A Self-Healing Crystal That Repairs Multiple Cracks.

We report both cracking and self-healing in crystals occurring during a thermal phase transition, followed by a topochemical polymerization. A squaramide-based monomer was designed where the azide and alkyne units of adjacent molecules are positioned favorably for a topochemical click reaction. The monomer undergoes spontaneous single-crystal-to-single-crystal (SCSC) polymerization at room temperature via regiospecific 1,3-dipolar cycloaddition, yielding the corresponding triazole-linked polymer in a few days. When heated at 60 °C, the polymerization completes in a SCSC manner in 24 h. Upon continuous heating from room temperature to 110 °C, the monomer crystals develop multiple cracks, and they self-heal immediately. The cracking occurs due to a thermal phase transition, as evidenced by differential scanning calorimetry (DSC). The cracks heal either upon further heating or upon cooling of the crystals due to the topochemical polymerization or reversal of the phase transition, respectively. Increasing the heating rate leads to the formation of longer and wider cracks, which also heal instantaneously. The self-healed crystals retained their integrity and the crystal structure of the self-healed crystals was analyzed by single-crystal X-ray diffraction. The quality of the self-healed crystals and their diffraction ability conform to those of the completely reacted crystals at room temperature or at 60 °C without developing cracks. This work demonstrates a novel mechanism for self-healing of molecular crystals that could expand the horizon of these materials for a plethora of applications.

Adamantoid Scaffolds for Multiple Cargo Loading and Cellular Delivery as ß-Cyclodextrin Inclusion Complexes.

There is huge demand for developing guests that bind ß-CD and can conjugate multiple cargos for cellular delivery. We synthesized trioxaadamantane derivatives, which can conjugate up to three cargos per guest. 1 H NMR titration and isothermal titration calorimetry revealed these guests form 1 : 1 inclusion complexes with ß-CD with association constants in the order of 103  M-1 . Co-crystallization of ß-CD with guests yielded crystals of their 1 : 1 inclusion complexes as determined by single-crystal X-ray diffraction. In all cases, trioxaadamantane core is buried within the hydrophobic cavity of ß-CD and three hydroxyl groups are exposed outside. We established biocompatibility using representative candidate G4 and its inclusion complex with ß-CD (ß-CD⊂G4), by MTT assay using HeLa cells. We incubated HeLa cells with rhodamine-conjugated G4 and established cellular cargo delivery using confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) analysis. For functional assay, we incubated HeLa cells with ß-CD-inclusion complexes of G4-derived prodrugs G6 and G7, containing one and three units of the antitumor drug (S)-(+)-camptothecin, respectively. Cells incubated with ß-CD⊂G7 displayed the highest internalization and uniform distribution of camptothecin. ß-CD⊂G7 showed higher cytotoxicity than G7, camptothecin, G6 and ß-CD⊂G6, affirming the efficiency of adamantoid derivatives in high-density loading and cargo delivery.

Topochemical polymerizations for the solid-state synthesis of organic polymers.

Topochemical polymerizations are solid-state reactions driven by the alignment of monomers in the crystalline state. The molecular confinement in the monomer crystal lattice offers precise control over the tacticity, packing and crystallinity of the polymer formed in the topochemical reaction. As topochemical reactions occur under solvent- and catalyst-free conditions, giving products in high yield and selectivity/specificity that do not require tedious chromatographic purification, topochemical polymerizations are highly attractive over traditional solution-phase polymer synthesis. By this method, polymers having sophisticated structures and desired topologies can be availed. Often, such ordered packing confers attractive properties to the topochemically-synthesized polymers. Diverse categories of topochemical polymerizations are known, such as polymerizations via [2+2], [4+4], [4+2], and [3+2] cycloadditions, and polymerization of diynes, triynes, dienes, trienes, and quinodimethanes, each of which proceed under suitable stimuli like heat, light or pressure. Each class of these reactions requires a unique packing arrangement of the corresponding monomers for the smooth reaction and produces polymers with distinct properties. This review is penned with the intent of bringing all the types of topochemical polymerizations into a single platform and communicating the versatility of these lattice-controlled polymerizations. We present a brief history of the development of each category and comprehensively review the topochemical synthesis of fully-organic polymers reported in the last twenty years, particularly in crystals. We mainly focus on the various molecular designs and crystal engineering strategies adopted to align monomers in a suitable orientation for polymerization. Finally, we analyze the current challenges and future perspectives in this research field.

Topochemical Postulates: Are They Relevant for Topochemical Reactions Occurring at Elevated Temperatures?

A rigid inositol-derived monomer functionalized with azide and alkyne as the complementary reactive groups (CRGs) crystallized as three distinct polymorphs I-III. Despite the unsuitable orientation of CRGs in the crystals for complete polymerization, all the three polymorphs underwent regiospecific and quantitative topochemical azide-alkyne cycloaddition (TAAC) polymerization upon heating to yield three different polymorphs of 1,2,3-triazol-1,4-diyl-linked-poly-neo-inositol. The molecules in these polymorphs exploit the weak intermolecular interactions, free space in the crystal lattice, and heat energy for their large and cooperative molecular motion to attain a transient reactive orientation, ultimately leading to the regiospecific TAAC reaction yielding distinct crystalline polymers. This study cautions that the overreliance on topochemical postulates for the prediction of topochemical reactivity at high temperatures could be misleading.

Tunable Mechanical Response from a Crystal Undergoing Topochemical Dimerization: Instant Explosion at a Faster Rate and Chemical Storage of a Harvestable Explosion at a Slower Rate.

Strain developed in crystals in response to stimuli causes mechanical response. Methods to tune such mechanical response is important for practical applications. Crystals of a monomer having azide and alkyne units pre-organized in a ready-to-react orientation, undergo thermal topochemical dimerization and show rate-dependent mechanical response. When the reaction rate is fast, the crystals explode violently. When the reaction rate is slow, the crystals absorb water from the surroundings contemporaneously with the reaction to form the dimer-hydrate in a single-crystal-to-single-crystal (SCSC) manner. Crystals of the dimer-hydrate upon dehydration also undergo explosion. Thus, at slow reaction rate, the strain gets stored in crystals by hydration and the explosion can be harvested, at will, by dehydration. Use of this rate-dependent explosion in the automatic activation of a remedial electrical circuit in case of a sudden rise in temperature has been demonstrated.

Single-crystal-to-single-crystal synthesis of a pseudostarch via topochemical azide-alkyne cycloaddition polymerization.

There is high demand for polysaccharide-mimics as enzyme-stable substitutes for polysaccharides for various applications. Circumventing the problems associated with the solution-phase synthesis of such polymers, we report here the synthesis of a crystalline polysaccharide-mimic by topochemical polymerization. By crystal engineering, we designed a topochemically reactive crystal of a glucose-mimicking monomer decorated with azide and alkyne units. In the crystal, the monomers arrange in head-to-tail fashion with their azide and alkyne groups in a ready-to-react antiparallel geometry, suitable for their topochemical azide-alkyne cycloaddition (TAAC) reaction. On heating the crystals, these pre-organized monomer molecules undergo regiospecific TAAC polymerization, yielding 1,4-triazolyl-linked pseudopolysaccharide (pseudostarch) in a single-crystal-to-single-crystal manner. This crystalline pseudostarch shows better thermal stability than its amorphous form and many natural polysaccharides.

Polymers with advanced structural and supramolecular features synthesized through topochemical polymerization.

Polymers are an integral part of our daily life. Hence, there are constant efforts towards synthesizing novel polymers with unique properties. As the composition and packing of polymer chains influence polymer's properties, sophisticated control over the molecular and supramolecular structure of the polymer helps tailor its properties as desired. However, such precise control via conventional solution-state synthesis is challenging. Topochemical polymerization (TP), a solvent- and catalyst-free reaction that occurs under the confinement of a crystal lattice, offers profound control over the molecular structure and supramolecular architecture of a polymer and usually results in ordered polymers. In particular, single-crystal-to-single-crystal (SCSC) TP is advantageous as we can correlate the structure and packing of polymer chains with their properties. By designing molecules appended with suitable reactive moieties and utilizing the principles of supramolecular chemistry to align them in a reactive orientation, the synthesis of higher-dimensional polymers and divergent topologies has been achieved via TP. Though there are a few reviews on TP in the literature, an exclusive review showcasing the topochemical synthesis of polymers with advanced structural features is not available. In this perspective, we present selected examples of the topochemical synthesis of organic polymers with sophisticated structures like ladders, tubular polymers, alternating copolymers, polymer blends, and other interesting topologies. We also detail some strategies adopted for obtaining distinct polymers from the same monomer. Finally, we highlight the main challenges and prospects for developing advanced polymers via TP and inspire future directions in this area.

Model molecules to classify CHO hydrogen-bonds.

We developed a set of conformationally locked molecules each of which makes a single CHO H-bond/short contact and has different electron density at the acceptor oxygen atom. The downfield shift of the 1H NMR signals due to the hydrogen involved in the CHO H-bond varied from 0.93-1.6 ppm, and the magnitude of Δδ is in correlation with the hybridization state of the acceptor oxygen and with the CHO H-bond strengths quantified using a computational method.

Correction: Model molecules to classify CHO hydrogen-bonds.

Correction for 'Model molecules to classify CHO hydrogen-bonds' by Amol M. Vibhute et al., Chem. Commun., 2018, 54, 4629-4632.

Regioselective SN2 reactions for rapid syntheses of azido-inositols by one-pot sequence-specific nucleophilysis.

Triflates of myo-inositol undergo facile solvolysis in DMSO and DMF yielding SN2 products substituted with O-nucleophiles; DMF showed slower kinetics. Axial O-triflate undergoes faster substitution than equatorial O-triflate. By exploiting this difference in kinetics, solvent-tuning and sequence-controlled nucleophilysis, rapid synthesis of three azido-inositols of myo-configuration from myo-inositol itself has been achieved.