Chem. Rev. 2001. 701, 1529-1358
`
`1629
`
`From Molecules to Crystal Engineering: Supramolecular lsomerism and
`Polymorphism in Network Solids
`
`Brian itiloulton and Michael J. Eaworotko"
`
`Department of CiiiS'flTi5fl}’, University of South Florida, 4202 East Fowter Avenue, SCA 400, Tampa, Fiorida 33520
`
`Received Septenitier 6. 2000
`
`Contents
`
`I.
`
`Introduction
`
`A. From Molecules to Crystal El"|giilUL2lillg
`B. Crystal Engineering vs Crystal Structure
`Prediction
`
`C. Supramolecular Isomerisrn
`II. Coordination Polymers
`A. OD (Discrete) Architectures
`8. 1D Coordination Polymers
`1. Stoichiometry of Metal to Ligand = M
`
`2. Stoichiometry of Metal and Spacer Ligand 1535 — 1:15
`
`1629
`
`1630
`1630
`
`1631
`1632
`1633
`1633
`1633
`
`C. 2D Coordination Polymers
`1' Square Gnds _
`2- Ulilfii ED Nfillilefilllffifi
`0- 30
`;' g::I:::[§[r:'|dNr:?:E$:$
`'
`3.
`:3ltlEi]e_rd3S|il Networks
`4.
`y ri
`tructures
`iii. Hydrogen-Bonded Networks
`A. DD (Discrete) Aggregates and ti) Networks
`8. 2D Networlts
`1. Derivatives of Triniosic Acid
`
`1835
`1535
`1535
`we
`
`__ _
`_A
`__
`__
`__
`_ H ___ _
`M
`Brian litoulton was born in Nova Scoiia. Canada. in 1970. Ito received
`his B.Sc. degree in Chemistry from Daihousie University in Halifax, Nova
`§:‘?.‘i‘3.‘i.“i;i:“’‘:.‘i.‘f.¥L“it'2liiiiii5i%i‘l‘iEil‘i‘i§i”.?l3i£§2l
`Zaworetko‘sgresearch group. He is curraritiywririgiiig toward his Phi).
`degree under Professor Zairiorotko at the University of South Florida in
`Tampa iii the area of crystal eiigineering.
`
`i542
`1643
`1644
`1544
`
`1650
`
`3. Hydrogen»Bonded Networks Sustained by 1545
`Organic ions
`C. 3D Networks
`
`1647
`
`1. Sell-Assembled Hydrogen-Bonded
`Diariioriduid Networks
`
`2. Modular Self-Assembly of
`Hydrogen-Bonded Diamondoid Networks
`3. Other 3D l-lydrogen-Bonded Networls
`Iii. Suprarnolecular lsomerism and Polymorphism
`A. Structural Stipramolecular isoniorism
`B.
`C- caleilane SUrJiflm0|9CU|¥3f 550m9i'|5m
`‘J. Potential Applications
`W Condusl-ms and Fume Directions
`W References
`'
`
`164?
`
`1649
`
`1549
`
`1651
`west
`1552
`1553
`1554
`165 4
`
`-
`I’ Introduction
`wrhereas Sing]e_C,—y5ta| X_I~a}- C,-y5ta|10graphy has
`represented an active area of research since shortly
`after the discovery of X—rays. the subjects of crystal
`design and crystal engineering have developed rap-
`idly only in recent years. This is presumably an
`
`.
`.
`.
`.
`t?';:?':'.;;.aii.i:°ii.‘;.;'et:.r:r:,t*:isi}'ieii:':i.ztteiietif
`degree in Chemistry in 1932 at the University of Alabama under the
`supervision oi Professor Atwood in the fold oforganoaluminunt chemistry.
`After compieting a_ postdoctoral fellowship with Professor Stobait atythe
`Uniiie_is.ty of trictoria, Caiiada, he accepted an Assistant Professor position
`at Saint Marys University it-ialilax, ixtosia Scotia) in 1995. His research
`program initially focused upon organometallic chemistry and ionic liquids
`but soon evolved toward the solid state. in particular crystal engineering
`of organic and metal—or§anic networks. He became Professor and Chair
`of Chemistry at the University of South Florida in Tampa, FL,
`in 1999.
`artifact of a number of factors. For example, the
`development of relatively low—cost and powerful
`Computers has not only enhanced crystal structure
`determination. but also crystal structure visualiza-
`
`Janet L. i1obbiiis.C$R. RPR
`
`'9 2001 An'.en'cai1 Chemical Society
`'|D.1D21lErS9E’G¢32 CCC: $35.00
`Published on Web 05i‘l2f2{JE|1
`
`Case No. 2:10-cv-05954
`Janssen Products. L.P. et al.
`v. Lupin Limited, at al.
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`

`
`1530 Chemical Reviews, 2001, Vol. lot, No. 5
`
`Nloulion and Zaworotko
`
`tion, database development and analysis. and reflec-
`tion analysis and processing. Simply put. X-ray
`crystallographic analysis has become less time con-
`suming, relativeiy inexpensive, and more readily
`available, even for larger andior difficult structures.
`The growth of crystal engineering has also coincided
`with advances in our understanding of intermolecu-
`lar interactions and supramolecular chemistry and
`the realization that several aspects of solid-state
`chemistry are of increasing relevance and can only
`be resolved with a better understanding of structure-
`function relationships. It is the latter that will be the
`primary focus of this review. which is to present an
`overview of how advances in supramolecular chem-
`istry l'lEW('. impacted the manner in which chemists
`view the existence of single crystals and, perhaps
`even more importantly, the design of new crystalline
`phases.
`
`A. From Molecules to Crystal Engineering
`
`"One of the continuing scandals in the physical
`sciences is that it remains in general impossible to
`predict the structure of even the simplest crystalline
`solids [from a knowledge of rheir chemical composi-
`tion." This provocative comment by Maddox‘
`il-
`luminates an issue that continues to represent a
`challenge of the highest level of scientific and tech-
`nological importance. Simply put, to quote Feynman.
`What would the properties ofmateriais be if we could‘
`really arrange the atoms the way We want them.7'2
`Such a dream generally remains to come to fruition,
`at least in terms of molecular scll"-assembly in the
`crystalline state. However,
`it has spawned and
`fuelled a seemingly exponential growth in research
`activity devoted to the subjects of crystal design and
`crystal engineering. Furthermore, the implications
`go beyond materials science since structure—function
`relationships in the solid state are of relevance to
`opportunities in the context of areas of interest that
`are as diverse as solvent-l‘ree synthesis and drug
`design and development. The term crystal engineer-
`ing was first coined in a contribution by G. M. J.
`Schmidt concerning the subject of organic solid-state
`photochemistry.3 Schmidt's article marked a thought
`evolution in at least two important ways. First, as
`implicit by use of the term crystal engineering, it
`became clear that,
`in appropriate circumstances.
`crystals could be thought of as the sum of a series of
`molecular recognition events, self-assembly, rather
`than the result of the need to “avoid El vacuum“. it.
`
`has subsequently become clear that crystal engineer-
`ing. especially in the context of organic solids.
`is
`intimately linked to concepts that have been devel-
`oped in supramoiecular chemistry. another field that
`has undergone explosive growth in recent years.
`Supramolecular chemistry. defined by Lehn as chem-
`istry beyond the molecule,"-5 and “supramolecular
`assemblies" are inherently linked to the concepts of
`crystal engineering. In this context. crystals might
`be regarded as being single chemical entities and as
`such are perhaps the ultimate examples of supra-
`molecular assemblies or supermolecules. Dunitz re-
`ferred to organic crystals as “supermolecule(s) par
`eXce11ence”.5-7 As revealed herein, this interpretation
`
`is fully consistent with the approaches to crystal
`engineering practiced by ourselves and others who
`are presently active in the field.
`Second. Schmidt's work emphasized that the physi-
`cal and chemical properties of crystalline solids are
`as critically dependent upon the distribution of
`moiecular components within the crystal lattice as
`the properties of its individual molecular components.
`Therefore. crystal engineering has implications that
`extend well beyond materials science and into areas
`as diverse as pharmaceutical development and syn-
`thetic chemistry. in the context of the former, there
`are important processes and intellectual property
`implications related to polymorphis1‘n.3"2 In the
`context of the latter, solid-phase organic synthesis
`can be solvent free and offer significant yield and
`regioselectivity advantages over solution—phase reac-
`tions. In other words. crystals should not be regarded
`as chemical graveyards. To the contrary, it is becom-
`ing increasingly clear that. binary or inclusion coni-
`pounds can be used to effect a diverse range of
`thermal and photochemical reactions in the solid
`state,” '5 including some that cannot be effected in
`solution.”"9
`In this contribution we concentrate upon advances
`that were spawned by a series of papers and mono-
`graphs in the 19805 by Deslraju2°‘Z2 and Etter23”25
`that conceiitrated upon using the Cambridge Struc-
`tural Databasezfi (CSD) for analysis and interpreta-
`tion of noncovalent bonding patterns in organic
`solids. It should be noted that a considerable body of
`work devoted to the subjects of crystal nucleation,
`gruvvth, and Inorphology was developed concurrently.
`This research, which could be perhaps termed "en-
`gineering crystals", is not the intended focus of this
`review and is exemplified by the work of research
`groups such as those of Cohen.“ Green,“ Addadi,29’33
`Mann and l'leywood.3‘-35 Thomas.35-37 and Davoy.33>39
`'l‘he seminal work by Desiraju and litter in solid-state
`organic chemistrv afforded the concept of supremo-
`Iccufar synrlions’/3 and led to hydrogen bonds being
`perhaps the most widely exploited of the noncovalent
`interactions in the context of crystal engineering.
`Their research programs addressed the use of hy-
`drogen bonding as a design element in crystal design
`and delineated the nature {strength and direction-
`ality} of the interaction. It is now readily accepted
`that these forces include weak hydrogen-bonding
`interactions such as C-l-l~--X and Cl-1---rt. Although
`Professor Desiraju continues his valuable contribu-
`Lions to the discipline. Professor Etter passed away
`in 1992.
`
`In this contribution, we attempt to address the
`challenges and opportunities represented by crystal
`engineering with particular emphasis upon how
`supramolecular concepts are important in helping us
`to understand supramolecular isomerism and super-
`structural diversity in the context of two classes of
`structure: coordination polymers and organic mo-
`lecular networks-
`
`B. Crystal Engineering vs Crystal Structure
`Prediction
`
`It is important to stress the significant conceptual
`difference between crystal engineering and crystal
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`From Molecules to Crystal Engineering
`
`Chemical Reviews, 2001. Vol. 101. No. 6
`
`I631
`
`structure prediction. in short, crystal structure pre-
`diction is precise {i.e.. space group and exact details
`of packing are defined) and deals primarily with
`known molecules or compositions of molecules. Crys-
`tal engineering is less precise {e.g.. network predic-
`tion) and most typically deals with entirely new
`phases, sometimes. but not necessarily.
`involving
`well-known molecules. Technological advances in
`experimental and computational methodology have
`accelerated the evolution of crystal engineering. In
`particular, the advent of COD diffractometers facili-
`tated the solution of crystal structures within hours
`or minutes rather than weeks or days and computa-
`tional advances have made use of databases and
`
`visualization software inexpensive and straightfor-
`ward. Therefore. although ab initio crystal structure
`prediction remains at best a significant challenge.““"‘3
`even for small molecules. crystal engineering has
`been able to develop rapidly because its objectives
`and modus operand)‘ are distinctly different from
`crystal structure prediction. The raison d’erre and
`strategies of crystal engineering are somewhat dif-
`ferent from those of crystal structure prediction since
`the former is primarily concerned with design and.
`although more restrictive in terms of molecular
`components that might be employed,
`is becoming
`increasingly synonymous with the concept of su-
`pramolecular synthesis of new solid-state structures.
`In other words. crystal engineering represents a
`paradigm lbr synthesis of new solid phases with
`predictable stoichiometry and architecture. In con-
`trast. predicting a crystal structure requires analysis
`of the recognition features of a molecular component
`in the context of how they will generate crystal-
`lographic symmetry operations and optimize close
`packing, i.e., it requires space group determination.
`Engineering and design are far less restrictive from
`a conceptual perspective since they focus more broadly
`upon the design of new and existing architectures.
`in effect, the principles of design are based upon a
`blueprint,
`in many cases a blueprint that is first
`recognized via a serendipitous discovery, and allow
`the designer to select components in a judicious
`manner. Therefore, a desired network structure or
`blueprint can be limited to chemical moieties,
`in
`many cases commercially available moieties, that are
`predisposed to a successful outcome.
`
`C. Supramolecular lsomerism
`
`Closely related to the well-documented {but not
`necessarily well understood) subject of polymorphism
`in crystalline solids is the existence ofsupramolecular
`isomerism“ in polymeric network structures. Su-
`pramolecular isomerisrn in this context is the exist-
`ence of more than one type of network superstructure
`for the same molecular building blocks and is there-
`fore related to structural isomerism at the molecular
`level. In other words. the relationship between su-
`pramolecular isomerism and molecules is similar to
`that between molecules and atoms. In some in-
`stances, supramolecular isomerism can be a conse-
`quence of the effect of the same molecular compo-
`nents generating different supramolecular synthons
`and could be synonymous with polymorphism. How-
`
`ever. in other situations. supramolecular isomerisrn
`is the existence ofdifferent arcliitectures (i.r,-., archi-
`tectural
`isomcrism‘-5} or supcrstructures.
`In this
`context, the presence of guest or solvent molecules
`that do not‘ directly participate in the network itself.
`especially in open framework structures, is important
`to note as it means that polymorphism represents an
`inappropriate term to describe the superstructural
`differences between network structures. indeed, it is
`reasonable to assert
`that polymorphism can be
`regarded as being a type of supramolecular isomer-
`ism but not necessarily vice versa. Pseudopolymor
`phisrn is a related term that has been mined to
`Categorize solvates.”-'” especially in the context of
`pharmaceutical solids. Since solvent molecules are
`often integral parts of the resulting network struc-
`tures, a pseudopolymorph is. at least from a Su-
`pramolecular perspective. a binary phase and an
`entirely different class of compound.
`
`The subject of supramolecular isomerism is impor-
`tant for a number of reasons. {I} investigation of the
`relationship between supramolecular isomerism and
`polymorphism represents a fundamental scientific
`challenge. However. when one considers that bulk
`properties of solids are critically dependent upon
`architecture and that crystal structure confirms
`composition of matter from a legal perspective. the
`applied relevance also becomes immediately appar-
`ent. Polymorphism in molecular crystals represents
`a phenomenon that is particularly important and
`ubiquitous in the context of pharmaceuticals and is
`receiving increasing attention from a scientific
`perspective.‘”"53 It should also be noted that Mc(_Irone
`was prompted to suggest that the “number offbrms
`known for a given compound is proportional to the
`time and money spent in research on that com-
`pound'.5" However. the generality of McCrone's state-
`ment remains ambiguous despite indications that
`polymorphism is more general than expected from
`the (381155 For example, Desiraju“ demonstrated
`that
`the frequency of occurrence of polymorphic
`modifications is not necessarily uniform in all cat-
`egories of substance. His analysis revealed that the
`phenomenon is probably more common with mol-
`ecules that have conformational flexibility andfor
`multiple groups capable of hydrogen bonding or
`coordination. Coincidentally and importantly, this is
`inherently the situation for many pharmaceuticals
`and conformational polymorphism is a subject in its
`own right.55'57 Desiraju also suggested that polymor-
`phism can be strongly solvent-dependent. In sum-
`mary, the relevance of polymorphism is clear but
`remains a subject that is not fully or widely under-
`stood at a fundamental level.
`
`(2) Control over supramolecular isomers and poly-
`morphs lies at the very heart of the concept of crystal
`engineering (i.e.. design ofsolids). However. there is
`presently very little understanding concerning even
`the existence of supramolecular isomers, never mind
`how to control them.
`
`(3) Supramolecular isomerism also lies at the heart
`of gaining a better understanding ofsupramolecular
`synthons and. by inference, how they develop and
`occur in other solid phases and even solution. The
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`
`1632 Chemical Reviews, 2001, Vol. 101, No. 6
`
`lulouiton and Zawurolko
`
`Scheme 1. Schematic Representation of Some of the Simple Network Architectures Structurally
`Characterized for Metal-Organic Polymers:
`(a) 2D Honeycomb. (I1) ID Ladder, {cl 3D OI.!lal’I(:dral,. (dl 3D
`Hexagonal Diamondoid. ((2) ED Square Grid, and If) ID Zigzag Chain
`
`)-
`)-
`T
`T
`"Y 'T "r
`
`}-
`‘I’
`
`'
`
`iii)
`
`l-
`
`-l
`
`Fm---a
`-
`
`.4
`
`(bi
`
`-we----y
`1
`T.-*.J"'
`1'' we
`
`{UJ
`
`(dl
`
`+- +- -+ per
`+-~+~+~— --_|-
`
`«
`_
`-i-—+—+—-l-
`{cl
`
`«i,
`5
`if?
`<.
`3
`(0
`
`Can1bridge Structural Database remains a very
`powerful tool in this context. but it must be remem-
`bered that even such a large database will not
`necessarily be reflective of the full range of com-
`pounds that will be isolated and characterized in
`future years.
`The conceptual link between polymorphism and
`Supramoiecular isomerism in organic and metal-
`organic networks is not immediately apparent. How-
`ever, since polymorplis can be rationalized on the
`basis of supramolecular interactions, polymorphism
`can be regarded as El type of suprarnulecular isomer-
`ism. implicitly, all sets of polymorphs can therefore
`be regarded as being supramolecular isomers of one
`another but the reverse is not necessarily the case.
`It should also be noted that solvates are almost
`
`always different compounds from a crystal engineer-
`ing perspective. The only exception would be in the
`case of inclusion compounds where the host frame-
`work remains intact
`in the presence of different
`solvent molecules. i.e., the solvent serves the function
`of being a guest molecule. Supramolecular isomerism
`as seen in metal-organic and organic networks may
`be classified based upon analogies drawn with isom-
`erism at the molecular level. Thus far it is appropri-
`ate to categorize the following classes of supra-
`molecular isomerism.
`
`Structural. The components of the network [i.e.,
`the metal moiety and the ligands the or exofunctional
`organic molecule) remain the same but a different
`superstructure exists.“ In such a situation,
`the
`networks are effectively different compounds even
`though their empirical formula and chemical com-
`ponents are identical.
`Conformational. Conformational changes in flex-
`ible ligands such as bis(4-pyridyllethane generate a
`different but often related network architecture.‘”
`
`Conformational polymorphism is a closely related
`sLil)_ject.55"“'
`Catenane. The different manner and degrees in
`which networks lnterpenetrate or interweave can
`afford significant variations in overall structure and
`properties depending upon the molecular building
`blocks that are utilized.“ Interpenetrated and non-
`interpenetrated structures are effectively different
`compounds because their bulk properties will be so
`different.
`
`Optical. Networks can be inherently chiral and
`can therefore crystallize in chiral (enantiomorphic)
`space groups. Therefore, an analogy can be drawn
`with hunmchiral compounds. This type of supra-
`molecular isomerism lies at the heart of an important
`issue: spontaneous resolution of chiral solids.59’55
`
`The remainder of this contribution reviews the
`subject of supramoiecular isomerism and how it leads
`to superstructural diversity in network solids. Em-
`phasis is placed upon rnetal— organic or coordination
`polymers and organic solids, respectively. However,
`it should be noted that the subject matter is divided
`along these lines for convenience only since the basic
`concepts apply equally well to both classes of com-
`pound.
`
`II. Coordination Polymers
`
`Coordination polymers exemplify how crystal en-
`gineering has become a paradigm for the design of
`new supramolecular structures. in this context, the
`work of Wells is exhaustive and seminal and can
`
`serve as a reference point. Wells was primarily
`concerned with the overall structure of solids. par-
`ticularly inorganic compounds.“-57 He defined crystal
`structures in terms of their topology by reducing
`them to a series of points (nodes) of a certain
`geometry (tetrahedral. trigonal planar, etc.) that are
`connected to a fixed number of other points. The
`resulting structures, which can also be calculated
`mathematically. can be either discrete (zem~dimen-
`sional) polyhedra or infinite (one-, two-, and three-
`dimensional) periodic nets.
`It is perhaps surprising that it took until the 19905
`for the approach of Wells to bear fruit in the labora-
`tory. Robsori“ 75 was primarily responsible for the
`initial studies that Facilitated rapid development of
`the field of coordination polymers alongside that of
`crystal engineering of organic solids. Robson extrapo-
`lated Wells work on inorganic network structures
`into the re'c1lrn of me1,al—organic Compounds and
`coordination polymers. In this context, the resulting
`"node and spacer“ approach has been remarkably
`Successful at producing predictable network archi-
`tectures. Scheme 1 illustrates some of the simplest
`architectures that can be generated by using com-
`monly available metal moieties and linking them
`with linear “spacer" ligands. Whereas diamondold
`networks represent a class of structure that could be
`described as mineralomimetic because there are
`
`many naturally occurring analogues, that is not the
`case for any of the other architectures illustrated in
`Scheme 1.
`The nature of these novel structures and their
`
`organic analogues and the diversity exhibited by their
`supramolecuiar isomers“ represent the primary focus
`for the remainder of this contribution. Such struc-
`
`tures are of interest for both conceptual reasons and
`because of their interesting properties. They are
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`
`from Molecules to Crystal Engineering
`
`Chemical Reviews, 2001. Vol. lUl. No. 6
`
`‘I633
`
`Scheme 2. 3D Models of the Regular (Platonic)
`and Semiregular (Archimedean) Solids
`
`“ %"~t-if-T ‘ 0 0 T.»
`
`
`
`structures. However. it should be stressed that the
`modular self-assembly approach applies equally well
`to all levels of dimensionality since the dimensional-
`ity is often determined directly by the node. There-
`fore. it is appropriate to include discrete [JD struc-
`tures in the discussion.
`
`A. OD (Discrete) Architectures
`
`ln addition to research that has focused upon
`infinite structures. the principles of self-assembly
`have also been applied toward the design and isola-
`tion of discrete molecular structures. Such structures
`
`are exemplified by molecular squares”-9’1“°3 and.
`more recently, by striking examples of new high
`molecular weight compounds that can be described
`as spheroid architectures.‘°9"27 The design principles
`behind the isolation and development of these new
`classes of compounds are based upon the concept of
`self-assembly in the context of geometric consider-
`ations found in regular (Platonic) and serniregular
`(Archimedean) solids. Such structures are also known
`in zeolites (e.g.. Linde A. which is based upon an
`eclgeskeleton generated by fused truncated octa-
`hedral”) and in biological self-assembled systems
`such as mammalian picornaoviruses93v99-WH3‘ and
`proteins.“ The 5 Platonic and 13 Archimedean
`solids”-*3 are illustrated in Scheme 2. They can be
`constructed at the molecular level by sharing of the
`edges of molecular moieties that have the shape of
`regular polygons.” i.e., triangles. squares, penta-
`gons. hexagons, and octagons. or by connecting mo-
`lecular vertexes with linear bifunctional
`rodlilte
`
`ligands.“‘‘’-“2 in the case of the former closed convex
`surfaces are generated. whereas for the latter all the
`Faces a re open windows. This subject is highly topical,
`and several
`recent
`review articles have
`ap-
`peared.“’°-‘12-"4-*1?-134 We shall therefore provide no
`further details. The primary purpose of highlighting
`such structures is that they have been developed
`using the same principles as those used for generat-
`ing the infinite structures described herein. Struc-
`tures such as molecular squares are in effect so-
`prarnolecular isomers of some of the infinite ll)
`structures described herein.
`
`B. 1D Coordination Polymers
`
`1. Siaichiometry of Metal (0 Ligand = 1:1
`Structural supramolecular isomerism is exempli-
`fied by the range of structures that has thus far been
`
`ideally suited to illustrate the concepts of Crystal
`engineering for the following reasons. (1) The diver-
`sity of structures that can be obtained from the
`simplest of components is quite remarkable. not only
`in the Context of coordination polymers but also in
`the context oi‘ organic solids and even.
`for
`that
`matter. discrete architectures. (2) Coordination poly-
`mers can be relevant in the context of inclusion
`
`chemistry. As should be clear from Scheme 1. a
`recurring feature of even the simplest network
`structures is the presence of voids or cavities that
`are inherently present because of the architecture
`itself and the dimensions of the spacer ligands. This
`feature is attracting considerable interesit, and there
`are a number of recent reports concerning open
`framework coordi nation polymers that exhibit hith-
`erto unprecedented levels of porosity and high levels
`of thermal stability. indeed, there already exists a
`diverse range of coordination polymers with higher
`effective surface areas than zeolites and stability to
`loss of guest.7“’3“ (3) From a design perspective, it
`should be clear from Scheme I
`that each of the
`
`two
`least
`networks illustrated is based upon at
`components (i.e.. the node and the spacer) and. as
`will become clear herein, such components can be
`preselected for their ability to self-assemble. The
`network structures can therefore be regarded as
`examples of blueprints for the construction of net-
`works that.
`in principle. can be generated from a
`diverse range of chemical components, i.e.. they are
`prototypal examples of modular fr:-inieworl-cs. It should
`be noted that
`the construction of networks from
`single-cotnponenl; Systerns also represents an impor-
`tant area of activity. Self—assembly of a single-
`molecular component. or "molecular tectonics", rep-
`resents a different approach to crystal design, and it
`must be remembered that most existing crystal
`structures are based upon a single component. How-
`ever, in order for single-component sell‘-assembly to
`be directly relevant in the context of crystal engi-
`neering, all tho molecular recognition foottires that
`lead to supramolecular synthons must be present in
`a single molecule. 1.3.5.7—Adomantanetetraacetic
`acid3535 and methanetetraacetic acid“ can be re-
`
`garded as being prototypal for Self-assembled dia-
`mondoid architectures. Both structures are sustained
`
`by one of the most well recognized supramolecular
`synthons—the carboxylic acid dimer.“ Pyridone dimers
`have been used in a fashion similar to build diamon-
`doid networks. in this case from tetralmdral tet1‘alt—
`ispyridones.““ A number of well-known inorganic
`structures can also be regarded as examples of self-
`assembly (e.g., ice, potassium dihydrogenphosphate).
`and one might even consider covalent bonds as
`conceptually related: diamond. Si. Ce, ZnS. BP.
`GaAs, ZnSe. CdS. CUlIlSEg. CuFeSz (chalcopyrite).
`However. this contribution will focus primarily upon
`the modular or multicornponent approach to crystal
`design. Coordination polymers and hydrogen-bonded
`structures with multiple complementary components
`can be regarded as being the consequence of modular
`self-assembly.“
`The remainder of this section will be organized
`according to the dimensionality of the observed
`
`Janssen Ex. 2043
`
`Lupin Ltd. v. Janssen Sciences Ireland UC
`|PR2015-01030
`
`(Page 5 of 30)
`
`

`
`1634 Chemical Heviews. ZGU1, Vol. 101. No. 6
`
`Mnulmn and Zaworolko
`
`Scheme 3. Schematic Representation of the Three
`Structural Supramolecular isomers Observed for
`Angular Nodes Generated by c1's-Substituted Metal
`Muietles:
`(a) DD Square. (h) 1D zigzag Chain. and
`(c) 11) Helix
`
`tr"
`l
`l
`'-lI._
`
`(al
`
`Q\\
`X2
`,x;:
`
`/_
`
`V
`
`v
`
`<
`\
`.>
`.4”
`(la)
`
`A
`\.
`.‘\
`
`4
`
`V
`
`9
`
`(cl
`
`in particular
`observed in coordination polymers.
`network structu res that have been observed for some
`of the simplest building blocks and stoichiomctrios.
`Scheme 3 illustrates the possible structures that can
`result l‘rom selliasscmbiy of either a c1'soctahedral
`or a cis-square planar metal and a linear “spacer”
`ligand. There are three obvious architectures that
`might result. and they are dramatically different
`from one another. The "square box" or "molecular
`square” architecture represents a discrete species
`that has been developed extensively in recent years
`by the groups of F-ujha| H16 S-tang’!l.ll][l.lE|2—l£M.]U7,ll2.lZCl
`and l—[upp.9”"9”‘“”'~135 The other two architectures
`are both examples of ID coordination polymers. but
`they are quite different from one another. The zigzag
`polymer‘33‘”“ has been fairly widely encountered.
`and such structures tend to pack efficiently and
`eschew open frameworks or cavities. The hellx“”“5‘
`remains quite rare in the context of coordination
`polymers. but there is added interest because it is
`inherently chiral regardless of what its oomponents
`might be. The inherent chirality of this architecture
`comes from spatial disposition rather than the pres-
`ence of chiral atoms, thereby illustrating an impor-
`tant aspect of the solid state:
`it is possible for achiral
`molecules to generate chiral crystals. To illust rate the
`potential for generation of chiral architectures from
`simple achiral building blocks, let us consider how
`one might design a homochiral crystal from simple
`molecular components.
`There would appear to be at least four strategies
`for the design of polar crystals that are independent
`of the need for homochiral molecular components: { ll
`achiral building blocks that crystallize in a chiral
`space group. (2) achiral molecular building blocks to
`build a chiral framework, (3) achiral host framework
`built from achiral molecular components with chiral
`guesL(s). and (4) achiral host framework built from
`acbiral molecular components with achiral guestis).
`Whereas exploitation of homochiral components
`represents the most obvious approach because the
`absence of a crystallographic center of inversion is
`guaranteed.
`it in no way implies or affords any
`
`
`
`Figure 1. Illustration of the crystal structure for [Ni[bipy)-
`{PhC0g )2{.VleOH);l-PhNOg:
`[a) portion of a single helical
`chain.
`(bl space-filling model illustrating the packing of
`adjacent helices and the resulting cavities occupied by
`(nitrubenzeneh adducts.
`(c) overhead view of packing of
`helices, and (cl) illustration of the dissymmetric nitroben-
`zene dimer.
`
`control over molecular orientation and. therefore,
`bulk polarity. Furthermore, reliance upon the use of
`pure enantiomers raises the substantial problem of
`requiring control over stereochemistry at the molec-
`ular level without yet solving the problem of control-
`ling stereochemistry at the supramolecular level.
`Indeed. strategy 1, which basically relies upon scr-
`endipity. offersjust as much chance of optimal control
`of crystal packing as the use of homochiral compo~
`nents. However,
`there are three types of polar
`architecture that do not need to be sustained by
`homochiral molecular components:
`helical net-
`works,"9-‘-“-'5‘-'59"“5 1D acentric networks sustained
`by head—to-tall stacking of complementary mole-
`cules.“"‘”5 and hostrguest networks which are polar
`because of the presence of acentric guest molecules
`or guest aggregates.“-'75-'77
`Although the crystallization process for strategies
`1-4 can inherently afford homochiral single crystals.
`only the use of homochiral components guarantees
`that all crystals in a batch will be of the same
`enantiomorph. Batches of crystals will often be
`heterochiral as both enantiomers tend to be formed
`equally during crystallization. Fortunately.
`it has
`been demonstrated that formation of homochiral bulk
`materials can be afforded by seeding with the desired
`cnantiomcr.‘53
`
`[Ni(bipy)(benzoate)2[McOH)2|'5" (bipy — 4.4-bipy—
`ridine). 1. illustrates the issues raised above. 1 self-
`assemblcs as a helical architecture that is sustained
`
`by linking of octahedral metal moieties with linear
`spacer ligands. Furthermore. it persists in the pres-
`ence of several guests. even if ihydroxybenzoatc
`ligands (i.e..
`ligands that are capabl