title: Thermodynamic characterization of three polymorphic forms of piracetam.
abstract: Combustion calorimetry, solution calorimetry, and differential scanning calorimetry (DSC) were used to determine the standard (p° = 0.1 MPa) molar enthalpies of formation of Forms I, II, and III piracetam at 298.15 K, namely, Δ(f) H(m)° (C(6)H(10)O(2)N(2), cr I) = -520.6 ± 1.6 kJ·mol(-1), Δ(f) H(m)° (C(6)H(10)O(2)N(2), cr II) = -523.8 ± 1.6 kJ·mol(-1), and Δ(f) H(m)° (C(6)H(10)O(2)N(2), cr III) = -524.1 ± 1.6 kJ·mol(-1). The enthalpy of formation of gaseous piracetam at 298.15 K was also derived as Δ(f) H(m)° (C(6)H(10)O(2)N(2), g) = -401.3 ± 2.1 kJ·mol(-1), by combining the standard molar enthalpy of formation of Form II piracetam with the corresponding enthalpy of sublimation, Δ(sub) H(m)° (C(6) H(10) O(2) N(2), cr II) = 122.5 ± 1.4 kJ·mol(-1), obtained by drop-sublimation Calvet microcalorimetry and the Knudsen effusion method. The Δ(f) H(m)° (C(6)H(10)O(2)N(2), g) value was used to assess the corresponding predictions by the B3LYP/cc-pVTZ (-335.3 kJ·mol(-1)), G3MP2 (-388.7 kJ·mol(-1)), and CBS-QB3 (-402.8 kJ·mol(-1)) methods, based on the calculation of the atomization enthalpy of piracetam. Finally, the results of the solution and DSC experiments indicate that the stability hierarchy of Forms I, II, and III piracetam at 298.15 K, for which there was conflicting evidence in the literature, is III > II > I.
authors.affiliation: Centro de Química Estrutural, Complexo Interdisciplinar, Instituto Superior Técnico, Lisboa, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Picciochi
authors.forename: Hermínio P
authors.initials: HP
authors.lastname: Diogo
authors.forename: Manuel E Minas
authors.initials: ME
authors.lastname: da Piedade
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D008958:Models, Molecular; D018697:Nootropic Agents / Q000737:chemistry*; D010889:Piracetam / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D018697:Nootropic Agents; D010889:Piracetam