We report combined experimental and theoretical studies on the complexation and liquid-liquid extraction of alkali and alkaline-earth cations by a series of calixarenes bearing various combinations of primary, secondary and tertiary amide substituents. Four mixed calixarene amides have been synthesized. Upon N-alkyl to N-H substitution on the amide binding sites, the binding strength of cations is reduced in methanol, and further, the extraction of cations from water into dichloromethane becomes highly inefficient. However, high complexation selectivities for Sr(2+) and Ca(2+) over Na(+) are achieved for a mixed primary/tertiary derivative. The structures of typical free and complexed ligands are elucidated by NMR analysis and by molecular dynamics simulations in methanol and chloroform solution. Simulations at the water/organic interface also reveal different behaviour of tertiary/secondary/primary amide complexes.