Definition and Emergence of Supramolecular ∗ Chemistry Jonathan W. Steed1, Jerry L. Atwood2, and Philip A. Gale3 1Durham University, Durham, UK 2University of Missouri, Columbia, MO, USA 3University of Southampton, Southampton, UK be a monatomic cation, a simple inorganic anion, an ion 1 Introduction 1 pair, or a more sophisticated molecule such as a hormone, pheromone, or neurotransmitter. More formally, the host is 2 Emergence 2 definedasthemolecularentitypossessingconvergent bind- 3 Conclusion 5 ing sites (e.g., Lewis basic donor atoms, hydrogen-bond References 5 donors, etc.). The guest possesses divergent binding sites (e.g., a spherical, Lewis acidic metal cation, or hydrogen- bond-accepting halide anion). In turn, a binding site is defined as a region of the host or guest capable of taking 1 INTRODUCTION part in a noncovalent interaction. The host–guest relation- ship has been defined by Donald Cram2 as follows: Althoughtheword“supramolecular”madeanearlyappear- Complexesarecomposedoftwoormoremoleculesorions ance in Webster’s Dictionary in 1903, “Supramolecular held together in unique structural relationships by electro- chemistry”initsmodernsensewasintroducedonlyin1978 static forces other than those of full covalent bonds . . . by Lehn, who defined it as the “. . .chemistry of molecu- molecular complexes are usually held together by hydro- lar assemblies and of the intermolecular bond.”1 Classic gen bonding, by ion pairing, by π-acid to π-base interac- tions,bymetal-to-ligandbinding,byvanderWaalsattrac- explanations of supramolecular chemistry describe it as tive forces, by solvent reorganising, and by partially made “chemistry beyond the molecule,” “the chemistry of the andbrokencovalentbonds(transitionstates). . .Highstruc- noncovalentbond,”and“nonmolecularchemistry,”oreven turalorganisationisusuallyproducedonlythroughmultiple “Legochemistry.”Theearlyworkinthefieldconcernedthe binding sites. . .A highly structured molecular complex is composedofatleastonehostandoneguestcomponent. . . formationofsupermoleculescomprisingtwocomponents,a Ahost–guestrelationshipinvolvesacomplementarystereo- host and a guest, which interact with one another in a non- electronicarrangementofbindingsitesinhostandguest. . . covalentmanner(Figure 1).Thehostisalargemoleculeor The host component is defined as an organic molecule or aggregatesuchasanenzymeorsynthetic cycliccompound ion whose binding sites converge in the complex. . . The possessingasizeable,centralhole,orcavity.Theguestmay guestcomponentasanymoleculeorionwhosebindingsites divergeinthecomplex. . . ∗AdaptedinpartfromSupramolecularChemistry,J.W.Steedand This description might well be generalized to remove J.L.Atwood,Wiley:Chichester,2ndEd.,2009. the word “organic,” since more recent work has revealed a wealth of inorganic hosts, such as zeolites3 and polyoxometallates,4 or mixed metal–organic coordination compounds, such as metal–organic frameworks (MOFs) SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc002 2 Concepts Molecular chemistry Supramolecular chemistry Host Molecular precursors Specific characteristic, function or properties: + Recognition Catalysis + + Transport Supermolecule (complex): Degree of order Covalent molecule: Chemical nature Guest Interactions between subunits Symmetry of packing Shape Intermolecular interactions Redox properties HOMO–LUMO gap Polarity Vibration and rotation Magnetism Chirality Figure 1 Definition of traditional supramolecular “host–guest” chemistry according to Lehn.5 (see Zeolitelike Metal–Organic Frameworks (ZMOFs): the supramolecular synthon approach of Desiraju in 1995. Design, Structure, and Properties, Supramolecular Mate- The years 1989 and 1995 mark milestones in the design rials Chemistry), which perform similar functions and may and synthesis of coordination polymer systems that have be thought of under the same umbrella. broughtabouttheexplosionofporousMOFchemistryover the past decade. Biological receptor–substrate supramolecular chemistry 2 EMERGENCE and, by generalization, the whole of modern host–guest chemistry has its roots in three core concepts: The original supramolecular host–guest complexes 1. TherecognitionbyPaulEhrlichin1906thatmolecules involve a host molecule that possesses an intrinsic molecu- do not act if they do not bind, Corporanonaguntnisi larcavityintowhichtheguestfits;hence,theyare,inprin- fixata; in this way, Ehrlich introduced the concept of a ciple, stable in all forms of matter (solid, liquid/solution, biological receptor. and the gas phase). The host–guest concept is much older 2. The recognition in 1894 by Emil Fischer that bind- than the work by Pedersen6 on hosts for alkali metal ions ing must be selective, as part of the study of recep- in the late 1960s that gave birth to modern supramolecu- tor–substrate binding by enzymes. He described this lar chemistry and can be dated back to the extensive body byalock-and-key imageofstericfitinwhichtheguest of clathrate or solid-state inclusion chemistry. This field begins with the twin descriptions of zeolites or “boiling stones”discoveredbyAxelCronstedtin1756andclathrate Substrate hydrates or “anomalous ice” prepared by Joseph Priestley in 1778. The evolution of this area is elucidated later in + Lock and key this work by Bishop (see Synthetic Clathrate Systems, Supramolecular Materials Chemistry) and forms much of the early part of our subjective timeline of supramolecular (a) Enzyme chemistry (Table 1). Interspersed among these milestones is the parallel birth of self-assembly as in the formation of self-assembled Complex monolayers first observed as the spreading of oil on water + by Benjamin Franklin in 1774, and the birth of nanochem- Induced fit istry (the 1818 recognition of the particle size-dependent (b) color of colloidal gold). We can also see the evolution of crystal engineering from the early topochemical postulate Figure 2 (a) Rigid lock and key and (b) induced fit models of and molecular engineering of von Hippel in the 1960s to enzyme–substrate (and hence host–guest) binding. SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc002 Definition and emergence of supramolecular chemistry 3 Table 1 An illustrative timeline charting the development of supramolecular chemistry from its roots in solid-state inclusion compounds, through the birth of macrocyclic host–guest chemistry in the 1960s to its modern incarnation in self-assembled materials and nanoscale chemistry. 1756 — AxelCronstedt:descriptionof“boilingstone”(zeolite) 1774 — BenjaminFranklin:spreadingofoilonwater 1778 — JosephPriestly:“anomalous ice” 1810 — SirHumphreyDavy:discoveryofchlorinehydrate 1818 — JeremiasBenjaminRichters:particlesizeexplanationforthecolorof“drinkablegold”;colloidalgoldknownsinceantiquity (e.g.,Lycurgus cup,fourthcenturyAD) 1823 — MichaelFaraday:formulaofchlorinehydrate 1841 — C.Schafha¨utl:studyofgraphiteintercalates 1849 — F.Wo¨hler:β-quinolH Sclathrate 2 1891 — VilliersandHebd:cyclodextrin inclusioncompounds 1891 — AgnesPockles:thefirstsurfacebalance,leadingtothedevelopment oftheLangmuirtroughandtheLangmuir–Blodgett technique 1893 — AlfredWerner:coordinationchemistry 1894 — EmilFischer:lock-and-key concept 1906 — PaulEhrlich:introductionoftheconcept ofareceptor 1937 — K.L.Wolf:thetermU¨bermoleku¨le iscoinedtodescribeorganizedentities arisingfromtheassociationofcoordinatively saturatedspecies(e.g.,theaceticaciddimer) 1939 — LinusPauling:hydrogenbondsareincluded inthegroundbreaking bookTheNatureoftheChemicalBond 1940 — M.F.Bengen:ureachannelinclusioncompounds 1945 — H.M.Powell:X-raycrystalstructuresofβ-quinolinclusioncompounds;theterm“clathrate” isintroducedtodescribe compounds whereonecomponent isenclosedwithintheframeworkofanother 1949 — BrownandFarthing:synthesisof[2.2]paracyclophane 1953 — WatsonandCrick:structureofDNA 1956 — DorothyCrowfootHodgkin:X-raycrystalstructureofvitaminB 12 1958 — DanielKoshland:induced fitmodel 1959 — DonaldCram:attempted synthesisofcyclophane charge-transfercomplexes with(NC) C=C(CN) 2 2 1961 — N.F.Curtis:firstSchiff’sbasemacrocycle fromacetoneandethylenediamine 1964 — BuschandJa¨ger:Schiff’sbasemacrocycles 1965 — OlgaKennard andJ.D.Bernal:TheCambridgeStructuralDatabase 1962 — vonHippel:birthofcrystalengineering 1967 — CharlesPedersen:crownethers 1968 — ParkandSimmons:Katapinand anionhosts 1968 — F.Toda:“wheel andaxel” inclusioncompoundhosts 1969 — Jean-MarieLehn:synthesisofthefirstcryptands 1969 — JerryAtwood:liquidclathratesfromalkylaluminumsalts 1969 — RonBreslow:catalysisbycyclodextrins 1971 — G.M.J.Schmidt:topochemistry 1973 — DonaldCram:spherandhostsproduced totesttheimportanceofpreorganization 1978 — Jean-MarieLehn:introductionoftheterm“supramolecularchemistry,”definedasthe“chemistryofmolecularassembliesand oftheintermolecular bond” 1976 — Deliberateclathratedesignstrategies;“hexahosts”D.D.MacNicol andlaterin1982“coordinatoclathrates” E.Weber 1979 — GokelandOkahara: developmentofthelariatethersasasubclassofhost 1981 — Vo¨gtleandWeber: podandhostsanddevelopmentofnomenclature 1986 — A.P.deSilva:fluorescentsensingofalkalimetalionsbycrownetherderivatives 1987 — AwardoftheNobelprizeforChemistrytoDonaldJ.Cram,Jean-MarieLehn,andCharlesJ.Pedersenfortheirworkin supramolecularchemistry 1989 — G.M.Whitesides:self-assembledthiolmonolayers ongold 1989 — R.Robson:3Dcoordination polymersbasedonrod-likelinkers 1991 — G.M.Whitesides:achemicalstrategyforthesynthesisofnanostructures 1994 — M.Brust:synthesisofthiol-stabilizedgoldnanoparticles 1995 — O.M.Yaghi:firstMOF;keycoordinationpolymerpapersbyM.J.ZaworotkoandJ.S.Moore 1995 — G.Desiraju:supramolecularsynthonapproachtocrystalengineering 1996 — Atwood,Davies,MacNicol,andVo¨gtle:publicationofComprehensiveSupramolecularChemistry containing contributions frommanykeygroupsandsummarizingthedevelopmentandstateoftheart 1996 — J.K.M.Sanders:thefirstexample ofadynamiccombinatorial chemistrysystem 1998 — RowanandNolte:helicalsupramolecularpolymersfromself-assembly 1999 — J.F.Stoddart:molecularelectronics basedoninterlockedmolecules 2004 — J.F.Stoddart:thefirstdiscreteBorromean-linkedmolecule,alandmarkintopological synthesis SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc002 4 Concepts has a geometric size or shape complementarity to the Receptor–substrate chemistry underwent a huge receptororhost(Figure 2a).Thisconceptlaidthebasis paradigm shift in 1958 with Koshland’s “induced fit” for molecularrecognition, the discrimination by a host model (Figure 2b), and these concepts have since per- between a number of different guests. meated throughout biological and abiotic supramolecular 3. The fact that selective binding must involve attraction chemistry. or mutual affinity between the host and guest. This Supramolecular chemistry as we understand it today has is, in effect, a generalization of Alfred Werner’s 1893 evolved to encompass not just host and guest chemistry theory of coordination chemistry, in which metal ions but also all aspects of self-assembly. It includes the design are coordinated by a regular polyhedron of ligands and function of molecular devices and molecular assem- binding by dative bonds. blies, noncovalent polymers, and soft materials such as Larger molecule (Host) Crystallization Smaller molecule (Guest) (a) Lattice inclusion host–guest complex or clathrate (Solid-state only) Covalent synthesis Small molecular ‘‘guest’’ Small molecules Large ‘‘host’’ molecule Host–guest complex (b) Covalent Spontaneous synthesis Larger molecule Small molecules (c) Self-assembled aggregate Figure 3 Key paradigms in supramolecular chemistry. (a) Solid-state clathrate paradigm, (b) molecular host–guest paradigm, and (c) self-assembly paradigm. SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc002 Definition and emergence of supramolecular chemistry 5 liquidcrystals,informednanoscalechemistry,and“bottom- devices,self-assemblyandself-organization,softmaterials, up” nanotechnology. In 2002, Lehn added a functional nanochemistry and nanotechnology, complex matter, and definition: “Supramolecular Chemistry aims at developing biological chemistry. Dario Braga has summed up the highly complex chemical systems from components inter- impact of supramolecular concepts in the following way9: acting by noncovalent intermolecular forces.”7 Hence, the The supramolecular perception of chemistry generated a current emphasis is on increasing complexity and hence true“paradigmshift”:fromtheonefocusedonatomsand increasingly sophisticated functionality and on the infor- bonds between atoms to the one focused on molecules and mation stored in molecular components that allows this bonds between molecules. In its burgeoning expansion the complexity to be achieved. supramolecular idea abated, logically, all traditional bar- Modern supramolecular systems are beginning to dis- riers between chemical subdivisions (organic, inorganic, organometallic, biological) calling attention to the collec- play complex emergent properties based on the nonlinear tivepropertiesgeneratedbytheassemblyofmoleculesand interactions between the molecular component parts. It is to the relationship between such collective properties and clear that there are certain properties and features that thoseoftheindividualcomponent. emerge according to the length scale on which a system assembles, and indeed on which it is studied. Thus, the way in which ostensibly easily understood molecular-level 3 CONCLUSION supramolecular interactions scale up into the nanoworld is not always predictable and represents the frontiers and It is clear that the molecular-level approach to understand- future of supramolecular science. As direct microscopic ing binding phenomena that gave rise to supramolecular imaging and manipulation on the multinanometer scale chemistry has found application in a vast array of phenom- become increasingly technologically feasible, it is increas- enaandistoagreatextentfuelingtheconceptsandgrowth ingly possible to study the fascinating consequences of ofavastswatheofchemicallyrelatedscience.Forexample, chemical emergence—the “arising of novel and coherent future applications of supramolecular chemistry in biologi- structures, patterns, and properties during the process of cal systems may include new treatments for disease by the self-organization in complex systems.”8 inhibition of protein–protein interactions or by the pertur- Fundamentally, supramolecular chemistry concerns the bation via synthetic channels or carriers of chemical and mutual interaction of molecules or molecular entities with potential gradients within cancer cells triggering apoptosis. discrete properties. This interaction is usually of a nonco- From molecules to supramolecular assemblies, to nano- valent type (an “intermolecular bond” such as a hydrogen materials and complex molecular biosystems, the ensuing bond, dipolar interaction, or π-stacking). Key to many def- chapters in these volumes capture in detail the backdrop initions of supramolecular chemistry is a sense of modu- and current state of the art in all of these fields that are larity. Supermolecules, in the broad sense, are aggregates driven or informed by supramolecular concepts. in which a number of components (of one or more type) cometogether,eitherspontaneouslyorbydesign,toforma larger entity with properties derived from those of its com- ponents. These aggregates can be of the host–guest type REFERENCES in which one molecule encapsulates the other or they can involve mutually complementary, or self-complementary, 1. J.-M. Lehn, Angew.Chem.Int.Ed.Engl., 1988, 27, 89. components of similar size in which there is no host or 2. D. J. Cram, Angew.Chem.Int.Ed.Engl., 1986, 25, 1039. guest. We can thus trace the evolution of supramolecular 3. R. Szostak, Molecular Sieves, Van Nostrand Reinhold, New chemistryfromtheoriginalsolid-state“clathrate”paradigm York, 1989. (Figure 3a), through the molecular host–guest paradigm 4. A. Muller, E. Krickemeyer, J. Meyer, etal., Angew. Chem. (Figure 3b) to the self-assembly paradigm (Figure 3c). Int.Ed.Engl., 1995, 34, 2122. As it is currently practiced, supramolecular chemistry, 5. J.-M. Lehn, Supramolecular Chemistry, 1st edn, Wiley-VCH with its emphasis on the interactions between molecules, Verlag GmbH, Weinheim, 1995. underpins a very wide variety of chemistry and materials 6. R. M. Izatt, Chem.Soc.Rev., 2007, 36, 143–147. science impinging on molecular host–guest chemistry, 7. J.-M. Lehn, Proc.Nal.Acad.Sci.U.S.A., 2002, 99, 4763. solid-state host–guest chemistry, crystal engineering and the understanding and control of the molecular solid state 8. J. Goldstein, Emergence:Complex.Organ., 1999, 1, 49. (including crystal structure calculation), supramolecular 9. D. Braga, Chem.Commun., 2003, 2751. SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc002 Supramolecular Interactions Dushyant B. Varshey, John R. G. Sander, Tomislav Frisˇcˇic´, and Leonard R. MacGillivray University of Iowa, Iowa City, IA, USA construction of complex molecules, otherwise unavailable 1 Introduction 9 via traditional approaches. An early transition toward this approach was realized when Emil Fischer, in 1894, pro- 2 Supramolecular Chemistry 9 posed the “lock-and-key” model for enzyme–substrate 3 Supramolecular Interactions 10 interactions.3Theelegantmechanismsofenzymesprovided 4 Construction of Supramolecular Compounds 16 basic principles for the new subject, namely, “Supramolec- 5 Host–Guest Chemistry 16 ularChemistry,”fromwhichprinciplesofmolecularrecog- 6 Molecular Recognition 16 nition and supramolecular function evolved.4,5 7 Self-Assembly 16 8 Supramolecular Structures via Molecular Recognition and Self-Assembly 17 2 SUPRAMOLECULAR CHEMISTRY 9 Conclusions 21 References 21 The term supramolecular chemistry was coined by Jean- Marie Lehn in 1969. Lehn defined supramolecular chem- istry as “the chemistry of molecular assemblies and inter- molecularbonds,”whichismorecommonlyreferredtothe 1 INTRODUCTION “chemistry beyond the molecule.”6 The Nobel Prize was awarded to Lehn, Charles Pedersen, and Donald Cram in 1987 for pioneering contributions to supramolecular chem- To achieve the impeccable ability of nature to construct istry.7 As molecules are built by connecting atoms by molecules (e.g., proteins), chemists have traditionally covalent bonds, supramolecular compounds are built by employed approaches at the molecular level. Molecu- linking molecules with intermolecular forces (Figure 1).8 lar chemistry, since the synthesis of urea by Wo¨hler in 1828,1 has relied on building molecules via stepwise for- Thus,inmolecularchemistry,precursormoleculesundergo covalent-bond making or breaking to produce a target mation and breakage of covalent bonds. Molecular tech- molecule A. In contrast, in supramolecular chemistry niquesofchemistshaveculminatedintothetotalsyntheses of sophisticated molecules (e.g., vitamin B12).2 How- molecule A can act as a host that interacts with a guest via noncovalent forces (e.g., hydrogen bonds) to form a ever, nature routinely utilizes noncovalent interactions to supermolecule B. organize molecules to form aggregates that perform spe- cific functions. Chemists now recognize advantages of the synthesis paradigm of biology that can facilitate the 2.1 Development of supramolecular chemistry The concepts and roots of supramolecular chemistry can be traced to the discovery of chloride hydrate by Sir SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc003 2 Concepts Molecular chemistry Pedersen(1967),14 whichwerecomparedtonaturalmacro- cycles(e.g.,ionophores,heme).Seminalcontributionswere then made by Pedersen and Lehn on crown ethers and cryptands (1960s),7 respectively, and Cram on spherands (1970s) (Figure 2).15 Moreover, the development of syn- Molecular precursors A thetic receptors introduced molecular recognition as an area that blossomed into supramolecular chemistry by Supramolecular chemistry collaborative concepts that stemmed from biology and physics. Supramolecular chemistry is now a major inter- disciplinary field that embodies the expertise of synthetic organic chemists, inorganic, and solid-state chemists, the- orists, physicists, and biologists that strive to develop new molecules and materials with unique properties and applications. A Guest Host B Figure 1 An illustration of molecular versus supramolecular 3 SUPRAMOLECULAR INTERACTIONS chemistry. Supramolecular compounds are formed by additive and Humphrey Davy in 1810.8,9 Development was initiated cooperative noncovalent interactions. The noncovalent through the understanding of selective binding of alkali- interactions include a wide range of attractive and repul- metal cations by natural,10 as well as synthetic, macro- sive forces. The most common noncovalent interactions, cyclic, and macropolycyclic ligands11–17 as described by along with approximate energies, are listed in Table 1.8 A Curtis (1961),11 Busch (1964),12 Ja¨ger (1964),13 and detailed understanding of the origins and scopes, as well H C 3 O N H3C CH3 O O O O O H3C O CH3 O O H3C CH3 O O O O O O O O O N H3C CH3 H C CH 3 3 (a) (b) (c) CH3 Figure 2 Early developments in supramolecular chemistry: (a) crown ether (Pedersen) (b) cryptand (Lehn) (c) spherands (Cram). Table 1 Common supramolecular interactions.8 Supramolecularinteractions Directionality Bondenergies (kJmol−1) Examples Ion–ion Nondirectional 100–350 NaCl vanderWaals Nondirectional <5 Inclusioncompounds Closed-shellmetal–metal Nondirectional 5–60 Argentophilic(Ag ···Ag) Ion–dipole Slightlydirectional 50–200 Na+ crownethercomplex Dipole–dipole Slightlydirectional 5–50 –C≡Ngroups Coordinationbonds Directional 100–300 M-pyridine Hydrogenbonds Directional 4–120 Carboxylicaciddimer Halogenbonds Directional 10–50 Sulfur–iodinecomplex π–π interactions Directional 2–50 Benzene(edge-to-face)DNA(face-to-face) Cation–π andanion–π interactions Directional 5–80 +N(CH ) ·(toluene) 3 4 SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc003 Supramolecular interactions 3 as the interplay, of such interactions is a major goal of researchers worldwide. K 3.1 Directional versus nondirectional Supramolecular interactions are used to construct assem- blies of molecules and/or ions that exhibit specific proper- tiesandfunctions.Directionalforcesareparticularlyuseful Figure 4 X-ray crystal structure of K+ encapsulated by since geometric and spatial control of interacting species dibenzo-18-crown-6 (anion omitted for clarity).26 can be optimized.8,18–20 Nondirectional forces, however, can be important in determining relative distances of inter- 3.3 Ion–dipole and dipole–dipole interactions acting partners and, when integrated with covalent bonds, can influence the orientations of partners in an assembly Ion–dipole and dipole–dipole interactions result from process.8,18–20 an electrostatic attraction between an ion and a neutral molecule with a dipole or two molecules with dipoles, respectively. The interactions are intermediate to weak in 3.2 Ion–ion and van der Waals strength. The solvation of metal cations (e.g., hydration) is dictated by ion–dipole interactions, while interactions Ion–ion and van der Waals forces lie at extremes in between highly polar molecules (e.g., nitriles) are dic- termsofstrength,withbothbeingnondirectional.Protypical tated by dipole–dipole interactions (Figure 4).26 Although examples of materials sustained by ion–ion interactions the interactions are predominantly based on electrostat- are the crystal structures of simple inorganic salts. The ics, a degree of directionality arises from the anisotropic electrostaticattractionbetweenthecationandanionisoften nature of the polar molecules. Dipole–dipole interactions manifestedinanisotropiclattice(e.g.,NaCl),reflectingthe can influence bulk physical properties (e.g., boiling point) nondirectionalnatureoftheionicforces.Theintegrationof and, owing to relative weakness, will often give rise to multiplespatialarrangementsandgeometriesofinteracting formalpositiveandnegativechargesintomolecularspecies molecules. (e.g.,macrocycle),however,canachievedirectionalcontrol of supramolecular association via ion–ion interactions (e.g., host–guest systems) (Figure 3).21–23 van der Waals 3.4 Closed-shell metal–metal interactions interactionsarisefromthepolarizationofanelectroncloud by the proximity of an adjacent nucleus.24 Molecules Interactionsbetweenclosed-shellmetalcationsofd8-d10-s2 considered “soft” exhibit the most pronounced van der systems(e.g.,Ag(I))aresignificantcontributorstostabiliz- Waals interactions, which will particularly be important in ing the assembly of inorganic, organometallic, and metal- a condensed phase (e.g., solid state) where solvent effects are eliminated.18 organic subunits.27 The interactions are weaker in strength than ionic and covalent bonds yet comparable to hydrogen bonds.27 Prominent examples include interactions of Ag(I) and Au(I) ions in the form of agentophilic and aurophilic forces respectively (Figure 5).28,29 The interactions can be Fe present in ligand-supported and ligand-unsupported envi- ronments.vanderWaalsinteractionsinvolvingligandscan, thus, impart directionality of an assembly process based on closed-shell forces. 3.5 Coordination bonds While the structural manifestations of coordination bonds find deep roots as discussed in the the work of Werner30,31 Figure 3 X-ray crystal structure example of ion–ion inter- involving transition—metal—ion complexes, coordina- actions demonstrated by the interaction of ammonium with tion bonds have found found widespread application in Fe(CN)63−.25 supramolecular chemistry.32–34 Coordination bonds are of SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc003 4 Concepts Ag Au F (a) (b) Figure 5 Agentophilic and aurophilic interactions in crystalline: (a) dinuclear complex [Ag (trans-1-(4-pyridyl)-2- 2 (phenyl)ethylene) ][CO CF ] and (b) [2]rotaxane with a Au(P(CH ) ) + rod.28,29 4 2 3 2 3 3 2 intermediate strength and, similar to hydrogen bonds, H Backbone reversible. The selection of an inert or labile coordination N H O Backbone bond is crucial to the assembly of supramolecular struc- N N O H O tures as the dynamic nature of the latter allows the com- R R N N H N H ponents of a supramolecular structure to undergo a series O H O H N O H N H of “error corrections” until the thermodynamically favored Carboxylic acid Guanine H productisachieved.Onceastablestructureisobtained,the (a) (b) Cytosine labile coordination bonds are capable of showing remark- able cooperativity to impart enhanced ligand stability.35 Figure 6 Hydrogen bonding: (a) carboxylic acid dimer and Coordination bonds also offer the panoply of tools sup- (b) DNA base pairing. plied by the field of inorganic chemistry (e.g., coordination number, chelation) to import function into supramolecu- lar structures. Consequently, coordination bonds offer a nature, dictating the recognition of substrates by enzymes unique and attractive means to modify the properties of and being responsible for maintaining the double-helical supramolecular structures and materials via both metal structure of DNA (Figure 6b). The International Union ions and ligands (e.g., magnetism, optical).36–41 Geomet- of Pure and Applied Chemistry (IUPAC) has recently ric parameters that define coordination bonds as derived established the hydrogen bond as “an attractive interaction from the field of inorganic chemistry are well docu- between a hydrogen atom from a molecule or a molecular mented.42 fragment X–H in which X is more electronegative than H, and an atom or a group of atoms in the same or a different molecule, in which there is evidence of bond 3.6 Hydrogen bonds formation.”46 Hydrogen bonds can have different lengths, strengths, and geometries (Table 2).8,16,43,47 A strong hydrogen bond Thehydrogenbond,owingtoarelativelystrongandhighly can resemble a covalent bond with respect to the energy directional nature, is often described as the “master-key” anisotropicinteraction.43Thefirstdescriptionofahydrogen required to break the interaction, while the energy of a bond was provided by Linus Pauling in 193144 in a paper weak hydrogen bond will be closer to a van der Waals force. Desiraju has described three extremes of hydrogen describing the nature of the chemical bond. The term addressed the incorrect assignment of a hydrogen bond bonds in the solid state. In the A–H···B hydrogen bond, within the [H : F : H]− ion. Pauling defined the hydrogen when both A and B are quite electronegative; for example, bond as a bond formed when the electronegativity of A N–H···O, the hydrogen bond is considered to be “strong” relative to H in an A–H covalent bond is such that it can or “conventional” (20–40kJmol−1).16,47 On the contrary, withdrawelectronsandleaveprotonspartiallyunshielded.45 if both A and B are moderate to weakly electronegative, To interact with the donor A–H bond, the acceptor B for example, C–H···O, the hydrogen bond is “weak” or must possess a lone pair of electrons or polarizable π “nonconventional” (2–20kJmol−1). electrons. In general, a hydrogen bond can be represented The strength of a hydrogen bond can reach a mostly as A–H···B, where a hydrogen atom acts as a bridge covalent level as in the HF2− ion (170kJmol−1). Hydro- between two atoms A and B. A prototypical example that gen bonds involving interactions of N–H, O–H, and alsoillustratesstructuralconsequencesofhydrogenbondsis C–H groups with double and triple bonds in the form the carboxylic acid dimer, which is sustained by two O–H of C=C and C≡C bonds, respectively, as well as aro- ···O forces (Figure 6a). Hydrogen bonds are ubiquitous in matics, have also become important for understanding SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc003 Supramolecular interactions 5 Table 2 Properties of hydrogen bonds.8,16,43 Strong Moderate Weak A–H···B Partiallycovalent Mostlyelectrostatic Electrostatic Energy 60–120kJmol−1 16–60kJmol−1 <12kJmol−1 Lengths(A˚) A–H∼H···B A–H<H···B A–H(cid:3)H···B H···B 1.2–1.5 1.5–2.2 2.2–3.2 A···B 2.2–2.5 2.5–3.2 3.2–4.0 ◦ Angles( ) 175–180 130–180 90–150 Examples Strongacids/bases; Acids;alcohols; Minorcomponents of protonsponge;HF biologicalmolecules bifurcatedbonds;C–H complexes ···O,O–H···π the stabilization of crystals, host–guest interactions, and biomolecules.48 3.7 Halogen bonds The concept of halogen bonding was largely pioneered by Resnati and Metrangolo in the 1990s and 2000s.49–52 The simplest definition of a halogen bond is an attrac- tive interaction between an electron-deficient halogen atom F I (i.e., the donor) and an electron-rich atom (i.e., the accep- tor).49,53 Experimental and theoretical studies demonstrate that the angle defined by the covalent bond and halo- gen bond interaction involving the donor atom exhibits a strong tendency toward linearity.54 The formation of Figure 7 Crystal packing view of α,ω-diiodoperfluoroalkanes encapsulated through interactions between the host’s I− and the a halogen bond can be accompanied with the elongation guests iodine. of the covalent bond that links the halogen atom to the rest of the donor molecule.50 Halogen atoms attached to electron-withdrawing substituents, such as perfluorinated approach of acceptor atoms, leading to the pronounced or unsaturated (e.g., acetylenic, aromatic) groups, act as linear nature of the halogen-bonding interaction. Although better halogen bond donors compared to parent hydrocar- computational and gas-phase studies have suggested that bon residues (Figure 7).52 Less electronegative atoms and halogen bonds can adopt a considerable range of strengths anionsmakebetterhalogen-bondacceptors.TheN-atomis, between10and200kJmol−1,50theforcestypicallyencoun- thus, a significantly more efficient halogen-bond acceptor tered in solids lie between 10 and 50kJmol−1.57 than the O-atom, and the I-atom provides a better acceptor While there are very few studies of halogen bond than very strong N-bases (e.g., dimethylaminopyridine).55 complexation in solution, there are numerous examples The covalent bond elongation and linearity of halo- in the solid state.49,50,58,59 Early cases of halogen bonds gen bond interaction are explained by the “σ-hole” con- involved simple molecules such as molecular iodine or cept.49,56 The σ-hole represents the deformation of the iodoform.60 An example is the the cocrystal of molecular electron density on the donor halogen atom, resulting in sulfur(S8)andiodoformwhereinthehalogenbondinvolves theformationofanareaofdiminishedelectrondensitythat an unusually short separation of 3.52A˚ between iodine roughly coincides with the σ*-antibonding orbital of the and sulfur atoms (Figure 8a).61 A series of isostructural covalent bond between the halogen and remaining donor cocrystals has more recently been described by Cincˇic´ and molecule. The area of positive potential is responsible for coworkerswhereinI-andBr-atomsresultedinisostructural halogen bond formation through the attractive interaction solids when used as donors for halogen bond formation with the electron-rich acceptor. Strong halogen bonding (Figure 8b).55 Auffinger and coworkers have proposed the can lead to partial donation of the acceptor electron den- importance of halogen bonds in biology.62 A survey of sity into the σ*-antibonding orbital, hence leading to elon- protein and nucleic acid structures revealed halogen bond gation of the covalent bond. The σ-hole is encircled by contacts with possible stabilizing roles in protein folding a ring of negative potential, which actively hinders the and ligand binding.63 SupramolecularChemistry:FromMoleculestoNanomaterials,Online2012JohnWiley&Sons,Ltd. Thisarticleis2012JohnWiley&Sons,Ltd. ThisarticlewaspublishedintheSupramolecularChemistry:FromMoleculestoNanomaterials in2012byJohnWiley&Sons,Ltd. DOI:10.1002/9780470661345.smc003