The synthesis and interaction of N,N',N'',N'''-tetramethyl-2,6,9,13-tetraaza[14]paracyclophanes (B323Me(4)) with nucleotides and inorganic phosphates is described. An easy methodology is used to define thermodynamic selectivity. The interaction of B323Me4 and ATP has been monitored by (1)H, (31)P NMR and by molecular mechanics, ruling out the possibility of the participation of pi-stacking interactions. Results show that N-methylation is accompanied by a strong increase in the interaction of the resulting macrocycle with ATP.