Control of size in losartan/copper(II) coordination complex hydrophobic precipitate

Reaction of highly soluble orally active, non-peptide antihypertensive drug losartan with copper(II) leads to the spontaneous formation of a very insoluble 2:1 covalent complex, which self assembles in a hydrophobic supramolecular structure of nanometric dimensions. Thermal analysis showed that Los/Cu(II) complex presents intermediate stability in comparison with its precursors KLos and Cu(OAc)2·H2O. Isothermal titration calorimetry indicated complexation to be a stepwise process, driven by enthalpy and entropy. Zeta potential and DLS measurements showed that it is possible to control the size and charge of nanoprecipitates by adjusting the relative concentration of Los− and Cu(II). [Display omitted] •Reaction of Cu(II) with losartan gives a Los/Cu(II) coordination complex.•Complexation is a stepwise process.•2:1 Los/Cu(II) stoichiometry is more favorable at high molar ratio.•Los/Cu(II) spontaneously aggregates into a hydrophobic nanoprecipitate.•The size and zeta potential could be controlled by the adjusting of Los/Cu(II) molar ratio.