Neighboring Cage Participation for Assisted Construction of Self-Assembled Multicavity Conjoined Cages and Augmented Guest Binding.

A set of Pd2L4, Pd3L4, and Pd4L4-type single-, double-, and triple-cavity cages are prepared by complexation of Pd(NO3)2 with designer bis-monodentate (L1), tris-monodentate (L2), and tetrakis-monodentate (L3) ligands. The Pd2L4 cage exists in equilibrium with a Pd3L6 cage; the equilibrium shifted to Pd2L4 at 70 °C or upon addition of pyrazine-N,N'-dioxide (PZDO). The Pd2L4 cage binds a PZDO molecule using electrostatic, bifurcated H-bonding and overcoordinated H-bonding interactions. The discrete Pd3L4 and Pd4L4 compounds are conjoined cages comprising of unequal sized Pd2L4 cages (bigger and smaller). The bigger unit of Pd3L4 cage selectively binds a PZDO, and the smaller one binds a nitrate, fluoride, chloride, or bromide. The Pd4L4 cage, having a central bigger Pd2L4 cavity and two smaller peripheral Pd2L4 cavities, binds one PZDO and two nitrate, fluoride, chloride, or bromide. The smaller cavity can be prepared individually from Pd(II) and bis-monodentate ligand (L4), however, in the presence of template like a nitrate, fluoride, chloride, or bromide; otherwise, it forms an oligomeric mixture. Notably, the conjoined Pd3L4 and Pd4L4 cages could be prepared with (preferably) or without using a template for smaller cavity, and the bigger Pd2L4 is formed by sacrificing the possibility of the Pd3L6 moiety. Thus, the conjoined cages are formed in a symbiotic manner where the neighboring cages participate in the formation of each other. The binding of PZDO shows that the presence of one neighboring cage (as in Pd3L4) augments the binding affinity and that is further augmented in the presence of two neighboring cages (as in Pd4L4).

Cage-To-Cage Transformations in Self-Assembled Coordination Cages Using "Acid/Base" or "Guest Binding-Induced Strain" as Stimuli.

Controlling supramolecular systems between different functional forms by utilizing acids/bases as stimuli is a formidable challenge, especially where labile coordination bonds are involved. A pair of acid/base responsive, interconvertible 1,5-enedione/pyrylium based Pd2L4-type cages are prepared that exhibit differential guest binding abilities towards disulfonates of varied sizes. A three-state switch has been achieved, where (i) a weakly coordinating base induced cage-to-cage transformation in the first step, (ii) a strongly coordinating base triggered cage disassembly as the second step, and (iii) the third step shows acid(strong) promoted generation of initial cage, thereby completing the cycle. To our surprise, binding of a specific disulfonate guest facilitated cage-to-cage transformations by inducing strain on the cage assembly thereby opening the labile pyrylium rings of the cage. Through a competitive guest binding study, we demonstrated the superior guest binding capability of the octacationic pyrylium-based cage over a similar-sized tetracationic cage. These results provide a reliable approach to reversibly modulate the guest binding properties of acid/base-responsive self-assembled coordination cages.

A Template-Free Pd2 L4 Cage with up to Nanomolar Affinity for Chloride in Aqueous Solutions.

Selective binding of chloride over the other most abundant anions in living organisms is pivotal due to its essential role in physiological functions. Herein, we report a template-free Pd2 L4 cage exhibiting high selectivity for medium-sized halides (i. e., Cl- , Br- ) in water owing to the size-discriminatory nature of the cage cavity. In pure water, this cage displays high selectivity and micromolar affinity for chloride. The cage shows no binding towards other biologically more abundant essential anions such as phosphates, carboxylates, or bicarbonate. This cage shows an unprecedented nanomolar affinity with 1 : 1 binding stoichiometry for chloride in aqueous-DMSO media. This high affinity was achieved with the best use of traditional hydrogen bonding and electrostatic interactions, as confirmed by single-crystal X-ray diffraction analysis. This well-defined cage sequestrates F- by cleaving a B-F bond in BF4 - in a facile manner in a nonpolar solvent or in the presence of excess ligand. This cage also demonstrates capture of the sub-ppm chloride level that is present in commercial D2 O samples.

A Template-Free Pd2 L4 Cage with up to Nanomolar Affinity for Chloride in Aqueous Solutions.

Invited for the cover of this issue is the group of Dillip Kumar Chand at the Indian Institute of Technology Madras. The image depicts the efficient chloride binding ability of a designer self-assembled coordination cage in water. The binding occurs selectively even in presence of models of biologically abundant anionic systems. Read the full text of the article at 10.1002/chem.202300891.

Intermolecular Acyl-Transfer Reactions in Molecular Crystals.

It is far more difficult to recognize and predict the chemical reactions that a molecule of an organic compound can undergo in crystalline (solid) state as compared to the solution state (the "organic functional group" approach), since the published data on solid-state structure-reactivity investigations and correlations are scant. The discovery of the first intermolecular acyl-transfer reaction in molecular crystals of racemic 2,4-di- O-benzoyl- myo-inositol-1,3,5-orthoformate (DiBz) during our attempts to develop methods for the synthesis of phosphoinositols, motivated us to find other molecular crystals capable of supporting similar reactions. Small changes to the molecular structure of DiBz yielded analogues with different crystal structures which showed varying degrees of acyl transfer reactivity as compared to the crystals of DiBz. A systematic investigation of the structures, polymorphism, cocrystallization behavior, and the corresponding reactivity of these crystals allowed us to correlate the acyl transfer reactivity with their structures and inherent noncovalent interactions and provided crucial insights into the mechanism of these reactions. Polymorphs or cocrystals of these compounds exhibited dissimilar reactivities due to differences in the molecular conformation and/or arrangements in their crystals. The knowledge of phase transitions between polymorphs enabled us to control and tune the reactivity in the solid state. We could identify three conditions essential for intermolecular acyl transfer: (i) favorable relative geometry of the electrophile (ester C═O) and the nucleophile (OH), (ii) noncovalent interactions (C-H···π) between the reacting molecules which help in maintaining the facility and specificity of the reaction, and (iii) the presence of channels in the lattice which enable propagation of the reaction in the crystal. Based on this supramolecular structure-reactivity correlation, we identified other molecular crystals (composed of molecules of widely different molecular structure from that of DiBz) from a survey of the Cambridge Structural Database (CSD) and predicted their acyl transfer reactivity. The increased availability of user-friendly modern X-ray diffractometers and related software has enabled efficient collection, analysis and interpretation of single crystal X-ray diffraction data, essential for such studies. The rapidly expanding CSD facilitates the identification of crystals with similar structures and reactivity patterns. In a wider perspective, facile reactions in molecular crystals fascinate chemists because these reactions usually exhibit unique product selectivity and have the potential to be developed as sustainable green reactions. We are optimistic that similar approaches for the study of other group transfer reactions in molecular crystals would augment and widen the scope of chemical reactions in molecular crystals in particular and the solid state in general. The ability to predict the reactivity of molecules in their crystals could find applications in organic synthesis, material science and industry. Realization of the involvement of inositol derivatives in cellular processes led to the discovery of cellular signal transduction mechanisms. The ability of inositol derivatives to support facile acyl-transfer reactions in the crystalline state might well have opened a new avenue for research in the area of organic solid-state reactions.

Low-Symmetry Self-Assembled Coordination Complexes with Exclusive Diastereoselectivity: Experimental and Computational Studies.

A pyridine/aniline appended unsymmetrical bidentate ligand N-(4-(4-aminobenzyl)phenyl)nicotinamide, investigated in this work has two well-separated coordination sites. Combination of the ligand with cis-protected palladium(II) (i.e., PdL') and palladium(II) in separate reactions produced the corresponding Pd2L'2Lun2 and extremely rare Pd2Lun4 type self-assembled binuclear complexes, respectively. Notably, both varieties of complexes are prepared from a common ligand system. Two diastereomers (i.e., (2,0) and (1,1)-forms) are possible for Pd2L'2Lun2 type complex, whereas four diastereomers (i.e., (4,0), (3,1), trans(2,2), and cis(2,2)-forms) can be imagined for the Pd2Lun4 type complex. However, exclusive diastereoselectivity was observed, and the complexes formed belong to (1,1)-Pd2L'2Lun2 and cis(2,2)-Pd2Lun4 forms. The diastereomers are predicted from NMR study in solution and DFT calculations in gas-phase and implicit-solvent media; however, single-crystal structures of both the complexes provided unambiguous support. The rare Pd2Lun4 type complex is studied in further detail. Parameters like counteranion, concentration, temperature, and stoichiometry of metal to ligand did not influence the diastereoselectivity in complex formation. DFT calculations show the cis(2,2) form to be the most stable, followed by the (3,1) isomer. The lowest conformational strain in the bound ligand strands in the cis(2,2)-arrangement along with optimal intermolecular interactions makes it the energetically most stable of all the isomers. Molecular dynamics (MD) simulations were carried out to visualize the self-assembly process toward the formation of Pd2Lun4 type complex and the free energy difference between the cis(2,2) and (3,1) isomers. Snapshots of MD simulation elucidate the step-by-step progress of complexation leading to the cis(2,2)-isomer.

Correlation of Intermolecular Acyl Transfer Reactivity with Noncovalent Lattice Interactions in Molecular Crystals: Toward Prediction of Reactivity of Organic Molecules in the Solid State.

Intermolecular acyl transfer reactivity in several molecular crystals was studied, and the outcome of the reactivity was analyzed in the light of structural information obtained from the crystals of the reactants. Minor changes in the molecular structure resulted in significant variations in the noncovalent interactions and packing of molecules in the crystal lattice, which drastically affected the facility of the intermolecular acyl transfer reactivity in these crystals. Analysis of the reactivity vs crystal structure data revealed dependence of the reactivity on electrophile···nucleophile interactions and C-H···π interactions between the reacting molecules. The presence of these noncovalent interactions augmented the acyl transfer reactivity, while their absence hindered the reactivity of the molecules in the crystal. The validity of these correlations allows the prediction of intermolecular acyl transfer reactivity in crystals and co-crystals of unknown reactivity. This crystal structure-reactivity correlation parallels the molecular structure-reactivity correlation in solution-state reactions, widely accepted as organic functional group transformations, and sets the stage for the development of a similar approach for reactions in the solid state.

Intramolecular Cyclization of Carbonate and Thiocarbonate Derivatives of myo-Inositol in the Solid State: Implications for Acyl Group Transfer Reactions in Molecular Crystals.

Racemic 4-O-phenoxycarbonyl and 4-O-phenoxythiocarbonyl derivatives of myo-inositol orthoformate undergo thermal intramolecular cyclization in the solid state to yield the corresponding 4,6-bridged carbonates and thiocarbonates, respectively. The thermal cyclization also occurs in the solution and molten states, but less efficiently, suggesting that these cyclization reactions are aided by molecular pre-organization, although not strictly topochemically controlled. Crystal structures of two carbonates and a thiocarbonate clearly revealed that the relative orientation of the electrophile and the nucleophile in the crystal lattice facilitates the intramolecular cyclization reaction and forbids the intermolecular reaction. The correlation observed between the chemical reactivity and the non-covalent interactions in the crystal of the reactants provides a way to estimate the chemical stability of analogous molecules in the solid state.

Reversible Mechanical Interlocking of D-Shaped Molecular Karabiners bearing Coordination-Bond Loaded Gates: Route to Self-Assembled [2]Catenanes.

Complexation of 1,4-phenylenebis(methylene) diisonicotinate, L1, with cis-protected Pd(II) components, [Pd(L')(NO3 )2 ], in an equimolar ratio yielded binuclear complexes, 1 a-d of [Pd2 (L')2 (L1)2 ](NO3 )4 formulation where L' stands for ethylenediamine (en), tetramethylethylenediamine (tmeda), 2,2'-bipyridine (bpy), and phenanthroline (phen). The combination of 4,4'-bipyridine, L2, with the cis-protected Pd(II) units is known to yield molecular squares, 2 a-d. However, 2 b-d coexist with the corresponding molecular triangles, 3 b-d. Combination of an equivalent each of the ligands L1 and L2 with two equivalents of cis-protected Pd(II) components in DMSO resulted in the D-shaped heteroligated complexes [Pd2 (L')2 (L1)(L2)](NO3 )4 , 4 a-d. Two units of the D-shaped complexes interlock, in a concentration dependent fashion, to form the corresponding [2]catenanes [Pd2 (L')2 (L1)(L2)]2 (NO3 )8 , 5 a-d under aqueous conditions. Crystal structures of the macrocycle [Pd2 (tmeda)2 (L1)(L2)](PF6 )4 , 4 b'', and the catenane [Pd2 (bpy)2 (L1)(L2)]2 (NO3 )8 , 5 c, provide unequivocal support for the proposed molecular architectures.

A pair of conjoined trinuclear sub-frameworks in a pentanuclear double-cavity discrete coordination cage.

Combination of Pd(ii) with selected bis-monodentate ligands produces the familiar multinuclear Pd m L2m type self-assembled "single-cavity discrete coordination cages" (SCDCC). If the ligand provides parallel coordination vectors, then it forms a binuclear Pd2L4 type cage, whereas utilization of ligands having appropriately divergent coordination vectors results in specific higher nuclear complexes. In contrast, preparation of emergent "multi-cavity discrete coordination cages" (MCDCC) using Pd(ii) and designer ligands is quite captivating where the neighboring cavities of the framework are conjoined with each other through a common metal center. A pair of conjoined binuclear Pd2L4 type sub-frameworks are present in a trinuclear Pd3L4 type double-cavity cage prepared from Pd(ii) and a tris-monodentate ligand having parallel coordination vectors. The present work envisioned a design to make double-cavity coordination cages having a pair of conjoined trinuclear Pd3L6 type sub-frameworks. To fulfill the objective we combined Pd(ii) with a mixture of designer bis-monodentate ligand (L) and tris-monodentate ligand (L') in a 5 : 4 : 4 ratio in one pot to afford the targeted pentanuclear type cage. The choice of bis-monodentate ligand L is based on the divergent nature of the coordination vectors suitable to produce a Pd3L6 type SCDCC. The tris-monodentate ligand L' having two arms is designed in such a manner that each of the arms reasonably resembles L. Study of the complexation behavior of Pd(ii) with L' provided additional guiding factors essential for the successful making of type MCDCC by integrative self-sorting. A few other MCDCC including lower symmetry versions were also prepared in the course of the work.

Identification of molecular crystals capable of undergoing an acyl-transfer reaction based on intermolecular interactions in the crystal lattice.

Investigation of the intermolecular acyl-transfer reactivity in molecular crystals of myo-inositol orthoester derivatives and its correlation with crystal structures enabled us to identify the essential parameters to support efficient acyl-transfer reactions in crystals: 1) the favorable geometry of the nucleophile (-OH) and the electrophile (C-O) and 2) the molecular assembly, reinforced by C-H⋅⋅⋅π interactions, which supports a domino-type reaction in crystals. These parameters were used to identify another reactive crystal through a data-mining study of the Cambridge Structural Database. A 2:1 co-crystal of 2,3-naphthalene diol and its di-p-methylbenzoate was selected as a potentially reactive crystal and its reactivity was tested by heating the co-crystals in the presence of solid sodium carbonate. A facile intermolecular p-toluoyl group transfer was observed as predicted. The successful identification of reactive crystals opens up a new method for the detection of molecular crystals capable of exhibiting acyl-transfer reactivity.

Comparison of racemic epi-inosose and (-)-epi-inosose.

The conversion of myo-inositol to epi-inositol can be achieved by the hydride reduction of an intermediate epi-inosose derived from myo-inositol. (-)-epi-Inosose, (I), crystallized in the monoclinic space group P2(1), with two independent molecules in the asymmetric unit [Hosomi et al. (2000). Acta Cryst. C56, e584-e585]. On the other hand, (2RS,3SR,5SR,6SR)-epi-inosose, C(6)H(10)O(6), (II), crystallized in the orthorhombic space group Pca2(1). Interestingly, the conformation of the molecules in the two structures is nearly the same, the only difference being the orientation of the C-3 and C-4 hydroxy H atoms. As a result, the molecular organization achieved mainly through strong O-H···O hydrogen bonding in the racemic and homochiral lattices is similar. The compound also follows Wallach's rule, in that the racemic crystals are denser than the optically active form.

Construction of Two-Component Chemically Reactive Supramolecular Assemblies-Acyl Migration Reactions in Cocrystals of Napthalene-2,3-Diol and Its Diesters.

Reactions in solids are of contemporary interest due to applications in pharmaceutical industries to environmental sustainability. Although several reactive crystals that support chemical reactions have been identified and characterized, the same cannot be said about reactive cocrystals. Earlier we correlated the facile acyl group transfer reactions in crystals with supramolecular parameters obtained from the crystal structures. The structure-reactivity correlation revealed the requirement of proper juxtaposition of electrophile (C=O) and the nucleophile (OH) with distance (∼3.2 Å) and angle (∼90°) along the chain structure. The current article describes the preparation of cocrystals that are capable of supporting intermolecular acyl group transfer reactions in a group of structurally similar molecules. The cocrystals of naphthalene 2,3-diol and its corresponding diesters showed a facile solid state acyl transfer reaction, which has been well correlated with their crystal structures.

Self-assembled conjoined-cages.

A self-assembled coordination cage usually possesses one well-defined three-dimensional (3D) cavity whereas infinite number of 3D-cavities are crafted in a designer metal-organic framework. Construction of a discrete coordination cage possessing multiple number of 3D-cavities is a challenging task. Here we report the peripheral decoration of a trinuclear [Pd3L6] core with one, two and three units of a [Pd2L4] entity for the preparation of multi-3D-cavity conjoined-cages of [Pd4(La)2(Lb)4], [Pd5(Lb)4(Lc)2] and [Pd6(Lc)6] formulations, respectively. Formation of the tetranuclear and pentanuclear complexes is attributed to the favorable integrative self-sorting of the participating components. Cage-fusion reactions and ligand-displacement-induced cage-to-cage transformation reactions are carried out using appropriately chosen ligand components and cages prepared in this work. The smaller [Pd2L4] cavity selectively binds one unit of NO3-, F-, Cl- or Br- while the larger [Pd3L6] cavity accommodates up to four DMSO molecules. Designing aspects of our conjoined-cages possess enough potential to inspire construction of exotic molecular architectures.

Two modes of O--H...O hydrogen bonding utilized in dimorphs of racemic 6-O-acryloyl-2-O-benzoyl-myo-inositol 1,3,5-orthoformate.

The title compound, C(17)H(16)O(8), yields conformational dimorphs [forms (I) and (II)] at room temperature, separately or concomitantly, depending on the solvent of crystallization. The yield of crystals of form (I) is always much more than that of crystals of form (II). The molecule has one donor -OH group that can make intermolecular O-H...O hydrogen bonds with one of the two acceptor C=O groups, as well as with the hydroxyl O atom; interestingly, each of the options is utilized separately in the dimorphs. The crystal structure of form (I) contains one molecule in the asymmetric unit and is organized as a planar sheet of centrosymmetric dimers via O-H...O hydrogen bonds involving the OH group and the carbonyl O atom of the acryloyl group. In the crystal structure of form (II), which contains two independent molecules in the asymmetric unit, two different O-H...O hydrogen bonds, viz. hydroxyl-hydroxyl and hydroxyl-carbonyl (benzoyl), connect the molecules in a layered arrangement. Another notable feature is the transformation of form (II) to form (I) via melt crystallization upon heating to 411 K. The higher yield of form (I) during crystallization and the thermal transition of form (II) to form (I) suggest that the association in form (I) is more highly favoured than that in form (II), which is valuable in understanding the priorities of molecular aggregation during nucleation of various polymorphs.