Ramababu Bolligarla

Design, synthesis, and discovery of novel non-peptide inhibitor of Caspase-3 using ligand based and structure based virtual screening approach

Caspase-3 belonging to a family of cysteine proteases is main executioner of apoptotic cascade pathway. The inhibitors of this protein are useful in the treatment of cardiomyopathy and neurodegenerative diseases. For the discovery of novel Caspase-3 non-peptide inhibitors from Maybridge database, ligand based and structure based virtual screening methods were used. Quantitative 3D pharmacophore models were generated using 25 known inhibitors of Caspase-3 and it was used as initial screen to retrieve the hits from the database. These compounds with high estimated activity were analyzed for drug like properties and docking studies were performed, to study the interaction between new hits and active site. One of the hits (AW01208), with good predictions was selected for synthesis and biological screening. This compound showed an inhibition activity against Caspase-3 in SKNH cell lines.

Influence of the substituents on the electronic and electrochemical properties of a new square-planar nickel-bis(quinoxaline-6,7-dithiolate) system: synthesis, spectroscopy, electrochemistry, crystallography, and theoretical investigation.

We describe the synthesis, crystal structures, electronic absorption spectra, and electrochemistry of a series of square-planar nickel-bis(quinoxaline-6,7-dithiolate) complexes with the general formula [Bu(4)N](2)[Ni(X(2)6,7-qdt)(2)], where X = H (1a), Ph (2a), Cl (3), and Me (4). The solution and solid-state electronic absorption spectral behavior and electrochemical properties of these compounds are strongly dependent on the electron donating/accepting nature of the substituent X, attached to the quinoxaline-6,7-dithiolate ring in the system [Bu(4)N](2)[Ni(X(2)6,7-qdt)(2)]. Particularly, the charge transfer (CT) transition bands observed in the visible region are greatly affected by the electronic nature of the substituent. A possible explanation for this influence of the substituents on electronic absorption and electrochemistry is described based on highest occupied molecular orbital (HOMO) to lowest unoccupied molecular orbital (LUMO) gaps, which is further supported by ground-state electronic structure calculations. In addition to this, the observed CT bands in all the complexes are sensitive to the solvent polarity. Interestingly, compounds 1a, 2a, 3, and 4 undergo reversible oxidation at very low oxidation potentials appearing at E(1/2) = +0.12 V, 0.033 V, 0.18 V, and 0.044 V vs Ag/AgCl, respectively, in MeOH solutions, corresponding to the respective couples [Ni(X(2)6,7-qdt)(2)](-)/[Ni(X(2)6,7-qdt)(2)](2-). Compounds 1a, 3, and 4 have been characterized unambiguously by single crystal X-ray structural analysis; compound 2a could not be characterized by single crystal X-ray structure determination because of the poor quality of the concerned crystals. Thus, we have synthesized the tetraphenyl phosphonium salt of the complex anion of 2a, [PPh(4)](2)[Ni(Ph(2)6,7-qdt)(2)]·3DMF (2b) for its structural characterization.

Dimensionality of coordination polymers decided by the type of hybridization of the central carbon atom of the solvent molecule that coordinates to an alkali metal cation: from discrete to 3D networks based on a gold(III) bis(dithiolene) complex

The solvent coordination with sodium metal ions leads to the formation of coordination polymers from discrete to 3D networks based on a gold bis(dithiolene) complex {[AuIII(btdt)2]−} (btdt = 2,1,3-benzenethiadiazole-5,6-dithilolate); all these complexes show great discrepancy in dimensionality of the self assembled coordinated networks due to the effect of solvents, which we have explained in terms of the difference in geometry of the hybridized orbitals of the central carbon attached to the coordinating atom (N or O in the present study).

New Square-Planar Bis(Dithiolene) Complexes: Synthesis, Crystallography, and Properties of [Bu4N][MIII(btdt)2] (M = Cu, Au) and [Bu4N]2[PtII(btdt)2] ({btdt}2– =2,1,3-Benzenethiadiazole-5,6-dithiolate)

The syntheses, crystal structures, and properties of three new coordination complexes [Bu4N][MIII(btdt)2] [M = Cu (1), Au (2)] and [Bu4N]2[PtII(btdt)2] (3) ({btdt}2– = 2,1,3-benzenethiadiazole-5,6-dithiolate) are described. Compounds 1–3 crystallize in a triclinic P-1, and monoclinic P2(1)/c and C2/c space groups, respectively. The {MS4} chromophore lies in almost a square-planar coordination environment in complex 1, but has a slightly distorted square-planar geometry around the central metal ion in compounds 2 and 3. Interactions in the solid state have been studied by intermolecular contacts, in particular, compounds 2 and 3 have been characterized by SN and SS non-covalent interactions among dithiolate complexes, resulting in two- and one-dimensional supramolecular motifs, respectively. Complexes 1–3 show broad absorption bands in the visible region, with that of 3 being sensitive to solvent polarity. Complex 1 exhibits a very low reduction potential for a CuIII-coordination complex, while the PtII complex 3 shows two irreversible oxidative responses at 0.45 V and 0.74 V versus Ag/AgCl, respectively.

6,7,6′,7′-Tetra­phenyl-2,2′-bi[1,3-dithia-5,8-diaza­cyclo­penta­[b]naphthalenyl­idene] chloro­form disolvate

The title compound, C42H24N4S4·2CHCl3, a symmetrical tetrathiafulvalene (TTF) derivative, was prepared by a triethylphosphite-mediated self-coupling reaction of 6,7-diphenyl-1,3-dithia-5,8-diazacyclopenta[b]napthalen-2-one. The asymmetric unit contains two TTF molecules and four chloroform solvent molecules. Cl⋯Cl interactions [contact distances = 3.263 (1)–3.395 (2) Å] are present between the solvent molecules, resulting in a tape along the bc plane. The crystal packing features weak C—H⋯Cl and C—H⋯N hydrogen bonds, resulting in the formation of a two-dimensional supramolecular network.