Ritesh Dubey

Intermolecular atom–atom bonds in crystals – a chemical perspective

Short atom–atom distances between molecules are almost always indicative of specific intermolecular bonding. These distances may be used to assess the significance of all hydrogen bonds, including the C–H⋯O and even weaker C–H⋯F varieties.

Extending the Supramolecular Synthon Based Fragment Approach (SBFA) for Transferability of Multipole Charge Density Parameters to Monofluorobenzoic Acids and their Cocrystals with Isonicotinamide: Importance of C–H···O, C–H···F, and F···F Intermolecular Regions

An extension of the supramolecular synthon-based fragment approach (SBFA) method for transferability of multipole charge density parameters to include weak supramolecular synthons is proposed. In particular, the SBFA method is applied to C-H···O, C-H···F, and F···F containing synthons. A high resolution charge density study has been performed on 4-fluorobenzoic acid to build a synthon library for C-H···F infinite chain interactions. Libraries for C-H···O and F···F synthons were taken from earlier work. The SBFA methodology was applied successfully to 2- and 3-fluorobenzoic acids, data sets for which were collected in a routine manner at 100 K, and the modularity of the synthons was demonstrated. Cocrystals of isonicotinamide with all three fluorobenzoic acids were also studied with the SBFA method. The topological analysis of inter- and intramolecular interaction regions was performed using Baders AIM approach. This study shows that the SBFA method is generally applicable to generate charge density maps using information from multiple intermolecular regions.

Crystal Structure and Prediction

The notion of structure is central to the subject of chemistry. This review traces the development of the idea of crystal structure since the time when a crystal structure could be determined from a three-dimensional diffraction pattern and assesses the feasibility of computationally predicting an unknown crystal structure of a given molecule. Crystal structure prediction is of considerable fundamental and applied importance, and its successful execution is by no means a solved problem. The ease of crystal structure determination today has resulted in the availability of large numbers of crystal structures of higher-energy polymorphs and pseudopolymorphs. These structural libraries lead to the concept of a crystal structure landscape. A crystal structure of a compound may accordingly be taken as a data point in such a landscape.

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

A logic driven synthetic approach is used in this first report of the isolation of stoichiometric four-component molecular solids. A possible extension to a five-component solid is also described.

Crystal landscape in the orcinol:4,4′-bipyridine system: synthon modularity, polymorphism and transferability of multipole charge density parameters

The role of the supramolecular synthon as the operational structural unit in the late stages of the crystallization event is highlighted with reference to polymorphs and pseudopolymorphs in the orcinol–bipyridine cocrystal system.

Combinatorial Crystal Synthesis: Structural Landscape of Phloroglucinol:1,2‐bis(4‐pyridyl)ethylene and Phloroglucinol:Phenazine

A large number of crystal forms, polymorphs and pseudopolymorphs, have been isolated in the phloroglucinol-dipyridylethylene (PGL:DPE) and phloroglucinol-phenazine (PGL:PHE) systems. An understanding of the intermolecular interactions and synthon preferences in these binary systems enables one to design a ternary molecular solid that consists of PGL, PHE, and DPE, and also others where DPE is replaced by other heterocycles. Clean isolation of these ternary cocrystals demonstrates synthon amplification during crystallization. These results point to the lesser likelihood of polymorphism in multicomponent crystals compared to single-component crystals. The appearance of several crystal forms during crystallization of a multicomponent system can be viewed as combinatorial crystal synthesis with synthon selection from a solution library. The resulting polymorphs and pseudopolymorphs that are obtained constitute a crystal structure landscape.

Combinatorial selection of molecular conformations and supramolecular synthons in quercetin cocrystal landscapes: a route to ternary solids

Crucial ‘purification’ steps inherent to the ‘selection’ of particular molecular conformations and supramolecular synthons in solution leads to a successful synthetic strategy for ternary solids, a normally difficult exercise in crystal engineering. This work also suggests a parallel between such strategies and combinatorial chemistry.

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

A combinatorial synthetic approach is described for the isolation of quaternary cocrystals. The strategy outlines chemical and geometrical modulations in the long-range synthon Aufbau modules (LSAMs) to systematically increase the number of components.

Combinatorial crystal synthesis of ternary solids based on 2-methylresorcinol

Cocrystallization experiments of 2-methylresorcinol with several N-bases were performed to identify selective and preferred crystallization routes in relevant structural landscapes. These preferred supramolecular synthon-based crystallization routes were further enhanced by using carefully chosen coformer combinations to synthesize stoichiometric ternary solids. The exercise consists of modular selection and amplification of supramolecular synthons from single through two- to three-component molecular solids, and is equivalent to solid state combinatorial synthesis.

Crystal engineering and the design of higher co-crystals

Crystallization is an ancient method of purification based on a phenomenon that excludes rather than includes. Thus, the synthesis of multi-component crystals is a challenging task and their isolation is often unpredictable. Obtaining a multicomponent crystal means that one is able to calibrate and assess intermolecular interactions rather carefully. The scope of crystal engineering is now well explored towards the designing of crystalline binary cocrystals. However, increasing the number of components in a cocrystal is a crystal engineering equivalent of synthetic complexity. Cocrystallization of a mixture of four compounds could, in principle, give not only binaries but also a number of ternaries. Ultimately, it would appear that the level and degree of control to design a quaternary cocrystal is formidable. This presentation will highlight the fact that through crystal engineering principles, we can design the fourand even higher-component molecular crystals. A concise synthetic strategy has been applied to increase the number of components in a crystal from one to two, to three, to four and eventually to five. Ten stoichiometric quaternary cocrystals and also one quintinary cocrystal having partial evidence of solid solution are designed. The strategy is based on the exploitation of the different environments of any particular component in a cocrystal.