Differential adduction of proteins vs. deoxynucleosides by methyl methanesulfonate and 1-methyl-1-nitrosourea in vitro

The reactions of two model mutagenic and carcinogenic alkylating agents, N-methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS), with proteins and deoxynucleosides in vitro, were investigated. The protein work used an approach involving trypsin digestion and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). This technique permitted identification of the specific location of protein adduction by both MNU and MMS with commercial apomyoglobin and human hemoglobin, under physiological conditions. MNU treatment resulted in predominantly carbamoylation adducts on the proteins, but in contrast only methylated protein adducts were found following treatment with MMS. Further analyses, using TurboSequest, and the Scoring Algorithm for Spectral Analysis (SALSA), revealed that MNU carbamoylation was specific for modification of either the N-terminal valine or the free amino group in lysine residues of apomyglobin and human hemoglobin. However, MMS methylation modified the N-terminal valine and histidine residues of the proteins. Despite their clear differences in protein modifications, MNU and MMS formed qualitatively the same methylated deoxynucleoside adduct profiles with all four deoxynucleosides in vitro under physiological conditions. In light of their different biological potencies, where MMS is considered a 'super clastogen' while MNU is a 'super mutagen', these differences in reaction products with proteins vs. deoxynucleosides may indicate that these two model alkylating agents work via different mechanisms to produce their mutagenic and carcinogenic effects.     

2,6‐Diaryl‐4,4‐disubstituted‐4H‐thiopyran: Source for spiro heterocycles

The 1,5‐diaryl‐3,3‐disubstituted‐1,5‐pentanedione on reaction with ammonium acetate, phosphorus pentoxide and phosphorus pentasulfide gave respective 1,4‐dihydropyridine, 4H‐pyran and 4H‐thiopyran. Novel spiro heterocycles have been obtained by the cyclocondensation of 4H‐thiopyran with hydrazine, hydroxylamine, urea and thiourea.     

Eudragit NE30D based metformin/gliclazide extended release tablets: formulation,characterisation and in vitro release studies

Metformin/Gliclazide extended release tablets were formulated with Eudragit NE30D by wet granulation technique. Two batches were prepared in order to study influence of drug polymer ratio on the tablet formation and in vitro drug release. The formulated tablets were characterized by disintegration time, hardness, friability, thickness, weight variation, and in vitro drug release. The percentage of polymer, with respect to Metformin/Gliclazide, required to produce tablets with acceptable qualities was 9 to 13.45. The percentage of polymer below this range released the drug immediately and above this range produced granules not suitable for tablet formation. The quantity of Metformin/Gliclazide present in the tablets and the release medium were estimated by a validated HPLC method. The formulated tablets had acceptable physicochemical characters and released the drug over 6-8 h. The data obtained from in vitro release studies were fitted with various kinetic models and was found to follow Higuchi kinetics.     

Biochemical relevance of Cr(III) complexes of isoniazid: synthesis,characterization, DFT,antibacterial screening,antioxidant activity and glucose-lowering effect in STZ-induced diabetic rats

Molecular mechanism suggests that the incorporation of an antioxidant organic moiety to chromium will be a sound strategy for the synthesis of safer and more effective hypoglycemic compounds. Two Schiff base ligands were derived by condensation of isonicotinyl hydrazide with salicylaldehyde/o-hydroxyacetophenone which further yield four novel chromium(III) complexes of types [Cr(L)Cl₂(H₂O)] and [Cr(L)₂]Cl. The ligands and complexes were characterized by analytical and spectroscopic techniques. DFT study at the basic set B3LYP and TD-SCF/6-311-G level was employed to confirm the geometry of the investigated compounds. Ligands were tested for their antioxidant activity and exhibited good antioxidant activity. Assessment of insulin-like activity of the complexes was initially performed in vitro by measuring the inhibition of α-amylase. The complex with highest in vitro activity was investigated for in vivo antidiabetic activity on the model of STZ-induced diabetic rats, which demonstrated that complex 4 significantly lowers the blood glucose level in rats. Toxicity level and antioxidant activity of the complex were also tested, which exhibit good tolerance level and antioxidant activity. Histological analysis of the pancreas of animals under investigation reveals the good condition of the pancreas treated with the complex. Ligands and complexes were also tested for antibacterial activity against Escherichia coli.

     

Preferential inclusion of food colours via formation of their inclusion complexes withβ-cyclodextrin (β-CD)

The encapsulation of commercially utilized food colours with-cyclodextrin is reported. Thus, inclusion complexes of Sunset Yellow, Amaranth, Ponceau 4R, Carmoisine, Fast Red E, Tartrazine and Erythrosine with-CD were prepared. The formation of inclusion complexes was established by, among other methods, UV, reflectance and X-ray diffraction techniques. The host-to-guest ratio was determined by a UV spectral method. The effect of inclusion with-CD on binary mixtures such as Raspberry Red, Tomato Red and Orange Red was also studied.     

Controlled pyrolysis of polyethylene/polypropylene/polystyrene mixed plastics with high impact polystyrene containing flame retardant: Effect of decabromo diphenylethane (DDE)

The pyrolysis of polyethylene(PE)/polypropylene(PP)/polystyrene(PS) mixed with high impact polystyrene (HIPS-Br) containing decabromo diphenylethane (DDE) as a brominated flame retardant with antimony trioxide as a synergist was performed under controlled temperature programmed pyrolysis (two steps) conditions to understand the decomposition behaviour and evolution of brominated hydrocarbons from flame-retardant additives. The liquid products were extensively analyzed by gas chromatographs equipped with FID, ECD, MSD, TCD, AED and FT-IR. The solid residue samples were analyzed by powder X-ray diffraction and combustion followed by ion-chromatography. The controlled pyrolysis of PE/PP/PS/HIPS-Br significantly affected the decomposition behaviour of HIPS-Br and subsequently the formation of decomposition products. GC/ECD analysis confirmed that the brominated hydrocarbons were concentrated in step 1 liquid products leaving less brominated hydrocarbons in the step 2 liquid products, similar to the decabromo diphenyl ether flame retardant containing mixed plastics. The yield of liquid products in step 1 from 3P/DDE-Sb(5) was 5 wt% and from 3P/DDE-Sb(0) was 2.4 wt%. The presence of antimony in the DDE containing plastics affected the yield of liquid, gas and residue products. ECD analysis showed that the presence of antimony increased the Br containing hydrocarbons and step 1 has 3-4 times higher brominated compounds than step 2 hydrocarbons in both the samples.     

Simultaneous determination of three organophosphorus pesticides in different food commodities by gas chromatography with mass spectrometry

A sensitive and selective gas chromatography with mass spectrometry method was developed for the simultaneous determination of three organophosphorus pesticides, namely, chlorpyrifos, malathion, and diazinon in three different food commodities (milk, apples, and drinking water) employing solid‐phase extraction for sample pretreatment. Pesticide extraction from different sample matrices was carried out on Chromabond C₁₈ cartridges using 3.0 mL of methanol and 3.0 mL of a mixture of dichloromethane/acetonitrile (1:1 v/v) as the eluting solvent. Analysis was carried out by gas chromatography coupled with mass spectrometry using selected‐ion monitoring mode. Good linear relationships were obtained in the range of 0.1–50 μg/L for chlorpyrifos, and 0.05–50 μg/L for both malathion and diazinon pesticides. Good repeatability and recoveries were obtained in the range of 78.54–86.73% for three pesticides under the optimized experimental conditions. The limit of detection ranged from 0.02 to 0.03 μg/L, and the limit of quantification ranged from 0.05 to 0.1 μg/L for all three pesticides. Finally, the developed method was successfully applied for the determination of three targeted pesticides in milk, apples, and drinking water samples each in triplicate. No pesticide was found in apple and milk samples, but chlorpyrifos was found in one drinking water sample below the quantification level.     

DNA-directed synthesis of aniline and 4-aminobiphenyl oligomers: programmed transfer of sequence information to a conjoined polymer nanowire

A new class of materials was prepared from aniline-containing oligomers that are covalently linked to the nucleobases of duplex DNA. Oligomers composed of repeating aniline (PANI) or 4-aminobiphenyl (PAB) units having the properties of conducting polymers conjoined to the DNA were prepared by the reaction of horseradish peroxidase and H2O2 with DNA having the appropriate monomers aligned within the major groove. These oligomers exhibit the spectral and chemical properties typical of para-linked polyanilines. This method of preparation enables utilization of the unique self-recognizing properties and sequence programmability of DNA to create tailored oligomers. This ability was demonstrated experimentally by preparation of PAB oligomers from alternating benzene and aniline monomers. Conjoined conducting polymers carrying the sequence information of DNA may have applicability as nanowires.     

Bulky N-substituted 1,3-benzazaphospholes: access via Pd-catalyzed C-N and C-P cross coupling, lithiation, and conversion to novel P=C-PtBu2 hybrid ligands

The syntheses of novel bulky N-substituted 1,3-benzazaphospholes are presented, together with their reactions with tert-butyllithium and coupling with tBu 2PCl to novel P, P'-hybrid ligands that combine the highly basic and bulky di- tert-butylphosphanyl group with pi-acidic low-coordinated phosphorus. The syntheses start with the preparation of new N-secondary 2-bromoanilines 1 by reduction of N-acyl 2-bromoanilides or more generally by Pd-catalyzed selective monoamination of o-dibromobenzene, followed by Pd-catalyzed C-P coupling with P(OEt) 3 to the respective 2-anilino-phosphonates 2. The next steps are reduction to 2-phosphanylanilines 3 and condensation with Me 2NCH(OMe) 2, which leads via phosphaalkenes 4 to the corresponding N-substituted benzazaphospholes 5. The reaction with tBuLi depends on the steric demand of the N substituent. Methyl, neopentyl-, and mesityl-derivatives were converted to P=C Li species 6 and coupled with tBu 2PCl to novel P=C-P tBu 2 ligands 7, whereas N-adamantyl and N-2,6-diisopropylphenyl-derivatives prefer addition of tBuLi at the PC bond to form dihydroderivatives. The chemical shifts of the low-coordinated phosphorus of 5 and 7 were found to reflect electronic and steric effects of the N substituents. The comparison of the crystal structures of N-neopentyl-1,3-benzazaphospholes 5 and 7 gives evidence of steric repulsion between the adjacent di- tert-butyl and neopentyl groups by the preferred anti orientation of the P- tert-butyl groups and moderate deviations of C2 and P3 of 7b from the ring plane.     

Anion sensing by Phenazine-based urea/thiourea receptors

The novel colorimetric receptors 2,3-bis-N-(9,10-diaza-anthracen-1-yl)-N′-phenylurea and 2,3-bis-N-(9,10-diaza-anthracen-1-yl)-N′-phenylthiourea have been prepared by the reaction of 2,3-diaminophenazine with phenylisocyanate and phenylisothiocyanate, respectively, in quantitative yields. The interaction and colorimetric sensing properties of receptor = 2 and 3 with different anions were investigated by naked eye, UV-vis and fluorescence spectroscopy in DMSO. The receptors effectively and selectively recognized biologically important F⁻, CH₃COO⁻, H₂P in the presence of other anions, such as Cl⁻, Br⁻, I⁻ and HS in DMSO.