Nigam P. Rath
University of Missouri–St. Louis
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Featured researches published by Nigam P. Rath.
Journal of the American Chemical Society | 2012
Anuj Kumar Sharma; Stephanie T. Pavlova; Jaekwang Kim; Darren Finkelstein; Nicholas J. Hawco; Nigam P. Rath; Jungsu Kim; Liviu M. Mirica
Abnormal interactions of Cu and Zn ions with the amyloid β (Aβ) peptide are proposed to play an important role in the pathogenesis of Alzheimers disease (AD). Disruption of these metal-peptide interactions using chemical agents holds considerable promise as a therapeutic strategy to combat this incurable disease. Reported herein are two bifunctional compounds (BFCs) L1 and L2 that contain both amyloid-binding and metal-chelating molecular motifs. Both L1 and L2 exhibit high stability constants for Cu(2+) and Zn(2+) and thus are good chelators for these metal ions. In addition, L1 and L2 show strong affinity toward Aβ species. Both compounds are efficient inhibitors of the metal-mediated aggregation of the Aβ(42) peptide and promote disaggregation of amyloid fibrils, as observed by ThT fluorescence, native gel electrophoresis/Western blotting, and transmission electron microscopy (TEM). Interestingly, the formation of soluble Aβ(42) oligomers in the presence of metal ions and BFCs leads to an increased cellular toxicity. These results suggest that for the Aβ(42) peptide-in contrast to the Aβ(40) peptide-the previously employed strategy of inhibiting Aβ aggregation and promoting amyloid fibril dissagregation may not be optimal for the development of potential AD therapeutics, due to formation of neurotoxic soluble Aβ(42) oligomers.
Chemical Communications | 2008
F. Christopher Pigge; Venu R. Vangala; Pradeep P. Kapadia; Dale C. Swenson; Nigam P. Rath
Bifurcated Ipi and IO[double bond, length as m-dash]C halogen bonding interactions assist in formation of unique iodo-arene trimers leading to nanoscale channels in inclusion complexes of trimesic acid iodophenolate.
Tetrahedron | 1999
Vijay Nair; K. V. Radhakrishnan; K. C. Sheela; Nigam P. Rath
Abstract Di- and tri-substituted o-benzoquinones on reaction with nitrile N-oxides afforded novel mono spirodioxazole derivatives. The reaction of monosubstituted o-benzoquinones with stable nitrile oxides resulted in the formation of bis adducts.
Journal of the American Chemical Society | 2011
Saeedeh Negin; Megan M. Daschbach; Oleg V. Kulikov; Nigam P. Rath; George W. Gokel
Pyrogallolarenes are tetrameric macrocycles that form from 1,2,3-trihydroxybenzene and aldehydes under acidic conditions. When 2-ethylbutanal or 2-propylpentanal was so treated, the branched-chain pyrogallolarenes crystallized as nanotubes or bilayers, respectively. When the behavior of each compound was assessed by using the planar bilayer conductance method, pore formation was observed. The properties of the pores were significantly different from each other, probably reflecting different types of pore organization within the membrane.
CrystEngComm | 2008
Christina E. Costin-Hogan; Chun-Long Chen; Emma Hughes; Austin Pickett; Richard Valencia; Nigam P. Rath; Alicia M. Beatty
Crystal structures having distinct structural motifs (0-D, 1-D, 2-D), are reported—the results of reactions of ortho-substituted phenylamines with cadmium halide salts. The aim of the study was to control the size and dimensionality of Cd(II) halide assemblies by changing the steric demands of the ortho substituents. The ultimate goal of the research is to synthesize cadmium halide clusters using rational and predictable methods. To this end, the synthesis and crystal structure of a new Cd3Cl126−cluster are also reported.
Inorganic Chemistry | 2014
Anuj Kumar Sharma; Jaekwang Kim; John T. Prior; Nicholas J. Hawco; Nigam P. Rath; Jungsu Kim; Liviu M. Mirica
Multifunctional metal chelators that can modulate the amyloid β (Aβ) peptide aggregation and its interaction with metal ions such as copper and zinc hold considerable promise as therapeutic agents for Alzheimer’s disease (AD). However, specific rather than systemic metal chelation by these compounds is needed in order to limit any side effects. Reported herein are two novel small bifunctional chelators, 2-[2-hydroxy-4-(diethylamino)phenyl]benzothiazole (L1) and 2-(2-hydroxy-3-methoxyphenyl)benzothiazole (L2), in which the metal-binding donor atoms are integrated within a molecular framework derived from the amyloid-binding fluorescent dye thioflavin T (ThT). The metal-binding properties of L1 and L2 were probed by pH spectrophotometric titrations to determine their pKa values and the corresponding metal complex stability constants, and the isolated metal complexes were structurally characterized. The amyloid-fibril-binding properties of L1 and L2 were investigated by fluorescence titrations and ThT competition assays. Interestingly, L1 and L2 do not lead to the formation of neurotoxic Aβ42 oligomers in the presence or absence of metal ions, as observed by native gel electrophoresis, Western blotting, and transmission electron microscopy. In addition, L1 and L2 were able to reduce the cell toxicity of preformed Aβ42 oligomers and of the copper-stabilized Aβ42 oligomers. Given their ability to reduce the toxicity of soluble Aβ42 and Cu-Aβ42 species, L1 and L2 are promising lead compounds for the development of chemical agents that can control the neurotoxicity of soluble Aβ42 species in AD.
Inorganica Chimica Acta | 1999
Jonathan Bould; Paul Cooke; Udo Dörfler; John D. Kennedy; Lawrence Barton; Nigam P. Rath; Mark Thornton-Pett
Abstract Reaction of [IrCl(CO)(PMe 3 ) 2 ] with [NEt 4 ][ nido -B 9 H 12 ] gives the ten-vertex eight-boron cluster species [(PMe 3 ) 4 (CO) 2 Ir 2 B 8 H 8 ]. This formally has a closo cluster electron count compatible with its closo structure. By contrast, ten-vertex eight-boron [(PMe 2 Ph) 4 Pd 2 B 8 H 10 ], isolated from [4-(NH 2 Ph)- arachno -B 9 H 13 ] and [PdCl 2 (PMe 2 Ph) 2 ], has a closo electron count but an arachno structure. The origins of this apparent anomaly are briefly addressed and enunciated.
Inorganic Chemistry | 2008
Remle Çelenligil-Çetin; Patrina Paraskevopoulou; Rupam Dinda; Richard J. Staples; Ekkehard Sinn; Nigam P. Rath; Pericles Stavropoulos
Functional systems that combine redox-active metals and noninnocent ligands are no longer rare chemical oddities; they are instead emerging as significant components of catalytic and enzymatic reactions. The present work examines the synthetic and functional aspects of iron compounds ligated by a family of new trisamidoamine ligands of the type [(RNC6H4)3N]3- (L1). When R is the electron-rich 4-t-Bu-Ph moiety, the ligand can undergo oxidative rearrangement and store oxidizing equivalents under specific conditions. Starting ferrous complexes of the general formula [(L1)FeIIsolv]- (solv=CH3CN, dimethylformamide) can be easily oxidized (a) by dioxygen to afford the corresponding [(L1)FeIIIOH]- complexes, featuring several cases of terminal hydroxo units, and (b) by organochlorides (R-Cl) to provide [(L1)FeIIIsolv] congeners and coupled R-R products. Efforts to synthesize [(L1)FeIII-O-FeIII(L1)]2- by using [Cl3FeIII-O-FeIIICl3]2- indicate that intrinsic FeIIICl units can oxidatively rearrange the ligand to afford [(L1re)(Cl)FeII][Et4N]2, although the oxidizing equivalent is not retained. Compound [(L1re)(Cl)FeII][Et4N]2 can be further oxidized to [(L1re-2)(Cl)FeIII][Et4N] by CH2Cl2. Finally, oxidation of [(L1)FeIIIsolv] by FeCl3 affords [(L1reH)(Cl)FeII(micro-Cl)2FeII(Cl)(L1re-2H)], which features a similar ligand rearrangement that also gives rise to a diamagnetic, doubly oxidized moiety. These results underscore the complexity of chemical transformations available to systems in which both the metal and the ligand are redox-active entities.
Tetrahedron Letters | 2000
Vijay Nair; K. C. Sheela; Nigam P. Rath; Guenter K. Eigendorf
Abstract Facile multicomponent reactions involving sarcosine and 1,2-diones such as isatin, acenaphthenequinone and cyclobutene-1,2-dione yielding novel spiropyrrolidine derivatives are described.
Inorganica Chimica Acta | 1997
Robert A. Stockland; Gordon K. Anderson; Nigam P. Rath
Abstract A series of hydride-bridged dipalladium complexes supported by bis(diphenylphosphino) methane (dppm) ligands has been prepared. The complexes [Pd 2 R 2 (μ-H) (μ.-dppm) 2 ] PF 6 (R = Me, Et, Bu, CH 2 SiMe 3 , Ph) were generated by reduction, using NaBH 3 CN, of the corresponding halide-bridged species. The products are thermally stable, yellow solids, and they have been characterized by 1H and 31 P[ 1 H] NMR spectroscopy. The ethyl complex [Pd2Et2(μ-H) (μ-dppm)2]PF 6 has been characterized further by X-ray crystallography. It crystallizes in the monoclinic space group P21 lc with a=10.6160 ( I ), 6=12.8637 (1 ), c=25.3739 (3) A, β=97.479 (1 )° and Z=2. The cation adopts an A-frame structure, with a Pd-Pd distance of 2.9933 (7) A.
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National Institute for Interdisciplinary Science and Technology
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