C. Malla Reddy

Bio: C. Malla Reddy is an academic researcher from Indian Institute of Science. The author has contributed to research in topics: Crystal structure & Amide. The author has an hindex of 33, co-authored 97 publications receiving 4350 citations. Previous affiliations of C. Malla Reddy include Indian Institute of Science Education and Research, Kolkata & University of Hyderabad.

Polymorphs, Salts, and Cocrystals: What’s in a Name?

Abstract: The December 2011 release of a draft United States Food and Drug Administration (FDA) guidance concerning regulatory classification of pharmaceutical cocrystals of active pharmaceutical ingredients (APIs) addressed two matters of topical interest to the crystal engineering and pharmaceutical science communities: (1) a proposed definition of cocrystals; (2) a proposed classification of pharmaceutical cocrystals as dissociable “API-excipient” molecular complexes. The Indo–U.S. Bilateral Meeting sponsored by the Indo–U.S. Science and Technology Forum titled The Evolving Role of Solid State Chemistry in Pharmaceutical Science was held in Manesar near Delhi, India, from February 2–4, 2012. A session of the meeting was devoted to discussion of the FDA guidance draft. The debate generated strong consensus on the need to define cocrystals more broadly and to classify them like salts. It was also concluded that the diversity of API crystal forms makes it difficult to classify solid forms into three categories that...

Isostructurality, Polymorphism and Mechanical Properties of Some Hexahalogenated Benzenes: The Nature of Halogen⋅⋅⋅Halogen Interactions

Abstract: The nature of intermolecular interactions between halogen atoms, X···X (X=C1, Br, I), continues to be of topical interest because these interactions may be used as design elements in crystal engineering. Hexahalogenated benzenes (C 6 Cl 6-n Br n , C 6 Cl 6-n I n , C 6 Br 6-n I n ) crystallise in two main packing modes, which take the monoclinic space group P2 1/n and the triclinic space group P1. The former, which is isostructural to C 6 Cl 6 , is more common. For molecules that lack inversion symmetry, adoption of this monoclinic structure would necessarily lead to crystallographic disorder. In C 6 Cl 6 , the planar molecules form Cl...Cl contacts and also π···π stacking interactions. When crystals of C 6 Cl 6 are compressed mechanically along their needle length, that is, [010], a bending deformation takes place, because of the stronger interactions in the stacking direction. Further compression propagates consecutively in a snakelike motion through the crystal, similar to what has been suggested for the motion of dislocations. The bending of C 6 Cl 6 crystals is related to the weakness of the Cl···Cl interactions compared with the stronger π···π stacking interactions. The triclinic packing is less common and is restricted to molecules that have a symmetrical (1,3,5- and 2,4,6-) halogen substitution pattern. This packing type is characterised by specific, polarisation-induced X···X interactions that result in threefold-symmetrical X 3 synthons, especially when X=I; this leads to a layered pseudohexagonal structure in which successive planar layers are inversion related and stacked so that bumps in one layer fit into the hollows of the next in a space-filling manner. The triclinic crystals shear on application of a mechanical stress only along the plane of deformation. This shearing arises from the sliding of layers against one another. Nonspecificity of the weak interlayer interactions here is demonstrated by the structure of twinned crystals of these compounds. One of the compounds studied (1,3,5-tribromo-2,4,6-triiodobenzene) is dimorphic, adopting both the monoclinic and triclinic structures, and the reasons for polymorphism are suggested. To summarise, both chemical and geometrical models need to be considered for X···X interactions in hexahalogenated benzenes. The X···X interactions in the monoclinic group are nonspecific, whereas in the triclinic group some X···X interactions are anisotropic, chemically specific and crystal-structure directing.

Elastic and bendable caffeine cocrystals: implications for the design of flexible organic materials.

Abstract: Molecular crystals are among the most ancient and highly investigated materials in chemistry. However, mechanical properties of these materials have remained relatively unexplored despite their unique applications in optoelectronics, mechanical actuators, artificial muscles, pharmaceuticals, and explosives. Conserving the orientational order of molecules and bonds is important for efficient charge transport and for the lifetime of organic light-emitting diodes, transistors, and solar cells. Hence, the realization of high-performance materials with excellent self-healing capabilities or efficient stress dissipating behaviors is attractive. For this reason, the remarkable properties displayed by natural fibres such as spider silk, muscle protein titin, cytoskeleton microtubules, etc. have recently sparked tremendous interest in establishing a reliable structure–property correlation to guide the design of their mimics for various applications. A good starting point for achieving such a goal is to study much simpler and easy-to-characterize organic crystals, which selfassemble through the same noncovalent interactions. It remains a challenge to simultaneously achieve both flexibility and crystallinity in organic materials because crystallinity positively correlates with brittleness. For example, compared to highly ordered molecular crystals, liquid crystals show greater flexibility, but are less crystalline. Desiraju and co-workers showed irreversible mechanical bending in organic crystals as mediated by the movement of molecular sheets through weak interactions between them. The plastic deformation disrupts the long-range order permanently. It was also shown that reversible molecular movements in organic crystals (e.g., in photomechanical bending), can perform work in devices. Herein we report a remarkably flexible, elastically bendable cocrystal solvate 1, formed from caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB), and methanol in a 1:1:< 1 ratio (Figure 1). The cocrystal solvate 1 retains a high internal order through an efficient stress dissipation mechanism, and hence is important in the context of crystal engineering and for the design of flexible organic materials. The single crystals of 1 could be obtained from a 1:1 molar solution of CAF and CNB in methanol by using a slow evaporation method (Figure 1). H NMR and thermogravimetric (TG) analyses have confirmed the presence of CAF, CNB, and methanol molecules in a 1:1:< 1 ratio within the lattice (see Figures S1 and S2 in the Supporting Information). The typically long needle crystals of 1 grow along the a axis (Figure 1 and Figure S4). When a straight crystal, having about a 0.1 mm thickness and 5 mm length, was pushed with a metal pin while being held with a pair of forceps (tweezers) from the opposite end, it transformed into a bent shape without breaking (Figure 2a–d and Figure S5). Further, it could be made into a loop by joining the two ends with a smooth curve (see Videos S1–S3 in the Supporting Information). Upon withdrawal of the force, the crystal quickly Figure 1. Single-crystal preparation of the cocrystal solvate 1 from a methanol solution of caffeine and 4-chloro-3-nitrobenzoic acid.

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

Abstract: ConspectusMechanical 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...

Spatially resolved analysis of short-range structure perturbations in a plastically bent molecular crystal

Abstract: The exceptional mechanical flexibility observed with certain organic crystals defies the common perception of single crystals as brittle objects. Here, we describe the morphostructural consequences of plastic deformation in crystals of hexachlorobenzene that can be bent mechanically at multiple locations to 360° with retention of macroscopic integrity. This extraordinary plasticity proceeds by segregation of the bent section into flexible layers that slide on top of each other, thereby generating domains with slightly different lattice orientations. Microscopic, spectroscopic and diffraction analyses of the bent crystal showed that the preservation of crystal integrity when stress is applied on the (001) face requires sliding of layers by breaking and re-formation of halogen-halogen interactions. Application of stress on the (100) face, in the direction where π···π interactions dominate the packing, leads to immediate crystal disintegration. Within a broader perspective, this study highlights the yet unrecognized extraordinary malleability of molecular crystals with strongly anisotropic supramolecular interactions.

Fast parallel algorithms for short-range molecular dynamics

Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

The Halogen Bond

Abstract: The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design.

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Abstract: : The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Crystal engineering: from molecule to crystal.

Abstract: How do molecules aggregate in solution, and how do these aggregates consolidate themselves in crystals? What is the relationship between the structure of a molecule and the structure of the crystal it forms? Why do some molecules adopt more than one crystal structure? Why do some crystal structures contain solvent? How does one design a crystal structure with a specified topology of molecules, or a specified coordination of molecules and/or ions, or with a specified property? What are the relationships between crystal structures and properties for molecular crystals? These are some of the questions that are being addressed today by the crystal engineering community, a group that draws from the larger communities of organic, inorganic, and physical chemists, crystallographers, and solid state scientists. This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design. It also provides a look to the future from the viewpoint of the author, and indicates some directions in which this field might be moving.