Refreshing the Legacy of Rudolf Nietzki: Benzene-1,2,4,5-tetramine and Related Compounds.

Like hydroquinones and quinones, aromatic compounds with multiple NH2 groups and the corresponding quinonediimines have the potential to serve as components of useful redox-active organic materials. Benzene-1,2,4,5-tetramine (BTA) and its oxidized form BTA-H2 offer a promising redox pair of this type, and the compounds have proven to be useful in many areas of chemistry. However, key aspects of their behavior have remained poorly studied, such as the nature of their protonated forms, their preferred molecular structures, their reactivity, and their organization in condensed phases. In the present work, we have used a combination of improved methods of synthesis, computation, spectroscopic studies, and structural analyses to develop a deeper understanding of BTA, BTA-H2, their salts, and related compounds. The new knowledge is expected to accelerate exploitation of the compounds in areas of materials science where desirable properties can only be attained by properly controlling the organization of molecular components.

Seeking Rules Governing Mixed Molecular Crystallization.

Mixed crystals result when components of the structure are randomly replaced by analogues in ratios that can be varied continuously over certain ranges. Mixed crystals are useful because their properties can be adjusted by increments, simply by altering the ratio of components. Unfortunately, no clear rules exist to predict when two compounds are similar enough to form mixed crystals containing substantial amounts of both. To gain further understanding, we have used single-crystal X-ray diffraction, computational methods, and other tools to study mixed crystallizations within a selected set of structurally related compounds. This work has allowed us to begin to clarify the rules governing the phenomenon by showing that mixed crystals can have compositions and properties that vary continuously over wide ranges, even when the individual components do not normally crystallize in the same way. Moreover, close agreement of the results of our experiments and computational modeling demonstrates that reliable predictions about mixed crystallization can be made, despite the complexity of the phenomenon.

Diphenoquinhydrones and Related Hydrogen-Bonded Charge-Transfer Complexes.

Benzoquinone and hydroquinone cocrystallize to form quinhydrone, a 1:1 complex with a characteristic structure in which the components are positioned by hydrogen bonds and charge-transfer interactions. We have found that analogous diphenoquinhydrones can be made by combining 4,4'-diphenoquinones with the corresponding 4,4'-dihydroxybiphenyls. In addition, mixed diphenoquinhydrones can be assembled from components with different substituents, and mismatched quinhydrones can be made from benzoquinones and dihydroxybiphenyls. In all cases, the components of the resulting structures are linked in alternation by O-H···O hydrogen bonds to form essentially planar chains, which stack to produce layers in which π-donors and π-acceptors are aligned by charge-transfer interactions. Geometric parameters, computational studies, and spectroscopic properties of diphenoquinhydrones show that the key intermolecular interactions are stronger than those in simple quinhydrone analogues. These findings demonstrate that the principles of modular construction underlying the formation of classical quinhydrones can be generalized to produce a broad range of hydrogen-bonded charge-transfer materials in which the components are positioned by design.

Diphenoquinones Redux.

Benzoquinones can undergo reversible reductions and are attractive candidates for use as active materials in green carbon-based batteries. Related compounds of potential utility include 4,4'-diphenoquinones, which have extended quinonoid structures with two carbonyl groups in different rings. Diphenoquinones are a poorly explored class of compounds, but a wide variety can be synthesized, isolated, crystallized, and fully characterized. Experimental and computational approaches have established that typical 4,4'-diphenoquinones have nearly planar cores in which two cyclohexadienone rings are joined by an unusually long interannular C═C bond. Derivatives unsubstituted at the 3,3',5,5'-positions react readily by hydration, dimerization, and other processes. Association of diphenoquinones in the solid state normally produces chains or sheets held together by multiple C-H···O interactions, giving structures that differ markedly from those of the corresponding 4,4'-dihydroxybiphenyls. Electrochemical studies in solution and in the solid state show that diphenoquinones are reduced rapidly and reversibly at potentials higher than those of analogous benzoquinones. Together, these results help bring diphenoquinones into the mainstream of modern chemistry and provide a foundation for developing redox-active derivatives for use in carbon-based electrochemical devices.

Surprising Chemistry of 6-Azidotetrazolo[5,1-a]phthalazine: What a Purported Natural Product Reveals about the Polymorphism of Explosives.

6-Azidotetrazolo[5,1-a]phthalazine (ATPH) is a nitrogen-rich compound of surprisingly broad interest. It is purported to be a natural product, yet it is closely related to substances developed as explosives and is highly polymorphic despite having a nearly planar structure with little flexibility. Seven solid forms of ATPH have been characterized by single-crystal X-ray diffraction. The structures show diverse patterns of molecular organization, including both stacked sheets and herringbone packing. In all cases, N···N and C-H···N interactions play key roles in ensuring molecular cohesion. The high polymorphism of ATPH appears to arise in part from the ability of virtually every atom of nitrogen and hydrogen in the molecule to take part in close N···N and C-H···N contacts. As a result, adjacent molecules can adopt many different relative orientations that are energetically similar, thereby generating a polymorphic landscape with an unusually high density of potential structures. This landscape has been explored in detail by the computational prediction of crystal structures. Studying ATPH has provided insights into the field of energetic materials, where access to multiple polymorphs can be used to improve performance and clarify how it depends on molecular packing. In addition, our work with ATPH shows how valuable insights into molecular crystallization, often gleaned from statistical analyses of structural databases, can also come from in-depth empirical and theoretical studies of single compounds that show distinctive behavior.

Using Nuclear Magnetic Resonance Spectroscopy to Probe Hydrogels Formed by Sodium Deoxycholate.

Hydrogels of bile acids and their salts are promising materials for drug delivery, cellular immobilization, and other applications. However, these hydrogels are poorly understood at the molecular level, and further study is needed to allow improved materials to be created by design. We have used NMR spectroscopy to probe hydrogels formed from mixtures of formic acid and sodium deoxycholate (NaDC), a common bile acid salt. By assaying the ratio of deoxycholate molecules that are immobilized as part of the fibrillar network of the hydrogels and those that can diffuse, we have found that 65% remain free under typical conditions. The network appears to be composed of both the acid and salt forms of deoxycholate, possibly because a degree of charge inhibits excessive aggregation and precipitation of the fibrils. Spin-spin relaxation times provided a molecular-level estimate of the temperature of gel-sol transition (42 °C), which is virtually the same as the value determined by analyzing macroscopic parameters. Saturation transfer difference (STD) NMR spectroscopy established that formic acid, which is present mainly as formate, is not immobilized as part of the gelating network. In contrast, HDO interacts with the network, which presumably has a surface with exposed hydrophilic groups that form hydrogen bonds with water. Moreover, the STD NMR experiments revealed that the network is a dynamic entity, with molecules of deoxycholate associating and dissociating reversibly. This exchange appears to occur preferentially by contact of the hydrophobic edges or faces of free molecules of deoxycholate with those of molecules immobilized as components of the network. In addition, DOSY experiments revealed that gelation has little effect on the diffusion of free NaDC and HDO.

Designing Tetraoxa[8]circulenes To Serve as Hosts and Sensors.

In D4-symmetric tetraoxa[8]circulenes, alternating fused benzene and furan rings form an octagonal array. These compounds are little known despite their novel properties, which include extended planar π-conjugation and a formally antiaromatic cyclooctatetraene core. Tetraoxa[8]circulenes can be formed by acid-induced cyclocondensations of suitable quinones, but existing methods often give very low yields. In addition, π-stacking of simple tetraoxa[8]circulenes reduces solubility and limits opportunities to form homogeneous mixtures or cocrystals with other compounds. To help make tetraoxa[8]circulenes more useful, we have developed better ways to synthesize them, and we have used these methods to produce awkwardly shaped derivatives with large concave electron-rich aromatic surfaces. These compounds crystallize to form open structures that can accommodate various guests, including C60. Analysis of the structures shows that the cyclooctatetraene core of the hosts exhibits surprising variations in C-C bond lengths and conjugation, which appear to be related to the gain or loss of aromaticity. This allows tetraoxa[8]circulenes to serve as sensitive probes of local molecular environment and to be used as sensors of electron-deficient species such as nitroaromatic compounds.

Predicting pKa Values of Quinols and Related Aromatic Compounds with Multiple OH Groups.

Quinonoid compounds play central roles as redox-active agents in photosynthesis and respiration and are also promising replacements for inorganic materials currently used in batteries. To design new quinonoid compounds and predict their state of protonation and redox behavior under various conditions, their pKa values must be known. Methods that can predict the pKa values of simple phenols cannot reliably handle complex analogues in which multiple OH groups are present and may form intramolecular hydrogen bonds. We have therefore developed a straightforward method based on a linear relationship between experimental pKa values and calculated differences in energy between quinols and their deprotonated forms. Simple adjustments allow reliable predictions of pKa values when intramolecular hydrogen bonds are present. Our approach has been validated by showing that predicted and experimental values for over 100 quinols and related compounds differ by an average of only 0.3 units. This accuracy makes it possible to select proper pKa values when experimental data vary, predict the acidity of quinols and related compounds before they are made, and determine the sites and orders of deprotonation in complex structures with multiple OH groups.

Phosphangulene: A Molecule for All Chemists.

Phosphangulene (1) is a hexacyclic triarylphosphine with a distinctive conical shape and other features that allow the compound to be viewed from diverse perspectives and to be embraced by chemists from different parts of the field as a molecule worthy of special attention. In recent work, phosphangulene and its derivatives have proven to be effective tools for probing general principles that govern molecular organization in solids. The phosphangulene family is particularly well-suited for these studies because systematic structural changes in the compounds are easy to introduce. In crystals of phosphangulene itself, molecules are stacked efficiently like hats, giving rise to an R3m structure that is polar and pyroelectric. Simple conversion of the compound into phosphangulene oxide (7a) or other chalcogenides blocks effective stacking and forces crystallization to produce alternative structures that have many suboptimal intermolecular interactions and vary little in energy as their geometries are altered. This leads to high levels of polymorphism, and phosphangulene oxide (7a) belongs to the elite set of compounds known to exist in five or more forms characterized by single-crystal X-ray diffraction. For similar reasons, phosphangulene chalcogenides form crystals with complex unit cells in which multiple inequivalent molecules are needed to optimize packing, and the compounds are also predisposed to form solvates and mixed crystals containing other molecules. For example, crystallization of a 1:1 mixture of phosphangulene and oxide 7a yielded needles composed of pure phosphangulene along with crystals of the oxide containing substantial amounts of phosphangulene. Phosphangulene has one known polymorph, and its crystallization rejects the oxide. In contrast, the oxide is highly polymorphic, and its crystallization is prone to errors in which molecules in the lattice are replaced by other compounds. Packing in crystals of the oxide appears to be so ineffective that the orientation and even the identity of the molecular components can be varied without imposing severe energetic penalties.Because substituted members of the phosphangulene family have awkward curved shapes that cannot be packed efficiently, they have emerged as highly effective partners for cocrystallizing fullerenes and for using concave-convex interactions to control how fullerenes can be organized in materials. This can be achieved without eliminating fullerene-fullerene contacts of the type needed to ensure conductivity. In addition, phosphangulene has created unlimited opportunities for making complex structures with large curved aromatic surfaces based on a new strategy in which the central atom of phosphorus is used to form covalent bonds with other elements or to introduce coordinative interactions with metals. In these ways, recent work has put phosphangulene in the spotlight as a compound of unusually broad interest and shown that it can appropriately be called a molecule for all chemists.

Atoms and the void: modular construction of ordered porous solids.

For millennia, humans have exploited the special properties of porous materials. Advances in recent years have yielded a new generation of finely structured porous materials that allow processes to be controlled at the molecular level. These materials are built by a strategy of modular construction, using molecular components designed to position their neighbors in ways that create predictable voids.

ROY Reclaims Its Crown: New Ways To Increase Polymorphic Diversity.

Chemical compounds that exist in multiple crystalline forms are said to exhibit polymorphism. Polymorphs have the same composition, but their structures and properties can vary markedly. In many fields, conditions for crystallizing compounds of interest are screened exhaustively to generate as many polymorphs as possible, from which the most advantageous form can be selected. We report new ways to search for polymorphs and increase polymorphic diversity, based on crystallization induced by suitably designed mixed-crystal seeds. The potential of the strategy has been demonstrated by using it to produce new polymorphs of the benchmark compound ROY as single crystals structurally characterized by X-ray diffraction. This allows ROY to reclaim its crown as the most polymorphic compound in the Cambridge Structural Database. More generally, the methods promise to become valuable tools for polymorphic screening in all fields where crystalline solids are used.

Modular Construction of Porous Hydrogen-Bonded Molecular Materials from Melams.

Ordered materials with predictable structures and properties can be made by a modular approach, using molecules designed to interact with neighbors and hold them in predetermined positions. Incorporating 4,6-diamino-1,3,5-triazin-2-yl (DAT) groups in modules is an effective way to direct assembly because each DAT group can form multiple N-H⋅⋅⋅N hydrogen bonds according to established patterns. We have found that modules with high densities of N(DAT)2 groups can be made by base-induced double triazinylations of readily available amines. The resulting modules can form structures held together by remarkably large numbers of hydrogen bonds per molecule. Even simple modules with only 1-3 N(DAT)2 groups and fewer than 70 non-hydrogen atoms can crystallize to form highly open networks in which each molecule engages in over 20 N-H⋅⋅⋅N hydrogen bonds, and more than 70 % of the volume is available for accommodating guests. In favorable cases, guests can be removed to create rigorously porous crystalline solids analogous to zeolites and metal-organic frameworks.

Controlling Molecular Organization by Using Phenyl Embraces of Multiple Trityl Groups.

Sixfold phenyl embraces are well-established aromatic interactions that are strong and directional. In addition, functional groups that are able to participate, such as triphenylmethyl (trityl), are easily incorporated in molecular structures. As a result, embraces offer a possible way to control molecular organization in materials. To test this notion, we used a hybrid organic-inorganic strategy to make compounds with multiple trityl groups. Trityl-substituted alkynylpyridines 3-5 react with Pd(II) to form square-planar 4:1 complexes with multiple divergent trityl groups poised to engage in embraces. The complexes were crystallized, and their structures were determined by X-ray diffraction. Surprisingly, few structures in this set of compounds were found to incorporate sixfold embraces. Our observations suggest that predictable molecular organization cannot normally be achieved using these embraces, which must compete with alternative aromatic interactions of similar energy.

Building Large Structures with Curved Aromatic Surfaces by Complexing Metals with Phosphangulene.

Phosphangulene (1) is a hexacyclic triarylphosphine with a distinctive conical shape and an electron-rich aromatic surface that is geometrically and electronically complementary to fullerenes such as C60 and C70. As a result, suitable derivatives of phosphangulene can cocrystallize with fullerenes or even bind them in solution. Surprisingly, previous work has largely overlooked the potential of phosphangulene to form complexes with metals, which offers a simple way to create large molecular structures with curved aromatic surfaces. To explore this approach, we have prepared and characterized a series of complexes of phosphangulene with Ag+ and Cu+. Our results show that Phang ligands are exceptional for many reasons. In particular, they can yield metal complexes with unique coordination, and the metal centers hold the concave aromatic surfaces of multiple ligands in various divergent arrays. Moreover, the rigid conical structure of phosphangulene gives the complexes an awkward shape that cannot be packed efficiently without complementary partners. As a result, metal complexes of phosphangulene are predisposed to cocrystallize with fullerenes, thereby yielding materials in which metals and fullerenes are brought together in ordered arrangements.

Triptycene 1,2-Quinones and Quinols: Permeable Crystalline Redox-Active Molecular Solids.

Suitably designed quinones and quinols are promising modules for the programmed construction of ordered redox-active molecular solids. To explore this potential, we have synthesized compounds 1-4, in which multiple 1,2-benzoquinone and 1,2-quinol units are attached to a triptycene core. The resulting molecules have topologies that disfavor efficient packing, and structural studies show that they crystallize to form open networks held together by characteristic attractive intermolecular forces, including O-H···O hydrogen bonds, C-H···O interactions, π-stacking, and dipolar interactions. Remarkably, the resulting solids are permeable and can undergo reversible redox reactions without loss of crystallinity. Our work may thereby help lead to the design of robust carbon-based batteries with electrodes derived from quinones, quinols, and other redox-active molecules abundantly produced by nature.

Chemical nanocavitation of surfaces to enhance the utility of stainless steel as a medical material.

While stainless steel is a broadly used alloy with interesting mechanical properties, its applications in medicine suffers from inherent biocompatibility limitations. An attractive opportunity to improve its performance is to alter its surface, but this has proven challenging. We now show how high range anodization conditions using H2SO4/H2O2 as an atypical electrolyte can efficiently nanocavitate the surface of both stainless steel SS304 and SS316 and create a topography with advantageous biomedical characteristics. We describe the structural and chemical features of the resulting surfaces, and propose a nanocorrosion/transpassivation/repassivation mechanism for its creation. Our approach creates a thin mesoporous layer of crystalline oxide that selectively promotes mammalian cell activity and limits bacterial adhesion. The modified surfaces favor the formation and maturation of focal adhesion plaques and environment-sensing filopodia with abundant extra small lateral membrane protrusions, suggesting an increase in membrane fluidity. These protrusions represent a yet undescribed cellular response. Such surfaces promise to facilitate the integration of implantable SS devices, in general. In addition, our strategy simultaneously provides a simple, commercially attractive way to control the adhesion of microorganisms, making nanostructured stainless steel broadly useful in hospital environments, in manufacturing medical devices, as well as offering possibilities for non-medical applications.

Predictably Ordered Open Hydrogen-Bonded Networks Built from Indeno[1,2-b]fluorenes.

Predictably ordered materials can be constructed by a modular strategy in which properly designed molecular components are positioned in space by reliable interactions. In principle, this approach can be used to control the arrangement of adjacent systems of π-conjugation, thereby creating molecular materials with valuable optoelectronic properties. To explore this possibility, we have synthesized compounds in which 2,4-diamino-1,3,5-triazinyl groups are attached to derivatives of 6,12-dihydroindeno[1,2-b]fluorene to produce molecules with well-defined cruciform topologies, extended π-conjugated aromatic cores, and an ability to form multiple hydrogen bonds. These compounds crystallize to form robust open hydrogen-bonded networks with parallel indenofluorenyl cores, significant volume (64-70%) available for accommodating guests, and characteristic luminescence. Our results will help permit the rational design of complex new molecular materials in which multiple optoelectronically active components are arranged in productive ways.

Molecular Organization of 2,1,3-Benzothiadiazoles in the Solid State.

Derivatives of 2,1,3-benzothiadiazole (1) are widely used in many areas of science and are particularly valuable as components of active layers in various thin-film optoelectronic devices. Even more effective benzothiadiazoles are likely to result if a deeper understanding of their preferred patterns of molecular association can be acquired. To provide new insight, we have analyzed the structures of compounds in which multiple benzothiadiazole units are attached to well-defined planar and nonplanar molecular cores. Our results show that molecular organization can be controlled in complex structures by using directional S···N bonding of benzothiadiazole units and other characteristic interactions. Moreover, the observed structures are distinctly different from those of analogous arenes. Replacing benzene rings in arenes by thiadiazoles thereby provides a strategy for making new compounds with extended systems of π-conjugation and unique patterns of molecular organization, including the ability to co-crystallize with the fullerenes C60 and C70.

Synthesis of Salts of 1,2,5,6- and 1,4,5,8-Naphthalenetetramine.

1,2,5,6-Naphthalenetetramine (1a), its 1,4,5,8-isomer (2a), and their salts are valuable precursors for synthesizing nitrogen-containing arenes and other targets of interest. We describe how salts of tetramines 1a and 2a can be made from simple protected derivatives of 1,5-naphthalenediamine (2d) by sequences of regioselective dinitration, deprotection, and reduction. Various shortcomings of previously reported syntheses of tetramines 1a and 2a can thereby be avoided. In addition, we report structural studies that may help clarify the mechanism of nitration and resolve an earlier controversy about the regioselectivity observed in nitrations of derivatives of 1,5-naphthalenediamine (2d).

Engineering Hydrogen-Bonded Hexagonal Networks Built from Flexible 1,3,5-Trisubstituted Derivatives of Benzene.

2,4-Diamino-1,3,5-triazinyl (DAT) groups are known to form N-H···N hydrogen bonds according to reliable patterns of self-association. In compounds 3a-c, three DAT groups are attached to trigonally substituted phenyl cores via identical flexible arms. Crystallization of compounds 3a-c produces robust networks in which each molecule is linked to its immediate neighbors by a total of 10-12 hydrogen bonds. In compound 3a, the DAT groups are designed to lie close to the plane of the phenyl core, thereby giving hydrogen-bonded sheets built from hexameric rosettes. In contrast, the more highly substituted phenyl cores of analogues 3b and 3c favor conformations in which the DAT groups are no longer coplanar, leading predictably to the formation of three-dimensional networks. In general, the nominally trigonal topologies of compounds 3a-c favor structures in which hexagonal networks are prominent, so they behave like trimesic acid despite their greater complexity and flexibility. The structures of all crystals incorporate open networks with significant fractions of volume accessible to guests (32-60%). Despite their flexibility, compounds 3a-c appear to be unable to assume conformations that pack efficiently and simultaneously allow the DAT groups to engage in normal hydrogen bonding.