Dichloromethane replacement: towards greener chromatography via Kirkwood-Buff integrals

Area of Science:

• Green Chemistry
• Analytical Chemistry
• Physical Chemistry

Background:

• Dichloromethane (DCM) is a widely used solvent in pharmaceutical development due to its favorable properties.
• However, its hazardous nature necessitates the search for safer, sustainable alternatives in line with green chemistry principles.

Purpose of the Study:

• To identify and validate bio-derived esters as direct replacements for DCM in thin-layer chromatography (TLC).
• To develop a statistical thermodynamic framework for elucidating intermolecular interactions influencing TLC retardation factors (Rf).

Main Methods:

• Experimental identification of bio-derived esters (tert-butyl acetate, sec-butyl acetate, ethyl isobutyrate, methyl pivalate) as DCM alternatives in TLC.
• Application of a statistical thermodynamic framework to quantify molecular interactions and Rf dependence on eluent concentration.
• Utilizing Kirkwood-Buff integrals (KBIs) to analyze analyte-eluent and analyte-solvent interactions.

Main Results:

• Bio-derived esters were experimentally confirmed as suitable replacements for DCM in TLC for analyzing common drug molecules.
• The statistical thermodynamic framework successfully correlated intermolecular interactions with observed Rf values.
• KBI terms at the dilute eluent limit provided theoretical validation for the green solvent replacements.

Conclusions:

• Safe and sustainable bio-derived esters can effectively replace DCM in TLC for pharmaceutical analysis.
• The presented thermodynamic framework offers a theoretical basis for understanding and predicting solvent behavior in chromatography.
• This work supports the advancement of green chemistry in pharmaceutical development.