Synthesis of new chiral heterocyclic Schiff base modulated Cu(II)/Zn(II) complexes: their comparative binding studies with CT-DNA, mononucleotides and cleavage activity

New Schiff base ligand L derived from the condensation reaction of 2-amino-3-formylchromone with (R)-2-amino-2-phenylethanol was synthesized and characterized which involves combination element of ammine functionality and naturally occurring heterocyclic chromone, 4H-benzopyran-4-one. Subsequently, their complexes 1 and 2 with Cu(NO?)? and Zn(NO?)?, respectively were prepared. The DNA binding studies of the ligand L and complexes 1 and 2 with CT-DNA as compared to classical anticancer drug cisplatin were carried out by employing different optical methods viz, UV-vis, fluorescence, circular dichroism and viscosity measurements. Furthermore, the absorption studies, 1H and 31P with mononucleotides were also monitored to examine the base specific interactions of the transition metal complexes which revealed a higher propensity of copper(II) complex 1 for 5'-GMP while for zinc(II) complex 2 towards 5'-TMP involving groove binding mechanism of the complexes towards DNA. The complex 1 exhibits a remarkable DNA cleavage activity with pBR322 DNA in presence of different activators and cleavage reaction involves various oxygen species suggesting the involvement of active oxygen species for the DNA scission.     

Structure and dynamics of highly PEG-ylated sterically stabilized micelles in aqueous media

Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We have studied sterically stabilized micelles (SSMs) of self-assembled DSPE–PEG2000 in pure water and isotonic HEPES-buffered saline solution. The observed SSM sizes of 2–15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration of DSPE–PEG2000 is 10 times higher in water than in buffer, and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we performed atomistic molecular dynamics simulations of solvated SSMs. Our modeling revealed that the observed assemblies have very different aggregation numbers (N(agg) ≈ 90 in saline solution and N(agg) < 8 in water) because of very different screening of their charged PO4(–) groups. We also demonstrate that the micelle cores can inflate and their coronas can fluctuate strongly, thus allowing storage and delivery of molecules with different chemistries.     

Caragisides A – C,New Isoflavone Glucosides from Caragana conferta with Inhibition of Platelet Aggregation

Caragisides A–C ( 1 – 3 , resp.), three new isoflavone glucosides, were isolated from the BuOH sub‐fraction of the EtOH extract of the whole plant of Caragana conferta, along with ononoside ( 4 ), reported for the first time from this species. The structures of the new compounds were elucidated by spectroscopic techniques including MS and 2D‐NMR spectroscopy. Compounds 1 – 3 showed significant inhibition of platelet aggregation.     

Carrageenan as an elicitor of induced secondary metabolites and its effects on various growth characters of chickpea and maize plants

The effects of polysaccharide elicitor k-carrageenan obtained from Hypnea musciformis, red algae on the production of Induced Secondary Metabolites, ISMs (the disease resistance compounds) and on various growth characters of chickpea and maize plants were studied. Experiments were conducted in the field of PCSIR Laboratories Complex Karachi during December 2008–April 2009 in randomized complete block design with three replications. Three elicitor treatments were used, a solid preparation in which the elicitor was mixed with soil (T₂ 1 mg/g) and applied around the seeds in the soil. The two other preparations were liquid, T₁ and T₃ at a concentration of 100 μg glc eq ml⁻¹ and were applied around the sowing seeds and as a foliar spray on the plants, respectively. Statistical analysis of the data revealed that these treatments significantly enhanced all the growth characters of chickpea except T₂ that gave the nonsignificant difference in the plant height. Maximum plant height (80.3 cm), number of pods plant⁻¹ (76.2), number of branches plant⁻¹ (25.0), number of leaves plant⁻¹ (125.6), earlier flowering and high ISMs contents in leaves, stem and grains of chickpea were recorded in T₁ treated chickpea plants. In maize plants only T₁ and T₃ treatments (with minor exceptions) had significant effects on few characters like plant height, stem diameter, number of leaves plant⁻¹ and on ISMs contents in leaves while number of cobs plant⁻¹ and flowering time were nonsignificantly affected by these treatments. These results suggested that k-carrageenan elicitor can be used as a potent plant protectant as well as growth promoting agent especially for chickpea plants.     

Synthesis, physical studies and uptake behavior of: copper(II) and lead(II) by Schiff base chelating resins

Two new chelating resins possessing multiple functional groups capable of coordinating with several metal ions are reported. The resins were synthesized by condensing Schiff bases derived from 2-aminophenol, 2-hydroxy-5-chloroaniline and terephthaldehyde with formaldehyde in an alkaline medium. The effects of pH and contact time of the Cu(2+) and Pb(2+) in aqueous solutions on the uptake behavior of the resins were studied. The metal ion uptake behavior of the resins was investigated by the batch method. Both the uptake and the selectivity of the resins towards the investigated metal ions were related to the structure of the resins, type of the metal ion and the uptake conditions. The resins showed maximum uptake capacity for Cu(2+) and Pb(2+) at pH 10. Cu(2+) was seen to undergo preferential adsorption in separate and mixture solutions of Cu(2+) and Pb(2+). Kinetic studies for the resins using Langmiur equation were also performed. The Schiff base monomers and their formaldehyde resins were characterized by elemental analyses, FTIR and (1)H NMR spectroscopy. The thermal stability of the resins was studied using TGA/DTG analysis.     

Synthesis of novel 2,3-substituted quinazolin-4-ones by condensation of alkyl or aromatic diamines with 5-(N-arylimino)-4-chloro-5H-1,2,3-dithiazoles

The work described in this paper is a further example of the utility of Appel's salt in the conception of novel heterocyclic rings. We confirmed that primary alkyldiamines may react easily with the methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-anthranilates to afford quinazolines, which are very interesting starting materials for the access to novel 2,3-condensed quinazolin-4-ones. On the other side, aromatic amines allow the synthesis of polycyclic molecules, which are structurally close to the model natural products (e.g., rutaecarpine, luotonine, tryptanthrine and vasicinone).     

Cation thin-layer chromatography in mixed organic solvents containing s-butylamine: Separation of Zn(II) from Cd(II) and Cu(II)

Summary A TLC method has been developed for the separation of Zn(II) from Cd(II) and Cu(II) on silica gel alyers with mixed organic solvents containing s-butylamine. The separation of Zn(II) from Cd(II) in the presence of certain anions and at various pH values of sample solution was examined. A mixture containign s-butylamine, acetone and formic acid in 262 was found to be the best solvent.     

A novel three carbon-amino grignard reagent: its use in an efficient pyrrolidine synthesis

A novel primary amino protected Grignard reagent has been developed; 2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane-1-propyl magnesium bromide 1a. Its usefulness is illustrated in the synthesis of 2-substituted pyrrolidines.     

Isolation of onosmins A and B, lipoxygenase inhibitors from Onosma hispida

Onosmins A (1) and B (2), lipoxygenase inhibitors, have been isolated from Onosma hispida. Their structures were established as 2-[(4-methylbenzyl)amino]benzoic acid (1) and methyl 2-[(4-methylbenzyl)amino]benzoate (2) through spectroscopic studies, including 2D-NMR. The known compounds apigenin (3), 6,4'-dimethoxy-3,5,7-trihydroxyflavone (4), 6,7-dimethoxy-3,5,4'-trihydroxyflavone (5) and apigenin 7-O-beta-D-glucoside (6) are also reported for the first time from this species. Compounds (1) and (2) inhibited lipoxygenase (LOX, EC 1.13.11.12) enzyme in a concentration-dependent fashion with IC50 values of 24.0 and 36.2 microM, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that the nature of inhibition was purely a non-competitive type, with K(i) values 22.0 microM and 31.1, respectively.     

Experimental/theoretical electrostatic properties of a styrylquinoline-type HIV-1 integrase inhibitor and its progenitors

We have established that polyhydroxylated styrylquinolines are potent inhibitors of HIV-1 integrase (IN). Among them, we have identified (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinolinecarboxylic acid (1) as a promising lead. Previous molecular dynamics simulations and docking procedures have shown that the inhibitory activity involves one or two metal cations (Mg2+), which are present in the vicinity of the active center of the enzyme. However, such methods are generally based on a force-field approach and still remain not as reliable as ab initio calculations with extended basis sets on the whole system. To go further in this area, the aim of the present study was to evaluate the predictive ability of the electron density and electrostatic properties in the structure-activity relationships of this class of HIV-1 antiviral drugs. The electron properties of the two chemical progenitors of 1 were derived from both high-resolution X-ray diffraction experiments and ab initio calculations. The twinning phenomenon and solvent disorder were observed during the crystal structure determination of 1. Molecule 1 exhibits a planar s-trans conformation, and a zwitterionic form in the crystalline state is obtained. This geometry was used for ab initio calculations, which were performed to characterize the electronic properties of 1. The electron densities, electrostatic potentials, and atomic charges of 1 and its progenitors are here compared and analyzed. The experimental and theoretical deformation density bond peaks are very comparable for the two progenitors. However, the experimental electrostatic potential is strongly affected by the crystal field and cannot straightforwardly be used as a predictive index. The weak difference in the theoretical electron densities between 1 and its progenitors reveals that each component of 1 conserves its intrinsic properties, an assumption reinforced by a 13C NMR study. This is also shown through an excellent correlation of the atomic charges for the common fragments. The electrostatic potential minima in zwitterionic and nonzwitterionic forms of 1 are discussed in relation with the localization of possible metal chelation sites.