Crystal property engineering using molecular-supramolecular equivalence: mechanical property alteration in hydrogen bonded systems.

Most crystal engineering strategies exercised until now mainly rely on the alteration of weak non-covalent interactions to design structures and thus properties. Examples of mechanical property alteration for a given structure type are rare with only a few halogen bonded cases. The modular nature of halogen bonds with interaction strength tunability makes the task straightforward to obtain property differentiated crystals. However, the design of such crystals using hydrogen bond interactions has proven to be non-trivial, because of its relatively higher difference in bonding energies, and more importantly, disparate geometries of the functional groups. In the present crystal property engineering exercise, with the support of CSD analysis, we replaced a supramolecular precursor that leads to plastically bendable crystals, with a molecular equivalent, and obtained an equivalent crystal structure. As a result, the new structure, with comparable hydrogen bonding chains, produces elastically bendable single crystals (as opposed to plastically bendable crystals). In addition, the crystals show multidirectional (here two) elastic bending as well as rare elastic twisting. The occurrence of multiple isostructural examples, including a solid solution, with identical properties further demonstrates the general applicability of the proposed model. Crystals cannot display the concerned mechanical property in the absence of the desired structure type and fracture in a brittle manner on application of an external stress. Nanomechanical experiments and energy framework calculations also complement our results. To the best of our knowledge, this is the first example of a rational crystal engineering exercise using solely hydrogen bond interactions to obtain property differentiated crystals. This strategy namely molecular-supramolecular equivalence has been unexplored till now to tune mechanical properties, and hence is useful for crystal property engineering.

Valorization of tuberose flower waste through development of therapeutic products using supercritical carbon dioxide extraction and microencapsulation technologies.

Tuberose flowers (Calcutta Single variety) valued as ornamentals globally, have short shelf-lives of 8 days at 4 ± 1 °C and are therefore discarded post senescence. Previous investigations from our laboratory have established that a combination treatment using GRAS preservatives [(sucrose (4%) and CaCl2 (0.02%)]-cum-gamma-irradiation (0.02 kGy) could extend its shelf-life to 24 days, when stored at 4 ± 1 °C with concomitant enhancement in the content of its bioactive principle, viz. methyl eugenol. Supercritical carbon dioxide (SC-CO2) extract of the tuberose flower wastes post combination treatment therefore had a higher methyl eugenol content (4.11 ± 0.05 µg/g), vis-à-vis its non-treated counterpart (2.03 ± 0.03 µg/g), and thus significantly higher antioxidant and antimicrobial potencies (MIC values of 1.83 ± 0.02 mg/ml and 1.98 ± 0.03 mg/ml against S. aureus ATCC 25923 strain and MDR strain, respectively). The microencapsulated powder of the extract (MEp) obtained by spray drying was applied for healing of epidermal wounds created on New Zealand white rabbits, post skin irritancy test (wherein no clinical sign of toxicity, redness or swelling was observed). When MEp was applied, accelerated healing occurred which commenced on day 2 and was completed by day 6 vis-à-vis that of the control powder set (without extract) which showed no signs of wound healing. Therefore, the sensorially compromised-senesced tuberose flowers, a rich source of methyl eugenol, has been successfully valorized through utilization of the same in developing a novel topical antibiotic powder against potent skin pathogens.

Temperature-Reliant Dynamic Properties and Elasto-Plastic to Plastic Crystal (Rotator) Phase Transition in a Metal Oxyacid Salt.

Although, dynamic crystals are attractive for use in many technologies, molecular level mechanisms of various solid-state dynamic processes and their interdependence, remain poorly understood. Here, we report a rare example of a dynamic crystal (1), involving a heavy transition metal, rhenium, with an initial two-face elasticity (within ≈1 % strain), followed by elasto-plastic deformation, at room temperature. Further, these crystals transform to a rotator (plastic) crystal phase at ≈105 °C, displaying exceptional malleability. Qualitative and quantitative mechanical tests, X-ray diffraction, µ-Raman and polarized light microscopy experiments reveal that the elasto-plastic deformation involves both partial molecular rotations and slip, while malleability in the rotator phase is facilitated by reorientational motions and increased symmetry (slip planes). Our work, connecting the plastically bendable (1D or 2D) crystals with the rotator phases (3D), is important for designing multi-functional dynamic crystals.

Reply to the 'Comment on "Trimorphs of 4-bromophenyl 4-bromobenzoate. Elastic, brittle, plastic"' by J. J. Whittaker, A. J. Brock, A. Grosjean, M. C. Pfrunder, J. C. McMurtrie and J. K. Clegg, Chem. Commun., 2021, 57, DOI: 10.1039/D0CC07668F.

Crystals that differ in their molecular constitution may yet share the same mechanical property, such as plastic deformation, because they are equivalent in a supramolecular sense.

Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid.

The non-steroidal anti-inflammatory drugs mefenamic acid (MFA) and tolfenamic acid (TFA) have a close resemblance in their molecular scaffold, whereby a methyl group in MFA is substituted by a chloro group in TFA. The present study demonstrates the isomorphous nature of these compounds in a series of their multicomponent solids. Furthermore, the unique nature of MFA and TFA has been demonstrated while excavating their alternate solid forms in that, by varying the drug (MFA or TFA) to coformer [4-di-methyl-amino-pyridine (DMAP)] stoichiometric ratio, both drugs have produced three different types of multicomponent crystals, viz. salt (1:1; API to coformer ratio), salt hydrate (1:1:1) and cocrystal salt (2:1). Interestingly, as anticipated from the close similarity of TFA and MFA structures, these multicomponent solids have shown an isomorphous relation. A thorough characterization and structural investigation of the new multicomponent forms of MFA and TFA revealed their similarity in terms of space group and structural packing with isomorphic nature among the pairs. Herein, the experimental results are generalized in a broader perspective for predictably identifying any possible new forms of comparable compounds by mapping their crystal structure landscapes. The utility of such an approach is evident from the identification of polymorph VI of TFA from hetero-seeding with isomorphous MFA form I from acetone-methanol (1:1) solution. That aside, a pseudopolymorph of TFA with di-methyl-formamide (DMF) was obtained, which also has some structural similarity to that of the solvate MFA:DMF. These new isostructural pairs are discussed in the context of solid form screening using structural landscape similarity.

From Molecules to Interactions to Crystal Engineering: Mechanical Properties of Organic Solids.

Mechanical properties of organic molecular crystals have been noted and studied over the years but the complexity of the subject and its relationship with diverse fields such as mechanochemistry, phase transformations, polymorphism, and chemical, mechanical, and materials engineering have slowed understanding. Any such understanding also needs conceptual advances-sophisticated instrumentation, computational modeling, and chemical insight-lack of such synergy has surely hindered progress in this important field. This Account describes our efforts at focusing down into this interesting subject from the viewpoint of crystal engineering, which is the synthesis and design of functional molecular solids. Mechanical properties of soft molecular crystals imply molecular movement within the solid; the type of property depends on the likelihood of such movement in relation to the applied stress, including the ability of molecules to restore themselves to their original positions when the stress is removed. Therefore, one is interested in properties such as elasticity, plasticity, and brittleness, which are linked to structural anisotropy and the degree to which a structure veers toward isotropic character. However, these matters are still by no means settled and are system dependent. While elasticity and brittleness are probably displayed by all molecular solids, the window of plasticity is perhaps the one that is most amenable to crystal engineering strategies and methods. In all this, one needs to note that mechanical properties have a kinetic component: a crystal that is elastic under slow stress application may become plastic or brittle if the same stress is applied quickly. In this context, nanoindentation studies have shown themselves to be of invaluable importance in understanding structural anisotropy. Several problems in solid state chemistry, including classical ones, such as the melting point alternation in aliphatic straight chain dicarboxylic acids and hardness modulation in solid solutions, have been understood more clearly with this technique. The way may even be open to picoindentation studies and the observation of molecular level movements. As in all types of crystal engineering, an understanding of the intermolecular interactions can lead to property oriented crystal design, and we present examples where complex properties may be deliberately turned on or off in organic crystals: one essentially fine-tunes the degree of isotropy/anisotropy by modulating interactions such as hydrogen bonding, halogen bonding, π···π interactions, and C-H···π interactions. The field is now wide open as is attested by the activities of several research groups working in the area. It is set to take off into the domains of smart materials, soft crystals, and superelasticity and a full understanding of solid state reactivity.

Trimorphs of 4-bromophenyl 4-bromobenzoate. Elastic, brittle, plastic.

Intermolecular interactions and crystal packing of three polymorphs of the title compound are described in the context of their different mechanical properties. Molecular features of compounds that may be prone to such property differentiated polymorphism are discussed.

Acid···Amide Supramolecular Synthon in Cocrystals: From Spectroscopic Detection to Property Engineering.

The acid···amide dimer heterosynthon in cocrystals of aromatic acids and primary amides is identified by marker peaks in the IR spectra that are characteristic of individual N-H···O and O-H···O interactions and also of the extended synthon. The O-H···O hydrogen bond is crucial to heterodimer formation in contrast to the N-H···O bond. A combinatorial study, tuning the chemical nature of acid and amide functionalities, leads to 22 cocrystals out of 36 crystallization attempts. Four quadrants I-IV are defined based on acidity and basicity of the acid and amide components. The strong acid-strong base combination in quadrant I favors the planar acid···amide heterodimer in its eight cocrystals. Quadrant IV with its weak acid-weak base combination is the least favored for the planar heterosynthon and synthon diversity is observed in the eight cocrystals obtained. The strong-weak and weak-strong combinations in quadrants II and III are expectedly ambivalent. This exercise highlights the effect of molecular features on supramolecular behavior. Quadrant I crystals, with their propensity for the planar acid···amide heterodimer are suitable for the engineering of crystals that can be sheared. This quadrant favors the formation of elastic crystals too. The overall result is that 57% (4 in 7) of all crystals in this quadrant are deformable, compared with 14% (1 in 7) in the three other quadrants. This work is a complete crystal engineering exercise from synthon identification to a particular desired crystal packing to property selection. One can virtually anticipate the mechanical property of a putative acid···amide cocrystal from a knowledge of just the molecular structures of the constituent acid and amide molecules.

A hand-twisted helical crystal based solely on hydrogen bonding.

A hand twistable hydrogen bonded two-dimensional plastic crystal, 4-pyridinyl 4-nitrobenzoate hydrate, is obtained from a brittle precursor using a retrosynthetic design strategy based on molecular/supramolecular equivalence.

σ-Hole and π-Hole Synthon Mimicry in Third-Generation Crystal Engineering: Design of Elastic Crystals.

Designing elastic crystals is a difficult task and is of relevance in potential applications from materials to biology. Here, multi-step crystal engineering based on σ-hole and π-hole synthon mimicry is performed to obtain binary organic molecular crystals with a high degree of flexibility. A structural model is proposed based only on σ-hole-oriented type-II halogen bonds with their characteristic orthogonal geometry. These σ-hole contacts are then partly replaced by chemically and geometrically similar π-hole synthons to obtain new crystals in the second step. In the final step, all the σ-hole interactions are replaced with π-hole interactions and elastic crystals of non-halogenated compounds are obtained. All the crystals obtained according to our protocols are found to be elastic. When crystals that do not conform to the desired structure type appeared, they were found to be brittle. This underlines the role of orthogonal-type interactions, whether they are of the σ-hole or π-hole type, in achieving elasticity. This is the first report in which π-hole interactions are used for property engineering. This example may illustrate a new generation of crystal engineering in which a particular property is associated more with topological rather than chemical attributes, although the significance of the latter cannot be completely excluded.

Crystal Engineering of Hand-Twisted Helical Crystals.

A strategy is outlined for the design of hand-twisted helical crystals. The starting point in the exercise is the one-dimensional (1D) plastic crystal, 1,4-dibromobenzene, which is then changed to a 1D elastic crystal, exemplified by 4-bromophenyl 4'-chlorobenzoate, by introduction of a molecular synthon -O-CO- in lieu of the supramolecular synthon Br···Br in the precursor. The 1D elastic crystals are next modified to two-dimensional (2D) elastic crystals, of the type 4-bromophenyl 4'-nitrobenzoate where the halogen bonding and C-H···O hydrogen bonding are well-matched. Finally, varying the interaction strengths in these 2D elastic crystals gives plastic crystals with two pairs of bendable faces but without slip planes. Typical examples are 4-chlorophenyl and 4-bromophenyl 4'-nitrobenzoate. This type of 2D plasticity represents a new type of bendable crystals in which plastic behavior is seen with a fair degree of isotropic character in the crystal packing. The presence of two sets of bendable faces, generally orthogonal to each other, allows for the possibility of hand-twisting of the crystals to give grossly helical morphologies. Accordingly, we propose the name hand-twisted helical crystals for these substances.

Using structural modularity in cocrystals to engineer properties: elasticity.

Cocrystal formation of heterocyclic bases with halogenated aromatic acids increases the tendency for stacking and with this, an increase in structural isotropy occurs that leads to crystal elasticity.