Investigation of Intermolecular Interactions in Molecular crystals containing

The existence of a given compound (organic, inorganic, metal-organic, macromolecule) in multiple phases is of significance in the understanding of structure-property relationships in crystalline compounds. This can arise from changes in molecular conformation or packing features in the crystal lattice. It is proposed to delineate the role and importance of different physical and chemical factors which aid the initial nucleation processes resulting in molecular recognition events and hence formation and growth of the nuclei. These nuclei aggregate together in the subsequent construction of the 3D assembly (utilizing the concept of symmetry) resulting in the formation of the solid. We are interested to evaluate the role of solvent polarity, sound and magnetic field which can influence the formation of polymorphs followed by subsequent characterization, scalability and reproducibility of these forms. These have subsequent implications in the drug industry especially in problems related to patent litigation and hence a complete investigation is deemed necessary.

In situ Cryocrystallography

In situ crystallization of a liquid, the subsequent determination of the molecular and crystal structure and consequently the study of intermolecular interactions is an area of contemporary interest. Most often such studies may allow for the generation of kinetically stable as well as thermodynamically stable crystalline forms. Nussbaumer and Boese first described the in situ cryocrystallization technique [http://www.ohcd-system.com.]. This technique can also be used to investigate phase transitions in cryo crystallized solids (active pharmaceutical ingredients and natural products), and to crystallize low-melting solids, ionic liquids and to generate polymorphs via different annealing procedures in compounds which are liquids at room temperature.

Electron Density Analysis in Molecular Crystals

Experimental Charge density studies from accurate X-ray data has only recently become a widely accepted tool to probe electronic structure and the charge distribution features in molecules that determines its intermolecular interactions. Furthermore one electron properties such as net atomic charges, electric field gradients, dipole moments and electrostatic potential derived from charge density experiments provides invaluable information that can guide the design of molecules for specified interactions. Furthermore, powerful insights into the nature and strength of hydrogen bonding with subsequent quantification in terms of topological parameters like electron density, Laplacian and local energy densities can be obtained. Such studies have been performed on active drug molecules to eludicate the role of electronic factors and understanding structure-drug activity relationships. Chemical carcinogens like poly-aromatic hydrocarbons, nitrosamines, opiates, dopamine (a neurotransmitter), phenothiazines have been studied using charge density analysis. Small biological molecules like nucleotides and steroidal molecules highlight the significance of molecular electrostatic potential as an important experimental parameter. Thus high-resolution X-ray data have been useful for obtaining predictions of chemical reactivity from molecular charge distribution. Recently, this field has caught the attention of inorganic chemists and the concept has been extended to understand structure, bonding and energetic in inorganic and organometallic materials. With this background, we intend to perform charge density analysis on molecules exhibiting biological activity and understand structure-reactivity relationships in materials.

Investigation of Intermolecular Interactions in Molecular crystals containing organic fluorin

The importance of strong and conventional H-bonding interactions has been well realised in the crystallographic literature. However the participation of halogens, particularly organic fluorine has remained controversial. It is of significance to realise the importance of weak intermolecular interactions involving organic fluorine in molecular solids. In this regard, such interactions have to be investigated both in presence and absence of strong H-bond donors and acceptors to delineate the contribution towards the stability of the crystal packing. Fluorine mediated interactions forms, dimeric motifs( hetero and homo- dimers of varying size), chains, chains of dimers utilizing the different symmetry elements to form the crystal. Furturistic studies are designed to understand the role of such weak interactions in different electronic and chemical environments of the fluorine atom.

• Polymorphism in 1-(4-fluorophenyl)-3, 6, 6-trimethyl-2-phenyl-1, 5, 6, 7 - tetrahydro -4H - indol-4-one: A subtle interplay of weak intermolecular interactions. Deepak Chopra, K. Nagarajan, T. N. Guru Row. Cryst Growth & Des, 2005, 5(3), 1035-1039.


• Pointers towards the occurrence of C-F…F-C interaction: Experimental charge density analysis of 1-(4-fluorophenyl)-3, 6, 6-trimethyl-2-phenyl-1, 5, 6, 7 – tetrahydro - 4H - indol-4-one and 1-(4-fluorophenyl)-6-methoxy-2-phenyl-1, 2, 3, 4-tetrahydroisoquinoline. Deepak Chopra, T. S. Cameron, R. D. Ferrara, T. N. Guru Row. J. Phys. Chem A., 2006, 110(35), 10465 – 10477.


• Insitu Cryo crystallography: Pathways to Study Intermolecular Interactions. Deepak Chopra, T. N. Guru Row. J. Ind. Inst. Sci., (Review), 2007, 87(2), 167-211.


• Evaluation of the interchangeability of C–H and C–F groups: insights from crystal packing in a series of isomeric fluorinated benzanilides*Deepak Chopra and T. N. Guru Row. CrystEngComm, 2008, 10, 54-67.*: Cited as the "Top Accessed Papers of 2008" in Royal Society of Chemistry. [http://www.rsc.org/Publishing/fusion/2009/Issue1/topaccessed.asp]


• 17α-Estradiol·1/2 H2O: Super-Structural Ordering, Electronic Properties, Chemical Bonding, and Biological Activity in Comparison with Other Estrogens. E. A. Zhurova, V. V. Zhurov, Deepak Chopra, A. I. Stash and A. A Pinkerton. J. Am. Chem. Soc., 2009, 131, 17260–17269.


• Chemical Bonding and Structure−Reactivity Correlation in Meldrum’s Acid: A Combined Experimental and Theoretical Electron Density Study. Deepak Chopra, V. V. Zhurov, E. A. Zhurova and A. A. Pinkerton. J. Org. Chem., 2009, 74, 2389–2395.


• Effect of substitution on molecular conformation and packing features in a series of aryl substituted ethyl-6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5- carboxylates. S. K. Nayak, K. N. Venugopala, Deepak Chopra, Vasu, T. N. Guru Row. CrystEngComm., 2010, 12, 1205 – 1216.


• Insights into conformational and packing features in a series of aryl substituted ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates. S. K. Nayak, K. N. Venugopala, Deepak Chopra, T. N. Guru Row. CrystEngComm., 2011, 13, 591-605.


• Role of Hetero-Halogen (F…X, X = Cl, Br, and I) or Homo-Halogen (X…X, X = F, Cl, Br, and I) Interactions in Substituted Benzanilides. Susanta K. Nayak, M. Kishore Reddy, Tayur. N. Guru Row, Deepak Chopra. Cryst. Growth. Des., 2011, 11, 1578-1596.


• Role of Organic Fluorine in Crystal Engineering. Deepak Chopra, T. N. Guru Row. CrystEngComm (Highlight), 2011, 13, 2175-2186. [The Highlight has been selected as a CrystEngComm Hot Article: [//blogs.rsc.org/ce/2011/02/23/highlight-organic-fluorine-in-crystal-engineering/].


• "Is Organic Fluorine really "not" Polarizable?" Deepak Chopra*, Cryst. Growth & Design. 2012, 12, 541 – 546. Disorder in mixed halogen containing benzanilides. Susanta K. Nayak, M. Kishore Reddy, Tayur. N. Guru Row*, Deepak Chopra*. CrystEngComm, 2012, 14, 200 – 210.


• Role of intermolecular interactions involving organic fluorine in trifluoromethylated benzanilides. Piyush Panini & Deepak Chopra*, CrystEngComm. 2012, 14, 1972 – 1989. [Cited as Hot Article in CEC: http://blogs.rsc.org/ce/category/hot-article/].

Group Homepage