Search

Singlet fission is a photophysical process that provides a pathway for more efficient harvesting of solar energy in photovoltaic devices. The design of singlet fission candidates is non-trivial and requires careful optimization of two key criteria: (1) correct energetic alignment and (2) appropriate intermolecular coupling. Meanwhile, this optimization must not come at the cost of molecular stability or feasibility for device applications. Cibalackrot is a historic and stable organic dye which, although it has been suggested to have ideal energetics, does not undergo singlet fission due to large interchromophore distances, as suggested by single crystal analysis. Thus, while the energetic alignment is satisfactory, the molecule does not have the desired intermolecular coupling. Herein, we improve this characteristic through molecular engineering with the first synthesis of an aza-cibalackrot and show, using ultrafast transient spectroscopy, that singlet fission is successfully "turned on."

Crystal engineering has, so far, exclusively focused on the development of advanced materials based on small organic molecules. We demonstrate how the cocrystallization of a polymer significantly enhances its thermal stability without compromising its mechanical flexibility, while isomorphous replacement of one of the cocrystal components enables the formation of solid solutions with melting points that can be readily fine-tuned over a practically wide temperature range. The results of this study credibly extend the scope of crystal engineering and cocrystallization from small molecules to polymers.

Intermolecular interactions play a fundamental role on the performance of conjugated materials in organic electronic devices, as they heavily influence their optoelectronic properties. Synthetic control over the solid state properties of organic optoelectronic materials is crucial to access real life applications. Perylene diimides (PDIs) are one of the most highly studied classes of organic fluorescent dyes. In the solid state, π-π stacking suppresses their emission, limiting their use in a variety of applications. Here, we report the synthesis of a novel PDI dye that is encapsulated by four alkylene straps. X-ray crystallography indicates that intermolecular π-π stacking is completely suppressed in the crystalline state. This is further validated by the photophysical properties of the dye in both solution and solid state and supported by theoretical calculations. However, we find that the introduction of the encapsulating "arms" results in the creation of charge-transfer states which modify the excited state properties. This article demonstrates that molecular encapsulation can be used as a powerful tool to tune intermolecular interactions and thereby gain an extra level of control over the solid state properties of organic optoelectronic materials.

We demonstrate that liquid additives can exert inhibitive or prohibitive effects on the mechanochemical formation of multi-component molecular crystals, and report that certain additives unexpectedly prompt the dismantling of such solids into physical mixtures of their constituents. Computational methods were employed in an attempt to identify possible reasons for these previously unrecognised effects of liquid additives on mechanochemical transformations., Liquid additives can exert catalytic, inhibitive or prohibitive effects on the mechanochemical formation of multi-component molecular crystals.

A structural study of two-dimensional inverted metal–organic frameworks demonstrates that the interior cavities of the framework structures can be systematically modified by changing the organic anion of a Cu(II)-paddlewheel unit. Changing the anion allows modifications to the shapes and sizes of the cavities in a series of isoreticular frameworks. The construction of the frameworks is based on the application of a tetrafunctional organic cyclobutane ligand synthesized in the organic solid state.

Co‐crystallisation is widely explored as a route to improve the physical properties of pharmaceutical active ingredients, but little is known about the fundamental mechanisms of the process. Herein, we apply a hyphenated differential scanning calorimetry—X‐ray diffraction technique to mimic the commercial hot melt extrusion process, and explore the heat‐induced synthesis of a series of new co‐crystals containing isonicotinamide. These comprise a 1:1 co‐crystal with 4‐hydroxybenzoic acid, 2:1 and 1:2 systems with 4‐hydroxyphenylacetic acid and a 1:1 crystal with 3,4‐dihydroxyphenylactic acid. The formation of co‐crystals during heating is complex mechanistically. In addition to co‐crystallisation, conversions between polymorphs of the co‐former starting materials and co‐crystal products are also observed. A subsequent study exploring the use of inkjet printing and milling to generate co‐crystals revealed that the synthetic approach has a major effect on the co‐crystal species and polymorphs produced., Co‐crystallisation is widely explored as a route to improve the physical properties of pharmaceutical active ingredients, but little is known about the fundamental mechanisms of the process. In this study, X‐ray diffraction was used to provide an unprecedented insight into pharmaceutical co‐crystallisation processes (see figure).

An introduction to the virtual special issue in honor of Prof. William Jones, wherein the authors reflect on his scientific career and his many outstanding contributions to organic solid-state chemistry.

The Strecker reaction is thought to offer a prebiotically plausible synthesis of amino acids, but is reversible at the high or low pH ranges needed to promote reactivity. Here the reaction of hydrogen cyanide and diamidophosphate is shown to provide stable phosphorylated amino acid precursors at neutral pH, which can be hydrolysed to amino acids or thiolysed to thioamides.

This Tutorial Review, aimed at both the novice and the seasoned solid-state chemist, provides a succinct overview of key findings that have, over the last half century, advanced our ability to make molecular crystals with targeted structures and desired properties. The article critically evaluates the efficiency and reliability of the well-established guidelines used by experimentalists in crystal engineering and highlights statistical and computational tools that are both advantageous to crystal design and accessible to experimental solid-state chemists.

A personal account of the hurdles encountered when studying each of the aspects of crystal engineering, namely, designing, building, and using crystal structures. Examples are given to illustrate the “backbreaking” nature of the crystal engineering endeavor, as well as the limitations of our current abilities to understand, engineer, and maintain molecular crystals.

The inability to obtain a crystal form that has previously been reliably prepared is an important concern for industrial solid-state scientists. In the present study, we extend further the evidence that such a phenomenon also applies to cocrystals. Specifically, we report further on the apparent "disappearing polymorphs" of a cocrystal composed of caffeine and citric acid. This study commenced at the University of Cambridge with the initial aim of gaining insight into the mechanisms associated with the mechanochemical formation of the known caffeine-citric-acid cocrystal, namely, Form I. A second polymorph, Form II, was later prepared mechanochemically through neat grinding, making it seemingly impossible to reproduce Form I in the same laboratory. Subsequent studies also resulted in the mechanochemical formation of another polymorph, Form III, for which no structural characterization has yet been possible. We therefore also focus on the understanding of the factors contributing to the inability to reproduce Form I after another polymorph has been obtained. Experiments were then extended to two other laboratories within different UK universities (De Montfort University Leicester and University College London) and revealed that, depending on the "apparent" level of contamination of a specific laboratory, different polymorphs can be obtained, but only one of them at any period of time. The inability to predict, control, and understand disappearing polymorphs remains a frustrating experience - even 25 years after Dunitz and Bernstein first stated that "we are far from being able to present a theory of disappearing polymorphs". In this context, we reason that a first step forward would consist of reporting comprehensive and detailed accounts for every example of apparently disappearing polymorphs, with the hope of finding similarities that can subsequently result in a better understanding and possible rationalization of the puzzling phenomenon of disappearing polymorphs. We here report what we know so far of the intriguing caffeine-citric-acid cocrystal system.

A central problem for the prebiotic synthesis of biological amino acids and nucleotides is to avoid the concomitant synthesis of undesired or irrelevant by-products. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. Here, we show that 2-aminothiazole reacts selectively with two- and three-carbon sugars (glycolaldehyde and glyceraldehyde, respectively), which results in their accumulation and purification as stable crystalline aminals. This permits ribonucleotide synthesis, even from complex sugar mixtures. Remarkably, aminal formation also overcomes the thermodynamically favoured isomerization of glyceraldehyde into dihydroxyacetone because only the aminal of glyceraldehyde separates from the equilibrating mixture. Finally, we show that aminal formation provides a novel pathway to amino acids that avoids the synthesis of the non-proteinogenic α,α-disubstituted analogues. The common physicochemical mechanism that controls the proteinogenic amino acid and ribonucleotide assembly from prebiotic mixtures suggests that these essential classes of metabolite had a unified chemical origin.

A crystal growth technique, interfacial cocrystallization, is demonstrated to be a simple and effective method for preparing multicomponent crystal forms. The technique is based on the generation of a liquid–liquid interface between two immiscible solutions of cocrystal-forming compounds, and its utility is demonstrated through the preparation of polymorphs and hydrates of caffeine cocrystals, involving three different hydroxy-2-naphthoic acids, including the formation of some with unexpected compositions.

L-Arabinose is an abundant resource available as a waste product of the sugar beet industry. Through use of a hydrazone-based strategy, L-arabinose was selectively dehydrated to form a chiral tetrahydrofuran on a multi-gram scale without the need for protecting groups. This approach was extended to other biomass-derived reducing sugars and the mechanism of the key cyclization investigated. This methodology was applied to the synthesis of a range of functionalized chiral tetrahydrofurans, as well as a formal synthesis of 3R-3-hydroxymuscarine.

We present the synthesis and characterization of a series of encapsulated diketopyrrolopyrrole red-emitting conjugated polymers. The novel materials display extremely high fluorescence quantum yields in both solution (>70%) and thin film (>20%). Both the absorption and emission spectra show clearer, more defined features compared to their naked counterparts demonstrating the suppression of inter and intramolecular aggregation. We find that the encapsulation results in decreased energetic disorder and a dramatic increase in backbone colinearity as evidenced by scanning tunnelling microscopy. This study paves the way for diketopyrrolopyrrole to be used in emissive solid state applications and demonstrates a novel method to reduce structural disorder in conjugated polymers.

The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are shown to react with a variety of alternative dienophiles to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3-alkoxy group on a furan Diels–Alder reaction.

Herein, we report a silver-free Pd(II)-catalyzed C(sp

Two new palladium-catalysed reactions have been developed for the synthesis of stable 4-substituted benzooxaborinin-1-ols. A palladium-catalysed cyclisation of ortho-alkenylbenzene boronic acids can be used to access 4-chlorobenzooxaborinin-1-ols via a Wacker-type oxidation and chlorination. Alternatively, ortho-alkynylbenzene boronic acids undergo a palladium-catalysed oxyallylation reaction to provide 4-allylbenzooxaborinin-1-ols.

We describe a conceptually novel “accelerated aging” approach for the synthesis of metal–organic materials. This approach, inspired by natural mineral weathering processes, enables the synthesis of metal–organic structures from simple and inexpensive solid reactants upon exposure to catalytic amounts of an ammonium salt under conditions of high humidity and mild temperatures (up to 45 °C). Accelerated aging exploits the inherent mobility of molecules and is entirely different from solution-based (precipitation, solvothermal synthesis) or other solvent-free (mechanochemical synthesis) approaches to metal–organic materials that require either bulk solvent and/or thermo- or mechanochemical intervention. The present proof-of-principle study of accelerated aging demonstrates the catalysed and topologically specific transformation of ZnO into unusual close-packed varieties of zeolitic imidazolate frameworks (ZIFs) in a static, non-agitated reaction mixture. The reactivity is readily scaled up, as demonstrated by performing selected syntheses of quartz- and diamondoid-topology close-packed ZIFs in ten gram amounts. The latter framework, previously obtained only by using a large excess of reagents under hydrothermal conditions, is transformed into the well-known open framework ZIF-8 by exposure to methanol vapours at room temperature, suggesting an alternative to both solvothermal and mechanochemical approaches to these materials. A tentative proton-transfer mechanism underpinning the catalytic effect in accelerated aging is proposed, involving protonated imidazole as an intermediate.

Treatment of an achiral molecular ladder of C 2 h symmetry composed of five edge-sharing cyclobutane rings, or a [5]-ladderane, with acid results in cis - to trans -isomerization of end pyridyl groups. Solution NMR spectroscopy and quantum chemical calculations support the isomerization to generate two diastereomers. The NMR data, however, could not lead to unambiguous configurational assignments of the two isomers. Single-crystal X-ray diffraction was employed to determine each configuration. One isomer readily crystallized as a pure form and X-ray diffraction revealed the molecule as being achiral based on C i symmetry. The second isomer resisted crystallization under a variety of conditions. Consequently, a strategy based on a cocrystallization was developed to generate single crystals of the second isomer. Cocrystallization of the isomer with a carboxylic acid readily afforded single crystals that confirmed a chiral ladderane based on C 2 symmetry. The chiral ladderane and acid self-assembled to generate a five-component hydrogen-bonded complex that packs to form large solvent-filled homochiral channels of nanometer-scale dimensions. Whereas cocrystallizations are frequently applied to structure determinations of proteins, our study represents the first application of a cocrystallization to confirm the relative configuration of a small-molecule diastereomer generated in a solution-phase organic synthesis.

This article outlines the benefits of using 'Design of Experiments' (DoE) optimisation during the development of new synthetic methodology. A particularly important factor in the development of new chemical reactions is the choice of solvent which can often drastically alter the efficiency and selectivity of a process. Whilst solvent optimisation is usually done in a non-systematic way based upon a chemist's intuition and previous laboratory experience, we illustrate how optimisation of the solvent for a reaction can be carried out by using a 'map of solvent space' in a DoE optimisation. A new solvent map has been developed specifically for optimisation of new chemical reactions using principle component analysis (PCA) incorporating 136 solvents with a wide range of properties. The new solvent map has been used to identify safer alternatives to toxic/hazardous solvents, and also in the optimisation of an S(N)Ar reaction.

Nearly twenty years ago, Dunitz and Bernstein described a selection of intriguing cases of polymorphs that disappear. The inability to obtain a crystal form that has previously been prepared is indeed a frustrating and potentially serious problem for solid-state scientists. This Review discusses recent occurrences and examples of disappearing polymorphs (as well as the emergence of elusive crystal forms) to demonstrate the enduring relevance of this troublesome, but always captivating, phenomenon in solid-state research. A number of these instances have been central issues in patent litigations. This Review, therefore, also highlights the complex relationship between crystal chemistry and the law.

Ultrasound-assisted crystallization (sonocrystalliza- tion) was used to prepare a mixture of nano- and micrometer- sized crystals of the monoclinic form of paracetamol—a widely used analgesic known for its particularly problematic mechan- ical behavior under compression (i.e. poor tabletability). The nano- and micrometer-sized crystals yielded a powder which exhibits elastic moduli and bulk cohesions that are significantly higher than those observed in samples consisting of macro- meter-sized crystals, thus leading to enhanced tabletability without the use of excipients, particle coating, salt, or cocrystal formation. Experimental compaction and finite element anal- ysis were utilized to rationalize the significantly improved compaction behavior of the monoclinic form of paracetamol. The current demand for organic nanomaterials (1, 2) has triggered the development of fabrication methods for organic nanocrystals. (3-10) Recent pharmaceutical and biomedical research has shown that molecular nanocrystals are highly valuable in the context of drug delivery, biolabeling, and biosensing. (11, 12) Nanosizing of molecular crystals has also become a particularly popular approach in drug development with poorly soluble pharmaceutical agents (13) and is mainly used to enhance the solubility and bioavailability of the drug candidate. (14, 15) Surprisingly, other applications of molecular crystals, despite their unique physicochemical properties, have been relatively unexplored in biomedical (and other) sciences. We show herein through the use of sonocrystalliza- tion, (16, 17) that is, the use of ultrasound to facilitate crystal

The mol­ecules of the title bis­(thio­morpholine) adduct of bis­(1,3-diphenyl­propane-1,3-dionato)cobalt(II), [Co(C15H12O2)2(C4H8NS)2], in the crystal structure are positioned on an inversion center at the inter­section of a twofold rotation axis and a perpendicular mirror plane. The two thio­morpholine ligands bond to the octahedral cobalt(II) ion in the axial coordination sites (trans configuration).

Photoreactive Ag(I) organosulfonate complexes involving (E)-methyl-3-(pyridin-3-yl)prop-2-enoate (3-PAMe) are reported. Argentophilic interactions stack 3-PAMe to undergo a head-to-head intermolecular [2+2] photodimerisation to generate (rctt)-dimethyl-3,4-bis(pyridine-3-yl)cyclobutane-1,2-dicarboxylate (3,3′-MeBPCD) in the solid state regioselectively and in quantitative yield. The organosulfonate participates in C–H…O interactions with the coordinated 3-pyridyl groups to effectively aid in crystal engineering of the reactivity.

Cocrystallisation of sildenafil with acetylsalicylic acid yields a 1 : 1 sildenafil–acetylsalicylic-acid cocrystal, as well as a 1 : 1 : 1 cocrystal salt involving a sildenafil cation, acetylsalicylate and salicylic acid. The 1 : 1 acetylsalicylic-acid-based cocrystal exhibits an enhanced intrinsic dissolution rate, as compared to sildenafil citrate (the active ingredient of Viagra®).

In the title complex, [Ni(C10H9O2)2(C10H17N)2], the Ni atom, which occupies a special position at an inversion centre, has an octa­hedral environment formed by four O atoms of two chelate benzoyl­acetonates [Ni—O 2.0409 (16) and 2.0187 (16) A, and O—Ni—O 90.36 (6)°] and two N atoms of the adamantylamine ligands [Ni—N = 2.176 (2) A]. The amine H atoms of the adamantylamine ligands do not participate in any hydrogen bonds, due to their steric shielding and the lack of accessible acceptors.

In the reaction of bis(1,3-di­phenyl-1,3-propane­dionato)­oxovanadium(IV) with pyridine, a 1:1 adduct is formed, viz bis(1,3-di­phenyl-1,3-propane­dionato-κ2O,O′)­oxo­(pyridine-κN)­vanadium(IV), [V(C15H10O2)2O(C5H5N)]. The V atom is surrounded by one pyridine ligand, two 1,3-di­phenyl-1,3-propandionate (dbm) ligands and one oxo group. The complex exhibits a distorted octahedral coordination, with the oxo group and pyridine ligand in a cis configuration. Pairs of mol­ecules of the adduct are connected by an intermolecular C41—H41⋯O1(−x, 2 − y, 1 − z) contact of 3.171 (3) A and thus form dimers in the solid state.

In the reaction of bis(1-phenyl­butane-1,3-dionato)­nickel(II) with di­methyl sulfoxide, the adduct bis­(di­methyl sulfoxide)­bis(1-phenyl­butane-1,3-dionato)­nickel(II), [Ni(C10H9O2)2(C2H6OS)2], is formed, in which two di­methyl sulfoxide (DMSO) mol­ecules are coordinated to the Ni atom through their O atoms in a trans arrangement. The compound crystallizes in space group P21/a with the Ni atom lying on a center of inversion. The coordination polyhedron around the Ni atom is a distorted octahedron. The chelate ring deviates slightly from planarity. The Ni—O bond distance to the DMSO O atom is slightly longer than that to the 1-phenyl­;butane-1,3-dionate ligand. In the crystal structure, two-dimensional frameworks are formed by C–H⋯O interactions.

In the adduct bis(1-phenyl-1,3-butanedionate)­bis(3-amino­pyridine)­nickel(II), [Ni(C10H9O2)2(C5H6N2)2], the NiII atom lies on a crystallographic center of symmetry. The coordination geometry around the NiII atom is distorted octahedral. Four O atoms of two 1-phenyl-1,3-butanedionate ligands form the equatorial plane, with Ni—O distances in the range 2.0160 (14)–2.0338 (14) A. The axial positions are occupied by N atoms of two 3-amino­pyridine ligands. The adduct mol­ecules translated by one unit along the a axis are linked by N—H⋯O hydrogen bonds, forming chains.

Nano- and micrometer-scale crystals of a self-assembled hexamer have been synthesized via sonochemistry. The application of ultrasonic irradiation afforded hollow rhombic-dodecahedral crystals of the C-methylcalix[4]resorcinarene hexamer. The formation of the hollow crystals is attributed to a reversed crystal growth mechanism heretofore described only in the synthesis of inorganic-based materials.

Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)(3) (M = Re, (99m)Tc) based radiopharmaceuticals. Both 'click, then chelate' and 'prelabel, then click' synthetic routes produced identical products in high yields and lacked metal-hydrazide/-hydrazone interactions, highlighting the potential of this click strategy.

Tetratopic rctt-tetrakis(4-pyridyl)cyclobutane acts as an angular bifunctional ligand that yields a single-stranded helicate coordination polymer based on a Ln(III) ion.

In this microreview, we show how principles of coordination-driven self -assembly can be used to direct chemical reactivity in the organic solid state. We also show how products obtained from the templated solid-state reactions can be used as organic building units of metal-organic frameworks and coordination capsules. Self-assembled structures based on dinuclear Zn-II and Ag-I complexes are used to direct stereocontrolled [2+2] photodimerizations of vinylpyridines in the solid state in up to quantitative yield. The products are used as bi- and polytopic ligands of self-assembled coordination capsules and metal-organic frameworks. We also describe emerging metal-based approaches to conduct mechanochemical reactions in organic solids. In addition to the field of supramolecular coordination chemistry, these observations impact the field of green chemistry.

We show that a molecule constructed from an organic solid-state synthesis, namely, rctt-1,3-bis(2-pyridyl)-2,4-bis(4-pyridyl)cyclobutane (ht-2,4 ‘-tpcb) upon reaction with Cu(II) and Zn(II) ions gives one- (1D) and two-dimensional (2D) metal-organic frameworks (MOFs) of composition [Cu(hfac)(2)(2,4 ‘-tpcb-ht)](infinity) (where: hfac=hexafluoroacetylacetonate) (1) and [Zn(2,4 ‘-tpcb-ht)(2)(H2O)(2)](infinity)(2+), (2). Each MOF possesses uncoordinated, or free, 2-pyridyl groups that decorate the walls of each extended structure. (c) 2006 Elsevier B.V. All rights reserved.

Cocrystals are multicomponent solids with organic molecules assembled in combination to form a crystalline solid with properties different than the individual components. A cocrystal typically consists of a target molecule crystallized with a second molecule, or cocrystal former, employed to influence properties of the target (e.g., solubility). The conformer interacts with the target via intermolecular forces (e.g., hydrogen bonds) that hold the components together. The modularity of a cocrystal makes such solids attractive for applications where fine-tuning of properties is important (e.g., optical). In this presentation, we describe the use of sonochemistry to form cocrystals of nanoscale dimensions. In contrast to single-component solids, cocrystals present a fundamentally different challenge with respect to those reprecipitation methods used to form nanocrystals since the components of a cocrystal will tend to exhibit different solubilities. We show that sonochemistry affords nano-cocrystals with properties (e.g., reactivity) that contrast solids of macroscale dimensions. Related applications of sonochemistry to afford single-component nanocrystals will also be presented.

Cocrystals are modular multicomponent solids with exceptional utility in synthetic chemistry and materials science. A variety of methods exist for the preparation of cocrystals, yet, some promising cocrystal phases have proven to be intractable synthetic targets. We describe a strategy for the synthesis of the pharmaceutically relevant (caffeine)·(benzoic acid) cocrystal (1), which persistently failed to form using a broad range of established techniques. State-of-the-art crystal structure prediction methods were employed to assess the possible existence of a thermodynamically stable form of 1, hence to identify appropriate heteronuclear seeds for cocrystallization. Once introduced, the designed heteronuclear seeds facilitated the formation of 1 and, significantly they (or seeds of the product cocrystal) continued to act as long-lasting laboratory “contaminants”, which encouraged cocrystal formation even when present at such low levels as to evade detection. The seeding technique described thus enables the synthesis of cocrystals regarded as unobtainable under desired conditions, and potentially signifies a new direction in the field of materials research.

Mechanochemical cocrystallisation was utilised to prepare fluorescein cocrystals involving pyridyl-based cocrystal formers, which exhibit different crystal structures, thermal and optical properties than those obtained via solution-based crystallisation.

An approach to form organic thin films that employs multicomponent solids in the form of co-crystals has been developed. The components direct an intermolecular [2+2] photodimerization that we demonstrate exhibits a change in solubility that can be exploited as a negative photoresist for use in photolithography.