Crystal structure and Hirshfeld surface analysis of 4,4'-di-meth-oxy-biphenyl-3,3',5,5'-tetra-carb-oxy-lic acid dihydrate.

In the crystal of the title compound, C18H14O10·2H2O, the arene rings of the biphenyl moiety are tilted at an angle of 24.3 (1)°, while the planes passing through the carboxyl groups are rotated at angles of 8.6 (1) and 7.7 (1)° out of the plane of the benzene ring to which they are attached. The crystal structure is essentially stabilized by O-H⋯O bonds. Here, the carboxyl groups of neighbouring host mol-ecules are connected by cyclic R 2 2(8) synthons, leading to the formation of a three-dimensional network. The water mol-ecules in turn form helical supra-molecular strands running in the direction of the crystallographic c-axis (chain-like water clusters). The second H atom of each water mol-ecule provides a link to a meth-oxy O atom of the host mol-ecule. A Hirshfeld surface analysis was performed to qu-antify the contributions of the different inter-molecular inter-actions, indicating that the most important contributions to the crystal packing are from H⋯O/O⋯H (37.0%), H⋯H (26.3%), H⋯C/C⋯H (18.5%) and C⋯O/O⋯C (9.5%) inter-actions.

Combination of Hydrogen and Halogen Bonds in the Crystal Structures of 5-Halogeno-1H-isatin-3-oximes: Involvement of the Oxime Functionality in Halogen Bonding.

Various functional groups have been considered as acceptors for halogen bonds, but the oxime functionality has received very little attention in this context. In this study, we focus on the analysis of the hydrogen and halogen bond preferences observed in the crystal structures of 5-halogeno-1H-isatin-3-oximes. These molecules can be involved in various non-covalent interactions, and the competition between these interactions has a decisive influence on their self-organization. In particular, we were interested to see whether the crystal structures of 5-halogeno-1H-isatin-3-oximes, especially bromine- and iodine-substituted ones, are characterized by the presence of halogen bonds formed with the oxime functionality. The oxime group proved its ability to compete with the other strong donor and acceptor sites by participating in the formation of cyclic hydrogen-bonded heterosynthons oxime∙∙∙amide and Ooxime∙∙∙Br/I halogen bonds.

Synthesis and crystal structures of two solvates of 1-{[2,6-bis-(hy-droxy-meth-yl)-4-methyl-phen-oxy]meth-yl}-3,5-bis-{[(4,6-di-methyl-pyridin-2-yl)amino]meth-yl}-2,4,6-tri-ethyl-benzene.

In the crystal structures of the formamide monosolvate (1a) and the n-propanol/H2O solvate/hydrate (1b) of the title compound, C38H50N4O3 (1), the tripodal host mol-ecule adopts a conformation in which the substituents attached to the central benzene ring are arranged in an alternating order above and below the ring plane. As a result of the different nature of the involved guest species, the crystal components in 1a create a three-dimensional supra-molecular architecture, while the crystal structure of 1b consists of two-dimensional supra-molecular aggregates extending parallel to the crystallographic ab plane.

Supramolecular Motifs in the Crystal Structures of Triethylbenzene Derivatives Bearing Pyridinium Subunits in Combination with Pyrimidinyl or Pyridinyl Groups.

A series of mono- and dicationic 1,3,5-trisubstituted 2,4,6-triethylbenzenes containing pyridinium groups in combination with aminopyrimidine-/aminopyridine-based recognition units were synthesized and crystallographically studied. The combination of neutral and ionic building blocks represents a promising strategy for the development of effective and selective artificial receptors for anionic substrates. In the crystalline state, the investigated compounds show a tendency to bind the counterion PF6- in the cavity formed by the three functionalized side-arms. The intermolecular interactions with the PF6- ion comprise N-H∙∙∙F and C-H∙∙∙F bonds. Detailed analysis of various supramolecular motifs, including interactions with solvent molecules, provides deeper insights into the processes of molecular recognition. The information obtained is useful in the development of new receptor molecules for anions and in the selection of the most appropriate counterion.

Compounds Derived from 9,9-Dialkylfluorenes: Syntheses, Crystal Structures and Initial Binding Studies (Part II).

New representatives of 2,4,7-trisubstituted 9,9-dialkyl-9H-fluorenes were prepared and used for crystallographic investigations as well as initial binding studies towards metal ions and carbohydrates. The binding studies, which included 1 H NMR spectroscopic titrations and fluorescence measurements, demonstrated the ability of the tested fluorene-based compounds to act as complexing agents for ionic and neutral substrates. Depending on the nature of the subunits of the fluorene derivatives, "turn on" or "turn off" fluorescent chemosensors can be developed. Compounds composed of 4,6-dimethylpyridin-2-yl-aminomethyl moieties have the potential to be used as sensitive "turn-on" chemosensors for some metal ions.

Cycloalkyl Groups as Building Blocks of Artificial Carbohydrate Receptors: Studies with Macrocycles Bearing Flexible Side-Arms.

The cyclopentyl group was expected to act as a building block for artificial carbohydrate receptors and to participate in van der Waals contacts with the carbohydrate substrate in a similar way as observed for the pyrrolidine ring of proline in the crystal structures of protein-carbohydrate complexes. Systematic binding studies with a series of 1,3,5-trisubstituted 2,4,6-triethylbenzenes bearing various cycloalkyl groups as recognition units provided indications of the involvement of these groups in the complexation process and showed the influence of the ring size on the receptor efficiency. Representatives of compounds that exhibit a macrocyclic backbone and flexible side arms were now chosen as further model systems to investigate whether the previously observed effects represent a general trend. Binding studies with these macrocycles towards ß-D-glucopyranoside, an all-equatorial substituted carbohydrate substrate, included 1H NMR spectroscopic titrations and microcalorimetric investigations. The performed studies confirmed the previously observed tendency and showed that the compound bearing cyclohexyl groups displays the best binding properties.

Crystal structure of the complex of 2,4,6-tri-ethyl-1,3,5-tris-[(4-methyl-1H-indazol-1-yl)meth-yl]-benzene with NH4PF6.

The complex of 2,4,6-tri-ethyl-1,3,5-tris-[(4-methyl-1H-indazol-1-yl)meth-yl]-benz-ene with ammonium hexa-fluorophosphate, C39H42N6·NH4 +·PF6 -, crystallizes in the monoclinic space group P21 with two mol-ecules of the receptor, two NH4 + and two PF6 - ions in the asymmetric unit. In each of the complexes the ammonium ion resides in the cavity of the receptor mol-ecule and is fixed in its position by three N-H⋯N bonds, while the remaining hydrogen atom of the cation acts as a bifurcated binding site for N-H⋯F bonding to the counter-anion. The crystal is composed of one-dimensional supra-molecular aggregates extending along the a-axis direction.

Synthesis and crystal structure of 1,3-bis-{[N,N-bis-(2-hy-droxy-eth-yl)amino]-meth-yl}-5-{[(4,6-di-methyl-pyridin-2-yl)amino]-meth-yl}-2,4,6-tri-ethyl-benzene.

In the crystal structure of the title compound, C30H50N4O4, the two bis-(hy-droxy-eth-yl)amino moieties and the 2,4-di-methyl-pyridinyl-amino unit of the mol-ecule are located on one side of the central benzene ring, while the ethyl substituents are oriented in the opposite direction. The dihedral angle between the planes of the aromatic rings is 73.6 (1)°. The conformation of the mol-ecule is stabilized by intra-molecular O-H⋯O (1.86-2.12 Å) and C-H⋯N (2.40, 2.54 Å) hydrogen bonds. Dimers of inversion-related mol-ecules represent the basic supra-molecular entities of the crystal structure. They are further connected via O-H⋯O hydrogen bonding into undulating layers extending parallel to the crystallographic bc plane. Inter-layer inter-action is accomplished by weak C-H⋯π contacts.

Crystal structures of methyl 3,5-di-methyl-benzoate, 3,5-bis-(bromo-meth-yl)phenyl acetate and 5-hy-droxy-benzene-1,3-dicarbaldehyde.

The crystal structures of the title compounds, methyl 3,5-di-methyl-benzoate (C10H12O2; 1), 3,5-bis-(bromo-meth-yl)phenyl acetate (C10H10Br2O2; 2) and 5-hy-droxy-benzene-1,3-dicarbaldehyde (C8H6O3; 3) were determined by single-crystal X-ray analysis. The crystals of 1 are composed of strands of C-H⋯O=C bonded mol-ecules, which are further arranged into layers. As a result of the presence of two bromo-methyl substituents in compound 2, mol-ecular dimers formed by crystallographically non-equivalent mol-ecules are connected to structurally different two-dimensional aggregates in which the bromine atoms participate in Br⋯Br bonds of type I and type II. In the case of compound 3, which possesses three donor/acceptor substituents, the mol-ecular association in the crystal creates a close three-dimensional network comprising Car-yl-H⋯Ohy-droxy, Cform-yl-H⋯Oform-yl and O-H⋯Oform-yl bonds.

Correction: Binding modes of methyl α-d-glucopyranoside to an artificial receptor in crystalline complexes.

[This corrects the article DOI: 10.1039/D1RA03390E.].

Promising Therapeutic Approach for SARS-CoV-2 Infections by Using a Rutin-Based Combination Therapy.

The development of new therapeutic approaches for SARS-CoV-2 infections is of particular current importance. The combination therapy proposed here is based on already proven, safe and inexpensive compounds. The natural compound rutin, one of the six therapy components, has the potential to inhibit both viral and host cell targets. In addition, this therapy involves the use of acetylsalicylic acid, vitamin C and vitamin D3 , which should be administered together with calcium and magnesium. The importance of each component is briefly described in this article. Due to multiple anti-infective properties of rutin, it provides a basis for combating a SARS-CoV-2 infection as well as various viral and bacterial co-infections. There are strong indications for a good effect of this simple combination therapy, especially in the early stages of infection. It has the potential to be of interest both prophylactically and therapeutically, and offers the possibility of protection against severe disease progression.

Crystal structure of 9,9-di-ethyl-9H-fluorene-2,4,7-tricarbaldehyde.

The title compound, C20H18O3, crystallizes in the space group P21/c with one mol-ecule in the asymmetric unit of the cell. The fluorene skeleton is nearly planar and the crystal structure is composed of mol-ecular layers extending parallel to the (302) plane. Within a layer, one formyl oxygen atom participates in the formation of a Carene-H⋯O bond, which is responsible for the formation of an inversion symmetric supra-molecular motif of graph set R 2 2(10). A second oxygen atom is involved in an intra-molecular Carene-H⋯O hydrogen bond and is further connected with a formyl hydrogen atom of an adjacent mol-ecule. A Hirshfeld surface analysis indicated that the most important contributions to the overall surface are from H⋯H (46.9%), O⋯H (27.9%) and C⋯H (17.8%) inter-actions.

Crystal structures of 2-[3,5-bis-(bromo-meth-yl)-2,4,6-tri-ethyl-benz-yl]isoindoline-1,3-dione and 2-{5-(bromo-meth-yl)-3-[(1,3-dioxoisoindolin-2-yl)meth-yl]-2,4,6-tri-ethyl-benz-yl}isoindoline-1,3-dione.

The title compounds, C23H25Br2NO2 (1) and C31H29BrN2O4 (2), crystallize in the space group P21/n with two (1-A and 1-B) and one mol-ecules, respectively, in the asymmetric unit of the cell. The mol-ecular conformation of these compounds is stabilized by intra-molecular C-H⋯O hydrogen bonds and C-H⋯N or C-H⋯π inter-actions. The crystal structure of 1 features a relatively strong Br⋯O=C halogen bond, which is not observed in the case of 2. Both crystal structures are characterized by the presence of C-H⋯Br hydrogen bonds and numerous inter-molecular C-H⋯O hydrogen-bonding inter-actions.

Crystal structure of a methanol solvate of a macrocycle bearing two flexible side-arms.

Di-tert-butyl N,N'-{[13,15,28,30,31,33-hexa-ethyl-3,10,18,25,32,34-hexa-aza-penta-cyclo-[25.3.1.15,8.112,16.120,23]tetra-triaconta-1(31),3,5,7,9,12(33),13,15,18,20,22,24,27,29-tetra-deca-ene-14,29-di-yl]bis-(methyl-ene)}dicarbamate methanol disolvate, C52H72N8O4·2CH3OH, was found to crystallize in the space group P21/c with one half of the macrocycle (host) and one mol-ecule of solvent (guest) in the asymmetric unit of the cell, i.e. the host mol-ecule is located on a crystallographic symmetry center. Within the 1:2 host-guest complex, the solvent mol-ecules are accommodated in the host cavity and held in their positions by O-H⋯N and N-H⋯O bonds, thus forming ring synthons of graph set R 2 2(7). The connection of the 1:2 host-guest complexes is accomplished by C-H⋯O, C-H⋯N and C-H⋯π inter-actions, which create a three-dimensional supra-molecular network.

Binding modes of methyl α-d-glucopyranoside to an artificial receptor in crystalline complexes.

Compared to the numerous X-ray crystal structures of protein-carbohydrate complexes, the successful elucidation of the crystal structures of complexes between artificial receptors and carbohydrates has been very rarely reported in the literature. In this work, we describe the binding modes of two complexes formed between methyl α-d-glucopyranoside and an artificial receptor belonging to the class of compounds consisting of a 1,3,5-trisubstituted 2,4,6-trialkylbenzene scaffold. It is particularly noteworthy that these two complexes are present in one crystal structure, as was observed by us for the first time in the case of the recently reported three crystal structures of the complexes with methyl ß-d-glucopyranoside, each containing two different receptor-carbohydrate complexes. The noncovalent interactions stabilizing the new complexes are compared with those observed in the aforementioned crystalline complexes with methyl ß-d-glucopyranoside.

Syntheses of Acyclic and Macrocyclic Compounds Derived from 9,9-Diethylfluorene (Part I).

A series of new 9,9-diethylfluorenes consisting of three side-arms each bearing a heterocyclic, bis(carboxymethyl)amino, bis(carbamoylmethyl)amino, bis(ethoxycarbonylmethyl)amino or an amino group were prepared on the basis of 2,4,7-tris(bromomethyl)-9,9-diethylfluorene. Imidazolyl, benzimidazolyl, pyrazolyl, pyrrolyl, 1,3-dioxoisoindolyl and pyridinium groups were taken into account as heterocyclic units, attached to the aromatic skeleton via -CH2-, -CH2NHCH2- or -CH2N=CH- linkers. In addition to the seventeen 2,4,7-trisubstituted 9,9-diethylfluorenes, two macrocyclic compounds were prepared on the basis of 2,7-bis(aminomethyl)-9,9-diethylfluorene. The excellent yield of the macrocyclization reaction is worth a special mention. Both the acyclic and the macrocyclic fluorene-based compounds have, among other things, the potential to act as artificial receptors for different substrates in analogy to the known receptors consisting of a benzene or biphenyl core.

Crystal structures of monohydrate and methanol solvate compounds of {1-[(3,5-bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzyl)amino]cyclopentyl}methanol.

In the title monohydrate compound, 1a, and the methanol solvate compound, 1b, the tri-ethyl-benzene derivative, C35H51N5O, has three functionalized side arms and three ethyl groups, the former being located on one side of the central benzene ring, while the latter are directed to the opposite side. Both the crystals are constructed of structurally similar dimers of 1:1 host-guest complexes held together by N-H⋯O and O-H⋯N hydrogen bonds, and in 1a additionally by O-H⋯O hydrogen bonds. The structure of 1b contains additional highly disordered solvent mol-ecules. Thus, the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] in PLATON was used to generate a modified data set, in which the contribution of the disordered mol-ecules to the structure amplitudes is eliminated. These solvent mol-ecules are not considered in the reported chemical formula.

Crystal structures of the dioxane hemisolvates of N-(7-bromo-methyl-1,8-naphthyridin-2-yl)acetamide and bis-[N-(7-di-bromo-methyl-1,8-naphthyridin-2-yl)acetamide].

The syntheses and crystal structures of N-(7-bromo-methyl-1,8-naphthyridin-2-yl)acetamide dioxane hemisolvate, C11H10BrN3O·0.5C4H8O2, (I), and bis-[N-(7-di-bromo-methyl-1,8-naphthyridin-2-yl)acetamide] dioxane hemisolvate, 2C11H9Br2N3O·0.5C4H8O2, (II), are described. The mol-ecules adopt a conformation with the N-H hydrogen pointing towards the lone electron pair of the adjacent naphthyridine N atom. The crystals of (I) are stabilized by a three-dimensional supra-molecular network comprising N-H⋯N, C-H⋯N and C-H⋯O hydrogen bonds, as well as C-Br⋯π halogen bonds. The crystals of compound (II) are stabilized by a three-dimensional supra-molecular network comprising N-H⋯N, C-H⋯N and C-H⋯O hydrogen bonds, as well as C-H⋯π contacts and C-Br⋯π halogen bonds. The structure of the substituent attached in the 7-position of the naphthyridine skeleton has a fundamental influence on the pattern of inter-molecular noncovalent bonding. While the Br atom of (I) participates in weak C-Br⋯Oguest and C-Br⋯π contacts, the Br atoms of compound (II) are involved in host-host inter-actions via C-Br⋯O=C, C-Br⋯N and C-Br⋯π bonding.

Carbohydrate receptors combining both a macrocyclic building block and flexible side arms as recognition units: binding properties of compounds with CH2OH groups as side arms.

New representatives of compounds combining both a macrocyclic building block and two flexible side arms as recognition units were prepared and their binding properties toward selected carbohydrates were evaluated. The aim of this study was to examine the effects of the replacement of the heterocycle-bearing side arms by smaller units, such as hydroxy groups, on the binding capability. The design of this type of receptor was inspired by the participation of the side chain hydroxy group of serine and threonine in the biorecognition of carbohydrates. Such structural modifications enable the recognition of structure-activity relationships, which are of high importance in the development of carbohydrate receptors with predictable binding strength and selectivity.