Search

Crystalline materials and crystallization processes play an important role in several fields of science, such as pharmaceuticals, material science, pigments, optoelectronics, catalysis and energy storage. Understanding and defining the right conditions of crystallization is therefore crucial. Among the several factors influencing the crystallization of a given compound, the choice of the solvent system is perhaps one of the most important. The nature of solvent–solute interactions can indeed have a role in promoting specific molecular assemblies, therefore affecting crystallisation rates of a crystal and often resulting in the nucleation of different polymorphs and solvates. Here we investigated the role of a binary mixture of solvent (water/acetone) in the crystallisation of a simple salt of 4-aminopyridinium chloride. Previous results on this compound showed that when crystallised from water it forms a simple hydrate structure, while in the presence of acetone, it undergoes a liquid-liquid phase separation, followed by the crystallisation of a complex structure belonging to the Frank–Kasper (FK) phases, a particular family of topologically close-packed structures never observed in small and rigid molecules. To broaden the understanding of how such a simple molecule may crystallise as an FK phase, we carried out the crystallization of the complex phase by antisolvent diffusion (in a mixture of water/acetone) and that of the monohydrate phase in water, monitoring the liquid precursors by liquid-state NMR. In particular, we applied 1H, 13C, 14N, 17O, and 35/37Cl NMR as a function of the concentration of 4APH+Cl− until the moment when precipitation of the crystalline phases occurred. Variations of chemical shifts, T1 relaxation times of 13C signals, and full-width at half-maximum of the signals of quadrupolar nuclei were also measured. The spatial proximity between the different species in the solution was investigated by NOE experiments. In order to support these results, we also performed Molecular Dynamics simulations, investigating the potential solute/solvents interactions. The results strongly suggest that acetone, instead of behaving as an anti-solvent, interacts directly with the solute, preventing the formation of the simple monohydrate structure and, at the same time, promoting specific molecular aggregations.

In this study, we have combined structural comparisons and the rugosity model to investigate experimental and predicted crystal structures from previous results of a crystal structure prediction study on a group of three rigid, planar small molecules, 2-methyl-, 3-methyl-, and 2,3-dimethyl-benzo[b]thiophene 1,1-dioxide. The results of the crystal structure comparisons provided some insights into the possibility that pairs of predictions, close in energy, might be related by potential phase transitions. In particular, we observed that for some pairs of predictions, a transformation from one type of crystal packing to the other would require only small shifts between adjacent molecules. This raised the question of whether only a few of these predictions can effectively be experimentally isolated. The calculations of the structural rugosity, a parameter that correlates surface rugosity with ease of crystallization, indicated smooth surfaces only for a few predictions. With the aim to isolate new polymorphs, we performed a small experimental study, limited to a few common solvents and crystallizations from the melt. Crystallizations from the melt selectively produced single crystals of new polymorphs for the 3-methyl- and the 2,3-methyl-benzothiophene derivatives. These showed good correlations with the above calculations, suggesting that the combination of crystal structure analysis and experimental screening might represent a useful approach in polymorphism screenings.

The coordination and sensing properties towards anions and transition metal ions of the simple novel fluorescent urea 1-(2-aminophenyl)-3-(naphthalen-1)-yl)urea (L) were investigated in solution, and in the solid state. An electron donating amine group in the molecular skeleton of L decreased the acidity of the urea NHs that are usually deprotonated by basic anions and allowed for a good degree of affinity towards fluoride in DMSO-d6-0.5 %H2O. Moreover, the amine moiety acted as a further binding group for metal ions. Indeed, L was able to bind Zn2+ both in solution and in the solid state, and to respond to the presence of this metal ion in MeCN with an enhancement of the fluorescence emission. Although solution studies evidenced the formation of a 1 : 1 complex of L with Zn2+, complexes with a 2 : 1 ligand-to-metal stoichiometry were isolated in the solid state. DFT calculations helped to clarify the stability reasons behind these results.

Molecular self-assembly is the spontaneous association of simple molecules into larger and ordered structures 1. It is the basis of several natural processes, such as the formation of colloids, crystals, proteins, viruses and double-helical DNA 2. Molecular self-assembly has inspired strategies for the rational design of materials with specific chemical and physical properties 3, and is one of the most important concepts in supramolecular chemistry. Although molecular self-assembly has been extensively investigated, understanding the rules governing this phenomenon remains challenging. Here we report on a simple hydrochloride salt of fampridine that crystallizes as four different structures, two of which adopt unusual self-assemblies consisting of polyhedral clusters of chloride and pyridinium ions. These two structures represent Frank–Kasper (FK) phases of a small and rigid organic molecule. Although discovered in metal alloys 4,5 more than 60 years ago, FK phases have recently been observed in several classes of supramolecular soft matter 6–11 and in gold nanocrystal superlattices 12 and remain the object of recent discoveries 13. In these systems, atoms or spherical assemblies of molecules are packed to form polyhedra with coordination numbers 12, 14, 15 or 16. The two FK structures reported here crystallize from a dense liquid phase and show a complexity that is generally not observed in small rigid organic molecules. Investigation of the precursor dense liquid phase by cryogenic electron microscopy reveals the presence of spherical aggregates with sizes ranging between 1.5 and 4.6 nanometres. These structures, together with the experimental procedure used for their preparation, invite interesting speculation about their formation and open different perspectives for the design of organic crystalline materials.

We exploit the possible link between structural surface roughness and difficulty of crystallisation. Polymorphs with smooth surfaces may nucleate and crystallise more readily than polymorphs with rough surfaces. The concept is applied to crystal structure prediction landscapes and reveals a promising complementary way of ranking putative crystal structures., The link between structural surface rugosity and ease of crystallisation has been explored (see picture). Smooth polymorphs were found to crystallise more readily than rough polymorphs. A code was written to compute crystal rugosity and applied to crystal structure prediction calculations, thus affording a new way of linking landscapes to experimentation.

In a previous crystallographic study on 4-aminopyridinium chloride, Frank-Kasper (FK) phases were serendipitously produced for the first time in a small organic molecule, showing that a simple organic salt can crystallise as hydrate phases of extraordinary complexity. These results raised questions on the mechanisms of formation of such phases, for instance, whether they arise from a specific pre-organization in the liquid state, probably following a non-classical nucleation path and, most importantly, opened discussions on whether this family of structures can be extended. Here we report the results from a classical molecular dynamics investigation aimed to give more insights on this matter. In particular, we modelled the thermal behaviour of an arbitrary FK phase of 4-aminopyridinium chloride prior the melting and after cooling the molten phase, exploring the mechanisms of dehydration of these phases and nucleation from the melt. The results, also confirmed by experiments, suggest that the dehydration of these phases can occur without dramatic changes in the crystal packing. This is also confirmed by simulating a stable anhydrous FK phase of 4-aminopyridinium chloride. Most importantly, molecular dynamics simulated by cooling the melt of this anhydrous phase, showed the formation of mainly two types of aggregates identical to those observed in the experimental crystal structures. These results confirm that other unknown FK structures might be obtained for our system, either from the melt or by dehydration of the known phases. Moreover, they provide further evidence that their crystallisation follows a non-classical path with a probable formation of two types of highly symmetric clusters that assemble into the solid-state only when the relative ratio of these reaches a threshold.

Almost 200 years ago, benzamide was reported as polymorphic with two of its forms (II and III) found to be difficult to crystallise. In a recent study, it was shown that benzamide form I can easily convert into benzamide form III using mechanochemistry in the presence of nicotinamide. Here we show, experimentally and computationally, that this transformation is the result of a thermodynamic switch between these two polymorphic forms driven by the formation of solid solutions with small amounts of nicotinamide. The presence of nicotinamide in the crystallisation environment promotes the robust and exclusive crystallisation of the elusive form III. These results represent a promising route to the synthesis and utilisation of elusive polymorphs of pharmaceutical interest. The formation of solid solutions can result in changes of relative stabilities of crystal polymorphs. Here, the elusive form III of benzamide is stabilized through solid solution formation with nicotinamide. It is shown, experimentally and computationally, how such thermodynamic switching allows for consistent and facile crystallization of the otherwise elusive benzamide form III.

We investigate the polymorphic behavior of benzamide, the first compound known to exhibit polymorphism, in the presence of small amounts of nicotinamide in the crystallization environment. A previous study by Emmerling et al.1 showed that the presence of nicotinamide promotes the transformation of the thermodynamic polymorph I of benzamide into its metastable polymorph III via mechanochemistry. We show that this transformation is the result of a thermodynamic switch between these two polymorphic forms driven by the formation of solid solutions with a small amount of nicotinamide. The presence of nicotinamide in the crystallization environment promotes the robust and exclusive crystallization of the elusive form III. These results represent a promising route to the synthesis and utilization of elusive polymorphs of pharmaceutical interest.

A novel family of amide-based receptors is herein described. Specifically, the role of the halogen substituents at the aryl moieties in the anion binding properties of a series of halogenated isophthalamides and dipicolineamides (L1-L6) was investigated both in solution and in the solid state in order to evaluate the incidence of all possible different and combined weak host-guest interactions. Only L5 and L6 bearing pentafluorophenyl rings as substituents have some affinities for the set of anions studied. In particular, in the case of L5 an interesting behaviour with the formation of a non-symmetric adduct with benzoate and dihydrogen phosphate was hypothesised by 1H- A nd 19F-NMR spectroscopy studies in solution and confirmed by theoretical calculation. The study of the crystal structures of the receptors demonstrated that the steric hindrance determined by the halogen substituents in the receptor molecules influences the accessibility of the anions to the isophthalamide or dipicoline amide NH moieties, thus modulating the affinity for the anion guests.

We describe here the synthesis and coordination properties of three new derivatives of [9]aneN3 containing phenyl/quinoline pendant arm derivatives (L1, L2 and L3, respectively) also featuring urea (L1–L2) or amide (L3) functions as “non-innocent” spacers. At first, L1, L2 and L3 were studied considering the interaction with a series of anions (AcO−, BzO−, H2PO4−, F−, and Cl−) by means of 1H NMR measurements. Subsequently, the optical responses of L2 and L3 in the presence of several metal ions Cd2+, Co2+, Cu2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Ni2+, Zn2+ and Pb2 were analysed in MeCN/H2O (4 : 1 v/v). As observed by spectrophotometric and spectrofluorimetric titrations, there were significant changes in the absorbance and fluorescent emission of L2 upon addition of increasing amounts of Cd2+, Zn2+, Pb2+ and Cu2+ in MeCN/H2O (4 : 1 v/v). In particular, titrations of L2 with Cd2+, Zn2+ or Pb2+ showed an almost comparable CHEF effect up to an M2+/L2 molar ratio of 1. Overall, no significant optical selectivity was observed in the case of L2. Conversely, L3 revealed an OFF–ON selective response only in the presence of the Zn2+ ion in MeCN/H2O (4 : 1 v/v), which can be attributed to the formation of both 1 : 1 and 1 : 2 metal-to-ligand complexes, as also confirmed by potentiometric measurements. Finally, crystals of [ZnL1(Ac)](Ac) (1), [CuL1(Cl)](Cl)·H2O (2) and [CuL3](NO3) (3) were grown and analysed by X-ray diffraction. 1 and 3 feature the metal center in a pseudo-octahedral coordination geometry coordinated also by the carbonyl group from one pendant arm, while in the case of 2, one of the six coordination sites in the final distorted octahedral geometry is occupied by the nitrogen donor from the urea group of one pendant arm.

The experimental observation that certain crystal faces do not grow, despite being in contact with supersaturated solution, is a widely reported phenomenon. This concept of a growth ‘dead zone’ has been known for many years but its origin remains an unresolved problem in crystal growth. Sometimes it seems to be an inherent feature of the solution growth process while at others it appears that an impurity is an essential element for its appearance. Here we review existing data and provide new experimental evidence to confirm the widespread existence of the dead zone across a range of molecular materials. Available crystal growth kinetics are confronted with mechanistic models. Examination of the packing arrangements of appropriate crystal faces suggests that this behavior is linked to molecular scale surface roughness.

We describe here the synthesis and coordination properties of three new derivatives of [9]aneN3 containing phenyl/quinoline pendant arm derivatives (L1, L2 and L3, respectively) also featuring urea (L1-L2) or amide (L3) functions as "non-innocent" spacers. At first, L1, L2 and L3 were studied considering the interaction with a series of anions (AcO-, BzO-, H2PO4-, F-, and Cl-) by means of 1H NMR measurements. Subsequently, the optical responses of L2 and L3 in the presence of several metal ions Cd2+, Co2+, Cu2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Ni2+, Zn2+ and Pb2 were analysed in MeCN/H2O (4 : 1 v/v). As observed by spectrophotometric and spectrofluorimetric titrations, there were significant changes in the absorbance and fluorescent emission of L2 upon addition of increasing amounts of Cd2+, Zn2+, Pb2+ and Cu2+ in MeCN/H2O (4 : 1 v/v). In particular, titrations of L2 with Cd2+, Zn2+ or Pb2+ showed an almost comparable CHEF effect up to an M2+/L2 molar ratio of 1. Overall, no significant optical selectivity was observed in the case of L2. Conversely, L3 revealed an OFF-ON selective response only in the presence of the Zn2+ ion in MeCN/H2O (4 : 1 v/v), which can be attributed to the formation of both 1 : 1 and 1 : 2 metal-to-ligand complexes, as also confirmed by potentiometric measurements. Finally, crystals of [ZnL1(Ac)](Ac) (1), [CuL1(Cl)](Cl)·H2O (2) and [CuL3](NO3) (3) were grown and analysed by X-ray diffraction. 1 and 3 feature the metal center in a pseudo-octahedral coordination geometry coordinated also by the carbonyl group from one pendant arm, while in the case of 2, one of the six coordination sites in the final distorted octahedral geometry is occupied by the nitrogen donor from the urea group of one pendant arm.

Molecular self-assembly is the spontaneous association of simple molecules into larger and ordered structures

Three new molecular CT adducts with dihalogens, based on 5,5-dimethyl-2-thiohydantoin (dth) and 1,5, 5-trimethyl-2-thiohydantoin (mdth) donor molecules have been synthesised and characterised by single crystal X-ray diffraction and their crystal structures compared with those of previously published analogous compounds to assess the role of molecular shape of the donors, and cooperativity and competition between hydrogen-bonds (HBs) and halogen-bonds (XBs) in defining the observed supramolecular architectures at the solid state. The study of the role played by these factors was supported by several computational tools. The structural feature at the base of the crystal packings observed is the formation of dimers of donor molecules via complementary N–H⋯O or N–H⋯S HBs. These dimers are arranged in space in 2D architectures via further interactions involving the S/Se⋯I–I/Br XBs. Interestingly, in most of the cases the XB interactions strengthen upon formation of the self-assembled H-bonded dimers, indicating a favourable cooperativity effect which is at the base of the supramolecular architectures formed.

Here we report a family of bis-amide receptors for anion binding that contain carboxylic acid groups vicinal to the amide function. Deprotonation of the carboxylic acids decreases the acidity of amide NHs, switching on the anion binding ability of the deprotonated receptors with selectivity for fluoride complexation. The proposed systems represent a unique example of anionic receptors able to bind anions via H-bonding.

The reactivity of the 2-arylselanyl pyridine derivatives L1–L4 towards dihalogens X2 (X = I, Br) and interhalogens IX (X = Cl, Br) was studied in CHCl3 or CH3CN. The solid products obtained were structurally characterized and their nature points out the preference for CT spoke adducts and for seesaw insertion adducts to be formed at the N-donor and Se-donor site, respectively. DFT calculations were performed to provide a rationale for the structural diversity observed in the products obtained.

A new family of bis-methylureas (L1–L6) have been synthesised and their ability to bind anions both in solution and in the solid state and to transport them through lipid membrane have been studied. From the solid state studies it has emerged that various conformations can be adopted by the receptors allowing the isolation of complexes of different stoichiometries (from 1 : 1 to 1 : 3). The transport studies highlighted the possibility to use bis-methylureas to mediate Cl? transport across membranes.

Novel crystal packings of the aspirin molecule and 17 molecules that are related to aspirin by substitution are studied using a computational approach. The packings are created by taking a crystal structure for which the crystal packing and molecular geometry have been determined experimentally and replacing the native molecule with a different one. The resulting crystal structures are optimized using molecular mechanics, followed by a quantum mechanical method based on density functional theory and including a correction for dispersive interactions. There are 21 known, experimental, crystal structures for the molecules considered, some of which are polymorphic. For any given molecule, the lowest, calculated lattice energy is always found to be that of a crystal structure which corresponds to experiment. For the three polymorphic molecules, the second lowest lattice energy is also found to correspond to an experimental structure. The agreement between the observation of a particular packing and its low ra...

Herein, we report the synthesis and the anion binding properties of a family of N,N′-diphenylureas L1-L15, bearing on the aromatic ring(s) halogens (chlorine and iodine) and/or nitro or trifluoromethyl electron-withdrawing groups. The analysis of the crystal structures obtained from single crystal X-ray diffraction experiments shows that self-assembled chains or tapes connected via N–H···O hydrogen bonds are the most commonly adopted arrangements for this type of molecules in the crystal lattice. In the presence of anion guests or solvent molecules with competing hydrogen bond donors and acceptors, other supramolecular arrangements can be observed. Solution studies conducted in DMSOd 6/0.5% H2O by means of 1H-NMR titrations show the formation of 1:1 adducts with all receptors. The different observed affinities of the receptors for the anion guests were rationalised in terms of steric hindrance of the substituents on the phenyl rings and their electron-withdrawing properties.

Phase diagrams of cocrystals often show a highly unsymmetrical nature. The solvent has an important impact on the overall aspect of these diagrams. In this paper, we show how the solvent affects the composition of the stoichiometric solid phase nucleated. Suitable conditions for nucleation and growth of a single 2:1 caffeine/maleic acid cocrystal are obtained in ethyl acetate, showing comparable solubility toward both caffeine and maleic acid. Through a full kinetic screen, we were able to identify, for the first time, reproducible conditions for the spontaneous crystallization of the 2:1 phase in solution. Furthermore, during the screening experiments, a hithertho unknown form of the 1:1 cocrystal phase was encountered. Structural X-ray diffraction analyses of both the 2:1, as well as the 1:1 polymorphic phases, show an out of plane maleic acid compound. The carboxylic acid groups are oriented in such a manner to promote intermolecular formation of hydrogen bonded synthons.

From an initial crystallographic study of a large family of ring-substituted 2-acetoxybenzoic acids, only one member - the 5-chloro derivative - showed polymorphism, with two forms (α and β) identified, the former having a marginally higher melting point. The two structures show a close 1-D similarity through a row of carboxylic dimers connected viaCl⋯O halogen bonds, which assemble to give an approximate 2-D similarity by the stacking of these rows in a second direction. However, the further packing arrangement of the resulting 2-D stacks is significantly different in the two forms, through different symmetry arrangements and subtle variations in C–H⋯O weak hydrogen bonds. A parallel crystal structure prediction (CSP) calculation identified the two experimental polymorphs in the correct stability order with effective energy rankings of 2 and 3 (lattice energy difference of 0.2 kcal mol−1). The lowest energy crystal structure found during the CSP, as yet not found experimentally, is more stable than the lowest energy observed polymorph by 0.08 kcal mol−1. The predicted forms mostly comprise pairs of structures with nearly identical crystal structure arrangements, which differ only in the positioning of the carboxylate protons in the common carboxylate-carboxylate hydrogen-bonded dimers, relative to the positions of the neighboring acetyl substituents (syn or anti). The CSP calculations identify the correct isomer for each polymorph. One of the additional predicted forms is found to have 3-D packing similarity, and others partial similarities, with the crystal structures of particular members of the extended aspirin family.

A number of ring-substituted aspirin molecules have been synthesised and their crystal structures determined. All contain the strongly H-bonded carboxylate dimer found in the two forms of aspirin itself. Detailed analysis of the further packing of this dimer reveals that the 5-chloro, 5-bromo and 5-iodo derivatives form an isostructural group, as do the 5-fluoro, 5-methyl and 5-nitro derivatives. The 3-methyl and 4-methyl structures have close 3D similarity and may be classified as pseudoisostructural. The structures of the first two groups have a common 1D stack of dimers which contributes to two different 2D layers. One of the 2D layers is found in the fluoro, nitro and 5-methyl isostructures and also in the 3-methyl and 4-methyl derivatives. The second layer motif is found in the chloro, bromo and iodo groups and is also present in the fluoro, nitro and 5-methyl structures. The 6-methyl structure shares a 1D motif with the chloro, bromo and iodo groups. The packing variations are linked to different types of intermolecular interactions. In the 5-Cl, Br, and I groups, we find short Hal⋯O contacts to the carboxylate carbonyl; in the 5-F, 5-NO2 and 5-Me derivatives we find the acyl⋯acyl dimer interaction, present also in aspirin form I. In addition, the 5-F structure contains F⋯O short contacts to a carboxylate hydroxyl oxygen and in the 5-NO2 we find N–O⋯H–C contacts to an acyl methyl group.

Three fluorescent asymmetric bis-urea receptors (L1-L3) have been synthesised. The binding properties of L1-L3 towards different anions (fluoride, acetate, hydrogencarbonate, dihydrogen phosphate, and hydrogen pyrophosphate HPpi(3-)) have been studied by means of (1)H-NMR, UV-Vis and fluorescence spectroscopy, single crystal X-ray diffraction, and theoretical calculations. In particular, a remarkable affinity for HPpi(3-) has been observed in the case L1 (DMSO-d6/0.5% H2O) which also acts as a fluorimetric chemosensor for this anion. Interestingly, when L1 is included in cetyltrimethylammonium (CTAB) micelles, hydrogen pyrophosphate recognition can also be achieved in pure water.

Nine tris-urea receptors (L(1)-L(9)) have been synthesised and shown to coordinate to a range of anionic guests both by (1)H NMR titration techniques and single crystal X-ray structural analysis. The compounds have been shown to be capable of mediating the exchange of chloride and nitrate and also chloride and bicarbonate across POPC or POPC : cholesterol 7 : 3 vesicle bilayer membranes at low transporter loadings. An interesting dependency of anion transport on the nature of the cation is evidence to suggest that a M(+)/Cl(-) cotransport process may also contribute to the release of chloride from the vesicles.

We reply to the comments raised by Ośmialowski and Kolehmainen in their discussion on conformations of ureidic receptors as set out in our article (M. Olivari et al., New J. Chem., 2013, 37, 663–669). Here we appreciate the common views we share and welcome the clarity this gives, and we discuss and question some of their criticisms of the original paper and clarify our opinion in this area.

This review describes the recent advances in the development of imaging agents based on silica nanoparticles. Different techniques (magnetic resonance imaging, optical imaging, positron emission tomography, X-ray computed tomography, and ultrasound imaging) are described as well as the possibility of combining together different imaging techniques in the same nanoplatform and simultaneously performing imaging and therapy.

A new fluorescent sensor for the highly sensitive and selective determination of La 3+ ion is developed. The sensing membrane was prepared by incorporating N , N ′-bis(dansylamidoethyl)- N , N ′-bis(2-pyridylmethyl)propylenediamine (L) as fluoroionophore in the plasticized PVC membrane containing o-NPOE as plasticizer. The proposed sensor displays a wide calibration range of 5.0 × 10 −9 to 5.0 × 10 −4 M with a low limit of detection of 2.0 × 10 −9 M in a solution of pH 6.0. This sensor has a relatively fast response time of less than 2 min. In addition to high stability and reproducibility, it shows a unique selectivity toward La 3+ ion with respect to common coexisting cations. The sensor can be regenerated by exposure to a solution of EDTA. The proposed sensor was successfully applied to the determination of La 3+ in aqueous solutions.

Two new asymmetric ureidic receptors L1 (1-(1H-indol-7-yl)-3-(quinolin-2-yl)urea) and L2 (1-(quinolin-2-yl)-3-(quinolin-8-yl)urea) have been synthesised and their affinity towards different anions tested in DMSO-d6. L1 adopts both in solution and in the solid state an (E,Z) conformation. A moderate affinity for acetate has been observed for L1 while no interaction has been observed for L2. The different behaviour has been ascribed to the presence/absence of the indole group. In the case of L1 the indole group causes the formation of a peculiar supramolecular architecture with two molecules of the receptor binding the anions in the (E,Z) conformation via H-bonds. L2 also adopts an (E,Z) conformation in the solid state. However, the absence of the indole group in L2 hampers the formation of the supramolecular assembly with the participation of anionic species.

Crystal structure packing analyses of a family of monosubstituted salicylic acids, including some hydrates, show a surprisingly varied choice of supramolecular arrangements, even though the expected carboxyl–carboxyl dimer occurs in 17 of the 24 structures studied, and the 2-hydroxyl group hydrogen bonds with the carboxyl carbonyl oxygen in all molecules. In three of the four hydrates (3-MeO, 3NO2 and 5-Cl), the water molecules disrupt the carboxyl–carboxyl dimer to form a centrosymmetric [carboxyl–water]2 cluster. In the fourth hydrate, of the 5-acetamido (ACM) derivative, one water molecule forms an (ACM)CO⋯H–O(H)⋯H–O(carbox) single bridge. In the 4-ACM structure, the acetamido and carboxyl groups interact via (ACM)CO⋯H–O(carbox) and (ACM–Me)C–H⋯OC(carbox) double bridges, whilst the 6-MeO molecules, in which the carboxyl OH group is H-bonding intramolecularly to the MeO oxygen, forming catemers via bifurcating carboxyl OH and CO functions. The remaining outlier is the 5-amino (5-NH2) derivative, which exists in a zwitterionic form, with one carboxyl oxygen forming a short O⋯H–N intermolecular bond to an –NH3+ group, whilst the second oxygen forms three longer O⋯H–N bonds to three different –NH3+ groups. The larger, “normal” group of 17 derivatives adopt 16 different structures, generally comprising stacks of molecules with varying relative shifts of the molecular planes, and interactions involving the substituents. Surprisingly, the family contains only two polymorphic pairs, 5-Br α, β and 5-I α, β, in each of which the forms show low similarities, but two isostructures, the 5-Br α and 5-I β forms.

Structural data on further examples of substituted acetylsalicylic acid (aspirin) derivatives have revealed additional recurring sub-structure relationships, and have enabled a detailed comparative assessment of the significant involvement of weak intermolecular interactions and shape-related packing features in the crystal structure assembly. Amongst the new structures reported, that of the 6-fluoroacetylysalicylic acid provides the first example of a carboxylate catemer structure in this series of compounds. The catemers are linked together by a number of C–H⋯O interactions and a C–H⋯F interaction. The former set includes the centrosymmetric acetyl dimer, first recognized in the structure of aspirin polymorph I.

Conformational polymorphism has previously been observed in 2,2-dichloro-4,4:6,6-bis(2,2′-dimethlypropane-1,3-dioxy)-cyclotriphosphazene and the crystal structures of two forms were reported. In that study the melting points of both forms (α and β) were reported as 211–212 °C and no investigation was made on the stability of, or the thermodynamic relationships between the polymorphs. In the present work the two forms were characterized by various analytical techniques, such as single-crystal X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), thermomicroscopy (TM) and variable temperature single crystal and powder X-ray diffraction. Thermal analysis suggests that the polymorphs are enantiotropically related and it is found that the solid–solid transformation of the β to α form may start with defects of α form inside the β form followed by a nucleation and growth type mechanism involving at least three main molecular centred events; conformational change, rotation and tilting.

The reactivity of zinc complexes with N,S-donor molecules may be of relevance to the study of Zn-metalloproteins and -metalloenzymes. In this context, the zinc complex [Zn(MeImSH)2I2] was synthesised by the reaction of zinc powder with the 1:1 iodine adduct of the drug methimazole [(MeImSH)·I2]. The molecular structure of the complex, elucidated by X-ray diffraction analysis, showed a tetrahedral zinc(II) centre coordinated by two neutral methimazole units (through the sulfur atoms) and two iodides. From the reaction of MeImSH and Zn powder, the complex [Zn(MeImSH)(MeImS)2] (MeImS = deprotonated form of methimazole) was separated and characterised. An analysis of the crystal packing of the neutral complexes [Zn(MeImSH)2X2] (X = I, Br and Cl) and the ionic complex [Zn(MeImSH)3I]I showed that in all of the complexes the sulfur atom, in addition to binding to the metal centre, contributes to the formation of 1-D chains built via C(4)–H⋯S and N–H⋯X interactions in the neutral complexes, and via C(4)–H⋯S and N–CH3⋯S interactions in the ionic complex [Zn(MeImSH)3I]I. The deprotonation/protonation of the coordinated methimazole units can modulate the coordination environment at the Zn core. From the reaction of complex [Zn(MeImSH)3I]I with a strong non-coordinating organic base, we have shown that, as a consequence of the NH deprotonation of methimazole S-coordinated to zinc(II), the ligand coordination mode changes from S-monodentate to N,S-bridging. Correspondingly, in the complex [Zn(MeImSH)(MeImS)2], the MeImS that displays the N,S-bridging mode at zinc can be N-protonated and thereby changes to the S-monodentate coordination.

A new family of bis-ureidic receptors (L(1)-L(6)) has been synthesised. The binding properties of L(1)-L(6) towards different anions (acetate, benzoate, glutarate, malonate, dihydrogen phosphate, hydrogen pyrophosphate, triphosphate, AMP and ADP) have been studied by means of (1)H-NMR, UV-Vis and fluorescence spectroscopies and a remarkable affinity for HPpi(3-) has been observed in the case L(3) (in DMSO-d6 and DMSO-d6-5% H2O) which also acts as a fluorimetric chemosensor, even to the naked eye, for this anion. Theoretical calculations helped us explain the binding properties observed.

Four new fluorescent chemosensors for metal ions based on 8-hydroxyquinoline (8-HDQ) derivatives and sulfur-containing macrocyclic units were synthesized and characterized, namely 1-(5-chloro-8-hydroxy-7-quinolinylmethyl)-1-aza-4,7,10-trithiacyclododecane (L1), 1-(5-chloro-8-hydroxy-7-quinolinylmethyl)-1-aza-4,13-dithia-7,10-dioxacyclopentadecane (L2), 1-(8-hydroxy-2-quinolinylmethyl)-1-aza-4,7,10-trithiacyclododecane (L3), and 1-(8-hydroxy-2-quinolinylmethyl)-1-aza-4,13-dithia-7,10-dioxacyclopentadecane (L4). Preliminary fluorimetric titrations indicated L1 as the only member of the family of ligands to give a selective CHEF-type response to the presence of Zn(2+) in MeCN-H2O (1:1, v/v) solutions, which allowed imaging of this metal ion in Cos-7 cells in vitro. The other ligands either did not show any fluorescence response (L3, L4) to any of the metal ions considered (Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Pb(2+)) or gave (L2) a CHEF-type response also to the presence of Cd(2+). The coordination properties of L1 towards Zn(2+) were, therefore, fully investigated by potentiometric measurements and absorption and emission spectroscopy at different pH values, which indicated that the formation of 2:1 L1/Zn(2+) complexes is responsible for the CHEF-type effect observed. The complexes [Zn(L1)2H2O](BF4)2 and [Zn(L3)](ClO4)2 were characterized in the solid state by X-ray crystallography, and DFT calculations were performed to understand the origin of the Zn(2+)/Cd(2+) optical discrimination of the 8-HDQ-based "conjugate" fluorescent chemosensors reported.