a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

b. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark

In the recently published paper Symmetry and chirality in crystals [Nespolo, M.; Benahsene, A. H. (2021). J. Appl. Cryst. 54, 1594-1599.], the authors state that `chiral crystal structures from achiral molecules can occur in 28 types of space group having screw axes n(p), with p =/= n/2, not in any Sohncke type of space group'. We argue that this is not true and demonstrate counter-examples of chiral structures from achiral molecules crystallizing in other Sohncke space groups apart from the proposed list of 28.

a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

b. Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

c. Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University, Maria Curie-Skłodowska Square 2, 20-031 Lublin, Poland

d. Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, 90-363 Lodz, Poland

e. ICGM, Univ Montpellier, CNRS, ENSCM, Montpellier 34296, France

We present a crystallographic and computational study of three hydantoin-based active pharmaceutical ingredients─nitrofurantoin, furazidin, and dantrolene─aimed at identifying factors resulting in different propensities of these compounds to form polymorphs, hydrates, solvates, and solvate-hydrates. This study is a continuation of our research toward understanding how small structural differences in closely related compounds affect their propensity to form different crystal phases, as all three compounds contain an imidazolidine-2,4-dione scaffold and a N-acyl hydrazone moiety and all form multiple crystalline phases. Crystallographic and computational analysis of the already known and newly obtained nitrofurantoin, furazidin, and dantrolene crystal structures was performed by dissecting the properties of individual molecules and searching for differences in the tendency to form hydrogen bonding patterns and characteristic packing features. The propensity to form solvates was found to correlate with the relative packing efficiency of neat polymorphs and solvates and the ability of molecules to pack efficiently in several different ways. Additionally, the differences in the propensity to form solvate-hydrates were attributed to the different stability of the hydrate phases.

a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

We present an experimental and computational study of solid solution formation between structurally highly similar active pharmaceutical ingredients droperidol and benperidol in nonsolvates, dihydrates, and several solvates formed by these compounds. We demonstrate that the formation of solid solutions strongly depends on the crystal structure of the phase. In some of the structures, almost complete replacement of benperidol with droperidol can be achieved, whereas in other structures, the replacement is possible only up to a limited molar ratio. However, only limited replacement of droperidol with benperidol can be achieved and only in some of the structures. The solid solution formation is primarily determined by the change in intermolecular interaction energy resulting from the molecule replacement. Only structures where molecule replacement allows the formation of efficient intermolecular interactions can be obtained experimentally. The results indicate that the energy requirements of intermolecular interaction changes to obtain solid solutions in the nonsolvated phase are less strict than those for solvates.

a. Department of Physical Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

b. Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

In this study, we present a detailed crystallographic analysis of multiple solvates of an antibacterial furazidin. Solvate formation of furazidin was investigated by crystallizing it from pure solvents and solvent–water mixtures. Crystal structure analysis of the obtained solvates and computational calculations were used to identify the main factors leading to the intermolecular interactions present in the solvate crystal structures and resulting in the formation of the observed solvates and solvate hydrates. Furazidin forms pure solvates and solvate hydrates with solvents having large hydrogen bond acceptor propensity and with a hydrogen bond donor and acceptor formic acid. In solvate hydrates, the incorporation of water allows the formation of additional hydrogen bonds and results in more efficient hydrogen bond networks in which water is “hooking” the organic solvent molecule, and this slightly reduces the cut-off of solvent hydrogen bond acceptor propensity required for obtaining a solvate. The crystal structures of all pure solvates are formed from molecule layers, and in almost all structures, the solvent is hydrogen-bonded to furazidin, but the packing in each solvate is unique. In contrast, the hydrogen bonding and packing in most solvate hydrates are nearly identical.