ALBERT

Description: Background: Reliable values for method validity of organochlorine pesticides determination were investigated, in water by solid phase extraction and in sediment by Soxhlet extraction, followed by gas chromatography equipped with an electron capture detector. Organochlorine pesticides are categorized as Persistent Organic Pollutants. Hence, critical decisions to control exposure to these chemicals in the environment are based on their levels in different media; it is important to find valid qualitative and quantitative results for these components. In analytical chemistry, internal quality procedures are applied to produce valid logical results.Result: In this study, 18 organochlorine pesticides were targeted for analysis and determination in water and river sediment. Experiments based on signal-to-noise ratio, calibration curve slope and laboratory fortified blank methods were conducted to determine the limits of qualification and quantification. The data were compared with each other. The limitation values, following Laboratory Fortified Blank, showed significant differences in the signal-to-noise ratio and calibration curve slope methods, which are assumed in the results for the sample concentration factor to be 1,000 times in water and 10 times in sediment matrices. The method detection limit values were found to be between 0.001 and 0.005 mug/L (mean of 0.002 +/- 0.001) and 0.001 and 0.005 mug/g (mean of 0.001 +/- 0.001). The quantification limits were found to be between 0.002 and 0.016 mug/L (mean of 0.006 +/- 0.004) and 0.003 and 0.017 mug/g (mean of 0.005 +/- 0.003 mug/L) for water and sediment, respectively, based on the laboratory fortified blank method. Because of different slopes in the calibration methods, it was also found that the limitation values for some components from the internal standard were higher than from external standard calibration, because in the latter a factor for injection efficiency is applied for calibration. Conclusion: Technically, there are differentiations between detection limits for quality and quantity from component to component, resulting from noise, response factors of instruments and matrix interference. However, the calculation method is the cause of differentiation for each component of the different methods. The results show that for no matter what component, the relationship between these levels in different methods is approximately: Signal to Noise : Calibration Slope = 1:10. Therefore, due to different methods to determine LOD and LOQ, the values will be different. In the current study, laboratory fortified blank is the best method, with lower limitation values for Soxhlet and solid phase extraction of OCPs from sediment and water, respectively.

Description: Background: The serious impact effects of persistent organic pollutants such as organochlorine pesticides, especially dichlorodiphenyltrichloroethane family (DDTs) and hexachlorocyclohexane isomers (HCHs) have been causing widespread concern, despite effective control on their manufacturing, agricultural and vector practices. In that, in addition to the previous global limitations on DDTs usage, alpha-HCH, beta-HCH and lindane have also became an on-going topic of global relevance based on the latest Stockholm Convention list on 10th of May 2009. Concentrations of dichlorodiphenyltrichloroethane family (DDTs) and hexachlorocyclohexane isomers (HCHs) were determined by GC-ECD in Cameron Highlands, the main vegetables and flowers farming area in Malaysia as an agricultural tropical environment. A total of 112 surface water and sediment samples at eight points were collected along the main rivers in the area namely Telom and Bertam in the dry and wet seasons of 2011. Results: Total concentration of HCH isomers ranged from not detected to 25.03 ng/L in the water (mean of 5.55 +/-6.0 ng/L), while, it ranged from 0.002 to 59.17 ng/g (mean of 8.06+/-9.39 ng/g) in the sediment. Total concentration of DDT and its metabolites in the water samples varied from not detected to 8.0 ng/L (mean of 0.90+/-1.66 ng/g), whereas, it was in the range of 0.025 to 23.24 ng/g (mean of 2.55+/-4.0 ng/g) in the surface sediment samples. The ratio of HCHs and DDTs composition indicated an obvious historical usage and new inputs of these pesticides. Among alpha, beta, gamma and delta isomers of HCH, gamma was the most dominant component in the sediment and water as well. Some seasonal variations in the level of selected pesticides were noted. Conclusions: The results illustrate distribution, behaviour and fate of HCHs, and DDTs have closely connected with topological and meteorological properties of the area beyond their chemical characterizations. The features of environmental circumstances exceed one or more of these characters in importance than the other. Although the results show that the situation is better than 1998, the impact of persistent agrochemicals such as lindane and 4,4[prime]DDE are revealed in a key tropical area of Malaysia.

Description: Background: Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. Results: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17beta-hydroxy-2-(hydroxy-methyl)-17alpha-methyl-5alpha-androstan-1-en-3-one (2), 2alpha,17alpha-di(hydroxyl-methyl)-5alpha-androstan-3beta,17beta-diol (3), 17alpha-methyl-5alpha-androstan-2alpha,3beta,17beta-triol (4), 17beta-hydroxy-2-(hydroxymethyl)-17alpha-methyl-androst-1,4-dien-3-one (5), 17beta-hydroxy-2alpha-(hydroxy-methyl)-17alpha-methyl-5alpha-androstan-3-one (6), and 2alpha-(hydroxymethyl)-17alpha-methyl-5alpha-androstan-3beta-17beta-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2--5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1--7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 mug/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 mug/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. Conclusion: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.

Description: Background: Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate (1), by using plant and microbial cultures. Results: The biotransformation of ethynodiol diacetate (1) with Cunninghamella elegans and plant cell suspension cultures of Ocimum basilicum and Azadirachta indica is being reported here for the first time. Biotransformation of 1 with Cunninghamella elegans yielded three new hydroxylated compounds, characterized as 17alpha-ethynylestr-4-en-3beta,17beta-diacetoxy-6alpha-ol (2), 17alpha-ethynylestr-4-en-3beta,17beta-diacetoxy-6beta-ol (3), and 17alpha-ethynylestr-4-en-3beta,17beta-diacetoxy-10beta-ol (4) and a known metabolite, 17alpha-ethynyl-17beta-acetoxyestr-4-en-3-one (5). The biotransformations of 1 with Ocimum basilicum included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17alpha-ethynyl-17beta-acetoxyestr-4-en-3-one (5), 17alpha-ethynyl-17beta-hydroxyestr-4-en-3-one (6), 17alpha-ethynyl-3 beta-hydroxy-17beta-acetoxyestr-4-ene (7) and 17alpha-ethynyl-5alpha,17beta-dihydroxyestr-3-ene (8). Biotransformation of 1 with Azadirachta indica culture yielded compounds 5 and 6. Spectroscopic data of compound 8 is being reported for the first time. Structure of compound 6 was unambiguously deduced through single-crystal x-ray diffraction studies. Conclusion: Biotransformation of an oral contraceptive, ethynodiol diacetate (1), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.

Description: Background: For centuries silver salts have been used as antimicrobial agents for humans. The activity of silver cations varies on their bioavailability. So delivery methods, solubility and ionization of the silver sources are important parameters to deal metals in biological systems. The bonding of silver cations to biologically compatible ligands enhances their bioavailability and ultimately the activity. Furthermore, due to significant safety profiles, researchers are now interested to explore their anticancer potential. On the other hand, imidazole/benzimidazole-based compounds have been found to have diverse biological and clinical applications due to being structural isosters of naturally occurring nucleotides; which allow such compounds to interact easily with biopolymers of the living system. This property of benzimidazole constituted compounds has created interest in researchers to further explore their biological applications.The connection of these biologically active moieties (silver & azoles) through Ag-NHC bonding provided a biologically enhanced entity that was tested for human colorectal cancer cells (HCT 116). Results: N-ipropylbenzimidazole was synthesized by reaction of benzimidazole with ipropyl bromide. The subsequent treatment of the resulting N-alkylbenzimidazole with ortho/meta/para-(bromomethylene) benzene afforded corresponding bis-benzimidazolium bromides (5-7). The counter anion (Br-) of each salt was replaced by hexaflourophosphate (PF6-) for the ease of handling and further purification (8-10). Each salt (Ligand), in halide form, was further allowed to react with Ag2O with stirring at room temperature for a period of two days to synthesize dinuclear Ag(I)-NHC complexes (11-13). All synthesized compounds were characterized by spectroscopic techniques and microanalysis. Molecular structures of compounds 5, 9 & 10 were established through single crystal x-ray diffraction technique. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116). Results showed that the ligands (5-10) showed mild to negligible cytotoxicity on HCT 116 cells whereas respective silver complexes (11-13) exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 9.7 to 44.5 muM. Interestingly, the complex 13 having para-xylyl spacer was found the most active (IC50 9.7 muM) that verifies our previously reported results. Conclusions: All the bis-benzimidazolium salts (8-10) were found inactive whereas after bonding with silver cations, the Ag(I)-NHC complexes (11-13) showed a dose dependent cytotoxic activity. This proved that silver practice an important role in death of cancer cells. Also, the N-alkyl/aryl substitutions and ortho/metal/para xylyl units regulate the cytotoxicity. Based on the previous and current results it can be concluded that the dinuclear Ag(I)-NHC complexes are potential anticancer agents and could probably be the potential source of chemotherapeutic drugs.

Description: The optimization processes of photo degradation are complicated and expensive when it isperformed with traditional methods such as one variable at a time. In this research, thecondition of ortho-cresol (o-cresol) photo degradation was optimized by using a semiempirical method. First of all, the experiments were designed with four effective factorsincluding irradiation time, pH, photo catalyst's amount, o-cresol concentration and photodegradation % as response by response surface methodology (RSM). The RSM used centralcomposite design (CCD) method consists of 30 runs to obtain the actual responses. Theactual responses were fitted with the second order algebraic polynomial equation to select amodel (suggested model). The suggested model was validated by a few numbers of excellentstatistical evidences in analysis of variance (ANOVA). The used evidences include high Fvalue(143.12), very low P-value (

Description: Background: The interactions of p-cresol photocatalytic degradation components were studied by response surface methodology. The study was designed by central composite design using the irradiation time, pH, the amount of photocatalyst and the p-cresol concentration as variables. The design was performed to obtain photodegradation % as actual responses. The actual responses were fitted with linear, two factor interactions, cubic and [left-to-right mark] quadratic model to select an appropriate model. The selected model was validated by analysis of variance which provided evidences such as high F-value (845.09), very low P-value (

Description: Due to the increasing industrial use of titanium compounds, its determination is the subject of considerable efforts. The ionophore or the membrane active recognition is the most important component of any polymeric membrane sensor. The sensor respond depends on the ionophore and bonding between the ionophore and the target ion. Ionophores with molecule-sized dimensions containing cavities or semi-cavities can surround the target ion. The bond between ionophore and target ion gives different selectivity and sensitivity toward the other ions. Therefore, ionophores with different binding strengths can be used in the sensor. In the present work, poly(vinyl chloride) (PVC) based membrane incorporating tris(2 pyridyl) methylamine (tpm) as an ionophore have been prepared and explored as a titanium(III) selective sensor. The strengths of the ion-ionophore (Ti(OH)2+-tpm) interactions and the role of ionophore on membrane was performed by various techniques such as elemental analysis, UV-Vis, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and powder X-ray diffraction (XRD). All data approve the successful incorporation of organic group via covalent bond.

Description: Background: The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application. Results: A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3--9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and beta-glucuronidase and alpha-glucosidase inhibitory activities. Compound 3 (IC50 = 56.26 +/- 3.18 muM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50 = 105.9 +/- 1.1 muM). Compounds 8a (IC50 = 13.2 +/- 0.34 muM) and 8b (IC50 = 14.1 +/- 0.28 muM) found as potent inhibitor of alpha-glucusidase several fold more active than the standard acarbose (IC50 = 841 +/- 1.73 muM). Most promising results were obtained in beta-glucuronidase enzyme inhibition assay. Compounds 5 (IC50 = 0.13 +/- 0.019 muM), 6 (IC50 = 19.9 +/- 0.285 muM), 8a (IC50 = 1.2 +/- 0.0785 muM) and 9 (IC50 = 0.003 +/- 0.09 muM) showed a potent inhibition of beta-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50 = 45.75 +/- 2.16 muM). Conclusions: Synthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated.

Description: Background: Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. Green chemistry uses highly efficient and environmentally benign synthetic protocols to deliver lifesaving medicines, accelerating lead optimization processes in drug discovery, with reduced unnecessary environmental impact. From this view point, it is desirable to use water instead of organic solvents as a reaction medium, since water is safe, abundant and an environmentally benign solvent. Results: A convenient one-pot method for the efficient synthesis of the novel Zwitterion derivatives 4a-p via a three-component condensation reaction of barbituric acid derivatives 1a,b, dimedone 2, and various aldehydes 3 in the presence of aqueous diethylamine media is described. This new approach is environmentally benign, with clean synthetic procedure, short reaction times and easy work-up procedure which proceeded smoothly to provide excellent yield (88-98%). The synthesized products were characterized by elemental analysis, IR, MS, NMR and CHN analysis. The structure of 4a was further confirmed by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic space group Pbca with alpha = 14.6669 (5) A, b = 18.3084 (6) A, c = 19.0294 (6) A, alpha = 90[ring operator], beta = 90[ring operator], = 90[ring operator], V = 5109.9 (3) A3, and Z = 8. The molecules are packed in crystal structure by weak intermolecular C-H . . .O hydrogen bonding interactions. Conclusions: An environmentally benign Aldol-Michael protocol for the synthesis of dimedone-barbituric derivatives using aqueous diethylamine medium is achieved.