Keisham Sarjit Singh

Ruthenium(II)-catalyzed synthesis of pyrrole- and indole-fused isocoumarins by C-H bond activation in DMF and water

Pyrrole‐ and indole‐fused isocoumarins constitute important structural units in natural products and pharmacophores, although the direct and selective bifunctionalization of pyrrole and indole remain a challenge. Herein, we report a one‐pot synthesis of pyrrole‐ and indole‐fused isocoumarins from simple 1‐methylpyrrole‐2‐carboxylic acid and 1‐methylindole‐3‐carboxylic acid by annulation with alkynes in the presence of a ruthenium(II) catalyst based on [RuCl2(p‐cymene)]2 with Cu(OAc)2⋅H2O as the oxidant in DMF. This ruthenium(II)‐catalyzed transformation was shown to be profitably performed in water as the solvent. The reaction, which involves carboxylate coordination, activation of the heterocyclic sp2 C−H bond, and insertion of the alkyne, is regioselective, which leads to good yields of the isocoumarins.

Iridium (III) and rhodium (III) triazoles by 1,3-dipolar cycloadditons to a coordinated azide in iridium (III) and rhodium (III) compounds

The reaction of [(η5-C5Me5)M(μCl)Cl]2 with the ligand (L∩L) in the presence of sodium methoxide yielded compounds of general formula [(η5-C5Me5)M(L∩L)Cl] (1–10) (where M = Ir or Rh and L∩L = N∩O or O∩O chelate ligands). Azido complexes of formulation [(η5-C5Me5)M(L∩L)N3] (11–20) have been prepared by the reaction of [(η5-C5Me5)M(μN3)(X)]2 (X = Cl or N3) with the corresponding ligands or by the direct reaction of [(η5-C5Me5)M(L∩L)Cl] with NaN3. These azido complexes [(η5-C5Me5)M(L∩L)N3] undergo 1,3-dipolar cycloaddition reaction with substituted alkynes in CH2Cl2 and for the first time in ethanol at room temperature to yield iridium (III) and rhodium (III) triazoles (21–28). The compounds were characterized on the basis of spectroscopic data, and the molecular structures of 2 and 26 have been established by single crystal X-ray diffraction. Graphical Abstract Azido complexes of general formula [(η5-C5Me5)M(L∩L)N3] have been prepared by the reaction of [(η5-C5Me5)M(µN3)(X)]2 (M = Ir or Rh and X = Cl or N3) with the corresponding ligands or by the direct reaction of [{(η5-C5Me5)M(L∩L)Cl}] with NaN3 (L∩L = N∩O or O∩O chelate ligands). The azido complexes [(η5-C5Me5)M(L∩L)N3] undergo 1,3-dipolar cycloaddition reaction with substituted alkynes in CH2Cl2 and ethanol at room temperature giving iridium (III) or rhodium (III) triazoles [(η5-C5Me5)M (L∩L){N3C2(CO2R)2}].

Vibrational Spectroscopy for Structural Characterization of Bioactive Compounds

Abstract Vibrational spectroscopy is a widely used analytical technique that requires a short analysis time, less sample quantity, and provides nondestructive and situ analysis of biological samples. Infrared and Raman spectroscopies have been used for the characterization of organic and inorganic compounds as well as natural products including macromolecules such as polysaccharides, proteins, and highly insoluble melanin pigments. Although the techniques give less precise structural information, they are widely used for fast, nondestructive, and green analysis, which is not possible with the other complementary techniques such as NMR and mass spectroscopies. The technique coupled with NMR and mass can provide a strong platform for natural product analysis. This chapter presents the basic concepts of infrared and Raman spectroscopies and their application to the structure characterization of compounds such as polysaccharides, alkaloids, terpenes, flavonoids, sterols, sideorophores, and insoluble melanin pigments isolated from marine organisms.

Synthesis and electronic properties of ester substituted 1,4-dicyanodibenzodioxins and evaluation of anti-proliferative activity of all isomeric 1,2-, 2,3- and 1,4-dicyanodibenzodioxins against HeLa cell line

1,4-Dicyanodibenzodioxins bearing carboxy methyl ester groups were synthesized using our established one-step SNAr coupling reaction between ortho- and meta-ester substituted catechols and perfluorinated terephthalonitrile. These are the first examples of 1,4-dicyanodibenzodioxins substituted at both the benzene moieties. Optical spectra were similar to the earlier examples reported, with a marginal blue shift for the ester dibenzodioxins. Theoretical analysis of the molecular orbitals reveals modest destabilization of the frontier molecular orbitals of one carboxy methyl ester isomer over the other and overall higher HOMO-LUMO gap for both isomers when compared to the earlier published 1,4-dicyanodibenzodioxins. In vitro cytotoxicity against human cervical cancer HeLa cell line was evaluated for these two compounds and all other previously published dibenzodioxins from our laboratory (1,4-dicyano, 1,2-dicyano and 2,3-dicyano variants). A number of derivatives showed anti-tumor activity in μM ranges and also exhibited no cytotoxicity against normal HEK 293 cell line. Mechanistic investigation of cell death pathways indicated high levels of reactive oxygen species (ROS) in the dibenzodioxin treated tumor cell lines along with cellular nuclear fragmentation, both of which are markers of the apoptotic cell death pathway.

Iridium(III) and Rhodium(III) compounds of dipyridyl-N-alkylimine and dipyridyl-NH-ketimine: Spectral characterization and crystal structure

AbstractPentamethylcyclopentadienyl iridium(III) and rhodium(III) complexes of formulation [(η5-C 5Me 5)M{(C 5H4N) 2C=NR)}Cl]PF 6 were prepared by the reaction of [MCl 2(η5-C 5Me 5)] 2(M = Ir or Rh) with dipyridyl-N-alkylimine ligands, (C 5H4N) 2C=NR (R = Me or Et) in the presence of NH 4PF6 at room temperature. The reaction also produced an unexpected dipyridyl-NH-ketimine organometallic compound [(η5-C 5Me 5)M {(C 5H4N) 2C=NH}Cl]PF 6 as minor product when the reaction was performed under refluxing acetonitrile. The NH-ketimine compounds were formed via N-C single bond cleavage of imine ligand resulting in coordination of the transformed ligand, (C 5H4N) 2C=NH to the metal centre. Complexes were obtained as their hexafluorophosphate salts and characterized based on IR, NMR and ESI-MS spectroscopic data. Authenticity of NH-ketimine organometallic compound was established by single crystal X-ray analysis of a representative compound, which crystallized in orthorhombic space group Pbcn and has a pseudo-octahedral geometry around the metal ion. Graphical AbstractPentamethylcyclopentadienyl iridium(III) and rhodium(III) complexes containing dipyridyl-N-alkylimine and dipyridyl-NH-ketimine ligands of formulation [(η5-C5Me5)M{(C5H4N)2C=NR}Cl]PF6 and [(η5-C5Me5)M{(C5H4N)2C=NH}Cl]PF6 were synthesized and characterized on the basis of spectroscopic data. Solid state structure of one representative NH-ketimine compound [6]PF6 has been determined by X-ray crystallography

Mass Spectrometry for Determination of Bioactive Compounds

Abstract Mass spectrometry (MS) has emerged as an invaluable technique with a wide array of applications ranging from forensic, proteomic, and metabolomic to clinical studies. With the development of different ionization techniques and mass analyzers, even challenging samples can be analyzed, thereby making mass spectrometry an important analytical tool in the field of characterization of bioactive molecules ranging from small metabolites to large macromolecular assemblies. MS is the only technique that offers the combination of high sensitivity with structural information. This chapter demonstrates the application of MS in the determination of different classes of bioactive compounds with a special emphasis on peptides, alkaloids, and lipids. A case study has been demonstrated for each class of compounds that might be helpful for early learners in the field of mass spectrometry. This also shall be of interest to the biochemical, biomedical, and pharmaceutical communities, and those working in other branches of analytical bioscience.