Strategy and Methodology in the Synthesis of Multicomponent Molecular Solids: The Quest for Higher Cocrystals.

Crystal engineering is the art and science of making crystals by design. Crystallization is inherently a purifying phenomenon. Bringing together more than one organic compound into the same crystal always needs deliberate action. Cocrystals are important because they offer a route to the controlled modulation of crystal properties. The route to cocrystal synthesis was opened up with the heterosynthon concept, which considers the complementary recognition of chemical groups from different molecules. Using this concept, binary cocrystals of enormous variety have been generated, even as crystal engineering has evolved into a form of solid-state supramolecular synthesis. Introducing a third component (a component is somewhat arbitrarily defined as an organic substance that is a solid at room temperature, mostly with the idea of excluding solvates) in a stoichiometric manner requires substantially greater effort and a careful balance of intermolecular interactions-their strengths, directional properties, and distance falloff characteristics. The first systematic ternary cocrystal synthesis was reported around 15 years ago. Drawing in a fourth component in stoichiometric amounts is exceedingly difficult, and we reported such syntheses in 2016. To date, a limited number of ternary cocrystals have been realized (around 120 in all, with a half from our group) and an even smaller number of quaternary cocrystals (around 30, all from our group, barring one). It is impressive that our experiments largely yielded the intended higher cocrystal (three- or four-component) with very small traces of contaminating binaries and pure compounds. A fifth or sixth component may be brought into the solid in the manner of a solid solution in that these components are situated at one of the sites of the quaternary cocrystal. To date, five components have not been included stoichiometrically within the same crystal. This is still an open challenge. The merit in synthesizing (higher) cocrystals is that one can systematically engineer property modularity: Each component is associated with a distinct property. This is important in the pharmaceutical industry, where each component can, in principle, confer a different, desirable property-drug action, solubility, or permeability. However, difficult synthetic targets are also addressed in chemistry simply because they are there. The intellectual satisfaction in making something that is very difficult to make renders the enterprise worthwhile in itself, and new chemistry usually gets uncovered in the process. The development of synthetic organic chemistry can undoubtedly be credited to various reliable methods for chemical transformations, and many difficult total syntheses were achieved by employing these methods over two centuries of research. In contrast, supramolecular synthesis (of multicomponent cocrystals and other assemblies) is in no way at a similar level of sophistication because the subject is still relatively young. Our group and others have reported the synthesis of many higher cocrystals with reliable, reproducible, and robust design strategies. There is a general perception that the isolation of some of these cocrystals is a matter of luck! The crux of this Account is that far from being a serendipitous matter, higher cocrystals may only be made with a judicious combination of strategy and methodology-the essence of synthesis.

Four- and five-component molecular solids: crystal engineering strategies based on structural inequivalence.

A synthetic strategy is described for the co-crystallization of four- and five-component molecular crystals, based on the fact that if any particular chemical constituent of a lower cocrystal is found in two different structural environments, these differences may be exploited to increase the number of components in the solid. 2-Methylresorcinol and tetramethylpyrazine are basic template molecules that allow for further supramolecular homologation. Ten stoichiometric quaternary cocrystals and one quintinary cocrystal with some solid solution character are reported. Cocrystals that do not lend themselves to such homologation are termed synthetic dead ends.

Quaternary cocrystals: combinatorial synthetic strategies based on long-range synthon Aufbau modules (LSAM).

A synthetic strategy is outlined whereby a binary cocrystal may be developed in turn into a ternary and finally into a quaternary cocrystal. The strategy hinges on the concept of the long-range synthon Aufbau module (LSAM) which is a large supramolecular synthon containing more than one type of intermolecular interaction. Modulation of these interactions may be possible with the use of additional molecular components so that higher level cocrystals are produced. We report six quaternary cocrystals here. All are obtained as nearly exclusive crystallization products when four appropriate solid compounds are taken together in solution for crystallization.

Photocatalytic degradation of herbicide bentazone in aqueous suspension of TiO2: mineralization, identification of intermediates and reaction pathways.

Semiconductor-mediated hydrogen peroxide-assisted photocatalytic degradation of a selected herbicide, Bentazone (1) has been investigated in aqueous suspensions of TiO2 under a variety of conditions. The degradation was studied by monitoring the depletion in total organic carbon content as a function of irradiation time. The degradation kinetics was investigated under different conditions such as type of TiO2 (Anatase/Anatase-Rutile mixture), reaction pH, catalyst dosage and hydrogen peroxide (H202) concentration. The degradation rates were found to be strongly influenced by all the above parameters. Titanium dioxide Degussa P25 was found to be more efficient as compared with other two commercially available TiO2 powders like Hombikat UV100 and PC500 from Millennium Inorganic Chemicals. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of the irradiated mixture of Bentazone (1) indicates the formation of several intermediate products which have been characterized on the basis of molecular ion/mass fragmentation pattern and also on comparison with the National Institute of Standards and Technology (NIST) library. Plausible mechanism for the formation of different products during photocatalytic treatment of Bentazone in the presence of TiO2 has been proposed. The use of H202 substantially increased the efficiency of TiO2 photocatalytic degradation.

Photocatalytic degradation of a widely used insecticide Thiamethoxam in aqueous suspension of TiO2: adsorption, kinetics, product analysis and toxicity assessment.

This paper deals with the study of photocatalyzed degradation of an insecticide, Thiamethoxam in aqueous suspension of TiO2. The adsorption of Thiamethoxam on TiO2 surface under dark conditions was also investigated in order to find out equilibrium adsorption constant. The degradation kinetics was studied using spectrophotometric method under various conditions such as substrate concentration, type of catalyst, catalyst dosage, pH, and in the presence of electron acceptors such as hydrogen peroxide, potassium bromate, and ammonium persulphate under continuous purging of atmospheric oxygen, and the degradation rates were found to be strongly influenced by these parameters. The results manifested that the photocatalysis of Thiamethoxam follows pseudo-first-order kinetics. The toxicity assessments of the irradiated samples were carried out using human erythrocytes as a model system under in vitro conditions. GC-MS study showed the formation of several intermediate products which were characterised based on their molecular mass and mass fragmentation pattern. A probable mechanism for the formation of various products formed during the photocatalytic process of Thiamethoxam was also proposed.

Photoassisted degradation of a herbicide derivative, dinoseb, in aqueous suspension of titania.

The titanium dioxide (TiO(2)) photoassisted degradation of herbicide dinoseb has been examined in aqueous suspensions under UV light irradiation. The degradation kinetics were studied under various conditions such as substrate concentration, type of catalyst, catalyst dosage, pH, and light intensity as well as in presence of electron acceptors such as hydrogen peroxide, potassium bromate, and potassium persulphate under continuous air purging, and the degradation rates were found to be strongly influenced by these parameters. The Degussa P25 was found to be more efficient photocatalyst as compared to other photocatalysts tested. Dinoseb was found to degrade efficiently in acidic pH and all the electron acceptors studied enhanced the degradation rate. The results manifested that the photocatalysis of dinoseb followed pseudo-first-order kinetics. A qualitative study of the degradation products generated during the process was performed by GC-MS, and a degradation mechanism was proposed.