatography (TRLC) is an emerging green high performance liquid chromatography (HPLC) mode allowing reversed phase-type separations while necessitating only water as the mobile phase. The columns therein are typically packed with silica particles to which stimuli-responsive polymers are anchored. In hydrophobic interaction TRLC, such polymers depict a loss of water solubility when increasing the temperature above a characteristic conversion temperature, causing large changes in retention over quite narrow and mild temperature ranges (~5–55 °C). TRLC circumvents the concerns about analyte or column degradation that can occur when implementing high temperatures (>80 °C) on conventional reversed- phase columns. It allows for high performance liquid chromatography (HPLC) using only water often spiked with the additives typically used in reversed-phase LC. Therefore, this separation mode allows for greener, cheaper, and isocratic analyses under non-denaturing conditions. The absence of compositional solvent gradients also allows for the exploitation of temperature gradients in combination with refractive index detection. Purely aqueous hydrophobic interaction TRLC is mostly applicable for solutes depicting a 1 < LogP < 5, yet these ranges can be expanded through implementation of combined aqueous or organic mobiles phases, while preserving the temperature-responsive effects. In this first TRLC installment, our recent developments, new possibilities, and current limitations of the use of 1-D TRLC are discussed, while the column performance is described with respect to the fundamentals of HPLC.