Crystal Engineering in the Desiraju Research Group in Bangalore

Over the years, crystal engineering has transformed into a mature and multidisciplinary subject. New understanding, challenges, and opportunities have emerged in the design of complex structures and structure-property evaluation. Revolutionary pathways adopted by many leaders have shaped and directed this subject. In this short essay to celebrate the 60th birthday of Prof. Gautam R. Desiraju, we, his current research group members, contemplate the development of some of the topics explored by our group in the context of the overall subject. These topics, though not entirely new, are of significant interest to the crystal engineering community.

A galactose-functionalized dendritic siRNA-nanovector to potentiate hepatitis C inhibition in liver cells

A RNAi based antiviral strategy holds the promise to impede hepatitis C viral (HCV) infection overcoming the problem of emergence of drug resistant variants, usually encountered in the interferon free direct-acting antiviral therapy. Targeted delivery of siRNA helps minimize adverse `off-target' effects and maximize the efficacy of therapeutic response. Herein, we report the delivery of siRNA against the conserved 5'-untranslated region (UTR) of HCV RNA using a liver-targeted dendritic nano-vector functionalized with a galactopyranoside ligand (DG). Physico-chemical characterization revealed finer details of complexation of DG with siRNA, whereas molecular dynamic simulations demonstrated sugar moieties projecting ``out'' in the complex. Preferential delivery of siRNA to the liver was achieved through a highly specific ligand-receptor interaction between dendritic galactose and the asialoglycoprotein receptor. The siRNA-DG complex exhibited perinuclear localization in liver cells and co-localization with viral proteins. The histopathological studies showed the systemic tolerance and biocompatibility of DG. Further, whole body imaging and immunohistochemistry studies confirmed the preferential delivery of the nucleic acid to mice liver. Significant decrease in HCV RNA levels (up to 75%) was achieved in HCV subgenomic replicon and full length HCV-JFH1 infectious cell culture systems. The multidisciplinary approach provides the `proof of concept' for restricted delivery of therapeutic siRNAs using a target oriented dendritic nano-vector.

Archean tectonics and crustal evolution of the Biligiri Rangan Block, southern India

The Southern Granulite Terrain in India is a collage of crustal blocks ranging in age from Archean to Neoproterozoic. This study investigate the tectonic evolution of one of the northernmost block- the Biligiri Block (BRB) through a multidisciplinary approach involving field investigation, petrographic studies, LA-ICPMS zircon U-Pb geochronology, Hf isotopic analyses, metamorphic P-T phase diagram computations, and crustal thickness modeling. The garnet bearing quartzofeldspathic gneiss from the central BRB preserve Mesoarchean magmatic zircons with ages between 3207 and 2806 Ma and positive epsilon Hf value (+2.7) which possibly indicates vestiges of a Mesoarchean primitive continental crust. The occurrence of quartzite-iron formation intercalation as well as ultramafic lenses along the western boundary of the BRB is interpreted to indicate that the Kollegal structural lineament is a possible paleo-suture. Phase diagram computation of a metagabbro from the southwestern periphery of the Kollegal suture zone reveals high-pressure (similar to 18.5 kbar) and medium-temperature (similar to 840 degrees C) metamorphism, likely during eastward subduction of the Western Dharwar oceanic crust beneath the Mesoarchean BRB. In the model presented here, slab subduction, melting and underplating processes generated arc magmatism and subsequent charnockitization within the BRB between ca. 2650 Ma and ca. 2498 Ma. These results thus reveal Meso- to Neoarchean tectonic evolution of the BRB. The spatial variation of crustal thickness, derived from flexure inversion technique, provides additional constraints on the tectonic linkage of the BRB with its surrounding terrains. In conjunction with published data, the Moyar and the Kollegal suture zones are considered to mark the trace of ocean closure along which the Nilgiri and Biligiri Rangan Blocks accreted on to the Western Dharwar Craton. (C) 2016 Elsevier B.V. All rights reserved.