Exploring the Co-Crystallization Landscape of One-Dimensional Coordination Polymers Using a Molecular Electrostatic Potential-Driven Approach.

The ability of coordination polymers (CPs) to form multicomponent heteromeric materials, where the key structural features of the parent CP are retained, has been explored via molecular electrostatic potential-driven co-crystallization technologies. Thirteen co-formers presenting hydrogen-bond donors activated through a variety of electron-withdrawing functionalities were employed, and the extent of activation was evaluated using molecular electrostatic potential values. Attempted co-crystallizations of the seven most promising co-formers with a family of nine CPs ([CdX'2(X-pz)2]n; X' = I, Br, and Cl; X = I, Br, and Cl) resulted in six successful outcomes; all four of the structurally characterized compounds displayed the intended hydrogen bond. The rationalization of the main structural features revealed that strict structural and electrostatic requirements were imposed on effective co-formers; only co-formers with highly activated hydrogen-bond donors, and with a 1,4-orientation of electron-withdrawing moieties bearing effective acceptor sites, were successfully implemented into the three-dimensional architectures composed of one-dimensional building units of CPs.

Competition between chalcogen and halogen bonding assessed through isostructural species.

The amino group of 2-amino-5-(4-halophenyl)-1,3,4-chalcogenadiazole has been replaced with bromo/iodo substituents to obtain a library of four compositionally related compounds. These are 2-iodo-5-(4-iodophenyl)-1,3,4-thiadiazole, C8H4I2N2S, 2-bromo-5-(4-bromophenyl)-1,3,4-selenadiazole, C8H4Br2N2Se, 2-bromo-5-(4-iodophenyl)-1,3,4-selenadiazole, C8H4BrIN2Se, and 2-bromo-5-(4-iodophenyl)-1,3,4-thiadiazole, C8H4BrIN2S. All were isostructural and contained bifurcated Ch...N (Ch is chalcogen) and X...X (X is halogen) interactions forming a zigzag packing motif. The noncovalent Ch...N interaction between the chalcogen-bond donor and the best-acceptor N atom appeared preferentially instead of a possible halogen bond to the same N atom. Hirshfeld surface analysis and energy framework calculations showed that, collectively, a bifurcated chalcogen bond was stronger than halogen bonding and this is more structurally influential in this system.

Evaluating structure-property relationship in a new family of mechanically flexible co-crystals.

A structure-property analysis of ten compositionally and chemically similar co-crystals of N-(pyridin-2-yl)alkylamides and carboxylic acids shows that three co-crystals of targets bearing a methyl chain were brittle, while the remaining co-crystals of targets bearing ethyl or propyl chains were flexible. Five of these displayed elastic deformation while two displayed plastic deformation. Compounds with different mechanical behaviour (brittle, plastic, and elastic deformation) in response to external mechanical stimuli could be organized into structurally similar groups based on the presence of specific intermolecular interactions and packing features in each crystal structure.

Influence of Multiple Binding Sites on the Supramolecular Assembly of N-[(3-pyridinylamino) Thioxomethyl] Carbamates.

In this study, we investigated how the presence of multiple intermolecular interaction sites influences the heteromeric supramolecular assembly of N-[(3-pyridinylamino) thioxomethyl] carbamates with fluoroiodobenzenes. Three targets­R-N-[(3-pyridinylamino) thioxomethyl] carbamate (R = methyl, ethyl, and isobutyl)­were selected and crystallized, resulting in three parent structures, five co-crystals, and one co-crystal solvate. Three hydrogen-bonded parent crystal structures were stabilized by N-H···N hydrogen bonding and assembled into layers that stacked on top of one another. Molecular electrostatic potential surfaces were employed to rank binding sites (Npyr > C=S > C=O) in order to predict the dominant interactions. The N-H⋯H hydrogen bond was replaced by I⋯Npyr in 3/6 cases, I⋯C=S in 4/6 cases, and I⋯O=C in 1 case. Interestingly, the I⋯C=S halogen bond coexisted twice with I⋯Npyr and I⋯O=C. Overall, the MEPs were fairly reliable for predicting co-crystallization outcomes; however, it is crucial to also consider factors such as molecular flexibility. Finally, halogen-bond donors are capable of competing for acceptor sites, even in the presence of strong hydrogen-bond donors.

Intermolecular binding preferences of haloethynyl halogen-bond donors as a function of molecular electrostatic potentials in a family of N-(pyridin-2-yl)amides.

In order to explore how σ-hole potentials, as evaluated by molecular electrostatic potential (MEP) calculations, affect the ability of halogen atoms to engage in structure-directing intermolecular interactions, we synthesized four series of ethynyl halogen-substituted amide containing pyridines (activated targets); (N-(pyridin-2-yl)benzamides (Bz-act-X), N-(pyridin-2-yl)picolinamides (2act-X), N-(pyridin-2-yl)nicotinamides (3act-X) and N-(pyridin-2-yl) isonicotinamides (4act-X), where X = Cl/Br/I. The molecules are deliberately equipped with three distinctly different halogen-bond acceptor sites, π, N(pyr), and O[double bond, length as m-dash]C, to determine binding site preferences of different halogen-bond donors. Crystallographic data for ten (out of a possible twelve) new compounds were thus analyzed and compared with data for the corresponding unactivated species. The calculated MEPs of all the halogen atoms were higher in the activated targets in comparison to the unactivated targets and were in the order of iodine ≈ chloroethynyl < bromoethynyl < iodoethynyl. This increased positive σ-hole potential led to a subsequent increase in propensity for halogen-bond formation. Two of the four chloroethynyl structures showed halogen bonding, and all three of the structurally characterized bromoethynyl species engaged in halogen bonding. The analogous unactived species showed no halogen bonds. Each chloroethynyl donor selected a π-cloud as acceptor and the bromoethynyl halogen-bond donors opted for either π or N(pyr) sites, whereas all halogen bonds involving an iodoethynyl halogen-bond donor (including both polymorphs of Bz-act-I) engaged exclusively with a N(pyr) acceptor site.

The Balance between Hydrogen Bonds, Halogen Bonds, and Chalcogen Bonds in the Crystal Structures of a Series of 1,3,4-Chalcogenadiazoles.

In order to explore how specific atom-to-atom replacements change the electrostatic potentials on 1,3,4-chalcogenadiazole derivatives, and to deliberately alter the balance between intermolecular interactions, four target molecules were synthesized and characterized. DFT calculations indicated that the atom-to-atom substitution of Br with I, and S with Se enhanced the σ-hole potentials, thus increasing the structure directing ability of halogen bonds and chalcogen bonds as compared to intermolecular hydrogen bonding. The delicate balance between these intermolecular forces was further underlined by the formation of two polymorphs of 5-(4-iodophenyl)-1,3,4-thiadiazol-2-amine; Form I displayed all three interactions while Form II only showed hydrogen and chalcogen bonding. The results emphasize that the deliberate alterations of the electrostatic potential on polarizable atoms can cause specific and deliberate changes to the main synthons and subsequent assemblies in the structures of this family of compounds.

Establishing Halogen-Bond Preferences in Molecules with Multiple Acceptor Sites.

The interplay between hydrogen bonds (HBs) and halogen bonds (XBs), has been addressed by co-crystallizing two halogen bond donors, 1,4-diiodotetrafluorbenzene(DITFB) and 1,3,5-trifluoro-2,4,6-triiodobenzene(TITFB) with four series of targets; N-(pyridin-2-yl)benzamide (Bz-X), N-(pyridin-2-yl)picolinamides (2Pyr-X), N-(pyridin-2-yl)nicotinamides (3Pyr-X), N-(pyridin-2-yl)isonicotinamides (4Pyr-X); X=H/Cl/Br/I. The structural outcomes were compared with interactions in the targets themselves. 13 co-crystals were analysed by single-crystal X-ray diffraction (SCXRD). In all three co-crystals from the 2Pyr series, the intramolecular HB remained intact while the XB donors engaged with the N(pyr) or O=C sites. In the ten co-crystals from the other three series, the intermolecular HBs present in the individual targets were disrupted in 9/10 cases. Overall, the acceptor sites selected by the halogen-bond donors in these targets were distributed as follows; N(pyr)=81 %, O=C (15 %) or π (4 %).

The Impact of Halogen Substituents on the Synthesis and Structure of Co-Crystals of Pyridine Amides.

Strategies for co-crystal synthesis tend to employ either hydrogen- or halogen-bonds between different molecules. However, when both interactions are present, the structural influence that they may exert on the resulting assembly is difficult to predict a priori. To shed some light on this supramolecular challenge, we attempted to co-crystallize ten aliphatic dicarboxylic acids (co-formers) with three groups of target molecules; N-(pyridin-2-yl)picolinamides (2Pyr-X), N-(pyridin-2-yl)nicotinamides (3Pyr-X), N-(pyridin-2-yl)isonicotinamides (4Pyr-X); X=Cl/ Br/ I. The structural outcomes were compared with co-crystals prepared from the non-halogenated targets. As expected, none of the reactions with 2Pyr-X produced co-crystals due to the presence of a very stable intramolecular N-H···N hydrogen bond. In the 3Pyr series, all six structures obtained showed the same synthons, -COOH···N(py) and -COOH···N(py)-NH, that were found in the non-halogenated parent 3Pyr and were additionally accompanied by structure directing X···O(OH) interactions (X=Br/I). The co-crystals of the unhalogenated parent 4Pyr co-crystals assembled via intermolecular -COOH···N(py) and -COOH···N(py)-NH synthons. Three of the analogues 4Pyr-X co-crystals displayed only COOH···N(py) and -COOH···N(py)-NH interactions. The three co-crystals of 4Pyr-X with fumaric acid (for which no analogues structures with 4Pyr are known) formed -COOH···N(py)-NH and -NH···O=C hydrogen bonds and showed no structure-directing halogen bonds. In three co-crystals of 4Pyr-I in which -COOH···N(py)-NH hydrogen bond was present, a halogen-bond based -I···N(py) synthon replaced the -COOH···N(py) motif observed in the parent structures. The structural influence of the halogen atoms increased in the order of Cl < Br < I, as the size of σ-holes increased. Finally, it is noteworthy that isostructurality among structures of the homomeric targets was not translated to structural similarities between their respective co-crystals.

Exploring and predicting intermolecular binding preferences in crystalline Cu(ii) coordination complexes.

A simple model focusing on electrostatic contributions to interaction energies was found to be very effective for rationalizing the appearance of specific supramolecular interactions in a series of Cu(ii) coordination compounds. The experimental space was provided by a combination of Cu(ii) cations with acac-based anions (hexafluoracetylacetonato and trifluoracetylacetonato) and a series of pyridine-oxime ligands (3-pyridinealdoxime, methyl 3-pyridyl ketoxime, 4-pyridinealdoxime, methyl 4-pyridyl ketoxime, phenyl 4-pyridyl ketoxime). The calculated molecular electrostatic potential (MEP) values at competing hydrogen-bond acceptor sites, for ten structurally characterized complexes, provided guidelines for predicting supramolecular connectivity in cases when the MEP difference exceeded certain cut-off values, while two different and well-defined outcomes are possible within the so called 'grey zone', delineated by a range of MEP differences. It was also shown that the structural outcome within this region is determined by the influence of relatively weak, but distinct, auxillary interactions.

Mechanically Responsive Crystalline Coordination Polymers with Controllable Elasticity.

Crystalline coordination polymers tend to be brittle and inelastic, however, we now describe a family of such compounds that are capable of displaying mechanical elasticity in response to external pressure. The design approach successfully targets structural features that are critical for producing the desired mechanical output. The elastic crystals all comprise 1D cadmium(II) halide polymeric chains with adjacent metal centres bridged by two halide ions resulting in the required stacking interactions and short "4 Å" crystallographic axes. These polymeric chains (structural "spines") are further organized via hydrogen bonds and halogen bonds perpendicular to the direction of the chains. By carefully altering the strength and the geometry of these non-covalent interactions, we have demonstrated that it is possible to control the extent of elastic bending in crystalline coordination compounds.

Modulating the physical properties of solid forms of urea using co-crystallization technology.

The solid-form landscape of urea was explored using full interaction maps (FIMs) and data from the CSD to develop optimum protocols for synthesizing co-crystals of urea. As a result, 49 of the 60 attempted reactions produced new co-crystals, and the crystal structures of four of these are presented. Moreover, the goal of reducing the solubility and lowering the hygroscopicity of the parent compound was achieved, which in turn offers new opportunities for application as a slow-release fertilizer with limited hygroscopicity, thereby reducing many current problems of transport, handling, and storage of urea.

Structural Examination of Halogen-Bonded Co-Crystals of Tritopic Acceptors.

A series of tritopic N-heterocyclic compounds containing electrostatically and geometrically equivalent binding sites were synthesized and subjected to systematic co-crystallizations with selected perfluoroiodoarenes in order to map out their structural landscapes. More than 70% of the attempted reactions produced a co-crystal as indicated by IR spectroscopy. Four new crystal structures are reported and in all of them, at least one potential binding site on the acceptor is left vacant. The absence of halogen bonds to all sites can be ascribed primarily due to deactivation of the σ-hole on the iodo-arene donors and partially due to steric hindrance. The tritopic acceptors containing 5,6-dimethylbenzimidazole derivatives yield discrete tetrameric aggregates in the solid state, whereas the pyrazole and imidazole analogues assemble into halogen-bonded 1-D chains.

Building inorganic supramolecular architectures using principles adopted from the organic solid state.

In order to develop transferable and practical avenues for the assembly of coordination complexes into architectures with specific dimensionality, a strategy utilizing ligands capable of simultaneous metal coordination and self-complementary hydrogen bonding is presented. The three ligands used, 2(1H)-pyrazinone, 4(3H)-pyrimidinone and 4(3H)-quinazolinone, consistently deliver the required synthetic vectors in a series of CdII coordination polymers, allowing for reproducible supramolecular synthesis that is insensitive to the different steric and geometric demands from potentially disruptive counterions. In all nine crystallographically characterized compounds presented here, directional intermolecular N-H⋯O hydrogen bonds between ligands on adjacent complex building blocks drive the assembly and orientation of discrete building blocks into largely predictable topologies. Furthermore, whether the solids are prepared from solution or through liquid-assisted grinding, the structural outcome is the same, thus emphasizing the robustness of the synthetic protocol. The details of the molecular recognition events that take place in this series of compounds have been clearly delineated and rationalized in the context of calculated molecular electrostatic potential surfaces.

A new tecton with parallel halogen-bond donors: a path to supramolecular rectangles.

A new tecton, 1,8-diiodoethynylanthracene, with two halogen-bond donor sites was synthesized and characterized. This tecton is capable of forming two parallel halogen bonds at once, which makes it a useful building block for the construction of a variety of supramolecular squares and rectangles.

Probing Metal Ion Complexation of Ligands with Multiple Metal Binding Sites: The Case of Spiropyrans.

Among known molecular switches, spiropyrans attract considerable interest because of their reversible responsiveness to external stimuli and the deep conformational and electronic changes that characterize the switching process between the two isomeric forms [spiropyran (SP) and merocyanine (MC)]. Metal coordination is one of the most interesting aspects of spiropyrans for its potential in sensing, catalysis, and medicinal chemistry, but little is known about the details surrounding spiropyran-metal ion binding. We investigated the interplay between an N-modified 8-methoxy-6-nitrospiropyran (SP-E), designed to provide appropriate molecular flexibility and a range of competing/collaborative metal binding sites, with Mg2+ , Cu2+ and Zn2+ , which were chosen for their similar coordination geometry preferences while differing in their hard/soft character. The formed molecular complexes were studied by means of UV/Vis, fluorescence, and NMR spectroscopies and mass spectrometry, and the crystal structure of the SP-E-Cu complex was also obtained. The results indicate that the Mg2+ , Zn2+ and Cu2+ complexes have identical coordination stoichiometry. Furthermore, the Mg2+ and Zn2+ complexes display fluorescence properties in solution and visible-light responsiveness. These results provide important spectroscopic and structural information that can serve as a foundation for rational design of spiropyran-based smart materials for metal sensing and scavenging applications.

A systematic structural study of halogen bonding versus hydrogen bonding within competitive supramolecular systems.

As halogen bonds gain prevalence in supramolecular synthesis and materials chemistry, it has become necessary to examine more closely how such interactions compete with or complement hydrogen bonds whenever both are present within the same system. As hydrogen and halogen bonds have several fundamental features in common, it is often difficult to predict which will be the primary interaction in a supramolecular system, especially as they have comparable strength and geometric requirements. To address this challenge, a series of molecules containing both hydrogen- and halogen-bond donors were co-crystallized with various monotopic, ditopic symmetric and ditopic asymmetric acceptor molecules. The outcome of each reaction was examined using IR spectroscopy and, whenever possible, single-crystal X-ray diffraction. 24 crystal structures were obtained and subsequently analyzed, and the synthon preferences of the competing hydrogen- and halogen-bond donors were rationalized against a background of calculated molecular electrostatic potential values. It has been shown that readily accessible electrostatic potentials can offer useful practical guidelines for predicting the most likely primary synthons in these co-crystals as long as the potential differences are weighted appropriately.