MMH-2 as a new approach for the prediction of intermolecular interactions: the crystal packing of acetamide

Abstract

A new approach (MMH-2) was applied and tested for the prediction of intermolecular interactions in the crystal packing of acetamide. In MMH-2, energies of random molecular interaction configurations are computed. It uses molecular association quantities from statistical thermodynamics in order to obtain intermolecular interaction motifs that follow a ranking process. The most important motifs are optimized. Here, the AM1 semiempirical Hamiltonian was applied for the calculation and optimization of each obtained configuration and a comparison to MP2 results is provided. Such a stepwise procedure follows the assumed genesis of crystal growth without using experimental input. For evaluation purposes, graph set analysis was used to classify the structural patterns of both acetamide polymorphs. It was also necessary to introduce a new geometrical similarity index for the comparison of calculated and experimental motifs. As a result, all experimental hydrogen bond patterns were found and molecular synthons in both polymorphic acetamide structures were predicted as local minima. This suggests a new strategy for crystal structure prediction of flexible molecules with a possible subsequent progress in crystal engineering in silico.

Explaining the interactions between metaldehyde and acidic surface groups of activated carbon under different pH conditions

“…The MMH methodology usually hinges on semiempirical methods [20][21][22][23][24][25][36][37][38] (ΔEASSOC) from now [25]. A Boltzmann distribution is used to calculate the thermally averaged state of the typical macroscopic system at room temperature (298.15 K).…”

“…Although, the Gibbs's free energy of association (∆G ୟୱୱ୭ୡ ) is the thermodynamic criteria used to define the spontaneity of a process, the association energy (∆E ୟୱୱ୭ୡ ) was used in this study. This criterion has been profusely used in the past [20][21][22][23][24][25][36][37][38], since it is computationally simpler compared to ∆G ୟୱୱ୭ୡ , and it avoids having to calculate the association entropies. The ∆E ୟୱୱ୭ୡ is defined as…”

Evaluation of the molecular inclusion process of β-hexachlorocyclohexane in cyclodextrins

“…38 Although the Gibbs free energy of association (DG assoc ) is the thermodynamic criterion used to dene the spontaneity of a process, here, the association energy (DE assoc ) was preferred. This criterion has been widely used in the past [39][40][41][42] because it is simpler from a computational point of view; also, it avoids the necessity of calculating the association entropies. DE assoc is dened as:…”

“…A favorable thermodynamic association implies that the supermolecule will be more stable than the isolated molecules; namely, a greater absolute value of DE assoc corresponds to more energetically favorable associations. The MMH methodology usually works with semiempirical methods [39][40][41][42][43][44] for the evaluation of the energies while using statistical mechanics to obtain thermodynamic properties related to the molecular association. 38 The main procedure of this approach constructs several random non-redundant molecular geometries, starting from the independently optimized structures of the interacting molecules, in order to explore the conguration space of the formed complexes.…”

A theoretical study on structural, spectroscopic and energetic properties of acetamide clusters [CH3CONH2] (n = 1–15)

“…Codorniu-Herna´ndez et al have applied a MMH-2 method in order to understand crystal packing of acetamide. 25 Based on an approach which utilizes molecular association quantities from statistical thermodynamics to obtain intermolecular interaction motifs, followed by a ranking process, they were able to predict all structures found in a graph set analysis of the experimental patterns for various acetamide polymorphs. In this process AM1 is used as an underlying theoretical model to compare the results.…”