Engineering Crystal Properties through Solid Solutions - Crystal

Apr 30, 2018 - Journal of Chemical Education · Journal of Chemical Information and .... Department of Chemical Sciences and Bernal Institute, Universi...
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Engineering Crystal Properties through Solid Solutions Matteo Lusi Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b01643 • Publication Date (Web): 30 Apr 2018 Downloaded from http://pubs.acs.org on May 1, 2018

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Crystal Growth & Design

Engineering Crystal Properties through Solid Solutions Matteo Lusi* Department of Chemical Sciences and Bernal Institute, University of Limerick, Castletroy, Co. Limerick, Ireland. solid_solutions; mixed_crystals; alloys; crystal_engineering

Abstract The control of structures and properties in crystalline materials has many returns that justify the increasing efforts in this direction. Traditionally, crystal engineering focused on the rational design of single component molecular crystals or supramolecular compounds (i.e. cocrystals). More recently, reports on crystalline solid solutions have become common in crystal engineering research. Crystalline solid solutions are characterized by a structural disorder that enables the variation of stoichiometry in continuum. Often such variation corresponds to a variation of structural and physicochemical properties, and offers an opportunity for the materials’ finetuning. In some cases, though, new and unexpected properties emerge. As illustrated here, both behaviors make solid solutions particularly relevant to the scope of crystal engineering.

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Introduction In recent years, the number of publications that focus on some aspect of solid state chemistry has grown faster than, for example, those focusing on more traditional synthetic ones (Figure 1).

Figure 1. Proportion of papers containing the key words “synthesis” and “solid-state”, over the past century (from the Scifinder® database).

Such interest is fueled by the need of new materials for technological applications, or better performing solid forms of active pharmaceutical ingredients (API) and agrochemicals. Indeed, many physicochemical properties of a material depend on its composition (chemical identity and stoichiometry) as well as its structure (polymorphs, defects, morphology etc.). Then, the full control over composition and structure is required to produce a material with optimal physical and chemical properties for the intended application. The design, synthesis, modification, and characterization of crystal structures and their properties fall within the scope of crystal engineering.1

Crystal engineering

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The first recorded use of ‘crystal engineering’ is attributed to Pepinsky.2 He noted that in a series of salts the substitution of the organic cation afforded crystals whose ‘cells and symmetries are to a good extent controllable’. In his words, through such substitution ‘crystals with advantageous properties can be "engineered"’.2 Later, Schmidt regarded the control of molecular packing as ‘a problem of crystal engineering’.3 Early attempts at crystal engineering exploited supramolecular interactions4 to rationalize the features observed in known crystal s structures and to design new ones.5,6 Even today the most successful strategy to engineering supramolecular crystals7 utilizes relatively weak interactions such as hydrogen and halogen bond that drive the (self-)assembly8 of chosen chemical species.911

A similar approach is applied to metal complexes and coordination polymers in which organic

and inorganic species are bonded by a stronger chemical (coordination) bond.10,12,13 Currently crystal engineering is identified as the branch of solid state chemistry that focuses on organic and “metal-organic” materials such as salts, molecular crystals and coordination polymers.14-18

Multicomponent crystals Supramolecular self-assembly enables the utilization of molecules and ions as building blocks or tectons.19 In many cases, the supramolecular interactions (synthons)20 and their motifs and patterns6,21 are so robust that the same supramolecular structures are produced consistently by building blocks that present the appropriate functional groups. This approach allows for a rational modification of the crystal structure22 whereby the degree of fine-tuning is determined by the difference in size and shape between equivalent building blocks.23

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Such a supramolecular approach is particularly convenient when applied to multicomponent crystals. In fact the combination of more than one substance increases the potential for structural variability, which in single component crystals is limited to the phenomenon of polymorphism (Figure 2). Self-assembly has been successfully exploited to produce multicomponent crystals of neutral24 and charged13 species as well as multiple-phase composite solids.25 In these materials, which include metal complexes, salts, cocrystals and, more recently, ionic cocrystals,26 multiple components co-crystallize in a stoichiometric ratio and behave as a supramolecular compound. These compounds obey Dalton’s law of multiple proportion27 and, generally, in their crystals, each component occupies well-defined crystallographic positions.28,29 A different type of multicomponent material is represented by solid solutions.30,31 These phase are characterized by a structural disorder,32 which is responsible for properties that are typical of liquid solutions. As with their liquid counterpart, the stoichiometry of solid solutions is not limited to a single integral value but can be varied in continuum. Indeed, as for liquid solution, solubility in the solid state does not need to be complete but can be observed in a limited composition range. Most importantly, the stoichiometry variation produces a continuous variation of structural, thermal and chemical properties (colligative), making these materials particularly amenable to fine-tuning (Figure 2). Often solid solutions have properties that are between those of the pure components but, in some cases, new properties arise. In both cases, as illustrated in below, crystalline solid solutions represent an opportunity to understand the structure

property

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Figure 2: Example of structural relationship and variability possible for single component crystals (polymorphism), multicomponent crystal (discrete variations) and crystalline solid solutions

/

mixed

crystals

(continuous

variation).

Nomenclature: solid solutions, mixed crystals et cetera: Since its introduction in 19th century,33 the expression ‘solid solution’ has been used in a variety of contexts to refer to both crystalline and amorphous solids. Historically, probably due to the technical limitations that prevented accurate structural characterization, the main criterion for the identification of these phases has been their chemical composition (stoichiometry). In this sense the term has indicated any solid that did not obey Dalton’s law of multiple proportions.27 This included substitutional crystals and partially occupied host/guest systems,30 as well as interstitial and intercalated compounds.34 The expression ‘mixed crystal’35 has been used with multiple meanings indicating crystalline solid solutions as well as physical mixtures. In his seminal book,30 Kitaigorodskii used ‘mixed crystals’ to refer to molecular crystals in the broadest sense. In that case, the expression was also used for single component structures with Zˈ>1 or physical mixtures of polymorphs.36 Even recently, the term was used for common cocrystals,37 ‘mixture of phases’38 and simple salts.39

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‘Mixed crystal’ is sometimes also used for organic and coordination polymers, which are single macromolecules or blends rather than molecular crystals. Most often, though, the use of ‘mixed crystal’ is limited to crystalline solid solutions of discrete molecules. More recently the expressions mixed cocrystal40 or cocrystal solid solution41 have also been defined. These materials are cocrystals in which the structural function of a single conformer is ensured by two or more molecules that can be present in a variable ratio.42 Desiraju showed that solid solutions of 3 and 4 component cocrystals can be designed through crystal engineering.43,44 The term alloy, originally used only for metallic materials such as solid solutions, mixtures and intermetallic and non-stoichiometric compounds,45,46 has also indicated both molecular47,48 crystals and coordination polymers.49,50 In this case the qualifier ‘organic’51,52 is added to highlight the difference from the original use of the term. Within the field of porous coordination polymers, the expression ‘multivariate MOFs’ has also been used, to indicate solid solutions of porous coordination polymers.53 In future, this plethora of terms needs to be rationalized and a homogeneous and a shared nomenclature needs to be defined for this class of materials.

Solid solutions in crystal engineering Solid solutions of molecular and polymeric materials have been studied long before the concepts and strategies of crystal engineering were formalized.54,55 Most publications describe the relationship between composition and structure. At the same time, there are numerous examples that demonstrate how it is possible to fine-tune in continuum many properties such as thermal and chemical stability, piezoelectricity, photochromism, hardness etc. (vide infra). Such a level of control is unmatched in other areas of molecular and supramolecular chemistry, and, as

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illustrated in the examples below opens new possibility for the rational design of structures as well as physicochemical properties for technological, pharmaceutical, and chemical separation/storage applications.

Crystal structures Solid solutions are constantly investigated to rationally modifying structures and to gain insight into crystal packing principles.56-60 Vagard’s law states that in a solid solution a linear correlation exists between composition and unit cell dimensions.61,62 The relationship, originally observed in metals and inorganic salts, also applies to molecular crystals,63 zero dimensional metal complexes47 and coordination polymers.64,65 In larger systems, deviations from strict linearity are common.66 An accurate structure analysis of these crystals can reveal the causes of such deviation and help understanding the structure-composition relationship. For example in BiSX1-xYx (X, Y = Cl, Br, I) the anisotropic unit cell variation is due to a rotation of the bismuth halide complex, which is consequent of the progressive elongation of the halogen-halogen interaction.67 In the organic acridine/phenazine system the increased H•••H steric hindrance causes similar molecular rotation that is responsible for the non-linear relationship between volume and composition (Figure 3).68

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Figure 3: Direct comparison of the crystal structures of acridine/phenazine solid solutions structures with 45 (blue), 68 (green) and 75% (red) acridine composition; the short H•••H contacts

are

highlighted

in

the

red

circle.

Structural changes can also occur in a discontinuous fashion. A centrosymmetric racemic crystal will converts into a chiral one as soon as the enantiomeric enrichment begins, i.e. when the first molecule is substituted in the racemate.58 At the same time such loss of symmetry is not always recognizable crystallographically. For example the recently reported solid solution of Dand L-malic acid could only be solved in the centrosymmetric C2/c space group despite simple geometrical considerations impose a chiral structure (Figure 4).69 For this reason the effects of chiral (and polar) enrichment has been interpreted as a ‘continuous loss of symmetry’ and it is observed in properties such as the intensity of the second harmonic.30,70-72

Figure 4: schematic representation of the racemic, solid solution and enantiopure crystals in the D-malic acid / L-malic acid system.

Other

discontinuous

transitions

are

observed

between

insulator/conductor

or

para/ferromagnetic states.73 Here it must be stressed that the existence of different crystal forms as a consequence of varied composition cannot be regarded as polymorphism. In fact these phases would not lead to identical liquid or vapor state.74 On the other hand crystalline solid

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solutions can exhibit polymorphism whereby a single chemical composition affords multiple crystal forms. In these cases the stability of each from can vary with composition.75 In some case, the structure of a mixed crystal differs from those of the parent components. For example, solid solutions of the organic salts of tetracyano-p-quinodimethane with tetraselenafulvalene and tetrathiafulvalene show enhanced electronic properties that are attributed to the disordering of the molecular stacking.51 Lahav showed that chirality appeared upon inclusion of non-chiral of cinnamic acid molecules in centrosymmetric cinnamamide structures.76,77 In that case the reduction of symmetry was explained by the occlusion of specific crystal faces as the crystal grows. In a similar way, Kahr explained the long-known “double refraction” of mixed crystals of the isomorphous barium and lead nitrates whereby the partial “segregation” of the cations causes a symmetry reduction from the centrosymmetric Pa3ത space group to the non-centrosymmetric R3.78

Technologically relevant properties Solid solutions have been studied for almost a century to investigate the effect of chemical composition on optical, electric and photochemical properties.79 Diluted solid solutions of chlorophyll were found to alter yield and lifetime of the chlorophyll triplet state as well as the wavelength of maximum absorption.80 Similarly, organic crystals of α-naphthylphenylbiphenyl diamine (α-NPD) can be mixed with rubrene to produce white organic light-emitting diodes (OLED).81,82 Due to the low concentration of the solute, these phases should perhaps be referred to as doped organic materials rather than solid solutions.83 Jones et al. have promoted photoreactivity in photostable benzylbenzylidenecyclopentanones by mixing chloro, bromo and methyl derivatives of the same moleucule.84 Oashi and coworkers

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measured the photoreactivity of 3-chloro-, 3-bromo- and 3-methylpyridine complexes and showed that the rate of reaction depends on the size of the cavity around the reactive group. Then they modify the cavity size by making solid solutions, which confirmed their theory and proved that the rate of reaction could be tuned.84,85 A similar mechanism is behind the improved water and light stability of Pigment Red 170. Here denser, and hence more stable structures, are obtained through mixed crystals with bromo, chloro, fluoro and methyl substituted analogues.86 Lahav and coworkers investigated and explained the origin of polarity and pyroelectricity in cinnamamide/thienylacrylamide, and asparagine/aspartic acid systems.71,76,77,87 As discussed above, the reduction of crystal symmetry was attributed to a non-homogeneous distribution of the component within the mixed crystal. Hulliger et al. have discussed the polarity in solid solutions of polar 4-chloro-4ˈ-nitrostilbene molecules and nonpolar 4,4ˈ-dinitrostilbene.70 The photochromism of yellow, red and blue diarylethenes can be tuned by preparing two- and three-component crystalline solid solutions. The solid solutions enable access to intermediate color tones.88 In hydrogen bonded mixed salts of bipiridinium metal halide, color and light absorbance can be tuned by substitution of chloride and bromide ligands through solid-gas reactions.65 Solid solutions of photochromic fulgide enables the modification of both absorption spectra and mechanical properties of the crystalline product (Figure 5).89

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Figure 5: Variation of absorbance measured for the peak in the visible portion of the spectrum as a function of coloring and bleaching cycles in a series of fulgide compounds: (a) p-methyl- (1E), p-chloro- (2E), and p-methyl-/p-chloro-fulgide (MIX-1E) (b) p-methyl- (1E), p-bromo (3E), and p-methyl-/p-bromo-fulgide (MIX-2E). Reprinted with permission from Ref. 85. Copyright © 2017

American

Chemical

Society.

Mixed organometallic crystals have been known for over thirty years. Ward prepared functionalized solid solutions of ferrocene and ruthenocene complexes and showed that the optical properties of the material follow the Beer’s law.90 Braga, Grepioni and co-workers reported one of the first example of ferrocenium/cobaltocenium system that show complete solubility.47 Those solid solutions enabled the fine-tuning of the polymorphic and melting transitions with a 20 °C range.

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Pharmaceuticals Arguably, the most detailed description of pharmaceutical solid solutions is related to the separation and purification of enantiomers and racemic mixtures. In fact in such processes racemic solid solutions can be produced. This large body of work includes the theoretical background needed to understand thermodynamic and kinetic behaviors of molecular solid solutions. The topic is frequently reviewed and will not be treated here.91,92 The pharmaceutical industry has long investigated solid solutions and eutectic mixtures with the idea of modifying the dissolution rate and absorption of drugs.93 Goldberg et al. published a series of papers on mixed acetaminophen-urea,94 chloramphenicol-urea95 and griseofulvinsuccinic acid systems.96 They reported that the dissolution rate in solid solutions of these materials could increase up to seven times. Similar results were reported for steroids in the mid1970s,97-99 although early substitutional solid solutions of cholesterol had been known for almost fifty years.100 More recently, solid solutions of drug molecules are being investigated to improve the thermal and mechanical response of the product, which are important for the materials manufacturing, tableting and storage. Braga, Grepioni and co-workers have reported binary and ternary solid solutions of chloro-, bromo- and methyl- para substituted benzyl alchool.59,101 Their work shows that a variation of composition could raise the melting point of the product from 53 to 80 °C (Figure 6). The hydrogen bonded salt (±)-4-methylmethcathinone hydrochloride undergoes an enantiotropic phase transition upon cooling. Oswald and coworkers have reported that, in the solid solution (±)-4-methylmethcathinone HX (X = Cl or Br), the polymorphic transition

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temperature could be altered by up to 80 °C depending on the amount of bromide.102 Desiraju observed that omeprazole crystallizes as a tautomeric solid solution. Then the relative tautomeric composition can be controlled by varying the crystallization temperature and affects the hardness of the crystals, which could be relevant in manufacturing processes.103

Figure 6: melting point of the three-component system of chloro-, bromo- and methyl- para substituted benzyl alchool. Reproduced from Ref 55 with permission of The Royal Society of Chemistry.

Recently, solid solutions have been prepared for pharmaceutical cocrystals.40 Neutral APIs can be crystallized with two or more similar coformers that can substitute one another in a variable ratio.60,69

Then, the use of mixed coformers can help increasing structural and chemical

variability as well as modifying molecular solubility in the solid state. For instance, Zhang reported the phase diagrams of the ibuprofen enantiomers with 4,4ˈ-bipyridine and suggested the potential use of that solid solution for enantiomeric separation.104 Non-stoichiometric hydrates are another type of solid solutions that are sometimes encountered amongst pharmaceutical crystals. In LY297802 (Vedaclidine) tartrate the water content varies in

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continuum, from anhydrous to the hemihydrate form, as function of external humidity.105 Paroxetine HCl absorbs up to 0.8 equivalents of water and the absorption is associated with a continuous structure transformation in which the unit cell volume increases from 915 Å3 for the anhydrous phase to 948 Å3 for the fully hydrated phase.106 In many cases, though, nonstoichiometric hydrates are characterized by channels that water can fill reversibly without structural changes. In crystals of sitafloxacin the water content can change between a di- and a sesquihydrate form without macroscopic structural changes.107 Manufacturing and storage of these crystals represent a serious technical challenge as any variation of temperature and humidity can affect the product’s composition, structure and properties.

Inclusion compounds Inclusion compounds have been investigated for chemical separation. Typically a host material would preferentially absorb one compound from a mixture or a solution. For example water and urea clathrates have been studied for almost hundred years for scientific curiosity, but also for molecular separation, sensing and storage.34 In these inclusion compounds the simultaneous crystallization of multiple guests (and solvents) is a common phenomenon that reduces the material selectivity.108 For example 9,99-(biphenyl-4,49-diyl)difluoren-9-ol crystallizes with both THF and diethyl ether. Recrystallization from a mixture of those solvents produces a solid solution in which both solvents are included as guests (Figure 7).109 In the analogue 9,9′-(ethyne1,2-diyl)bisIJfluoren-9-ol) host, selectivity towards butanol and propanol guests varies with crystallization temperature.110 Petit and coworkers describe the chiral discrimination of modified cyclodextrine towards the enantiomers of p-bromophenylethanol.111 In that case, the formation of a solid solution reduces the selectivity of the host toward the chiral guest.

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Figure 7. 9,99-(biphenyl-4,49-diyl)difluoren-9-ol forms a mixed clathrates with THF and diethyl ether in which the oxygen of the guest is H-bonded to the alcohol of the host.

On the contrary, host structures with mixed molecular components can be readily prepared to rationally modify the properties of the material. For example, Cooper prepared a porous cocrystalline solid solution by mixing three organic cages in a 0.5:x:(0.5-x) composition. The product composition affects the BET measured for the product.112 The Werner complexes [MCl2(4-PhPy)4] (M = Ni, Co) show different affinity towards a mixture of xylenes absorbing the three isomers. In the mixed-metal solid solution, at 1:1 composition [Ni0.5Co0.5Cl2(4-PhPy)4] the affinity towards the para-xylene isomer is suppressed and the selectivity towards the meta and ortho isomers is enhanced.113 Davis reported a steroidal organic alloy that produced channels whose cavity can be decorated with a variety of functional groups. In that polymeric solid solution the different substituents affected the size and polarity of the cavity.49

Solid solutions of coordination polymers In the past thirty years, 1-, 2- or 3-dimensional coordination polymers have been a rewarding object of study for crystal engineers.10 In many cases the robustness of coordination bond

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enables the design of porous architectures: i.e. porous coordination polymers (PCP) and metal organic frameworks (MOFs).114-117 Nassimbeni reported that, in a series of non-porous 1-d coordination polymers of Ni and Cd thiocyanate, thermal stability could be varied within a 120 °C range depending on the ratio between Cd and Ni.64 In the 2-d {[(4,4´-bipyridine)ZnCl2]}n polymer, the Zn atom is tetrahedrally coordinated at room temperature and octahedrally coordinated at low temperature. The partial replacement of Zn with Co enforces the octahedral geometry at room temperature (Figure 8), representing an example of how solid solutions can force a particular chemical connectivity/symmetry and contrast self-assembly.118

Figure 8: Room temperature structure of {[(4,4´-bipyridine)ZnCl2]}n (top) and {[(4,4´-

(bottom).

bipyridine)CoCl2]}n

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Due to the fast expansion of the field, many solid solution of porous coordination polymers PCPs and metal organic frameworks MOFs are constantly reported. Feng showed that mixing variable amount of imidazole and 5-methylbenzimidazole in the synthesis of a porous tetrahedral imidazolate framework (TIF), could serve to control connectivity and topology.119 Gao tuned the UV spectrum and magnetic properties of a chiral porous coordination polymer by mixing variable amount of Co and Ni metal centers with D-(+)-camphoric acid and 1,4-di-(1-imidazolylmethyl)-benzene ligands.120 Yaghi showed the degree of variability possible for these materials by mixing multiple ligands and included up to eight different functional groups in a single prototypal MOF.

53

Remarkably the solid solutions exhibited up to 4 times better selectivity for

CO2 over CO. As reported by Kitagawa and coworkers interdigitated 2-d layer coordination polymer such as [{Zn(5-MeO-ip)(bpy)}]n (CID 5) and [{Zn(5-NO2-ip)(bpy)}]n (CID-6) with ip = isophthalate and bpy = bipyridine undergo a phase transformation, from a non-porous to a porous structure, upon sorption of CO2. In the solid solution [{Zn(5-NO2-ip)1−x(5-MeO-ip)x(bpy)}]n the relative 5NO2-ip/5-MeO-ip composition affects the partial pressure at which the transformation occurs: ‘gate opening pressure’ (Figure 9).121 In a more recent paper, the authors observed that in the same porous coordination polymer, the relative 5-NO2-ip/5-MeO-ip composition affects the rotational frequency of the bipyridine linkers.122

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Figure 9: CO2 sorption isotherms recorded at 195 K for [{Zn(5-NO2-ip)(bpy)}]n (CID-5) [(5MeO-ip)x(bpy)}]n (CID-6) and the solid solution [(5-MeO-ip)x(bpy)}]n (CID-5/6). Adapted from Ref. 117 Copyright © 2000 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons,

Inc.

Framework flexibility and sorption isotherms were also tuned in a pillared-layer MOF obtained by mixing a number of substituted 1,4-benzenedicarboxylate by Schwedler et al.123 Cui showed that chiral multivariate MOFs, with up to three different metallosalen-based linkers, possess enhanced catalytic activity compared to the physical mixture of the parent compounds.124 Due to the wide scientific interest around these materials, dedicated reviews that summarize mixed components PCPs and MOFs are available.125,126 Here, it must be noted that as the complexity of these structures increases, the presence of multiple components do not always result in solid solutions. Different components can act as different structural elements being in a fixed stoichiometry or they can form a composites in an epitaxial architecture: core-shell crystals127 and COREMOFS.128

Summary and Perspective

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In the past six decades the idea of crystal engineering has evolved from a utopic dream to a concrete possibility. This slow evolution began with the study of salts and single component organic crystals and then involved more complex multiple component molecular compounds and coordination polymers. For those species, crystal structures and properties can (somewhat) be predicted and rationally designed exploiting the knowledge of supramolecular interactions. The full success of this activity will have a positive impact in our technological development. In fact most drug substances, dyes and light harvesting systems are crystalline materials made of zero dimensional organic molecules or metal complexes and can be treated as supramolecular entities. The same supramolecular approach can be applied also to multidimensional coordination polymers that characterize most porous solids for molecular storage, separation and sensing. In both cases the degree of control is limited by the difference between available chemical building blocks, which is discrete. Such limitations can be overcome through the preparation of solid solutions: multicomponent phases with variable stoichiometry. Beside the traditional work on metals (alloys) and inorganic salts, many examples of solid solutions include pharmaceuticals, functional materials, inclusion compounds and porous solids. The literature reviewed here shows that those solid solutions can be exploited to enforce a desired molecular connectivity and crystal symmetry and to fine-tune unit cell dimension as well as many other physicochemical properties. In some case, solid solutions of molecular and polymeric materials can produce in exotic features that are not observed in the parent compounds. In other cases, solid solutions are reported as an inconvenient phenomenon that needs to be avoided. Example of the latter include purification, chiral resolution and molecular separation processes. In any case, crystals with variable stoichiometry can help the understanding the principles of crystal packing and the solid state in general. In other words, solid solutions

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have the potential to transform the field of crystal engineering. In particular, the preparation of cocrystalline solid solutions represents a promising strategy that adds the fine-tuning of the latter to the structure variability typical of the former. Such level of control is hard to match in molecular chemistry. Ideally, the ultimate crystal engineer will assemble any molecules in the desired structure and will be able to control unit cell size and symmetry as well as any physicochemical properties. It is perhaps questionable whether real world applications require the degree of control enabled by solid solutions. Perhaps traditional supramolecular compounds (e.g. cocrystals) can produce enough variability for practical uses. However, the study of solid solutions answers an aesthetic demand that is implicit in each scientific activity.129,130 In this sense these material certainly deserves some attention in crystal engineering.

Corresponding Author * AD1_028, University of Limerick, Castletroy, Co. Limerick, Ireland. E-mail: [email protected] Funding Sources The Author thanks the Science Foundation Ireland (SFI) for the grant 15/SIRG/3577. REFERENCES (1) (2) (3) (4)

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Crystal Growth & Design

SYNOPSIS Crystalline solid solutions represent an opportunity to produce and finely tune the desired properties in molecular and polymeric crystalline materials. Here the current literature on crystalline solid solutions is reviewed and discussed from a crystal engineering perspective.

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