title: Control of size in losartan/copper(II) coordination complex hydrophobic precipitate.
abstract: 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).
authors.affiliation: Departamento de Farmácia, Universidade Federal de Juiz de Fora (UFJF), Campus Governador Valadares, Av. Dr. Raimundo Monteiro de Rezende, 330, Centro, 35010-177 Governador Valadares, MG, Brazil. angelomld@gmail.com
authors.forename: Ângelo M L
authors.initials: ÂM
authors.lastname: Denadai
authors.forename: Jeferson G
authors.initials: JG
authors.lastname: Da Silva
authors.forename: Pedro P G
authors.initials: PP
authors.lastname: Guimarães
authors.forename: Leonardo Bertolini S
authors.initials: LB
authors.lastname: Gomes
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Mangrich
authors.forename: Edivaltrys I P
authors.initials: EI
authors.lastname: de Rezende
authors.forename: Izabela M P
authors.initials: IM
authors.lastname: Daniel
authors.forename: Heloísa
authors.initials: H
authors.lastname: Beraldo
authors.forename: Rubén D
authors.initials: RD
authors.lastname: Sinisterra
mesh_terms: D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008027:Light; D019808:Losartan / Q000737:chemistry*; D017711:Nonlinear Dynamics; D010316:Particle Size; D012044:Regression Analysis; D012542:Scattering, Radiation; D012995:Solubility; D012996:Solutions; D055672:Static Electricity; D013816:Thermodynamics; D013818:Thermogravimetry; D017186:Titrimetry; D014867:Water / Q000737:chemistry
chemical_list: D056831:Coordination Complexes; D012996:Solutions; D014867:Water; D003300:Copper; D019808:Losartan
keywords: CRS; Control of size; Coordination complex; Copper; D(h); DLS; DSC; EPR; HP; Hydrophobic precipitate; ITC; KLos; Los; Los(−); Los/Cu(II); Losartan; R; Stepwise complexation; TGA; ZP; [KLos]/[Cu(OAc)(2)] molar ratio; bonded losartan; controlled release system; differential scanning calorimetry; dynamic light scattering; electron paramagnetic resonance spectroscopy; hydrodynamic diameter; hydrophobic precipitate; isothermal titration calorimetry; losartan anion; losartan potassium; losartan/copper coordination complex; molar partial enthalpy of titrant; thermodynamic parameter of reaction; thermogravimetric analysis; zeta potential; Δ(r)X°