Sublimation of Molecular Crystals: Prediction of Sublimation Functions on the Basis of HYBOT Physicochemical Descriptors and Structural Clusterization

Abstract

Quantitative structure−property relationship (QSPR) models on the basis of HYBOT physicochemical descriptors (molecular polarizability, the sum of all H-bond acceptor, and the sum of H-bond donor factors in a molecule) have been developed to predict sublimation enthalpies and Gibbs energies of molecular crystals. The experimental database analyzed includes 1766 values of sublimation enthalpies and 965 values of Gibbs energies. Fragmentation of the training sets for structurally similar groups/clusters both for enthalpies and Gibbs energies has been carried out using Tanimoto similarity coefficients T c with the restriction of 0.5 ≤ T c ≤ 1. According to this approach, any thermodynamic function, Y (i) (where Y = ΔG sub 298, ΔH sub 298, ΔS sub 298), has been calculated on the basis of experimental values of the same function of structurally closely related compounds (nearest neighbors, nn), Y (nn), and the difference in their relevant physicochemical descriptors, ΔY: Y (i) = Y (nn) + ΔY. The value of unknown thermodynamic function has been calculated as a mean value from the values obtained for each of the elements in a cluster.

Two-component molecular crystals: evaluation of the formation thermodynamics based on melting points and sublimation data

“…The literature data show that in structurally similar compounds (according to Tanimoto similarity coefficients), there is a linear correlation between ΔG 298 sub and T fus . 39 The crystal structure of a two-component co-crystal (with any stoichiometry) can be considered structurally similar to that of the individual compounds. In other words, the experimental values of ΔG 298 sub vs. T fus of the individual compounds and the cocrystal belong to one (and the same) cluster.…”

“…Some ideas of the presented approach are described in the work by Perlovich and Raevsky. 39 3.2.3. Two-component crystals with unknown melting points.…”

Polymorphism of monotropic forms: relationships between thermochemical and structural characteristics

“…It is well known that the solubility ratio of polymorphic forms is related to the ratio of their Gibbs energies of sublimation. On the other hand, we have previously shown that there is a correlation between the sublimation Gibbs energies and melting temperatures for structurally related compounds (Perlovich & Raevsky, 2010). Thus, the melting temperature can be interpreted as a measure of the Gibbs energy of a crystal form and its solubility.…”

Novel drug–drug cocrystals of carbamazepine with para-aminosalicylic acid: screening, crystal structures and comparative study of carbamazepine cocrystal formation thermodynamics

“…Nevertheless, we tried to estimate the standard thermodynamic functions of sublimation (Gibbs energy and enthalpy) using the following approach partially described by us in 2010. 46 We have formed a database including the sublimation Gibbs energy and enthalpy of molecular crystals published up to 2016 inclusive. Moreover, the database included the melting temperatures of individual compounds.…”

“…As a result, the database included 1515 molecular crystals. As we showed earlier, 46 if from the available database we select structurally related compounds based on Tanimoto similarity indices (T c ), the experimental values can be described by the correlation equation within the given group/cluster:…”