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1 Chapter 1Figure 1.1 Schematic of interactions between a halogen atom and a Lewis base...Figure 1.2 Molecular electrostatic potential maps drawn at the isodensity su...Figure 1.3 Early halogen bonding cocrystals from Hassel. Bromine/benzene add...Figure 1.4 Table from the 1968 solid‐state review by Bent.Figure 1.5 ChemDraw figure highlighting the use of alkyl‐ and aryl‐dihaloper...Figure 1.6 ChemDraw figure depicting the structural scheme for both type I (...Figure 1.7 Halogen bond contacts between DMAP halogen bond acceptor nitrogen...Figure 1.8 Six halogen bond donors were systematically evaluated computation...Figure 1.9 Examples of simultaneous halogen and hydrogen bonding in the cons...Figure 1.10 Methods to enhance the potency of a halogen bond donor. The Chem...Figure 1.11 Representative examples of N‐iodoimide halogen bond donors (a). ...Figure 1.12 Examples of halogen bond mediated [2 + 2] photodimerization of o...Figure 1.13 Cocrystallization components and pre‐polymerization structures o...Figure 1.14 Computed ESP maps on 0.001 au molecular surfaces of (a) iodobenz...Figure 1.15 Simplified orbital‐interaction diagrams for (a) hydrogen‐bonded ...Figure 1.16 DFT–SAPT decomposition analysis of H3CBr⋯NH3 (solid lines) and FFigure 1.17 The first example of a halogen bonding LC developed by Bruce. Al...Figure 1.18 The first example of a photoactive halogen bonding LC developed ...Figure 1.19 The first example of a polymeric halogen bonding LC developed by...Figure 1.20 (a) Chemical structure of the halogen bond and hydrogen bond don...Figure 1.21 Monomers M1 and M2 were subjected to RAFT polymerization with bu...

2 Chapter 2Figure 2.1 Association constants between N‐halosaccharins and 4‐methoxy‐2‐pi...Figure 2.2 Bis(pyridine)halonium ions employed in NMR spectroscopic studies ...Scheme 2.1 Formation of supramolecular capsule1·2 by fourfold halogen bondin...Figure 2.3 Metal fluoride complexes investigated as halogen bond acceptors....Scheme 2.2 A tridentate halogen bond donor–acceptor pair.Figure 2.4 Halogen bond donor and acceptor macromolecules.Figure 2.5 Compounds used for the preparation of halogen bond acceptor‐ and ...Figure 2.6 Receptors that incorporate arene‐based halogen bond donors.Figure 2.7 ortho‐Phenylethynylene derivatives used in spectroscopic studies ...Figure 2.8 Molecular torsion balances used to estimate the strength of halog...Figure 2.9 Representative iodoperfluoroarene‐based multidentate anion recept...Figure 2.10 A sulfonyl‐substituted bis(iodoarene) anion receptor.Figure 2.11 Receptors that employ haloarene groups in combination with other...Figure 2.12 An oligo(phenylene)‐based anion transporter.Figure 2.13 Association constants of a substituted 5‐iodo‐1,2,3‐triazole wit...Scheme 2.3 Self‐complementary halogen bonding species capable of dimerizatio...Figure 2.14 A pH‐switchable self‐complementary halogen bonding motif.Scheme 2.4 Formation of a catenane through pyridine–iodopyridinium halogen b...Figure 2.15 Representative classes of halogenated heterocycles that have bee...Figure 2.16 Anion recognition in aqueous solvent using heteroarene‐derived h...Figure 2.17 Examples of bi‐ and tridentate molecular recognition using iodod...Figure 2.18 Cyclic peptides used to probe halogen bonding interactions of β‐...

3 Chapter 3Figure 3.1 Cartoon representation of the sulfate‐binding protein.Figure 3.2 Resnati and Metrangolo's heteroditopic iodoperfluoroarene recepto...Figure 3.3 Taylor's tripodal receptor capable of Cl coordination thro...Figure 3.4 Huber's tridentate receptor 3, capable of three‐point XB formatio...Figure 3.5 Most commonly employed XB donors for recognition purposes.Figure 3.6 Beer's macrocyclic haloimidazolium cyclophane receptors.Scheme 3.1 Kubik's tridentate XB cyclo‐pseudopeptide6.Figure 3.7 Cartoon representation of (a) [2]rotaxane and (b) [2]catenane.Scheme 3.2 (a) Wasserman's statistical synthesis of a [2]catenane. (b) Sauva...Figure 3.8 Chloride anion‐templated assembly of a [2]pseudorotaxane.Scheme 3.3 Discrete chloride anion‐templated assembly of a [2]rotaxane.Scheme 3.4 Chloride anion‐templated assembly of a [2]catenane via amide cond...Scheme 3.5 [2]Pseudorotaxane formation mediated by XB‐anion interactions.Scheme 3.6 Synthesis of the first XB‐anion‐templated [2]rotaxane.Figure 3.9 Beer's XB and HB water‐soluble [2]rotaxanes.Figure 3.10 Beer's series of acyclic XB‐anion receptors with electron‐withdr...Scheme 3.7 Chloride anion‐templated amide condensation clipping reaction syn...Figure 3.11 XB and HB perfluoroaryl‐functionalized [2]rotaxanes.Figure 3.12 Beer's XB [2]rotaxane, capable of binding nitrate in D2O:[D6]‐ac...Scheme 3.8 [2]Pseudorotaxanes with a range of XB donors and a pyridine‐based...Figure 3.13 [2]Catenane templated via a single charge‐assisted halogen bond....Figure 3.14 A series of 4‐halopyridinium [2]catenanes as halide receptors....Figure 3.15 A bis‐iodotriazole pyridinium containing [2]catenane.Figure 3.16 Tetradentate XB donor [2]catenane host structure.Figure 3.17 Schematic representation of ambidentate nature of the iodotriazo...Scheme 3.9 The first report of an XB [2]rotaxane synthesis via CuAAC‐AMT rea...Figure 3.18 Truncated structures of monocationic[2]rotaxanes48–50·PF6....Figure 3.19 Neutral XB [2]rotaxanes containing regioisomeric macrocycles.Figure 3.20 [2]Rotaxanes with XB donor axle components.Figure 3.21 XB rotaxane with secondary amine functionality in axle and macro...Figure 3.22 Truncated structure showing orthosteric control and conformation...Figure 3.23 Beer's acyclic BINOL‐based receptor 56·PF6 and a [2]rotaxane 57·...Scheme 3.10 A naphthalene‐based [2]catenane synthesized by double clipping X...Figure 3.24 XB [2]rotaxane 60·PF6 capable of anion sensing.Figure 3.25 Ru(II) appended XB rotaxane and acyclic receptor capable of iodi...Figure 3.26 Chiral XB [3]rotaxane capable of dicarboxylate recognition and s...Figure 3.27 Beer's ferrocene appended XB [2]rotaxane capable of electrochemi...Figure 3.28 Truncated structure of 65·2PF6 two‐station [2]rotaxane with anio...Figure 3.29 A mixed XB/HB nitrate‐selective [3]rotaxane shuttle.Figure 3.30 Truncated structure of Beer's pH‐responsive anion shuttle.Figure 3.31 Molina's hydrogen pyrophosphate‐responsive foldamer.Figure 3.32 Berryman's XB‐iodide‐induced triple helicate.Figure 3.33 Beer's XB foldamer, capable of selective iodide recognition in w...Figure 3.34 Representation of the 2 : 1 71:I complex formed in water....

4 Chapter 4Figure 4.1 Schematic representations of (a) a classical two‐center halogen b...Figure 4.2 The molecular orbital system of the three‐center, four‐electron ...Figure 4.3 The strength of the three‐center halogen bond depends on the natu...Figure 4.4 Schematic presentation of electrophilic halogenation of alkenes. ...Figure 4.5 Structures of the three‐center halogen‐bonded complexes [bis(pyr...Figure 4.6 Energy potentials of halogen motion in a three‐center [D⋯X⋯D]+...Figure 4.7 Calculated NN distances for (a) [(1,2‐bis(pyridin‐2‐ylethynyl)b...Figure 4.8 Crystal structure of [bis(2‐imidazolidinethione)iodine(I)]+ ...Figure 4.9 Crystal structures of (a) [Se⋯I⋯Se]+ complex and (b) two thr...Figure 4.10 The X‐ray structure of an asymmetric three‐center halogen bond c...Figure 4.11 Crystal structures of (a) [bis(pyridine)silver(I)]+ OTs...Figure 4.12 Crystal structures of the halogen bond complexes between (a) N‐...Figure 4.13 Comparison of the distances between electron donors (NO/N) in ...Figure 4.14 Three‐center halogen bonds undergo proton exchange in protic sol...Figure 4.15 A cyclic bis(pyridine)‐type ligand, designed to study [N⋯X⋯N]+...Figure 4.16 Examples of a three‐center halogen‐bonded (a) capsule and (b) c...Figure 4.17 [Bis(pyridine)iodine(I)]+ tetrafluoroborate can be used as ...Figure 4.18 (a) Cyclization reaction of carbonyl groups with alkynes. The r...Figure 4.19 The proposed mechanism of cyclobromination of 4‐penten‐1‐ol ind...Figure 4.20 Reactions of alkenes with halonium ions that are stabilized by ...Figure 4.21 Plausible mechanism for the oxidation reactions of alcohols, as ...Figure 4.22 The mechanism of bromolactonization of unsaturated carboxylic a...Figure 4.23 Structures of (a) (DHQD)2PHAL and DCDMH [60] and (b) the catalyt...Figure 4.24 Structures of the three‐center halogen‐bonded (a) dimeric and (...Figure 4.25 Crystal structures of three‐center halogen‐bonded (a) dimeric c...Figure 4.26 Crystal structure of the three‐center halogen‐bonded helix. Cou...Figure 4.27 Crystal structures of the three‐center halogen‐bonded [R‐COOI...

5 Chapter 5Figure 5.1 Decomposition of an experimental spectrum of a solution in liquid...Figure 5.2 Gogoi's 2‐chloropyridine–ICl complex.Figure 5.3 Halogen bond complex of molecular iodine and tetramethylthiourea....Figure 5.4 Hydrogen bonding of triethylamine with chloroform (a) versus halo...Figure 5.5 Huber's 2‐haloimidazolium salt and its interaction mode with a tr...Figure 5.6 Interactions of halogen bond donors with solvent molecules. Examp...Figure 5.7 Bowling's system for studying intramolecular halogen bonding.Figure 5.8 β‐Hairpin peptide displaying interstrand halogen bonding.Figure 5.9 Multidentate halogen bonding systems developed by Huber et al. Wh...Figure 5.10 Intramolecular hydrogen bonded–halogen bond in anion binding.Figure 5.11 An example of Diederich's supramolecular capsules held together ...Figure 5.12 Diederich's strong halogen bonding system, where 4‐(2‐iodoethyny...Figure 5.13 Representation of van't Hoff analysis of Diederich's halogen bon...Figure 5.14 Beer's halogen bond acyclic receptor (to the left) that complexe...Figure 5.15 Chemical double‐mutant cycle containing a potential halogen bond...Figure 5.16 Example of a Job plot showing 1 : 1 stoichiometry of binding, wi...Figure 5.17 Taylor's tridentate halogen bond donor, with three separate halo...Figure 5.18 Halogen bond complex of 4‐methylpyridine and Philp's iodotriazol...Figure 5.19 An example of Rissanen's N‐halosaccharin‐pyridine N‐oxide haloge...Figure 5.20 Monomers of Jiang's two halogen bonding systems. Top: two repres...Figure 5.21 Berryman's halogen bonding triple helicate from a side‐on perspe...Figure 5.22 Schubert's double bidentate system displaying an orthogonal arra...Figure 5.23 Main NOEs seen in a 1H,19F HOESY experiment by Ciancaleoni et al...Figure 5.24 Beer's macrocyclic haloimidazolium anion receptor in solution, r...Figure 5.25 Philp's iodotriazole dimer in solution.Figure 5.26 Erdelyi's symmetric [NXN]+ system, with 3‐center‐4‐electro...Figure 5.27 TEMPO radical resonance forms.Figure 5.28 Micallef's halogen bond complex of (TMIO)2‐DITFB.Figure 5.29 Lucarini's organic radical probe displaying halogen bonding to q...

6 Chapter 6Scheme 6.1 Examples of artificial and naturally occurring anion transporters...Scheme 6.2 Synthesis of calix[4]arene‐based transporters 10–13. (a) A...Figure 6.1 (a–f) DTF (PBE1PBE/6‐311G**) optimized TMACl complexes of calix[...Scheme 6.3 Synthesis of oxacalix[2]arene[2]triazine‐based transporters 18–2...Figure 6.2 Examples of the use of crystallography to help elucidate the rol...Figure 6.3 The HPTS assay. (a) Schematic representation of the HPTS assay in...Figure 6.4 Schematic representation of symport and antiport transport mechan...Scheme 6.4 Molecular structures of the small molecules tested as halogen bon...Figure 6.5 Conductance experiments in planar lipid bilayer membranes. (a) T...Figure 6.6 (a) Evolution of the effective molar concentration to achieve 50...Scheme 6.5 Synthesis of rigid‐rod p‐oligophenyl‐based transporters 47–54...Figure 6.7 (a,b) Evolution of the effective molar concentration to achieve ...Scheme 6.6 Synthesis of the library of pore‐forming peptides tested by Zeng ...Scheme 6.7 Molecular structures of the pore‐forming peptides used by Zeng an...Figure 6.8 (a) Computationally optimized H‐bonded octamer formed from pore‐...

7 Chapter 7Scheme 7.1 Selected examples for stoichiometric applications of iodine in or...Scheme 7.2 The first iodine‐catalyzed reaction. (Hibbert [10a] and Conant an...Scheme 7.3 Suggested activation mechanisms of molecular iodine with a typica...Figure 7.1 Crystal structures and selected bond lengths (in Å) featuring int...Scheme 7.4 Selected association constants and energies (in kJ/mol) for the i...Figure 7.2 Crystal structures and selected bond lengths (in Å) of interactio...Scheme 7.5 Equilibrium constants for the heterolytic cleavage of molecular i...Scheme 7.6 Iodine splitting in the presence of aza‐crown ethers. (Hasani and...Scheme 7.7 Potential decomposition reactions of molecular iodine in aqueous ...Scheme 7.8 Latimer diagrams with the standard potentials (in V) for iodine a...Scheme 7.9 Selected examples for iodine‐catalyzed Michael additions. (Banik ...Scheme 7.10 Iodine‐catalyzed Michael additions between indoles and α,β‐unsat...Scheme 7.11 Calculated effect of halogen bonding by molecular iodine on the ...Scheme 7.12 Examples for iodine‐catalyzed Knoevenagel condensations. (Ren an...Scheme 7.13 Example for an iodine‐catalyzed hetero‐Diels–Alder reaction. (Li...Figure 7.3 Iodine‐catalyzed carbonyl‐olefin metathesis. (Tran et al. [49c].)...Scheme 7.14 Iodine‐mediated cyclopropanation with the proposed mechanism. (L...Scheme 7.15 Iodine‐mediated synthesis of pyrroles. (Li et al. [50].)Scheme 7.16 Proposed reaction mechanism for the iodine‐catalyzed diaza‐Nazar...Figure 7.4 Iodine‐catalyzed Nazarov cyclizations. (Koenig et al. [53].)Scheme 7.17 Examples for iodine‐catalyzed esterifications and transesterific...Scheme 7.18 Examples for iodine‐catalyzed ester hydrolysis of biomolecules. ...Scheme 7.19 Iodine‐catalyzed acetalizations and deacetalizations. (Kumar et ...Scheme 7.20 Examples for iodine‐catalyzed synthesis of 1,1‐diacetates and di...Scheme 7.21 Iodine‐catalyzed etherifications [58,72,73].Scheme 7.22 Examples for iodine‐catalyzed Friedel–Crafts alkylations [75–77]...Scheme 7.23 Examples for iodine‐catalyzed Friedel–Crafts acylations [79–81]....Scheme 7.24 Iodine‐catalyzed isomerization of 1‐butene and cis‐2‐butene to t...Scheme 7.25 cis–trans Isomerization of fatty acid derivatives in the p...Scheme 7.26 Proposed reaction mechanism for the iodine‐catalyzed isomerizati...Scheme 7.27 Iodine‐catalyzed dimerization of 1,1‐diphenylethene. (Evans et a...Scheme 7.28 Iodine‐mediated cationic polymerization of furfuryl alcohol. (Go...Scheme 7.29 Proposed reaction mechanism for an iodine‐catalyzed Povarov reac...Scheme 7.30 Iodine‐catalyzed synthesis of dihydropyridines. (Ko et al. [99]....Scheme 7.31 Iodine‐catalyzed synthesis of trans‐fused pyrano[3,2‐c]benzopyra...Scheme 7.32 Iodine‐catalyzed cascade reaction for the synthesis of spirodihy...Scheme 7.33 Iodine‐mediated pyrrole activation ([102,103], MW: microwave irr...Scheme 7.34 Proposed mechanism for the iodine‐catalyzed quinoline synthesis....

8 Chapter 8Scheme 8.1 Outline of transient XB catalysis in halogenation/halocylizations...Scheme 8.2 XB‐promoted photochemical reactions.Figure 8.1 General outline of XB‐induced organocatalysis.Scheme 8.3 XB‐induced halide abstraction reactions. (a) Ritter‐type reaction...Figure 8.2 Cationic XB donors.Figure 8.3 Neutral multidentate XB donors.Scheme 8.4 Reactions involving XB‐catalyzed halide abstraction. (a) Halide a...Scheme 8.5 XB‐mediated polymerizations. (a) Neutral group activation.(b)...Scheme 8.6 Reduction of quinolones through XB interaction. (a) Neutral XB do...Scheme 8.7 XB‐catalyzed Diels–Alder reactions. (a) Diels–Alder reaction. (b)...Scheme 8.8 XB‐catalyzed Michael addition of indoles.Scheme 8.9 XB‐catalyzed conjugate addition of thiophenes.Scheme 8.10 XB‐promoted Nazarov cyclization..)Scheme 8.11 Friedel–Crafts alkylation of indoles with aldehydes and ketones....Scheme 8.12 Multistage strain‐release glycosylation through XB.Scheme 8.13 Bromocarbocyclization via halogen bonding.Scheme 8.14 Diaryliodonium‐saltcatalyzed three‐component Mannich reac...Figure 8.4 Iodine (III) derivatives used as halogen bonding organocatalysts....Scheme 8.15 Umpolung CC bond formation involving an iodolium ylide‐halogen ...Scheme 8.16 Iodoalkyne‐induced activation of thioamides.Scheme 8.17 Organocatalysis by neutral C(sp3)–halogen‐based XB donors. (a) S...Scheme 8.18 XB‐catalyzed organocatalysis in water by an amino acid‐based XB ...Figure 8.5 Tetrapodal XB donor showing strong halide binding in water.Scheme 8.19 XB‐promoted selective oxidation of aryl(heteroaryl)methanes.Scheme 8.20 [4 + 2] Cycloaddition reactions via XB‐π activation.Figure 8.6 Triazolium‐based chiral XB donors.Scheme 8.21 Bis(imidazolium)‐based bidentate chiral XB donors in asymmetric ...Scheme 8.22 Chiral pentanidium salts as phase‐transfer catalysts.Scheme 8.23 XB‐catalyzed asymmetric Michael–Henry reaction in synthesis of t...Scheme 8.24 Enantioselective Mannich reactions with a quinidine‐based cataly...Scheme 8.25 SN2(X) reaction with subsequent chirality transfer via ion pairi...Scheme 8.26 XB‐induced preorganization of chiral catalysts.Scheme 8.27 XB‐assembled bidentate phosphine complexed Rh(I) catalysts.Figure 8.7 Stabilization of reaction precursors through XB.Scheme 8.28 XB template‐induced macrocyclization.Scheme 8.29 Thiourea/XB donor cocatalysis for direct N‐glycofunctionalizatio...

9 Chapter 9Figure 9.1 (a) Cyclic voltammograms of TCQ in the presence of increasing met...Figure 9.2 Chemical structures of IEDT and diodo(ethylenedithio)tetrathiaful...Figure 9.3 Concept of electrochemical XB activation.Figure 9.4 Cyclic voltammograms of TCQ (0.5 mM) on a glassy carbon electrode...Figure 9.5 (a) Variation of the potential shift (Δ) corresponding to ...Figure 9.6 Ferrocene‐based XB donor receptors.Figure 9.7 SWV of 3‐XB‐Fc (a) and 3‐HB‐Fc (b) (0.25 ...Figure 9.8 Structure and design features of the target all‐XB redox‐active [...Figure 9.9 TTF derivatives.Figure 9.10 (a) Electrostatic surface potentials of 1‐TTF. (b) Stabili...Figure 9.11 (a) CV of 1‐TTF (left) and 2‐TTF (right) (0.25 mM) o...Figure 9.12 (a) Dependence of the first oxidation potential shift (ΔE′) of 1...Figure 9.13 (a) Variation of the potential shift (ΔE 0′) of the first w...Figure 9.14 Bipyridinium derivatives. (Mullaney et al. [51]; Creste et al. [...Figure 9.15 (a) CVs of 2‐XB‐MV (0.25 mM) on a glassy carbon elec...Figure 9.16 CVs of SAMs of SAM‐4‐TTF (a) and SAM‐5‐TTF...Figure 9.17 Principle of electrochemically driven XB formation in the presen...Figure 9.18 (a) Schematic representation of the foldamer SAM on a gold elect...Figure 9.19 (a) Molecular structure of the titanium dioxide grafted dye (X =...Figure 9.20 (a) Proposed mechanism for XB‐assisted ET between NO2‐CBr3 (R–Br...

10 Chapter 10Figure 10.1 Biomolecular origami. (a) DNA origami in which a single strand o...Figure 10.2 Examples of halogenated nucleic acids and amino acids. On the le...Figure 10.3 Comparing the hydrogen bond (H‐bond) and the halogen bond (X‐bon...Figure 10.4 Electrostatic model for and effects on halogen bonds. (a) The σ‐...Figure 10.5 Relationships between hydrogen bonds and halogen bonds. (a) Comp...Figure 10.6 The H‐bond enhanced X‐bond (HBeXB). QM calculated electrostatic ...Figure 10.7 Intertwined, intercalated parallel helices of d(ACBrUCGGABrUGA)....Figure 10.8 Effect of an X‐bond on the transition from duplex to four‐strand...Figure 10.9 Comparing the octamer structure of the unmodified to the hexamer...Figure 10.10 Assembly of d(GBrCGAGAGC). The interface is shown that hold two...Figure 10.11 Competition between H‐bonds and X‐bonds to control the isomer c...Figure 10.12 Comparison of X‐bonding energies for halogen substituents (X = ...Figure 10.13 Orthogonal X‐bonds from diiodotetrafluorobenzene to H‐bonded N‐...Figure 10.14 X‐bond stabilization of β‐conformation in a cyclic peptide. NMR...Figure 10.15 Peptide foldamers incorporating eight halogenated α/L‐sulfono‐γ...Figure 10.16 Effect of halogenated amino acids on the structure and stabilit...Figure 10.17 Structure of meta‐halotyrosine at position 18 at the active sit...Figure 10.18 Predicted X‐bonded nucleic acid base pairs and quartets. The le...

11 Chapter 11Scheme 11.1 (a) Schematic illustration of halogen and chalcogen bonds (R1 is...Scheme 11.2 (a) ChB donor abilities of Se and Te.(b) Effect of electron ...Scheme 11.3 (a) Positive charge‐assisted chalcogen bonding in 914.(b) N...Scheme 11.4 Reaction of 18 with Na2Ch2.Scheme 11.5 Intramolecular TeN types of chalcogen bonding in organote...Scheme 11.6 Intramolecular SeN types of chalcogen bonding in asymmetr...Scheme 11.7 SeO chalcogen bonding in asymmetric reaction of diselenid...Scheme 11.8 Role of intramolecular SeS interactions in asymmetric add...Scheme 11.9 (a) Michael addition of 5‐methoxy‐1H‐indole to (E)‐(2‐nitrovinyl...Scheme 11.10 (a) Chalcogen bond‐assisted solvolysis of (bromomethylene)diben...Scheme 11.11 Chalcogen bond‐promoted CCl bond activation in 1‐chloroisochro...Scheme 11.12 (a) One‐pot synthesis of seven‐membered N‐heterocycles. (b) ChB...Scheme 11.13 Intramolecular chalcogen bond‐supported intermediates in the en...Scheme 11.14 Anion binding modes of ChB donor receptors.Scheme 11.15 Negative charge‐assisted chalcogen bonds in mono‐ and bidentate...Scheme 11.16 Positive charge‐assisted chalcogen bonding in the detection of ...Scheme 11.17 Acyclic HaB‐ and ChB‐based receptors for the recognition of I...Scheme 11.18 ChB‐promoted anion transport.

Halogen Bonding in Solution

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