Shahulhameed Sabiah

An efficient synthesis of N-nitrosamines under solvent, metal and acid free conditions using tert-butyl nitrite

Synthesis of various N-nitroso compounds from secondary amines is reported using tert-butyl nitrite (TBN) under solvent free conditions. Broad substrate scope, metal and acid free conditions, easy isolation procedure and excellent yields are few important features of this methodology. The acid labile protecting groups such as tert-butyldimethylsilyl (TBDMS) and tert-butyloxycarbonyl (Boc) as well as sensitive functional groups such as phenols, olefins and alkynes are found to be stable under the standard reaction conditions. Besides N-nitrosation, TBN is also found to be an efficient reagent in few other transformations including aryl hydrazines to aryl azides and primary amides to carboxylic acids under mild conditions.

Bio-based green solvent for the catalyst free oxidation of arylboronic acids into phenols

A bio-based green solvent, lactic acid, is found to be an efficient reaction medium for the catalyst free oxidation of arylboronic acids into phenols with aqueous hydrogen peroxide. Various substituted arylboronic acids have undergone ipso-hydroxylation smoothly at room temperature to provide corresponding phenols in excellent yields. Remarkably, the oxidation susceptible functional groups such as sulphide, ketone, aldehyde and olefin are tolerated under the reaction conditions. Over all, lactic acid showed higher efficiency as a solvent medium when compared with conventional acetic acid.

Mononuclear Cu(II) and Zn(II) complexes with a simple diamine ligand: synthesis, structure, phosphodiester binding and DNA cleavage studies

Two mononuclear complexes, [Cu(dach)2(ClO4)2] 1a and [Zn(dach)2](ClO4)2 2a, with simple 1,2-diaminocyclohexane (dach) ligands were synthesized and characterized by elemental analysis, UV-Vis, EPR and IR spectroscopy. The single crystal XRD of 1a and 2a shows that the metal ion has octahedral and tetrahedral geometry, respectively. Both complexes bind with phosphodiesters such as BNPP (bis(p-nitrophenyl)phosphate) and DPP (diphenylphosphate) and their binding affinity was studied by electronic absorption spectroscopy. Complex 1a binds with DPP with Kb = 23 M−1 and 2a shows Kb = 1.15 × 103 M−1. Both complexes interact with BNPP to result in [Cu(dach)2(BNPP)2] 3, [Zn(dach)2(BNPP)2] 4, respectively. These phosphate adducts were well characterized by different spectroscopic techniques and single crystal XRD. The X-ray structures confirm that complexes 3 and 4 are mononuclear with Cu(II) and Zn(II) in octahedral geometry provided by two bidentate dach ligands and two monodentate O donors from BNPP moieties. The nuclease activity of 1a and 2a with supercoiled plasmid DNA pBR322 was examined by gel electrophoresis, which reveals that complex 1a exhibits a significant DNA cleavage activity via oxidative mechanism whereas the corresponding complex 2a did not cleave the DNA. To understand the stereo chemical influence of the dach ligand on DNA cleavage activity, copper and zinc complexes derived from enantiopure form of dach namely [Cu((R,R)-trans-dach)2(ClO4)2] 1b, [Cu((S,S)-trans-dach)2(ClO4)2] 1c & [Cu(cis-dach)2(ClO4)2] 1d and [Zn((R,R)-trans-dach)2](ClO4)2 2b, [Zn((S,S)-trans-dach)2](ClO4)2 2c & [Zn(cis-dach)2](ClO4)2 2d were also investigated. All the Cu(II) complexes oxidatively cleave pBR322 at 25 µM, out of which complex 1b is remarkable to cleave up to 20% Form II and 80% Form III. The binding affinity of these complexes with CT-DNA (Calf thymus-DNA) was studied by electronic absorption spectroscopy and showed moderate to strong Kb values. Electrochemical analyses, viscosity measurements and circular dichroism (CD) studies were carriedout to understand the mode of binding with CT-DNA. The shift in ΔEp, E1/2 and Ipc values suggest that there is a groove interaction existing between CT-DNA and copper complexes. The groove binding is further supported by viscosity measurements and CD spectra.

A metal free reduction of aryl-N-nitrosamines to the corresponding hydrazines using a sustainable reductant thiourea dioxide

Reduction of aryl-N-nitrosamines to the corresponding hydrazines is reported under metal free conditions using a sustainable industrial reductant thiourea dioxide (TDO). The reaction takes place under mild conditions in an aqueous medium to provide good to excellent yields of the desired products. Sensitive functional groups such as olefins, alkynes and aryl halides were found to be stable during the reduction while a wide range of aryl-N-nitrosamines were successfully converted to the desired hydrazines. One-pot synthesis of arylhydrazines from their corresponding secondary amines via an N-nitrosamine intermediate was established.

Phosphoester binding, DNA binding, DNA cleavage and in vitro cytotoxicity studies of simple heteroleptic copper(II) complexes with bidentate ligands

Abstract Two mononuclear heteroleptic copper complexes, [Cu(±trans-dach)(bpy)](ClO4)2 1a and [Cu(±trans-dach)(phen)](ClO4)2 2a [dach = 1,2-diaminocyclohexane, bpy = 2,2′-bipyridine and phen = 1,10-phenanthroline], were synthesized and analyzed by CHN analysis, electronic absorption, FT-IR spectroscopy, EPR, and SXRD. The molecular structures of 1a and 2a showed octahedral geometry around Cu(II). Both complexes interacted with phosphoesters and DNA. Their binding affinities with diphenylphosphate, di n-butylphosphate, trimethylphosphate, and triphenylphosphate were studied by UV–vis spectroscopy. For understanding the stereochemical role of dach ligand toward DNA interaction, enantiopure DACH complexes [Cu(R,R-trans-dach(bpy)](ClO4)2 1b, [Cu(S,S-trans-dach)(bpy)](ClO4)2 1c, [Cu(cis-dach)(bpy)](ClO4)2 1d, [Cu(R,R-trans-dach)(phen)](ClO4)2 2b, [Cu(S,S-trans-dach)(phen)](ClO4)2 2c, and [Cu(cis-dach)(phen)](ClO4)2 2d were synthesized and analyzed. All complexes interacted with calf thymus-DNA (CT-DNA) as studied by UV–vis spectroscopy. The nature of binding to CT-DNA was groove/electrostatic as supported by circular dichroism, cyclic voltammetry, and docking studies. Complexes were able to cleave plasmid DNA at 12.5 µM (1a–d) and 6 µM (2a–d), where 2d showed 64% Form II and 36% Form III. The in vitro cytotoxic studies of two different cancer cell lines showed inhibition with low IC50 value in comparison to reference control (cisplatin). These complexes are efficient in inducing apoptosis in cancer cells, making them viable for potent anticancer activity. Graphical Abstract