The TACO Puzzle: A Phase-Transition Mystery Revisited

Abstract

The organic salt (5-methyl-1-thia-5-azacyclo-octane-1-oxide) perchlorate (TACO) is known to undergo a single-crystal-to-single-crystal phase transition in the 276–298 K T range without a change in the external shape of the sample. Despite extensive computational and experimental investigations, no safe conclusions about the transition mechanism could be drawn till now. The two packing patterns are very similar, and symmetry is conserved, apart from an interchange of cell axes from P21/c (α-TACO, low-T) to P21/a (β-TACO, high-T). Yet, the phase transition implies a significant conformational rearrangement, coupled with ∼180°-wide rotations, of 1/2 of the cations, in conjunction with reorientation of the anions. Here, we analyze the crystal packing of the two phases in terms of pairwise molecule–molecule interaction energies, as derived from the PIXEL approach. Rigid-body molecular reorientations are simulated by solid-state Monte Carlo calculations, while the likelihood of conformational rearrangements is estimated through gas-phase density functional theory M06/6-311G­(p,d) simulations. We demonstrate that rotational motion of the cations is not hampered by substantial energetic barriers, while the ring flip can be described as a two-step process with a main kinetic barrier of ∼45 kJ·mol–1, which might explain the metastable behavior of the β phase at low T. A possible mechanism of the phase transition is proposed, accounting for the present computational evidences in the context of the former experimental findings.

Dynamic simulation of liquid molecular nanoclusters: structure, stability and quantification of internal (pseudo)symmetries

“…A, B and C factors are calculated from basic properties like local charge, ionization potential and polarizability for each atom pair in each molecule. More detail can be found in the Literature [12][13][14][15][16] and in the documentation available on line. 17 This scheme has been optimized to reproduce the properties of a hundreds of organic compounds in the liquid or crystalline state and owes its success to exhaustive parameter fitting.…”

Molecular dynamics simulation of organic crystals: introducing the CLP-dyncry environment

“…To fill this gap, a new sequence of computer programs, the CLPdyncry suite, has been designed explicitly for application to the condensed states of small organic molecules, and has recently been applied with quantitative success to liquids and liquid droplets (Gavezzotti & Lo Presti, 2019). Along with standard MD algorithms, the suite includes an intermolecular force field called AA-CLP (atom-atom Coulomb-London-Pauli) (Gavezzotti, 2013(Gavezzotti, , 2011 that has been shown to be a versatile tool for the static or Monte Carlo simulation of organic crystals (Gavezzotti & Lo Presti, 2015Gavezzotti et al, , 2018Colombo et al, 2017;Lo Presti, 2014, 2018. Incidentally, its functional form cannot be adapted to any of the currently available environments, as the intermolecular part of its potential is generated for each different molecule from general atomic and molecular parameters (Gavezzotti, 2011).…”

Correlations of Crystal Structure and Solubility in Organic Salts: The Case of the Antiplasmodial Drug Piperaquine

“…The very low solubility of this compound can be thus ascribed to a very high lattice stability. This latter fact, as in chloroquine 6 and organic salts in general, 49,68 is due to more favorable electrostatic interactions. A survey of Mulliken charges on oxygen and hydrogen atoms in organic anions (Table S17 4).…”

“…Crystal cohesive energies, E coh , are defined as − The summation runs over the n molecules in the unit cell, whose total electronic energy is E bulk ; E iso, i is the energy of the i th molecule extracted from the crystal (keyword MOLECULE), frozen at its solid-state conformation. The negative Δ E rel, i term accounts for the relaxation energy: i.e., for the energy difference between a molecule fully relaxed in vacuo and the same molecule at its solid-state geometry.…”