Carboxylated Pillar[5]arene (CPA5), first reported by Ogoshi in 2010 [1], is highly symmetrical pillar-shaped compound, composed of hydroquinone units linked by methylene bridges at the para-positions, modified by ten carboxylic acid groups. Its rigid hydrophobic, electron-rich cavity combined with its water solubility make it great candidate as host molecule for various electron-deficient guest or other neutral molecules. Moreover, carboxyl groups, that can take part in proton transfer, are located at the terminal positions of flexible aliphatic chains, so they can adjust to the size and shape of guests.

In 2015 Danylyuk described crystal self-assemby of CPA5 in its complex with ethanol molecules [2]. Authors described the chains of CPA5 molecules connected via cyclic carboxylic-carboxylic hydrogen bonds (HBs) as main supramolecular motif. Introduction of tertacaine guest reorganized the formation of HBs. Inspired by this result, we decided to investigate how guest molecules, decorated with different functional groups, affect on the self-assembly of the host.

Here we want to present our results on the X-ray structures of CPA5 in the form of its host-guest complexes with viologens, guanidine and amidine compounds. Our study on the CPA5-viologens complexes shows that the main chain motif is dictated by very strong carboxylic-carboxylate HBs [3]. Altering the guest into an amidine or guanidine molecules changes main synthon into amidinium-carboxyl/ate and guanidinium-carboxyl/ate HBs. In a broader perspective our results may have potential applications in drug delivery and molecular recognition systems.

[1] Ogoshi, T., Hashizume, M., Yamagishi, T., Nakamoto, Y. (2010). ChemComm, 21, 3708.

[2] Danylyuk, O., Sashuk, V. (2015). CrystEngComm, 17, 719.

[3] Butkiewicz, H., Kosiorek, S., Sashuk, V., Danylyuk, O. (2021). CrystEngComm, 23, 1075.

Supramolecular arrangements in the crystal structures and the interaction energy calculations of resonance-assisted hydrogen-bridged (RAHB) rings - RAHB/RAHB and RAHB/C₆-aromatic contacts

J. P. Blagojević Filipović¹, S. D. Zarić²

¹Innovation Centre of the Faculty of Chemistry, Studentski trg 12-16, Belgrade, Serbia, ²Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia szaric@chem.bg.ac.rs

The Cambridge Structural Database (CSD) is searched for mutual contacts between six-membered resonance-assisted hydrogen-bridged rings (RAHB) (the example of a fragment is shown in Fig. 1a) [1] and for contacts between six-membered RAHB rings and C₆-aromatic rings (Fig. 1b). There is a quite large prevalence of parallel contacts in the set of RAHB/RAHB contacts, since 91% from totally 678 contacts found are parallel contacts, mostly with antiparallel orientation of the rings [1]. At the other side, the prevalence of parallel contacts in the set of RAHB/C₆-aromatic contacts is not so pronounced, since 59% from totally 677 contacts found are parallel contacts. The distances between the interacting ring planes are mostly between 3.0 and 4.0 Å, while horizontal displacements are mostly in the range 0.0-3.0 Å in both parallel RAHB/RAHB and RAHB/C₆-aromatic contacts.

Figure 1. The examples of fragments used in CSD search for a) six-membered RAHB/RAHB contacts; b) six-membered RAHB/C₆-aromatic contacts

The interaction energy calculations were performed on stacked dimer model systems based on abundance in the CSD. The strongest calculated RAHB/RAHB interaction is -4.7 kcal/mol, while the strongest calculated RAHB/benzene interaction is significantly weaker -3.7 kcal/mol. However, RAHB/RAHB stacking interactions can be stronger or weaker than the corresponding RAHB/benzene stacking interactions, depending on the RAHB ring system. The Symmetry Adopted Perturbation Theory (SAPT) calculations show that the dominant contribution in total RAHB/RAHB stacking interaction energy is the dispersion term, which can be mostly or completely cancelled by the exchange repulsion term, hence, the electrostatic term can be effectively dominant. Depending on the RAHB ring system, the electrostatic contribution can be practically equal to the net dispersion contribution (the sum of dispersion and exchange-repulsion terms) [1]. The electrostatic term is effectively dominant in all RAHB/benzene systems observed, due to the almost complete cancellation of the dispersion by the exchange-repulsion terms.

[1] Blagojević Filipović, J. P., Hall, M. B. & Zarić, S. D. (2019).Cryst. Growth Des. 19, 5619.

Keywords: stacking; RAHB; CSD

This work was supported by the Serbian Ministry of Education, Science and Technological Development (Grant number 172065).

Within the relevant field of metal-containing polymers and their applications in the biomedical context [1], a Silver(I) coordination polymer of formula [(bpy)Ag]OTf_∞ presenting polymorphism has been synthetized through reaction between the N^N ligand 2,2’-bipyridine (bpy) and Silver trifluoromethanesulfonate (AgOTf). By varying the stoichiometric ratios and the order of the addition of the reagents along the synthetic routine, two polymorphs have been synthesized and structurally characterized. The first polymorph of [(bpy)Ag]OTf_∞, the α-form, crystallized in the P3₁21 space group, is characterized by the alternance, along the polymeric chain, of Ag(I) ions with linear and tetrahedral geometry (Fig.1); this arrangement results in the generation of chiral helices [2]. In a second polymorph of [(bpy)Ag]OTf_∞, indicated as the β-form (P2₁/c space group), prepared by modifying the synthetic procedure adopted previously, all the Ag(I) ion adopts a slightly distorted linear geometry. The silver ions are coordinated to the nitrogen atoms of bridging bpy ligands, while the non-coordinated OTf anions are found weakly interacting with the metal centres (Fig.1). The β-polymorph presents a zig-zag conformation which, as already reported for 1D organic polymers [3], can generate pocket-like cavities able to accommodate organic molecules through non-covalent interactions, rising the role of inorganic-polymer co-former in the formation of biologically active co-crystals. Hence, the β-form of [(bpy)Ag]OTf_∞ was used for the preparation of an inorganic-polymer co-crystal by using curcumin (curc) as the organic bioactive molecule. The [(bpy)Ag]OTf_∞-curc co-crystal was obtained through a quick solution reaction and characterized through several techniques, including Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), ¹H-NMR, UV-visible and Infrared Spectroscopies. The instauration of weak intermolecular interactions between the keto-enolic function of curc and both the Ag(I) cationic chains and the triflate anions of the inorganic-polymer is the driving force for the formation of this multicomponent material. Considering the multiple biological functions of curc [4] and the well-known antimicrobial activity of silver compounds [5], the [(bpy)Ag]OTf_∞-curc co-crystal could represent a multi-functional supramolecular system. Moreover, embedding the [(bpy)Ag]OTf_∞-curc co-crystal into an ethylcellulose (EC) polymeric matrix, antimicrobial films with potential biomedical and food-packaging applications have been obtained and characterized.

[1] Yan, Y.; Zhang, Z.; Ren, L.; Chuanbing, T.; (2016) Chem. Soc. Rev., 45, 5232

[2] Bellusci, A.; Ghedini, M.; Giorgini, L.; Gozzo, F.; Szerb, E. I.; Crispini, A.; Pucci, D. (2009) Dalt. Trans. 36, 7381.

[3] Chappa, P.; Maruthapillai, A.; Voguri, R.; Dey, A.; Ghosal, S.; Basha, M. A. (2018) Cryst. Growth Des. 18, 7590.

[4] Gupta, N.; Verma, K.; Nalla, S.; Kulshreshtha, A.; Lall, R.; Prasad, S. (2020) Molecules, 25, 1. [5] Scarpelli F., Crispini A., Giorno E., Marchetti F., Pettinari R., Di Nicola C., De Santo M. P., Fuoco E., Berardi R., Alfano P., Caputo P., Policastro D., Oliviero Rossi C., Aiello I. (2020). ChemPlusChem 85, 426.

Crystal structures of diastereomeric salt pairs, as well as double salts are rare to find in the literature. Present work involves the crystallization and structural elucidation of two constitutional isomer double salts along with their related diastereomeric salt pairs. The investigated systems are 1-cyclohexylethylammonium 2-chloromandelate (S-S, R-S, SS-SR) and 1- cyclohexylethylammonium 4-chloromandelate (R-R, S-R, SS-SR). Alongside structural elucidation, the thermal properties of all diastereomers and double salts have been determined and compared. In the crystal of five of the six chiral salts, hydrogen bonded layers are formed with the participation of the ionic groups and the hydroxyl group of the mandelate anion. In one structure, the formation of one-dimensional hydrogen bonded columns is observed. Due to the different position of the chlorine substituent in the two compound families, the halogen interactions are oriented towards the inside of the hydrogen-bonded structures or positioned between the layers and establish a relatively strong connection between them. The two different halogen positions and every possible combination of configurations in the six investigated salts provide a quite detailed landscape of the effect of stereochemistry on the solid-state structure of the salts.

Knowledge on conformation and crystal structures (including crystal polymorphs and solvatomorphs) is important in the use and development of active pharmaceutical ingredients (API). Polymorphism plays a very important role in the bioavailability of a drug [1] as the physico-chemical properties (e.g. solubility, stability) of polymorphs can differ significantly [2]. Clopamide (4-chloro-N-2,6-dimethylpiperidin-1-yl)-3-sulfamoylbenzamide) drug is used worldwide in the treatment of hypertension and oedema and despite its medical application the crystal structure has not yet been investigated. It has also been shown that some diuretic may also cause urinary loss of certain trace elements or modify their levels in blood and may induce changes in the levels of copper in normal hypertensives [3]. According to the molecular structure it is noticeable that the carbonyl oxygen and the piperidine nitrogen of Clopamide are able to coordinate to metal centres, so the complexation of Clopamide with metal ions in the human body may be responsible for this side effect (Fig. 1). To gain a better insight into the structure and interaction of this drug molecule with metal ions, structural study of Clopamide compound and its coordination compounds with copper(II) have been studied under different crystallization conditions. The crystal structure of this drug and its copper(II) complexes were studied by screening different solvatomorph and polymorph crystals and the structures were determined by single-crystal X-ray diffraction. Our challenge was to detect the conformations and possible arrangements of the complexes induced by coordination bond and by different secondary interactions. These investigations enrich the knowledge on the aspects which contribute to the development of materials with specific properties. The crystal structures of anhydrous, and hemihydrate form of Clopamide have been determined. We present how the inclusion of water contributes to the crystal perfection of the drug crystals. The newly defined chalcogen bonds are recognised in the Clopamide anhydrate crystals being in competition with intramolecular halogen bonds. The bis-ligand copper(II) complex crystals were synthesized from the homolouges series of alcohols, with the inclusion of solvent molecules, resulting four isostructural [4] crystals with increasing size of void and unit cell volumes in the order of MeOH, EtOH, PrOH and iPrOH. From organic solvents, three solvent free polymorphs and a crystal containing dichloromethane was prepared. All Cu(II) compounds are of square-planar geometry, in which copper(II) centres are coordinated by piperidine-N and carbonyl-O donor atoms in a five-membered chelate ring with the two ligands in trans positions. The 2,6-dimethylpiperidine units of the molecule is perpendicular to the plane of the coordination sphere, preventing axial coordination of solvate molecules. The solution structure of the copper(II) complex have been investigated in DMSO by EPR spectroscopy.

Previously it was revealed very frequent occurrence of the specific ferrocene-ferrocene dimers in the ferrocene containing crystal structures [1]. Thus, the analysis of the Cambridge Structural Databank (CSD) showed that nearly 60% of monosubstituted ferrocene derivatives form robust ferrocene dimers composed of two Fc units in parallel orientation (see Figure below). Formation of the dimer is based on an excellent electrostatic complementarity between the Fc units (Figure below). A subsequent theoretical study [2] revealed the significant stabilization energy of −5.7 kcal/mol for this specific interaction with dispersion as the most important attractive contribution. In the present work, we have used the CSD to explore the same interaction between metallocene units but this time analyzed in all metallocene based crystal structures. We have found that all metallocenes equally as ferrocene derivatives are able to form the dimers with very similar geometrical parameters. In addition, we have investigated the supramolecular aggregation of the dimers into chains of different geometry.

[1] Bogdanović, G. A. & Novaković, S. B. (2011). CrystEngComm 13, 6930-6932.

[2] Vargas-Caamal, A. et al. (2016). Phys. Chem. Chem. Phys. 18, 550-556.

The identification of differences and similarities in non-covalent interactions of molecules in closely related solids (polymorphs, solvates, homologues, isostructural series, and others) is crucial for crystal engineering. However, crystalline environment also affects molecular reactivity within a "reaction cavity" or conformations of flexible molecules. Analysis of contributions of various types of non-covalent interactions to the molecular surface allows their comparison in different solid forms both in terms of molecular functional groups, and in the context of crystal field effect. The advantages of this approach include rapid calculations, consideration of 3D screening effect, and investigation of strong and week, hydrophobic and hydrophilic, rare and abundant interactions from unified positions. Particularly, the molecular Voronoi surfaces give qualitative, quantitative and visual representation of all types of intra- and intermolecular non-covalent interactions in crystals of inorganic, organic and macromolecular compounds (Fig. 1).

We applied the molecular Voronoi surfaces for analysis of non-covalent interactions in a number of bulky organic and organoelement molecular compounds. An approach to analyze conformation polymorphs was demonstrated on the example of photochromic N-salicylideneanilines, and (2',4'-dinitrobenzyl)pyridine derivatives. Interplay of hydrogen and halogen bonds was studied for polymorphs of alkylboron-capped iron(II) and cobalt(II) hexachloroclathrochelates, and for a series of polybromide salts. The effect of crystalline environment on molecular conformations of a flexible imatinib molecule, and on a photoinitiated solid-state reaction of eicosaborate isomerization were studied. Non-covalent interactions of imatinib, abirateron and bicalutamide in their polymorphs, solvates, salts and ligand-receptor complexes were compared. The molecular Voronoi surfaces were proved to be suitable for understanding of the interplay between intermolecular strong and weak interactions, effect of a particular contact on molecular and material properties, and were found to be applicable to a large number of objects.

Cocrystallization is becoming a more and more popular method to obtain new forms of drugs in the pharmaceutical industry. In this way, their physicochemical properties, like solubility, bioavailability, permeability through biological membranes, stability can be modified without affecting their pharmacological properties [1]. Cocrystals are homogeneous solids consisting of components in a neutral or ionic form, which are solids under ambient conditions, in a specific stoichiometric ratio. Such combinations of APIs (active pharmaceutical ingredients) with appropriately selected coformers are defined as pharmaceutical cocrystals [2].

The main goal of the study was to use purine alkaloids, such as theobromine, theophylline, and caffeine for cocrystallization with trimesic (TMSA) and hemimellitic acid (HMLA) [3]. Theobromine forms cocrystals TBR·TMSA and TBR·HMLA. Caffeine forms the cocrystal CAF·TMSA and the cocrystal hydrate CAF·HMLA·H₂O. Theophylline forms TPH·TMSA and TPH·HMLA cocrystals, the cocrystal hydrate TPH·TMSA·2H₂O and the salt hydrate (TPH)⁺·(HMLA)^-·2H₂O. The reactions were carried out in solution and by neat or liquid-assisted grinding in a ball mill. Powder analysis showed that 7 out of 8 solids were obtained by mechanochemical synthesis. All obtained multicomponent complexes were structurally characterized by the single-crystal X-ray diffraction method. The use of compounds with slight structural differences allowed the investigation of the complexity of specific non-covalent interactions formation. Selected coformers can form strong hydrogen bonds with the carboxyl groups participation, therefore 3 types of supramolecular synthons have been distinguished: alkaloid-alkaloid, alkaloid-acid and acid-acid synthons.

X-ray structural analysis showed the dominant role of alkaloid-acid and acid-acid interactions. These studies also show that it is sometimes possible to predict what non-covalent interactions will be responsible for the arrangement of molecules in the crystal lattice of the synthesized complex. However, the study of the self-assembly processes of molecules in systems with many functional groups is well-founded as the complexity of supramolecular synthons shows that the crystal structure design is often laborious.

Additionally, UV-Vis measurements determined the effect of the cocrystallization of purine alkaloids on their solubility in water.

[1] Kumar S., Nanda A. (2017), Pharmaceutical Cocrystals: An Overview, Indian J. Pharm. Sci., 79, 858-871.

[2] Duggirala N. K., Perry M. L., Almarsson Ö., Zaworotko M. J. (2016), Pharmaceutical cocrystals: along the path to improve medicines, Chem. Commun., 52, 640-655.

[3] Gołdyn M., Larowska D., Bartoszak-Adamska E. (2021), Novel Purine Alkaloid Cocrystals with Trimesic and Hemimellitic Acids as Coformers: Synthetic Approach and Supramolecular Analysis, Cryst. Growth Des., 21, 396-413.

Polymorphism is of significant interest owing to its potential to influence the physiochemical properties of pharmaceuticals and other materials. The high directionality and the intrinsic tunability of the intermolecular halogen bond make it a compelling design element in crystal engineering. In this work, we describe various polymorphs of halogen-bonded co-crystals constructed from 2,3,5,6-tetramethylpyrazine with different halogen bond donors (1,4-diiodotetrafluorobenzene, 1,3,5-trifluoro-2,4,6-triiodobenzene, and their bromo- and chloro-analogues). Polymorphic cocrystals are obtained from solution-based and solid-based methods. Solution-based methods are implemented by manipulating the solvent system mixture and the mixing temperature while solid-based cocrystals are obtained via co-sublimation and mechanochemical techniques. Co-crystal structures are characterized via single crystal X-ray diffraction and powder X-ray diffraction. 13C solid-state nuclear magnetic resonance spectroscopic investigations of cocrystals are used to validate and further probe the polymorphic structures. This study serves as a holistic approach in investigating polymorphism and demonstrates the unquenchable importance of halogen bonding in crystal engineering.

In this work, we report a single-crystal structure of a new organic-inorganic hybrid material base on two different mononuclear halogenidometallate complexes, in which hexachloridorhodate (III) ([RhCl₆]^3-), tetrachloridoferrate (III) ([FeCl₄]^-) and chloride ions (Cl^-) are combined with the organic cation 1,6-diammoniumhexane (C₆H₁₈N₂²⁺) to form a three-dimensional (3D) framework via non-covalent ‘intermolecular’ interactions. Tetrakis(1,6-diammoniumhexane) hexachloridorhodate(III) tetrachlorioferrate(III) tetrachloride has been hydrothermally synthesized in concentrated hydrochloric acid solution. Red single crystals of the compound with sufficient size for X-ray structure determination were grown by slow evaporation of the hydrochloric acid solution of the hydrothermally treated reactants. The crystal structure analysis indicates that the titled compound crystallizes in the tetragonal space group I4₁/a with unit cell dimensions a = 19.154(3) Å, c =14.363(3) Å, and Z = 4. The solid with the sum formula C₂₄H₇₂Cl₁₄FeN₈Rh is formed by three types of distinct anionic units, [RhCl₆]^3-, [FeCl₄]^- and Cl^-, which are chargsed balanced by cations [C₆H₁₈N₂]²⁺. The asymmetric unit consists of one Rh, one Fe and one chloride atom viz. atom Cl(4), on special positions (fourfold axes, glide plane), three chloride atoms viz. atom Cl(3), Cl(2) and Cl(1), and one complete all-transoid zigzag chain-like 1,6-diammoniumhexane dication is placed in general positions. Cl(4) and Cl(3) occupy the axial and equatorial positions, respectively, in the slightly distorted octahedral geometry around Rh with bond lengths Rh-Cl(4) = 2.344(3) Å and Rh-Cl(3) = 2.355(2) Å. Cl(2) fills the coordination sphere in the tetrahedral geometry around Fe with bond length Fe-Cl(2) = 2.166(4) Å. Figure 1 depicts the asymmetric unit with atom numbering and colour legend. [C₆H₁₈N₂]₄[RhCl₆][FeCl₄]Cl₄ is isomorphous with the organic-inorganic hybrid compound containing 1,6-diammoniumhexane, hexachloroferrate (III), tetrachloroferrate (III) and chloride ions [C₆H₁₈N₂]₄[FeCl₆][FeCl₄]Cl₄ [1,2]. The solid-state structure of [C₆H₁₈N₂]₄[RhCl₆][FeCl₄]Cl₄ features a three-dimensional network of N-H···Cl hydrogen bonds between the ionic components. The N-H···Cl hydrogen bonds donate from the protonated amino groups (NH₃⁺) at both ends of the organic ion to the chloride ligands of [RhCl₆]^3- and free chloride ions with NH···Cl distances ranging from 3.124(8) to 3.309(7) and are to be considered as week interactions. Inorganic layers are built up from [RhCl₆]^3- octahedral and [FeCl₄]^- tetrahedral which are arranged in line along the crystallographic c-axis and the distance between metal centers is long (7.181 Å); the organic cationic species along with the free chloride anions are located between the inorganic layers and bound to each other by further N-H···Cl hydrogen bonds. In contrast, [FeCl₄]^- does not participate in any hydrogen bonding of significant strengths. It seems, the free chloride and [RhCl₆]^3- ions have priority to interacting with [C₆H₁₈N₂]²⁺. The titled organic-inorganic hybrid compound was also characterized by Fourier-transform infrared spectroscopy (FT-IR), elemental and differential scanning calorimetry (DSC) analyses, and powder X-ray diffraction (XRD). To the best of our knowledge, it is the example of a mixed-metal organic-inorganic hybrid compound base on mononuclear transition metal halide complexes.

Amines can (co)crystallize with water fairly well. The crystals can be formed mostly because both components form hydrogen bonds. Depending on the stoichiometric ratios, amines can create several hydrates with different amount of water per amine molecule. An excellent example is a piperidine - an aliphatic, heterocyclic secondary amine with a six-membered ring. This system can form five different hydrates [1]: the lower ones (containing ½ or 2 water molecules per amine) which present features characteristic for well-defined structures of cocrystals, and the higher hydrates (8.1, 9¾, 11) which have the architecture more similar to clathrate hydrates with the organic molecules embedded in the cages [2].

Steric hindrance is an interesting factor influencing the formation of hydrates. The presence of the substituent group (like a methyl group) in close proximity of the NH group can reduce an access for the other molecules and hence may lead to significant structural changes. Piperidine can be easily substituted with methyl groups in 2nd and/or in the 6th position, what maximizes the steric hindrance effect. Consequently the number of possible 2,2,6,6-tetramethylpiperidine hydrates might be expected to be smaller than for the parent piperidine system. Another possible modification of piperidine moiety is a replacement of carbon in the 4th position with an oxygen atom giving morpholine. Interestingly, despite of similar shape and properties to piperidine, the morpholine hydrates have not been discovered up-to-date. Therefore an intriguing problem appears whether the 3,3,5,5-tetramethyated morpholine is willing to cocrystallize with water. If so, do these hydrates reveal a similar kind of architectures to piperidine analogue or not?

Because both 2,2,6,6-tetramethylpiperidine or 3,3,5,5-tetramethylmorpholine and water are liquid at RT, amines and their hydrates were crystalized on the diffractometer, using in situ crystallization technique with IR laser [3]. As a result of throughout analyses crystals of both amines, but also of four hydrates were obtained and their structures were determined. The amines form hemihydrates and dihydrates. Interestingly, while hemihydrates of the amines have very similar, but not identical, structural motifs, dihydrates are isostructural. Despite of numerous attempts no higher hydrates (clathrate-like systems) could be obtained. This is probably due to too large size of the whole molecules to fit to the cavities observed in the clathrate hydrates.

[1] Dobrzycki, Ł., Socha, P., Ciesielski, A., Boese, R., Cyrański, M.K., (2019). Cryst. Growth Des., 19, 2, 1005-1020

[2] Sloan, E. D. (1990) “Clathrate Hydrates of Natural Gases”, Marcel Dekker, New York, USA

[3] Boese, R. (2014). Z. Kristallogr. 229, 595.

σ-hole interaction properties of divalent sulfur
Albert S. Lundembaa, Dikima D. Bibelayia, Juliette Pradonb* and Zéphyrin G. Yava*
Abstract
Non-covalent interactions like hydrogen bonds, aromatic stacking contacts and even σ-hole interactions are commonly observed in biologic macromolecular compounds like proteins, polysaccharides, and nucleic acids. These rather weak interactions often play a significant role in determining the tertiary structure of macromolecules. Evidence of σ-hole interactions has been given by both theoretical and experimental studies reported in the literature. The present study explores the σ-hole interaction properties of divalent sulfur groups (R1-S-R2) using the Cambridge Structural Database (CSD) in conjunction with ab initio calculations. CSD analysis revealed that 7 095 structures contained a divalent sulfur atom that formed an intermolecular σ-hole contact within the sum of the van der Waals radii with N, O, F, P, S, Cl, As, Se, Br, Sb, Te or I as the acceptor atom. The structural fragments (C,C)-S, (C,S)-S, (N,S)-S, (C,N)-S, (N,N)-S, (S,S)-S, (C,Se)-S, (C,P)-S, (C,Te)-S and (C,As)-S were each observed to exhibit intermolecular contacts that are potentially σ-hole interactions. The geometric preferences of some of these contacts indicated that genuine σ-hole interactions were likely. That finding was confirmed by the geometries of the optimised complexes formed by the σ-hole donors CH3O-S-OCH3 (KUYRIF), FOC-S-CN (AMOREA), (CH3)2N-S-Cl (VAMPEF) and CN-S-CN (fragment of GOJZUC) derived from the CSD. Values of the binding energy (BE) calculated with B3LYP were markedly smaller than values calculated with MP2, the latter being close to those with B3LYPD3-G and B3LYPD3-BJ. This suggested that dispersion interactions were in addition to σ-hole interactions the main forces stabilizing the complexes. The energy of the σ-hole interaction was dependent on the environment of the sulfur atom. The dependence agreed well with molecular electrostatic potential surfaces of the donors and partial charges of the sulfur atom predicted by ab initio calculations. The positive charge of the sulfur atom was enhanced when increasing the electron withdrawing effect of the substituents R1 and R2 in the following sequence: F>CH3O> CN>Cl>Br.

Hypodiphosphoric acid (H₄P₂O₆) – the structural analogue of diphosphoric acid (H₄P₂O₇) – contains two phosphorus atoms at the +4 oxidation state, which are connected by a direct covalent bond. After its synthesis was described in the 19th century, the mainstream of scientific research focused on the synthesis and physicochemical properties of its inorganic salts [1, 2].

In recent years, research has been intensified on organic-inorganic hybrids, including organic hypodiphosphates [3-5]. The lack of an oxygen bridge in hypodiphosphates contributes to their slightly higher stability (compared to diphosphates) and makes the ions/molecules more rigid. At the same time they still have six oxygen atoms capable of participating in the formation of networks stabilized by strong O–H···O hydrogen bonds, composed exclusively of hypodiphosphate anions and/or acid molecules. This is confirmed by the known hypodiphosphate crystals characterized by the presence of such substructures, with different architectures and dimensions.

In the present poster, the effect of methyl or amino substitution of thiazole ring on the hydrogen bond patterns observed in eight thiazolium hypodiphosphate crystals will be analyzed. It was found that the presence of one-, two- or three-dimensional anionic substructures was related to the degree of anion ionization and the size of the cation used. Monoanions form 3D hypodiphosphate networks, while ionic cocrystals containing dianions and hypodiphosphoric acid molecules (depending on the cation type) – 1D or 2D substructures. The presence of water molecules in the crystal results in the formation of higher dimensional inorganic substructures.

[1] Salzer, T. (1987). Liebigs Ann. 187, 322.

[2] Kinzhybalo, V., Otręba, M., Ślepokura, K. & Lis, T. (2021). Wiad. Chem. 75, 423.

[3] Otręba, M., Budzikur, D., Górecki, Ł. & Ślepokura. K. (2018). Acta Cryst. C74, 571.

[4] Emami, M., Ślepokura, K. A., Trzebiatowska, M., Noshiranzadeh, N. & Kinzhybalo, V. (2018). CrystEngComm.. 20, 5207.

[5] Budzikur, D., Szklarz, P., Kinzhybalo, V. & Ślepokura. K. (2020). Acta Cryst. B76, 939.

The physicochemical properties of solvated crystals are greatly influenced by the interactions between the solvent and solute. Therefore, various properties of solvated crystals, such as stability, spectral properties, and solubility, are variable depending on the type of solvent molecules included in the lattice. The design of solvated crystallization has attracted great attention as a means of modifying the properties of organic solids, especially in the fields of pharmaceuticals and organic optoelectronic materials. [1][2] Solvates formation of organic compounds is also important in the separation process in chemical industries. [3]

Bisphenol A derivatives are applied as a raw material of polymers for various applications. Solvates formation is applied in the process of industrial production of several bisphenol A derivatives. The bisphenol A derivative 1 shown in Fig. 1 (a) was found to form solvates with branched alcohols, but it was difficult to form solvates with linear alcohols. To clarify the observed difference in its solvation behavior, X-ray structure analysis was performed on its solvates with isopropanol (IPA), 2-butanol (2-BuOH), iso-butanol (i-BuOH), and water.

The result showed that the four solvated crystals involve 1 and a solvent molecule in a 1:1 ratio. The four solvated crystals were also found to be isomorphous. One solvent molecule in the crystals is linked to two neighboring molecules of 1 by intermolecular hydrogen bonds along the a-axis and included in the void surrounded by the bisphenol moieties. There found no significant structural difference in the arrangement of 1 itself in the four solvates, whereas the space around the solvent molecules was dependent on the size of a solvent molecule. To compare the differences between the space for solvent molecules, the three interatomic distances X, Y, and Z shown in Fig. 1 (b) were examined. The structure of the solvated crystals was found to be expanded along the Y direction due to the solvent molecules, whereas there was no remarkable difference in the other two directions as listed in Table 1. This structural feature could be correlated with the crystallization behavior of these solvates and their stability.

The understanding and control of intermolecular forces allows for the creation of supramolecular architectures held together by relatively weak, flexible interactions. The exploitation of π-π stacking interactions can produce materials with dynamic properties such as crystal to crystal transitions.[1] Co-facial π-interactions are also important in the preparation of semiconducting organic materials,[2] however, face-to-face π-stacking is generally repulsive and often disfavoured.[3]

In our development of an S_NAr-based methodology for the synthesis of heteropentacene analogues 1a-c we synthesised a series of electronically biased 1,2,3,4-tetrasubstituted dibenzodioxin (2a-c) and phenoxazine (3a-c­) derivatives.[4] An examination of the crystal structures of 2a-c and 3a-c indicates that a combination of electronic bias and C−H substitution affords compounds which tend to π-stack in a co-facial, antiparallel manner. A search of the Cambridge Structural database for representative structures was also conducted. The results indicate such motifs could be valuable building blocks for supramolecular design of materials held together by co-facial π-π stacking interactions.

References

1. Reger, D. L.; Horger, J. J.; Smith, M. D.; Long, G. J.; Grandjean, F. Inorg. Chem. 2011, 50 (2), 686–704.
2. Anthony, J. E. Angew. Chem. Int. Ed. 2008, 47 (3), 452–483.
3. Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112 (14), 5525–5534.
4. Hiscock, L. K.; Raycraft, B. M.; Wałęsa-Chorab, M.; Cambe, C.; Malinge, A.; Skene, W. G.; Taing, H.; Eichhorn, S. H.; Dawe, L. N.; Maly, K. E. Chem. Eur. J. 2019, 25 (4), 1018–1028.

Targeting the polyamine biosynthetic pathway by inhibiting ornithine decarboxylase (ODC) is a powerful approach in the fight against both viruses and cancers.

D,L-alpha-ifluoromethylornithine (also called DFMO, eflornithine, ornidyl) is the best-known inhibitor of ODC and a broad-spectrum, unique therapeutical agent. It is promising pan-drug against diverse cancers, such as leukemia, skin cancer, breast cancer, prostate cancer and pancreatic cancer, cervical, small-cell lung cancer and melanoma, gastric cancer, colorectal cancer, neuroblastoma, glial tumors, such as malignant gliomas, as well as antiviral pan-drug, against RNA and DNA viruses, inter alia against dengue virus, zika, chikungunya virus, hepatitis B virus, human cytomegalovirus, herpes simplex virus, coxsackievirus B3, ebola, hepatitis C virus, sindbis virus, Japanese encephalitis virus, yellow fever virus, enterovirus 71, polio, rift valley fever virus, vesicular stomatitis virus, rabies virus, la crosse virus, semliki forst virus, as well as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Here, we present the first supramolecular study focusing on the structure of DFMO. We discuss qualitative and quantitative survey of non-covalent interactions via Hirshfeld surface, molecular electrostatic potential, enrichment ratio and energy frameworks analysis visualizing 3-D topology of interactions in order to understand the differences in the cooperativity of interactions involved in the formation of supramolecular synthons at the subsequent levels of well-organized supramolecular self-assembly, in comparison with the ornithine structure.

In the light of the drug discovery, supramolecular studies of amino acids, essential constituents of proteins, are of prime importance. In brief, the same amino-carboxy synthons are observed in the bio-system containing DFMO.

References

Bojarska J, New R, Borowiecki P, Remko M, Breza M, Madura ID, Fruzi ´nski A, Pietrzak A and Wolf WM (2021) The First Insight Into the Supramolecular System of D,L[1]α-Difluoromethylornithine: A New Antiviral Perspective. Front. Chem. 9:679776. doi: 10.3389/fchem.2021.679776