A Drug–Drug Multicomponent Crystal of Metformin and Dobesilate: Crystal Structure Analysis and Hygroscopicity Property

A drug–drug multicomponent crystal consisting of metformin (MET) and dobesilate (DBS) was prospectively connected by solvent cooling and evaporating co-crystallization using the multicomponent crystal strategy, not only to optimize the physicochemical properties of single drugs, but also to play a role in the cooperative effect of DBS with the potential vascular protective effects of MET against diabetic retinopathy (DR). The crystal structure analysis demonstrated that MET and DBS were coupled in a 3D supramolecular structure connected by hydrogen-bonding interactions with a molar ratio of 1:1. Almost all hydrogen bond donors and receptors of MET and DBS participated in the bonding, which hindered the combination of remaining potential hydrogen bond sites and water molecules, resulting in a lower hygroscopicity property than MET alone.     

Identification of an Overlooked Halogen-Bond Synthon and Its Application in Designing Fluorescent Materials

Research on new supramolecular synthons facilitates the progress of materials design. Herein, the ability of sp² carbonyl oxygen atoms to act as halogen-bond acceptors was established through cocrystallization. Four sets of carbonyl compounds, including aldehydes, ketones, esters, and amides, were selected as halogen-bond acceptors. In the absence of strong hydrogen bonds, 14 out of 16 combinations of halogen-bond donors and acceptors could form cocrystals, whereby the supramolecular synthon C=O ⋅⋅⋅ X acts as the main interaction. Further, the geometric parameters of the C=O ⋅⋅⋅ X interaction were statistically revealed on the basis of the crystallographic database. The bifurcated interaction mode that has been observed in other halogen-bond synthons rarely occurs in the case of C=O ⋅⋅⋅ X. The robustness of C=O ⋅⋅⋅ X makes its application in crystal engineering possible and opens up new opportunities in designing multicomponent fluorescent materials, as indicated by multicolor emission of cocrystals D through C=O ⋅⋅⋅ X interactions.     

Semi-synthesis and Crystal Structure of Sophoridine N-oxide

Sophoridine N-oxide was synthesized and characterized by 1H-NMR,EI-MS,IR and elemental analysis,together with X-ray single-crystal diffraction analysis,and its crystal structure was reported for the first time.The crystal belongs to the orthorhombic system,space group P212121 with a = 8.321(2),b = 15.650(3),c = 24.352(5) ,V = 3171.1(11) 3,Z = 8,Dc = 1.258 g/cm3,λ(CuKα) = 1.54178,F(000) = 1440,the final R = 0.0351 and wR = 0.0970.The crystal structure shows Sophoridine N-oxide crystallizes with two host molecules of similar conformation and four water solvent molecules in the asymmetric unit.In the crystal structure,intermolecular O-H…O hydrogen bonds link the constituent molecules into a 2D layer structure,which further extends to a 3D supramolecular architecture via Van der Waals interactions and intermolecular O-H…O hydrogen bonds.     

Double Chalcogen Bonds: Crystal Engineering Stratagems via Diffraction and Multinuclear Solid-State Magnetic Resonance Spectroscopy

Group 16 chalcogens potentially provide Lewis-acidic σ-holes, which are able to form attractive supramolecular interactions with electron rich partners through chalcogen bonds. Here, a multifaceted experimental and computational study of a large series of novel chalcogen-bonded cocrystals, prepared using the principles of crystal engineering, is presented. Single-crystal X-ray diffraction studies reveal that dicyanoselenadiazole and dicyanotelluradiazole derivatives work as promising supramolecular synthons with the ability to form double chalcogen bonds with a wide range of electron donors including halides and oxygen- and nitrogen-containing heterocycles. Extensive ⁷⁷Se and ¹²⁵Te solid-state nuclear magnetic resonance spectroscopic investigations of cocrystals establish correlations between the NMR parameters of selenium and tellurium and the local chalcogen bonding geometry. The relationships between the electronic environment of the chalcogen bond and the ⁷⁷Se and ¹²⁵Te chemical shift tensors were elucidated through a natural localized molecular orbital density functional theory analysis. This systematic study of chalcogen-bond-based crystal engineering lays the foundations for the preparation of the various multicomponent systems and establishes solid-state NMR protocols to detect these interactions in powdered materials.     

Co‐crystals with Acetylene: Small Is not Simple!

Acetylene is an amazingly versatile component for the formation of co‐crystals. It requires careful handling and special techniques for crystallisation, but the efforts seem to be rewarding when attaining co‐crystals with small molecules as partners. Many basic questions such as the dominance of specific heterogeneous intermolecular interactions, their driving force for the formation of multicomponent crystals instead of neat ones are expected to be easily analysed. The underlying packing patterns and resulting stoichiometries based on the known supramolecular synthons seem to be straightforward for such small molecules and crystal engineering, considered as the prototype of supramolecular synthesis, should be a simple task. Nineteen co‐crystals with acetylene are presented in this paper, some of which have been previously reported individually. An attempt has been made to find features shared by the groups of co‐crystals, including those that could not be co‐crystallised. But in spite of clear ideas and experiences from previous experiments, surprisingly almost none of systems reached our expectations. Our intuitive approach was not fulfilled, which demonstrates that multicomponent crystals even of small molecules will remain a great challenge for theoretical methods and the crystal structures shown herein represent good candidates for future testing. On the other hand, we wish to encourage other groups to present their views on the crystal structures with an unbiased approach that may offer a better explanation than we are able to outline in this article.     

Crystal engineering: a holistic view

Crystal engineering, the design of molecular solids, is the synthesis of functional solid-state structures from neutral or ionic building blocks, using intermolecular interactions in the design strategy. Hydrogen bonds, coordination bonds, and other less directed interactions define substructural patterns, referred to in the literature as supramolecular synthons and secondary building units. Crystal engineering has considerable overlap with supramolecular chemistry, X-ray crystallography, materials science, and solid-state chemistry and yet it is a distinct discipline in itself. The subject goes beyond the traditional divisions of organic, inorganic, and physical chemistry, and this makes for a very eclectic blend of ideas and techniques. The purpose of this Review is to highlight some current challenges in this rapidly evolving subject. Among the topics discussed are the nature of intermolecular interactions and their role in crystal design, the sometimes diverging perceptions of the geometrical and chemical models for a molecular crystal, the relationship of these models to polymorphism, knowledge-based computational prediction of crystal structures, and efforts at mapping the pathway of the crystallization reaction.     

Crystal Structure of 2,6-Dihistidine Dimethyl Ester Pyridine Acylamine Monohydrate

The crystal structure of the title compound,C21H25N7O7,has been determined in the orthorhombic space group C222(1) with a=8.993(10),b=12.149(14),c=22.20(2) and Z=4.There exist intramolecular C-H…O and N-H…N hydrogen bonds in the title crystal structure.The intermolecular N-H…N and C-H…O hydrogen bonds together with π-π stacking interactions(face-to-face) link the molecules into an infinite three-dimensional supramolecular network.     

An Easy Access to Organic Salt‐Based Stimuli‐Responsive and Multifunctional Supramolecular Hydrogels

By exploiting orthogonal hydrogen bonding involving supramolecular synthons and hydrophobic/hydrophilic interactions, a new series of simple organic salt based hydrogelators derived from pyrene butyric acid and its β‐alanine amide derivative, and various primary amines has been achieved. The hydrogels were characterised by microscopy, table‐top rheology and dynamic rheology. FTIR, variable‐temperature ¹H NMR and emission spectroscopy established the role of various supramolecular interactions such as hydrogen bonding and π–π stacking in hydrogelation. Single‐crystal X‐ray diffraction (SXRD) studies supported the conclusion that orthogonal hydrogen bonding involving amide–amide and primary ammonium monocarboxylate (PAM) synthons indeed played a crucial role in hydrogelation. The hydrogels were found to be stimuli‐responsive and were capable of sensing ammonia and adsorbing water‐soluble dye (methylene blue). All the hydrogelators were biocompatible (MTT assay in RAW 264.7 cells), indicating their suitability for use in drug delivery.     

Synthesis and Crystal Structure of a 3-D Hydrogen-bonded Supramolecular Decavanadate Compound [Habo]6[V10O28]·2C3H7OH·2H2O

A new inorganic-organic hybrid supramolecular compound [Habo]6[V10O28]·solvents and its crystal structure was reported as follows: monoclinic, space group P21/n, a =11.419(9), b = 16.811(16), c = 15.521(12) (A), β= 102.98(2)°, V= 2903(4) (A)3, Z = 4, C15H46N3O19V5,Mr = 827.25, Dc = 1.893 g/cm3, λ(MoKα) = 0.71073 A,μ = 1.636 mm-1, F(000) = 1696, the final R =0.0696 and wR = 0.1361 for 4641 observed reflections with I ＞ 2σ(I). The compound is based on decavanadate clusters [V 1oO28]6-. The hydrogen bonding interactions among Habo+ cations, solvents and decavanadate clusters extend 1 into a three-dimensional supramolecular architecture.     

Construction of hydrogen-bonded ternary organic crystals derived from L-tartaric acid and their application to enantioseparation of secondary alcohols

Ternary organic crystals consisting of an L-tartaric acid-derived dicarboxylic acid, a commercially available achiral diamine, and a chiral secondary alcohol have been developed and characterized by X-ray crystallography. 1D, 2D, and 3D hydrogen-bonded supramolecular networks were constructed, depending on the structure of the diamine used. Benzylic and aliphatic secondary alcohols were enantioselectively incorporated into the crystal and were successfully enantioseparated with up to 86 and 79% enantiomeric excess (ee), respectively. Selective incorporation of one enantiomer of 2-butanol, which is a small chiral aliphatic alcohol, was achieved by the cooperative effects of hydrogen bonds, CH···π interactions, and van der Waals interactions between the guest and host molecules, with the aid of two water molecules. The high host potential of the binary supramolecular system is mainly attributed to the skewed conformation of two rigid aromatic groups of tartaric acid derivatives, which prevents dense packing of the molecules and enhances the formation of multicomponent inclusion crystals.     

Supramolecular synthons and pattern recognition in adenine amides – synthesis,structures and thermal properties

An effective method for the synthesis of novel adenine amides was developed and successfully implemented, leading to 4-propyloxy-N-(9H-purin-6-yl)benzamide (1) and 4-dodecyloxy-N-(9H-purin-6-yl)benzamide (2). The compounds were fully characterised by means of spectroscopic (¹H NMR, ¹³C NMR, FT-IR) and thermal (TG, DSC) analysis. The crystallographic analysis revealed that the formation of supramolecular chains relies on hydrogen bonding between amide functionalities. All supramolecular synthons found in the crystal structure of 1 were confirmed with the temperature-dependent IR method. The temperature-dependent IR method is useful in determining supramolecular interactions for compound 2, for which the crystal structure could not be obtained. A detailed analysis of temperature-dependent FT-IR spectra was used for the first time to identify the hydrogen bonds that exist in the solid state of our compounds; it can therefore be considered a promising method for the pattern recognition of hydrogen bonding in supramolecular chemistry.     

Hydrothermal Synthesis and Crystal Structure of a Novel Polymolybdic（VI） Acid： {[H3O]2^＋[Mo2O4（OH）6^]2-}n

1 INTRODUCTION Coordination polymers[1～3] with one-, two- or three-dimensional structure and supramolecular compounds[4, 5] formed by weak interactions, such as hydrogen bonds, Van Der Waals’ forces, short-range exclusion forces, etc., have a variety of possible applications ranging from semicon- ductor to catalysts and potentially valuable pro- perties reminiscent of zeolites. So, considerable increasing attention has been focused on the syn- thesis or building of these coordination po…     

Construction of interesting organic supramolecular structures with synthons cooperation in the cocrystals of 1H-benzotriazole and hydroxybenzoic acids

Multifunctional molecules are capable of assembling via different supramolecular synthons,or hydrogen bond motifs,between the same or different functional groups,leading to the possibility of cocrystal.Utilization of the interplay of dimensionality(1-D,2-D and 3-D),orientation of functional groups of the building blocks,influence of rigid/flexible linking groups,and weak interactions provides an interesting route for the creation of novel supramolecular architectures in the crystal lattice.N-unsubstituted 1H-benzotriazole and carboxylic acid,being self-complementary molecules,offer a broad scope of study of binary compounds based on the complementary combination of H-bonding/donating sites.We report here the construction of three extended molecular networks in cocrystals of the carboxylic acid group of the acid and the 1H-benzotriazole triazole moiety.We have been able to identify four major supramolecualr synthons that would be helpful in the prediction of structural motifs for these kinds of studies.Interestingly,these heterosynthons are strikingly similar,to those of the homosynthons of the individual functional groups.The nature of the aza groups helps to enhance the overall volume of the crystal lattice thus leading to the formation of various supramolecular assemblies.Thermal stability of these compounds has been investigated by thermogravimetric analysis(TGA) of mass loss.     

Synthesis and Crystal Structure of 1,4-Bis(2-hydroxymethylphenyl)-1,4-dioxabutane

1 INTRODUCTION Macrocyclic ligands and their metal complexes have received much attention due to their applications in ion transport, ion separation and as models in biomimic researches[1~7]. The synthetic methods of macrocyclic ligands and their metal complexes are mainly divided into three kinds[8]. The first one is synthesizing free ligand, then forming the metal complexes; the second is template synthesis; and the third is synthesizing the end-off or side-off precursor ligand, then c…     

中心对称型4,4’-双(N’-取代酰基硫脲基)取代联苯类衍生物的 合成及其晶体结构

以苯甲酸和2,4-二氯苯氧乙酸为原料合成取代酰基异硫氰酸酯, 再分别与4,4’-联苯二胺和3,3’-二甲基-4,4’-联苯二胺反应, 合成了3种中心对称型4,4’-双(N’-取代酰基硫脲基)取代联苯类衍生物. 产物结构经紫外光谱、红外光谱和核磁共振谱确认, 并用X射线单晶衍射分析法测定了化合物4,4’-双(N’-苯甲酰基硫脲基)联苯的晶体结构, 该晶体属于三斜晶系, P-1空间群, 晶胞参数: a＝0.53447(11) nm, b＝1.03086(13) nm, c＝1.15550(13) nm, α＝98.24(3)°, β＝96.95(3)°, γ＝99.43(3)°, Z＝2, Dc＝1.379 g/cm3, V＝0.61472(16) nm3, F(000)＝266, R1＝0.0506, wR2＝0.1335. 该分子呈中心对称分布, 存在两种分子内氢键N—H…O和C—H…S, 形成了毗邻的两个六元环结构, 同时通过分子间氢键N—H…S在分子间形成的R22(8)环把分子连接成无限延伸的一维链状结构, 再通过两种CH-π相互作用形成三维超分子结构.     

六元瓜环与磺基水杨酸主客体配合物的晶体结构

合成了六元瓜环与磺基水杨酸主客体配合物,并测定了其单晶结构.晶体结构表明六元瓜环包结了3个水分子,磺基水杨酸位于六元瓜环的外侧,且与水分子通过氢键与六元瓜环相连,瓜环之间通过端口的羰基O原子、磺基水杨酸以及水分子间的氢键作用形成一维超分子.     

A systematic study of ligand intermolecular interactions in crystals of copper(II) complexes of bidentate guanidino derivatives

The synthesis and X-ray structures of four neutral copper(II) complexes and one cationic complex incorporating bidentate alkyl N-(4-oxo-5,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)imidocarbamate ligands are reported. The neutral complexes, which possess potential doublet (DA) hydrogen bonding motifs, form supramolecular structures based on synthons involving hydrogen bonding or phenyl embraces. The formation of sheets within the crystal through combination of these synthons, and the occurrence of guest molecules trapped in cavities between the sheets, are described. The cationic complex forms an extended hydrogen-bonded structure that incorporates nitrate ions. The structures of the five complexes are compared with others reported previously for complexes of related ligands.     

Crystal structure prediction of aminols: advantages of a supramolecular synthon approach with experimental structures

The supramolecular synthon approach to crystal structure prediction (CSP) takes into account the complexities inherent in crystallization. The synthon is a kinetically favored unit, and through analysis of commonly occurring synthons in a group of related compounds, kinetic factors are implicitly invoked. The working assumption is that while the experimental structure need not be at the global minimum, it will appear somewhere in a list of computationally generated structures so that it can be suitably identified and ranked upward using synthon information. These ideas are illustrated with a set of aminophenols, or aminols. In the first stage, a training database is created of the 10 isomeric methylaminophenols. The crystal structures of these compounds were determined. The prototypes 2-, 3-, and 4-aminophenols were also included in the training database. Small and large synthons in these 13 crystal structures were then identified. Small synthons are of high topological but low geometrical value and are used in negative screens to eliminate computationally derived structures that are chemically unreasonable. Large synthons are more restrictive geometrically and are used in positive screens ranking upward predicted structures that contain these more well-defined patterns. In the second stage, these screens are applied to CSP of nine new aminols carried out in 14 space groups. In each space group, up to 10 lowest energy structures were analyzed with respect to their synthon content. The results are encouraging, and the predictions were classified as good, unclear, or bad. Two predictions were verified with actual crystal structure determinations.     

Synthesis and Crystal Structure of a 3-D Hydrogen-bonded Supramolecular Decavanadate Compound [Habo]_6[V_(10)O_(28)]·2C_3H_7OH·2H_2O

1 INTRODUCTION The chemistry of polyoxometalates has been at- tracting much attention due to the richness in their structures, electron and proton storage abilities, ther- mal stability and applications in catalysis, medicine and surface sciences[1～3]. In recent years, the mixed- valence as well as full oxidized vanadium polyoxo- anions have been crystallized with a variety of orga- nic molecules as counteranions[4～8]. However, the guiding principles of the crystal structures of poly- o…