Thermodynamic parameters (deltaG°, deltaH°, TdeltaS°), obtained by means of potentiometric and ITC methods, for the binding equilibria involving anions of high negative charge, like SO42-, SeO42-, S2O32- and Co(CN)63-, and nitroso-amino-pyrimidine receptors in water showed that anion-pi interactions furnish a stabilization of about -10 kJ/mol to the free energy of association. These anion-pi interactions are almost athermic and favoured by large entropic contributions which are likely due to the fact that the anion-pyrimidine aggregation reduces the hydrophobic pyrimidine surface exposed to water, thus minimizing its disruptive effect on the dynamic water structure. The crystal structure of the {H4L[Co(CN)6]}•2H2O complex showed strong anion-pi interactions between Co(CN)63- and the protonated H4L3+ receptor. The CN•••centroid distance (2.786(3) Å), occurring with a cyanide N atom located almost above the centroid of the pyrimidine ring, is the shortest distance till now reported for the interaction between CN- ions and heteroaromatic rings.