Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`View Article Online / Journal Homepage / Table of Contents for this issue
`
`FEATURE ARTICLE
`
`www.rsc.org/chemcomm | ChemComm
`
`Making crystals from crystals: a green route to crystal engineering and
`polymorphismi
`
`Dario Braga* and Fabrizia Grepioni*
`
`Received (in Cambridge, UK) 6th April 2005, Accepted 12th May 2005
`First published as an Advance Article on the web I5th June 2005
`DOI: 10.1039Ib504668h
`
`Supramolecular reactions between crystalline materials as well as reactions between a crystalline
`material and a vapour can be used to generate new crystalline substances. These solvent-free
`processes can be exploited to prepare both hydrogen-bonded co-crystals and coordination
`networks. Solid—vapour reactions do not differ from solid—vapour uptake/release processes, and
`can also be used to prepare polymorphs and solvates. It is argued that solvent-less reactions
`involving molecular crystals represent a green route to supramolecular solid-state chemistry and
`crystal engineering.
`
`Introduction
`
`Making crystals by design is the paradigm of crystal engineer-
`ing.l The goal of this field of research is that of assembling
`functionalised molecular and ionic components into a target
`network of supramolecular interactions? Such “bottom-up”
`process generates collective supramolecular properties (e.g.
`magnetism, non-linear optics, conductivity, nano-porosity,
`etc.)
`from the convolution of the physical and chemical
`properties of the individual building blocks with the periodi-
`city and symmetry operators of the crystal (see Fig. l).3
`
`Dipartimento di Chimica G. Ciamician, University of Bologna, Via
`Selmi 2, 40126 Bologna, Italy. E—mail.' dari0.braga@unib0. it
`TDedicated to Professor Brian F. G. Johnson (Cambridge) on the
`occasion of his 67th birthday.
`
`Dario Braga is Professor of Chemistry at the University of
`Bologna. Presently, his main scientific interests are in the study
`of crystal polymorphism and in the crystal engineering exploita-
`tion ofhydrogen-bonding interaction between ions and in solvent-
`free gas—solid and solid—solid reactions. He received the
`Raffaello Nasini Prize from the Italian Society of Chemistry
`in 1988 for his studies on solid-state dynamic processes, and the
`FEDERCHIMICA Prize for 1995 for his research on the
`intermolecular interactions in organometallic systems. He has
`published more than 300 papers and reviews and organized
`several international conferences and schools on crystal engi-
`neering. He is Scientific Editor of the RSC journal
`CrystEngComm, a member of the international editorial board
`of Chem. Comm. and Director of the Collegio Superiore of the
`Alma Mater Studiorum University of Bologna.
`
`is Associate Professor of Structural and
`Fabrizia Grepioni
`Functional Materials and of General Chemistry at the University
`of Bologna, after spending six years as Associate Professor at
`the University of Sassari. She received a PhD from the
`University of Bologna in 1990. She was awarded the 1997
`Raffaello Nasini Prize from the Italian Society of Chemistry for
`her studies on intermolecular
`interactions in organometallic
`solids. She has published more than 200 papers. Her scientific
`interests are in the fields of crystal engineering and molecular
`crystal polymorphism.
`
`The research work of many groups worldwide follows two
`main directions:
`coordination networks4 and molecular
`
`materials,5 with many relevant crossing points in between.
`The engineering of coordination networks can be described as
`periodical coordination chemistry,6 because the use of divergent
`polydentate ligand—metal coordination, as opposed to the more
`traditional convergent coordination chemistry of chelating
`ligands, extends coordination chemistry through space in
`1-D, 2-D and 3-D architectures (see Fig. 2). Even though
`periodical coordination chemistry is at present dominating the
`field, in terms of scientific output and of number of groups
`involved,
`the roots of crystal engineering are in molecular
`organic solid-state chemistry.7
`In molecular crystal engineering, on the other hand, the
`interactions of interest are mainly of the non-covalent type,
`e.g. van der Waals,8 hydrogen bonds,9 it-stacking”) etc. and
`their convolution with ionic interactions.”
`
`What is a molecular crystal,” then? An operative “crystal
`engineering” definition of a molecular crystal can be based on
`
`Non—cova|ent Einteractions
`
`Supermolecule
`
`Periodicity |_
`
`Crystal
`
`XOXOXO
`"" 919191
`XOXOXO
`
`Periodical supermolecule
`
`the collective
`Fig. 1 From molecules to periodical supermolecules:
`properties of molecular crystals result from the convolution of the
`properties of the individual molecular/ionic building blocks with
`the periodical distribution of intermolecular non-covalent bonding of
`the crystal.
`
`This journal is © The Royal Society of Chemistry 2005
`
`Chem. Commun., 2005, 3635-3645 | 3635
`
`Janssen Ex. 2013
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 1 of 11)
`
`

`
`“*3” db
`
`metal centre
`
`chelating
`
`I"!
`
`View Article Online
`
`In this feature article we will focus on the idea that reactions
`
`between crystalline solids and between crystalline solids and
`vapours represent viable alternative methods to prepare new
`crystalline materials, i.e.
`to make crystals from crystals.
`Our approach encompasses both the possibility of reacting a
`given crystalline material with another substance (which can be
`another crystalline materials, or a gas) and that of transforming
`a given crystalline material
`in a different one via a phase
`transition or via a loss of molecules (desolvation). Importantly,
`these “non-solution” approaches can be used not only to
`prepare new materials but also to generate new polymorphic
`or solvate modifications of the same substance.”
`
`Making crystals from crystals
`
`Crystal engineers are crystal makers. The ultimate step of a
`crystal engineering exercise is
`that of obtaining crystals,
`preferably single crystals of reasonable size that will allow to
`enjoy the speed and accuracy of single-crystal X-ray diffrac-
`tion experiments. Even though amorphous molecular mate-
`rials can be extremely interesting” and constitute a serious
`problem in studies of polymorphism,
`in crystal engineering
`studies the desired materials need to be — by definition — in the
`crystalline form.
`We have argued” that crystalline materials interesting for
`crystal engineering studies can also be obtained by reacting
`and transforming preformed crystals. This may be achieved by
`means of solvent-less processes,” such as those occurring
`between solids or between a solid and a vapour. Since
`processes of this type do not require recovery, storage and
`disposal of solvents, they are of interest in the field of “green
`chemistry”.25 In our approach reactions between molecular
`crystals and gases or other crystals are regarded as supramo-
`lecular reactions, whereby interactions, including coordination
`bonds, between reactants are broken while those of the
`product are being formed.” Solvent-free methods, however,
`still require that molecules are brought in contact for reaction.
`In general, fast and quantitative reactions can be achieved
`when finely ground powders (the large surface area helps
`molecular diffusion) are exposed to gaseous substances or co-
`ground with another powder. The two solvent-free processes
`are distinct but conceptually related, as depicted in the top part
`of Fig. 4.
`In order to set the scope of this contribution, we should
`point out that “single crystal” and “polycrystalline powder”
`are relative definitions, which only express the size of the
`crystals with respect to the technique in use. A polycrystalline
`material is composed of small single crystals,
`typically too
`small for single-crystal X-ray diffraction experiments; on the
`other hand, crystals suitable for X-ray diffraction are often too
`small for neutron diffraction and so forth. In the context of
`
`this article the term “making crystals from crystals” will be
`used mainly to indicate processes involving polycrystalline
`powders. We should warn the reader that we will not discuss
`intra-solid reactions,” such as topochemical reactions of the
`type explored by Schmidfl’
`in the early days of crystal
`engineering.7 These reactions are now experiencing a wave of
`renewed interest.” We shall
`also not discuss
`reactions
`
`
`
`
`
`Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`ligand
`
`coordination compound
`
`|—IMI—IMI—IMI—|
`M . .—. —»
`I
`I
`I
`metal diverging
`I—IMI—IMI-IMI-I
`"W
`I
`I
`I
`coordination network
`
`Fig. 2 Schematic representation of the relationship between mole-
`cular (top) and periodical (bottom) coordination chemistry: the use of
`bidentate ligand spacers allows construction of periodical coordination
`complexes.
`
`the energy ranking of the bonding interactions: the components
`ofa molecular crystal are held together by intermolecular links
`that are weaker than the covalent chemical bonds within the
`
`individual components, whether molecules or molecular ions.
`Hence, building blocks will retain, in general, their chemical
`and physical identity once evaporated or dissolved.
`This definition encompasses also the possibility of obtaining
`different crystal structures from the same building blocks, viz.
`crystal polymorphism (see Fig. 3),” by choosing different sets
`of non-covalent
`(supramolecular) bonds. We remind the
`reader
`that differences
`in supramolecular bonding may
`generate relevant differences in physical and chemical proper-
`ties, such as solubility, melting point, density, etc,” as well as
`different behaviours under mechanical or thermal stress, with
`
`relevant consequences on packaging and tableting,” hence on
`processing and marketing of commercial crystalline solids,
`such as pigments and drugs.” A further element of variability
`to consider when dealing with molecular crystals
`and
`polymorphs is
`the co-crystallization” of guest molecules,
`usually provided by the solvents of crystallization. Solvate
`crystals of a given chemical species, for which the unsolvated
`crystal
`is known, are also referred to (and not without
`controversyl3]”l8) as pseudo-polymorphs.
`
`poiymorph 1 \ /7 polymorph 2
`
`1. = solvent molecule
`
`o:o—
`1010
`some o—o:
`1010
`
`Fig. 3 From the same building block to polymorphs and to solvates
`
`involving single crystals.”
`
`3636 | Chem. Commun., 2005, 3635-3645
`
`This journal is © The Royal Society of Chemistry 2005
`
`Janssen Ex. 2013
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 2 of 11)
`
`

`
` solid + vapour
`
`solid reagents
`
`polycrystalline solid
`
` WD comparison
`crystallisation
`
`O99
`3&6‘
`UUU
`
`single crystal
`
`reagents in solution
`
`
`
`
`
`Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`Fig. 4 Schematic representation of the solid—solid and solid—Vapour
`processes and the strategy to obtain single crystals by recrystallisation
`via seeding.
`
`Grinding, milling, kneading, seeding
`
`Pioneering studies of reactions between molecular crystals
`were carried out by Rastogi et al. about forty years ago,26 and
`extended by Curtin and Paul
`in the l970s.27 Etter and
`collaborators investigated formation of hydrogen-bonded co-
`crystals by grinding of the solid components,28“ even in the
`presence of a third solid component.28]’
`In the case of
`2-aminobenzoic acid, Etter
`also showed grinding could
`determine polymorph interconversion.28"
`In spite of these early suggestive results methods based on
`(manual) grinding or (electromechanical) ball milling” are not
`very popular in academic chemistry labs, and are often
`dismissed as “non-chemical”, even though they are commonly
`used at
`industrial
`level mainly with inorganic solids and
`materials.3° Another industrially relevant process that can be
`applied on a
`small-scale research lab is
`the so called
`kneading,“ i.e.
`the use of small amounts of solvent or of a
`liquid reactant
`to accelerate (when not make altogether
`possible) the solid-state reactions carried out by grinding or
`milling.” Kneading has been described as a sort of “solvent
`catalysis” of the solid-state process, whereby the small amount
`of solvent provides a lubricant for molecular diffusion.l9“ The
`method is commonly employed, for example, in the prepara-
`tion of cyclodextrin inclusion compounds.33
`Whether a kneaded reaction between two solid phases can be
`regarded as a bona fide solid-state process is doubtful, as it is
`often the case with other mechanochemical reactions, because
`of the difficulty in controlling exact reaction conditions such as
`grinding time, temperature, pressure exerted by the operator,
`etc.. Even though a discussion of these extremely relevant
`aspects is beyond the scope of this article, one should consider,
`for example,
`that
`the heat generated in the course of a
`mechanochemical process can induce local melting of crystals
`or melting at the interface between the different crystals, so
`that the reaction takes place in the liquid phase even though
`solid products are ultimately recovered. The same reasoning
`applies to formation of eutectic phases19"=/I and to reactions
`occurring with a minimal amount of solvent (kneading).
`Another point to consider is that the polycrystalline nature
`of mechanochemical products makes impossible the use of
`
`View Article Online
`
`straightforward single-crystal diffraction methods, which are
`indispensable for a precise description of the structure of the
`crystal (the ultimate product of a crystal engineering experi-
`ment). Beside ab initio structure determination from powder
`diffraction data,34 which is not yet of widespread application,
`one has to resort to the a posteriori preparation of single
`crystals starting from the powdered product. In some cases,
`single crystals can be grown from solution by seeding, i.e. by
`using a
`small portion of
`the polycrystalline sample to
`“instruct” the crystallization process. Once the single-crystal
`structure is known, an X-ray powder pattern can be calculated
`and compared with the measured powder patterns of products
`obtained from subsequent preparations (see bottom part of
`Fig. 4). As for grinding and kneading, seeding procedures are
`commonly employed in industries to guarantee crystallizationl
`precipitation of the desired crystal form. Seeds of isostructural
`or quasi-isostructural species that crystallise well can also been
`employed to induce crystallisation of unyielding materials
`(lieteromolecular seeding).35 Of course, unintentional seeding
`may also alter the crystallization process in an undesired
`manner.“
`
`These aspects will be developed by means of examples, taken
`mainly from our own work, organized in the following four
`sections:
`
`(i) mechanochemical preparation of hydrogen-bonded
`adducts and cages
`(ii) mechanochemical preparation of coordination networks
`(iii)
`solid—vapour
`reactions
`involving hydrogen-bonded
`crystals
`(iv) induced polymorphism and solvate formation
`
`Mechanochemical preparation of hydrogen-bonded
`adducts
`
`Hydrogen-bonding interactions play a central role in mole-
`cular crystal engineering as witnessed by the vast literature on
`hydrogen-bonded crystals.”
`We have recently exploited inter-solid reactions between
`molecular crystals to prepare hydrogen-bonded adducts of
`organic and organometallic molecules. For example, crystals
`of
`the
`ferrocenyl
`dicarboxylic
`acid
`complex
`[Fe(n5-
`C5H4COOH)2]
`react with solid nitrogen-containing bases,
`such as 1,4-diazabicyclo[2.2.2]octane, 1,4-phenylenediamine,
`piperazine,
`trans-1,4-cyclohexanediamine and guanidinium
`carbonate,
`generating
`quantitatively
`the
`corresponding
`organic—organometallic adducts.38 The case of the adduct
`[N(CH2CH2)3NH][Fe(n5-C5H4COOH)(n5—C5H4COO)]
`(see
`Fig. 5) is particularly noteworthy because the same product
`can be obtained in three different ways:
`(i) by reaction of
`solid [Fe(n5-C5H4COOH)2] with vapours of l,4-diazabicy-
`clo[2.2.2]octane (which possesses
`a
`small but
`significant
`vapour
`pressure),
`(ii)
`by
`reaction
`of
`solid
`[Fe(n5-
`C5H4COOH)2] with
`solid
`1,4-diazabicyclo[2.2.2]octane,
`CGHIZNZ,
`i.e. by co-grinding of the two crystalline powders,
`and by reaction in MeOH solution of the two reactants. The
`fastest process is the solid—solid reaction. The base can be
`removed by mild thermal treatment, and the structure of the
`starting dicarboxylic acid is regenerated. The processes imply
`breaking and reassembling of hydrogen-bonded networks,
`
`This journal is © The Royal Society of Chemistry 2005
`
`Chem. Commun., 2005, 3635-3645 | 3637
`
`Janssen Ex. 2013
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 3 of 11)
`
`

`
`View Article Online
`
`the
`also exploited the great Versatility of
`We have
`organometallic
`zwitterion
`[Comm 5-C5H4COOH)(n5-
`C5H4COO)]41“ in the preparation of hybrid organometallic-
`inorganic salts, by reacting the solid complex with a number of
`M+XT salts (M+ = K+, Rb+, Cs+, NH4+; X’ = Cl’, Br’, I”,
`PFGT) and obtaining compounds of general formula [Col”(n5-
`C5H4COOH)(n5-C5H4COO)]2-M+X’.411’
`In
`some
`cases
`(M+ = Rb+, Cs+, X = Cl", Br”, I”) it has been necessary to
`resort to kneading by adding a few drops of water to the solid
`mixture in order
`to obtain the desired product. The
`polycrystalline products have been characterized by powder-
`and single crystal-X-ray diffraction as well as by a combina-
`tion of solution and solid-state NMR methods. This class of
`
`compounds is characterized by the presence of a supramole-
`cular cage formed by four zwitterionic molecules encapsulating
`the alkali or ammonium cations via O---M+ or O~--H—N
`
`interactions. The cage is sustained by 0-H---O hydrogen
`bonds between carboxylic —COOH and carboxylate —COO(’)
`groups, and by C—H~-‘O bonds between —CHCp and —CO
`groups, while the anions are layered in between the cationic
`complexes, as shown in Fig.
`7 in the case of [Co”l(n5-
`C5H4COOH)(n5-C5H4COO)]2-Cs+I’. It is fascinating to think
`of this inter-solid reaction as a sort of sophisticated solid-state
`“solvation” process of the cations by the organometallic
`complex.4l"
`
`Mechanochemical preparation of coordination
`networks
`
`Another relevant topic of crystal engineering is the prepara-
`tion of coordination networks (the literature is growing
`
`representation of
`Fig. 7 A pictorial
`[Com(n5—C5H4COOH)(n5—C5H4COO)]
`C5H4COOH)(n5—C5H4COO)]2-Cs+l’.
`
`the process
`and
`CS1
`
`leading from
`to
`[Co”1(n5—
`
`
`
`SOLID C
`
`VAPOR B
`
`W-c..e—~—
`
`Fig. 5 The solid—Vapour and solid—solid reactions involving 1.4-
`diazabicyclo[2.2.2]octane with formation of a
`linear chain of
`hydrogen—bonded [Fe(n5—C5H4COOH)(n5—C5H4COO)]' anions and
`monoprotonated [N(CH2CH2)3NH]+ cations. (Reprinted from ref. 35a
`with permission.)
`
`conformational change from cis to trans of the —COO/—COOH
`groups on the ferrocene diacid, and proton transfer from acid
`to base.
`
`the mechanochemical
`In the organic chemistry area,
`formation of hydrogen-bonded co—crystals between sulfona-
`mide (4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfona-
`mide) and aromatic carboxylic acids has been investigated by
`Caira et Lll.39
`
`acids
`dicarboxylic
`solid
`of
`mixing
`Mechanical
`HOOC(CH2),,COOH (n = 1-7) of Variable chain length
`together with the solid base 1,4-diazabicyclo[2.2.2]octane,
`[N(CH2CH2)3N], generates the corresponding salts or co-
`crystals of formula [N(CH2CH2)3N]—H—[OOC(CH2),,COOH]
`(n = 1-7) (see Fig. 6).” The reactions imply transformation
`of inter-acid 0-H---O bonds into hydrogen bonds of the
`O—H---N type
`between
`acid
`and
`base. The
`nature
`(whether neutral O—H~-‘N or charged (T)O~-~H—N(+)) of the
`hydrogen bond was established by means of solid-state NMR
`measurement.
`
`HOOC(CH2)nCOOH (n=l-7) +
`
`1
`
`Fig. 6 The reaction of solid dicarboxylic acids HOOC(CH2),,COOH
`(n =
`l—7) with the
`solid
`base
`l.4—diazabicyclo[2.2.2]octane.
`[N(CH2CH2)3N]. generates the corresponding salts or co—crystals of
`formula [N(CHZCHZ)3N]—H—[OOC(CH2),,COOH]
`(n = l—7). The
`O—H---O hydrogen bonds present in the solid acid are replaced by
`neutral O—H---N and charged (")0---H—N(+)
`interactions. with
`formation of dimeric units (17 = l) or infinite chains (17 = 2-7) (HCH
`atoms not shown for clarity).
`
`
`
`
`
`Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`3638 | Chem. Commun., 2005, 3635-3645
`
`This journal is © The Royal Society of Chemistry 2005
`
`Janssen Ex. 2013
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 4 of 11)
`
`

`
`exponentially).42 In our lab, we have begun to explore the
`mechanochemical preparation of coordination networks by
`using bidentate nitrogen bases.“ The coordination polymer
`Ag[N(CH2CH2)3N]2[CH3COO]-5H2O has been obtained by
`co-grinding in the solid state and in the air of silver acetate and
`[N(CH2CH2)3N] in 1:2 ratio (see Fig. 8(a)). The preparation of
`single crystals of Ag[N(CH2CH2)3N]2[CH3COO]-5H2O was
`obviously
`indispensable
`for
`the determination
`of
`the
`exact nature of the co-grinding product. One could thus
`establish
`that
`the
`coordination
`network
`in Ag[N-
`(CH2CH2)3N]2[CH3COO]-SHZO is
`based
`on
`chains
`of
`Ag‘ ' ‘[N(CH2CH2)3Nl‘ ' ‘Ag+‘ ' ‘[N(CH2CH2)3Nl‘ ' ‘Ag+a With
`each silver atom carrying an extra pendant [N(CH2CH2)3N]
`ligand and a coordinated water molecule in tetrahedral
`coordination geometry. When ZnCl2 is used instead of
`AgCH3COO in the equimolar reaction with [N(CH2CH2)3N],
`different products are obtained from solution and solid-state
`reactions, respectively. Fig. 8(b) shows that the structure of
`Zn[N(CH2CH2)3N]Cl2, crystallized from solution, is based on
`a one-dimensional zigzag coordination network constituted of
`alternating [N(CH2CH2)3N] and ZnCl2 units, joined by Zn—N
`bonds. Crystals of the product obtained by grinding have not
`been obtained and the details of this compound remain
`unknown. However, we have been able to demonstrate that the
`phase obtained by co-grinding can be transformed into the
`known anhydrous phase Zn[N(CH2CH2)3N]Cl2 by prolonged
`manual grinding.
`Other examples of mechanochemical preparation of coordi-
`nation complexes are known. Steed and Raston and co-
`workers have explored the use of mechanochemistry in the
`synthesis of extended supramolecular arrays.44 Grinding of
`Ni(NO3)2 with 1,10-phenanthroline (phen)
`resulted in the
`facile preparation of [Ni(phen)3]2+ accompanied by a dramatic
`and rapid colour change. Addition of the solid sodium salt of
`tetrasulfonatocalix[4]arene (tsc) gives two porous it-stacked
`supramolecular
`arrays
`[Ni(phen)3]2[tsc4T]-nH2O and the
`related
`[Na(H2O)4(phen)][Ni(phen)3]4[tsc4T][tsc5T]-nH2O
`depending on stoichiometry. It has also been reported that
`the co-grinding of copper(II) acetate hydrate with 1,3-di(4-
`pyridyl)propane (dpp) gives a gradual colour change from blue
`to blue—green over ca. 15 min. The resulting material was
`
`
`
`
`
`Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`A-.
`
`.,.<t»..
`
`.,.e..
`
`$3
`13
`ifi
`a
`@ me e.,.e e
`b ¢ m o‘:£
`Efl
`gfl
`
`View Article Online
`
`shown by solid-state NMR spectroscopy to comprise a 1D
`coordination polymer with water-filled pores. The same host
`structure,
`[{Cu(OAc)2}2(u-dpp)],,, could be obtained from
`solution containing methanol, acetic acid or ethylene glycol
`guest species.“
`
`Solid—vapour reactions involving hydrogen-bonded
`crystals
`
`Solid—vapour reactions are another solvent-free route to new
`materials. Reactions of
`this
`type have been extensively
`investigated in the organic field and nowadays hundreds of
`quantitative processes are known.“ Applications to organo-
`metallic cases are less popular.47
`We have investigated the reactivity towards vapours of acids
`and bases
`of
`the organometallic
`zwitterion
`[Co”l(n5-
`C5H4COOH)(n5-C5H4COO)], because the presence of one
`—COOH group, which can react with bases, and one —COO(’)
`group, which can react with acids, confers to this species a
`useful amphoteric behaviour. The reaction between a solid
`acid and a basic vapour was
`first
`investigated by the
`Italian scientist Pellizzari as early as in 1884.48 In the 1970s
`Paul and Curtin, beside studying solid—solid reactions,
`investigated solid—vapour
`reactions in a series of elegant
`studies.”
`
`[Co‘”(n5-C5H4COOH)(n5—C5H4COO)]
`zwitterion
`The
`undergoes fully reversible heterogeneous reactions with the
`hydrated vapours of
`a variety of acids
`(e.g. HCl,5°“
`CF3COOH,5°” HBF45”)
`and bases
`(e.g. NH3, NMe3,
`NH2Me47“), with formation of the corresponding salts.”
`Formation of the salts in the heterogeneous reactions was
`assessed by comparing observed X-ray powder diffraction
`patterns with those calculated on the basis of the single-crystal
`structures determined from crystals obtained from solution. In
`the case of vapours of aqueous HCl complete conversion of the
`neutral crystalline zwitterion into the crystalline chloride salt
`[Co”1(n5-C5H4COOH)2]Cl-H20 is attained in few minutes of
`exposure.5°“ The polycrystalline product can be converted
`back to neutral
`[Comm5-C5H4COOH)(n5-C5H4COO)] by
`heating the sample under
`low pressure (see Fig. 9(a)).
`The
`behaviour
`of
`[Co‘”(n5-C5H4COOH)(n5—C5H4COO)]
`towards NH3 is
`similar:
`exposure
`to vapours of wet
`ammonia quantitatively transforms the neutral complex into
`the
`hydrated
`ammonium salt
`[Col”(n5-C5H4COO)2]-
`[NH4]-3H2O.5°“ Absorption of ammonia is also fully rever-
`sible: upon thermal treatment the salts convert quantitatively
`into the neutral zwitterion (see Fig. 9(b)). Analogously
`[Comm5-C5H4COOH)(n5-C5H4COO)] reversibly reacts with
`cF3cooH,5°” CH2C1COOH,5°" CHF2COOH,5°" HBF4 and
`HCOOH,5°d without decomposition or detectable formation
`of amorphous material. The materials are robust and stable
`and can be cycled through release/absorption without decom-
`position.
`The
`reactions
`of
`[Co”I(n5-C5H4COOH)(n5-
`C5H4COO)] with HCl and CF3COOH were also investigated
`by AFM on single crystals.5°"
`The adduct with formic acidsod deserves a closer look,
`because upon crystal formation proton transfer does not take
`place,
`and
`the
`product
`[Co”l(n5-C5H4COOH)(n5-
`C5H4COO)][HCOOH]
`is
`a co-crystal
`rather
`than a salt
`
`OAg+
`
`o
`
`OC|- Q 2.12-
`
`Fig. 8 The coordination network in Ag[N(CH2CH2)3N]2[CH3COO]-
`SHZO (a) and in Zn[N(CH2CH2)3N]Cl2 (b).
`
`This journal is © The Royal Society of Chemistry 2005
`
`Chem. Commun., 2005, 3635-3645 | 3639
`
`Janssen Ex. 2013
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 5 of 11)
`
`

`
`View Article Online
`
`
`
`HCI hydrated vapours |my
`
`
`
`
`
`Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`[Co”1(C5H4COOH}(C5H4COO)]
`
`;\
`
`:r;.....
`va pours
`
`b
`
`$1\\
`E-:3... _,
`
`
`
`‘° *1‘-'1“ \‘l
`M.
`
`[Co' “(C5H4COO)2][N H4] ’3 H20
`
`[Co'“(C5H4COOH )(C5H4COO)][HCOOH]
`
`Fig. 9 The reversible reactions between anhydrous [Com(n5—C5H4COOH)(n5—C5H4COO)] and HCl (a). NH3 (b). and HCOOH (c) leading
`to formation of [Co‘”(n5—C5H4COOH)2]Cl-H20.
`[Co‘”(n5—C5H4COO)2][NH4]-3H2O. and [Co1”(n5—C5H4COOH)(n5—C5H4COO)][HCOOH].
`respectively.
`
`(Fig. 9(0)), as shown by both X-ray and CPMAS NMR
`spectroscopy.
`
`the zwitterion [CoI”(n5-C5H4COOH)(n5-
`In summary,
`C5H4COO)] can be said to behave as a solid amphoteric trap
`towards vapours of both acids and bases. Since the solid—
`vapour reactions occur with wet vapours, one may be brought
`to suppose that the reactions occur via a process of dissolution
`and recrystallisation, as the vapours are adsorbed by the
`crystalline powder. The reverse process, i.e. reconstruction of
`the zwitterion crystals, is more difficult to explain as it implies
`proton removal from the cationic acid. Moreover, the TGA
`experiments show that water of hydration is always released
`first, while the acid and the base come off only subsequently.
`Hence
`the participation in the reverse process of an
`intermediate liquid phase is unlike.
`On closing this section we would like to emphasize that
`heterogeneous solid—vapour reactions represent an alternative
`to nanoporosity (i.e. to zeolitic behaviour) for the controlled
`uptake and release of small molecules47 and are being actively
`investigated in the quest for solid-state sensors, reservoirs,
`filters and sieves for detecting or trapping small molecules.“
`
`Induced polymorphism and solvate formation
`
`the possibility of
`The paradigm of crystal engineering is
`obtaining an ordered and periodical organization of molecules
`or ions through space from the self-assembly of building
`blocks (see Fig. 1). The control of the assembly process
`depends on our capacity of instructing molecules or molecular
`ions how to recognize each other and form stable crystal
`nuclei, that eventually lead to the desired crystalline material.
`Clearly, if the instructions are not very precise and/or if other
`(uncontrolled or less controlled) external factors affect the
`process,
`the result can be unpredictable or admit multiple
`
`i.e. serendipitous polymorphism. The problem is
`solutions,
`further complicated by the possibility of obtaining different
`solvate forms. One can say that if the formation of polymorphs
`is a nuisance for crystal engineers, solvate formation can be a
`nightmare, because it is extremely difficult to predict whether a
`new species may crystallizes from solution with one or more
`molecules of solvent. However, while serendipitous poly-
`morphism and solvate formation are very common (“it
`happens” to crystallize the same substance as different crystals
`or solvates), intentional polymorphism is more difficult, as it
`requires the purposed investigation of the conditions to obtain
`different crystals for the same species.l3’52
`Thus far we have provided evidence that the solvent-free
`reaction of a molecular crystal with a vapour can be exploited
`to make new crystalline supramolecular aggregates. A useful
`notion is that the same approach can be used to prepare a new
`polymorplt or s0lvate.53 This section of the Feature Article will
`expand on this idea. We will show how mechanical treatment,
`vapour uptake and release and seeding can all be used to
`obtain new crystal forms. We will also discuss the useful
`possibility of obtaining interconversion of crystal forms as a
`function of pressure and temperature.
`We have come across a case of relationship between
`polymorphism and pseudo-polymorphism during the initial
`preparation of
`the
`zwitterion [Col”(r]5-C5H4COOH)(n5-
`C5H4COO)].38“ Single crystals of this molecule could be
`obtained by seea’ing a water solution obtained by dissolving
`the trihydrate [Co”‘(n5-C5H4COOH)(n5-C5H4COO)]-3H2O
`with seea’s prepared by
`step-wise dehydration of
`the
`hydrated species.38]’ A thermogravimetric experiment showed
`that
`[Co‘”(n5-C5H4COOH)(n5—C5H4COO)]-3H2O reversibly
`releases one water molecule at 378 K, while the loss of the two
`remaining water molecules occurs at ca. 506 K and is
`immediately followed by a phase transition. Subsequent
`
`3640 | Chem. Commun., 2005, 3635-3645
`
`This journal is © The Royal Society of Chemistry 2005
`
`Janssen Ex. 2013
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 6 of 11)
`
`

`
`
`
`
`
`Publishedon15June2005.Purchasedbyjmoore@pbwt.comon17July2015.
`
`View Article Online
`
`comparison of the calculated and measured powder diffracto-
`grams of the anhydrous phase confirms that
`the powder
`obtained at 506 K and the single crystals precipitated at room
`temperature
`after
`.seeding possess
`the
`same
`structure.
`Importantly, crystallization in the absence of
`seeds of
`[Co‘”(n5-C5H4COOH)(n5-C5H4COO)] yields the initial trihy-
`drate form [Co”‘(n5-C5H4COOH)(n5—C5H4COO)]-3H2O.
`In a similar process, crystals of [Ru(n6-C6H6)2][BF4]2 can be
`crystallized from nitromethane as the solvate form [Ru(n6-
`C6H6)2][BF4]2-MeNO2. These solvate crystals,
`if exposed to
`air,
`rapidly
`convert
`to
`the
`unsolvate
`form [Ru(n6-
`C6H6)2][BF4]2. The nature of this
`latter compound was
`established from single crystals obtained from water in the
`presence of seeds of the powder material obtained from
`desolvated crystals [Ru(n6-C6H6)2][BF4]2-MeNO2.54
`The opposite process, namely solvent uptake, can often be
`activated by mechanical
`treatment of unsolvated crystals.
`There are several reports on that even gentle grinding of a
`powder product to prepare a sample for powder diffraction
`may lead to the formation of a hydrated product.” In our lab,
`we have seen that the hydrated salt [Co(n5-C5H5)2]+[Fe(n5-
`C5H4COOH)(n5-C5H4COO)]’
`-H20 is obtained by simply
`grinding in the air
`the crystalline powder of
`[Co(n5-
`C5H5)2]+[Fe(n5-C5H4COOH)(n5-C5H4COO)]’
`that precipi-
`tates from THF or nitromethane on reacting [Co(n5-c5H5)2]
`with [Fe(n5-C5H4COOH)2].56“ Once [Co(n5-C5H5)2]+[Fe(n5-
`C5H4COOH)(n5-C5H4COO)]‘H20 has been obtained by
`grinding,
`its single crystals can be grown from water or
`nitromethane, while crystals of the anhydrous form are no
`longer observed. However, on heating, the hydrated form loses
`water at 373 K and reverts to the starting material.
`A related situation has been observed on reacting solid
`[N(CH2CH2)3N] with solid malonic acid [HOOC(CH2)COOH]
`in the molar 1:2 ratio.56]’ Two different crystal forms of the
`salt
`[HN(CH2CH2)3NH][OOC(CH2)COOH]2 are obtained
`depending on preparation technique (grinding or solution)
`and crystallization speed. Form I, containing mono-hydrogen
`malonate
`anions
`formin