Tuesday, January 28, 2020
Antimicrobial Activity of Pyrimidine-5-carboxylic Acid
Antimicrobial Activity of Pyrimidine-5-carboxylic Acid Antimicrobial activity of synthesized, novel hydroxamic acid of pyrimidine-5-carboxylic acid and its complexes with Cu(II), Ni(II), Co(II) and Zn(II) metal ions Bhawani Shankar, Rashmi Tomar, Madhu Godhara, Vijay Kumar Sharma ABSTRACT Four metal complexes of new hydroxamic acid, 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) with Cu(II), Ni(II), Co(II) and Zn(II) metal ions have been synthesized. The hydroxamic acid and its metal complexes were characterized by simple analytical techniques such as repeated melting point (M.P.) determination, elemental analysis, running their thin layer chromatography for single spot, and spectroscopic techniques such as I.R., H1-NMR and UV-Vis. (only for metal chelates) spectroscopy. Antimicrobial activity of the hydroxamic acid and their metal complexes were screened against two species of bacteria and two species of fungi by Serial Dilution Method. Metal complexes were found more active against both bacteria as well as fungi in antimicrobial screening test. Keywords Hydroxamic acids, antimicrobial activity, metal complexes INTRODUCTION Hydroxamic acids show a wide spectrum of biological activities and generally have low toxicities à ¯Ã‚ †º1à ¯Ã‚  -à ¯Ã‚ †º2à ¯Ã‚  . Hydroxamic acids are very well known for their antibacterial à ¯Ã‚ †º3à ¯Ã‚  -à ¯Ã‚ †º5à ¯Ã‚  , antifungal à ¯Ã‚ †º6à ¯Ã‚  -à ¯Ã‚ †º7à ¯Ã‚  , antitumor à ¯Ã‚ †º8à ¯Ã‚  -à ¯Ã‚ †º9à ¯Ã‚  , anticancer à ¯Ã‚ †º10à ¯Ã‚  , antituberculosis à ¯Ã‚ †º11à ¯Ã‚  and antimalerial à ¯Ã‚ †º12à ¯Ã‚  properties. Hydroxamic acids are inhibitors of enzymes such as prostaglandin H2 synthatase à ¯Ã‚ †º13à ¯Ã‚  , peroxidase à ¯Ã‚ †º14à ¯Ã‚  , urease à ¯Ã‚ †º15à ¯Ã‚  and matrix metalloproteinase à ¯Ã‚ †º16à ¯Ã‚  . Cinnamohydroxamic acids are used for treatment of the symptoms of asthma and other obstructive airway diseases which inhibit 5-lipoxygenase à ¯Ã‚ †º17à ¯Ã‚  . A number of hyd roxamic acid analogues have been shown to inhibit DNA (dinucleic acid) synthesis by inactivating the enzyme ribonucleotide reductase (RNR) à ¯Ã‚ †º18à ¯Ã‚  . Naturally occurringhydroxamic acid, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) is a powerfulantibiotic present inmaize à ¯Ã‚ †º19à ¯Ã‚  . Antiradical and antioxidant properties of hydroxamic acids have also been observed à ¯Ã‚ †º20à ¯Ã‚  . Hydroxamic acids play important role in many chemical, biochemical, pharmaceutical, analytical, and industrial fields à ¯Ã‚ †º21à ¯Ã‚  -à ¯Ã‚ †º25à ¯Ã‚  . These diverse biological activities of hydroxamic acids are due to their complexing properties towards transition metal ions à ¯Ã‚ †º26à ¯Ã‚  -à ¯Ã‚ †º27à ¯Ã‚  . Siderophores are Fe(III) complexes of naturally occurring hydroxamic acids, involved in the processes of iron transport from the environment to the living organisms à ¯Ã‚ †º28à ¯Ã ‚  -à ¯Ã‚ †º29à ¯Ã‚  . Hydroxamic acids after deprotonation acts as bidentate ligands and octahedral complexes are formed through the co-ordination of two oxygen atom of the –CONHO- group. This type of co-ordination have been studied with Cr(III), Fe(III), Ni(II), Co(II) and Zn(II) ions in solid state as well as in solutions, indicating the formation of octahedral complexes à ¯Ã‚ †º30à ¯Ã‚  . We report herein the synthesis, structural features and antimicrobial activity of new hydroxamic acid, 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) as well as their metal complexes 4a-d with Cu(II), Ni(II), Co(II) and Zn(II) metal salts. EXPERIMENTAL Reagents and methods All chemical used in the present investigation were of analytical reagent grade. 1,3- Di-p-tolylbarbituric acid was synthesized by previously known method in the laboratory. Copper acetate monohydrate, nickle acetate tetrahydrate, cobalt acetate tetrahydrate and zinc acetate dihydrate were purchased from E-Merck. Triethyl amine and ethyl chloroformate were purchased from Spectrochem. Hydroxylamine hydrochloride potassium hydroxide and diethyl ether were obtained from S.D. fine chemicals limited, India. All the synthesized compounds were analysed for C, H and N by elemental analyser, model 1108 (EL-III). H1-NMR spectra (400MHz) were recorded on JNM ECX- 400P (Jeol, USA) spectrometer using TMS as an internal standard. IR absorption spectra were recorded in the 400-4000 cm-1 range on a Perkin-Elmer FT-IR spectrometer model 2000 using KBr pallets. UV-Vis. spectra of metal complexes were recorded in DMSO solvent at room temperature on Simadzu Spectro Photometer model no. 1601. Melting poi nts were determined using Buchi M-560 and are uncorrected. These reactions were monitored by thin layer chromatography (TLC), on aluminium plates coated with silica gel 60 F254 (Merck). UV radiation and iodine were used as the visualizing agents. Synthesis of the hydroxamic acid 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) Synthesis of ligand 3 was carried out in two steps as follows: Step 1: Synthesis of ethyl 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylate (2). Ethyl 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylate (2) was synthesized by the reported method of Kuhne et al à ¯Ã‚ †º31à ¯Ã‚  . 1,3- Di-p-tolylbarbituric acid à ¯Ã‚ †º5g, 0.016 mol.à ¯Ã‚  and triethyl amine à ¯Ã‚ †º2.30ml, 0.0168 mol.à ¯Ã‚  and dimethyl aminopyridine (DMAP) à ¯Ã‚ †º0.10gà ¯Ã‚  were dissolved in 20 ml of dichloromethane (DCM) and the solution was cooled to 00 C. Then ethyl chloroformate à ¯Ã‚ †º1.60ml, 0.0165 mol.à ¯Ã‚  was added drop-wise over half an hour. The mixture was subsequently stirred for 12 hours at 00C, then, allowed to warm to the room temperature for 7 hours. The product is extracted in chloroform and dried over Na2SO4. Further, chloroform was evaporated to dryness and crude product was recrystallised from ethyl alcohol to yield pure 2. Step 2: 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) from ethyl 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylate (2). Synthesis of 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) was carried out by adopting a method similar to that described by Griffith et al à ¯Ã‚ †º32à ¯Ã‚  . The mixture of hydroxylamine hydrochloride à ¯Ã‚ †º1.87g, 0.026 mol. à ¯Ã‚  and aqueous potassium hydroxide à ¯Ã‚ †º2.19g, 0.039 mol. à ¯Ã‚  was added drop-wise to a methanolic solution of ethyl 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylate (2) à ¯Ã‚ †º5g, 0.013 mol. à ¯Ã‚  . The solution was stirred at room temperature for 72 hours and then acidified to pH 5.5 using 5% HCl solution. After filtration the solvent was removed in vacuo to yield a solid. The crude product was recrystallised from hot water to yield pure compound 3. Synthesis of metal complexes Synthesis of Cu(II), Ni(II), Co(II) and Zn(II) complexes of 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3). Copper acetate monohydrate à ¯Ã‚ †º0.136g, 0.00068 mol.à ¯Ã‚  in cold water was added with stirring to 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) à ¯Ã‚ †º0.50 g, 0.00136 mol.à ¯Ã‚  in EtOH (20 ml) in a round bottom flask. The contents were stirred for about 6 hours and then reduce to half volume under vacuo. Yellowish brown precipitate of 4a was appeared after adding petroleum ether. The precipitate was filtered, washed with small amounts of Et2O and dried over CaCl2 in a vacuum desiccator. Similarly, complexes 4b of Ni(II) , 4c of Co(II) and 4d of Zn(II) with 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) were synthesized by taking nickle acetate tetrahydrate, cobalt acetate tetrahydrate and zinc acetate dihydrate respectively. Infrared Spectra In the IR spectra (Table 1), carbonyl stretching vibrations of hydoxamic acid exhibit a medium sharp intensity band in the region 1660 cm-1 à ¯Ã‚ †º33à ¯Ã‚  . This band has shifted towards negative region 1626-1609 cm-1 in the metal complexes indicating the coordination of the ligand with the metal ion through oxygen of the carbonyl group. The symmetric N-O stretching vibrations, obtained in the region 1120 cm-1 in the IR spectra of ligands, have shifted to lower side in the IR spectra of their metal complexes suggesting the coordination of ligand to the metal ion through oxygen of the N-O moiety à ¯Ã‚ †º34à ¯Ã‚  . The presence of water molecules within coordination sphere of all chelates were supported by broad bands in the region 3450-3280 cm-1 and 850-800 cm-1 due to stretching and deformation modes of coordinated water molecules, respectively. The appearance of new band in the IR spectra of metal chelates in the region 551-519 cm-1 is probable due to forma tion of M-O bonds à ¯Ã‚ †º35à ¯Ã‚  . Table 1. IR spectral data of hydroxamic acid 3 and its metal complexes 4a-d. Compound à ¯Ã‚  ®(C=O)cm-1 à ¯Ã‚  ®(C-N) cm-1 à ¯Ã‚  ®(N-O) cm-1 à ¯Ã‚  ®(M-O) cm-1 3 1660 1349 1120 4a 1609 1327 1036 551 4b 1624 1355 1023 519 4c 1626 1384 1023 540 4d 1629 1350 1025 541 H1-NMR Spectra The hydroxamic acid 3 shows a one proton singlet at 1.14 due to –NH-O proton, probably due to magnetic anisotropy of the neighboring carbonyl group, electronegativity of nitrogen and H- bonding à ¯Ã‚ †º36à ¯Ã‚  . One proton singlet in hydroxamic acid 3 appear at 2.49 due to –N-OH proton à ¯Ã‚ †º37à ¯Ã‚  . Due to proton exchange in D2O this signal disappeared in the spectra indicating the possibility of –OH proton. Six protons multiplet for two Ar–CH3 group protons of hydroxamic acid 3 appear at 2.01 – 2.09. The hydroxamic acids 3 show a one proton singlet due to –C5H proton at 5.26. A multiplet due to eight protons of aromatic rings, Ar-H was observed at 7.17 7.20. H1-NMR of metal complexes 4a-d was not taken due to very less solubility in suitable organic solvents. UV- vis. Spectra Cu(II) complex In the electronic spectra of Cu(II) complex, 4a, three absorption bands in the region. 13157, 16949 and 23809 cm-1 have been observed, which correspond to the transitions 2B1g → 2A1g, 2B1g → 2B2g and 2B1g → 2E1g suggesting distorted octahedral geometry à ¯Ã‚ †º38à ¯Ã‚  -à ¯Ã‚ †º40à ¯Ã‚  . Ni(II) complex The electronic spectra of Ni(II) complex, 4b, exhibit three bonds in the region 13333, 16129 and 20833 corresponding to the transitions 3A2g → 2T2g(F), 3A2g → 3T1g(F), 3A2g → 3T1g(P) respectively which show an octahedral geometry for these complexes à ¯Ã‚ †º41à ¯Ã‚  -à ¯Ã‚ †º42à ¯Ã‚  . Co(II) complex In the electronic spectra of Co(II) complex, 4c three absorption bands in the region 12903, 14925 and 20200 cm-1 were seen, which may correspond to the transition 4T1g→ 4T2g(F), 4T1g → 4A2g (F) and 4T1g → 4T1g(P), respectively, indicating an octahedral geometry à ¯Ã‚ †º43à ¯Ã‚  -à ¯Ã‚ †º44à ¯Ã‚  . Zn (II) Complex No significant absorption was noticed in Zn(II) complex, 4d, above 400nm probably due to diamagnetic nature and completely filled d- orbitals. In the Zn(II) complex only transitions due to à ¯Ã‚  °Ãƒ ¯Ã¢â‚¬Å¡Ã‚ ®Ãƒ ¯Ã‚  °* and nà ¯Ã¢â‚¬Å¡Ã‚ ®Ãƒ ¯Ã‚  °* were seen. Antimicrobial activity Synthesized ligand 3 and metal chelates 4a-d were tested for their antimicrobial activity against two bacteria Staphylococcus aureus and Escherichia coli and two fungi Aspregillus flavus and Aspergillus niger by adopting Serial Dilution Method à ¯Ã‚ †º45à ¯Ã‚  -à ¯Ã‚ †º46à ¯Ã‚  .. The micro-organisms were cultured in nutrient agar medium à ¯Ã‚ †º46à ¯Ã‚  which was prepared by taking 6.0 gm peptone, 1.50 gm beef extract, 1.0 gm dextrose, 3.0 g yeast extract, 1.50 g agar (for slant) in 1 liter distilled water for bacteria and 10.0g peptone, 20.0g dextrose, 20.50g agar (for slant) in 1 liter distilled water for fungi. Measured quantities of the test compounds were dissolved in propylene glycol. First set was prepared for primary screening by taking 1ml (2000 µg/ml) of seeded broth (obtained by 1:100 dilution of the incubated micro-organism broth culture) in 10 well cleaned sterilized test tubes and gradual dilution process was continued for all the ten tubes using a fresh pipette each time. All the above sets of tubes were incubated at 37oC for 24 hours for bacteria and at 28oC for 96 hours for fungi. The Minimum Inhibitory Concentration (MIC) values were determined at the end of incubation period. Active synthesized compounds, found in the primary screening were further tested for secondary screening by taking 1ml (1500 µg/ml) of seeded broth against all microorganisms. RESULTS AND DISCUSSION In this present work synthesis of 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylic acid hydroxamide (3) was carried out by adding an aqueous solution of hydroxylamine hydrochloride and potassium hydroxide drop-wise to a methanolic solution of ethyl 2,4,6-trioxo-1,3-di-p-tolyl-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylate (2). The solution was continuously stirred for 72 hours at room temperature, which on acidification give crude solid. (Scheme I). Compound 3 on stirring with different metal salts, gave corresponding metal complexes 4a-d (Scheme II). All the metal complexes obtained were solid and stable at room temperature and insoluble in most of the common organic solvents. The spectroscopic and analytical data (Table 2) are in good agreement with theoretical values for the ligand and metal complexes. Table 2. Analytical data and physical properties of the hydroxamic acid 3 and metal complexes 4a-d. S.No. Compd Molecular Formula Color Percentage Elemental Analysis Calc./ (Found) M.P. /D.T. (oC) Yield (%) C H N 1 3 C19H17N3O5 Dark Pink 62.12 (61.90) 4.63 (4.52) 11.44 (11.28) 1560C 85% 2 4a à ¯Ã‚ †ºCu(C19H16N3O5)2.2H20à ¯Ã‚  Yellowish Brown 54.87 (53.27) 4.33 (4.30) 10.10 (9.90) 2480C 71% 3 4b à ¯Ã‚ †ºNi(C19H16N3O5)2.2H20à ¯Ã‚  Light Pink 55.22 (54.70) 4.39 (4.25) 10.13 (10.10) 2700C 70% 4 4c à ¯Ã‚ †ºCo(C19H16N3O5)2.2H20à ¯Ã‚  Pink 55.20 (54.70) 4.35 (4.25) 10.16 (10.20) 3220C 75% 5 4d à ¯Ã‚ †ºZn(C19H16N3O5)2.2H20à ¯Ã‚  Brown 54.67 (53.80) 4.32 (4.30) 10.07 (9.89) 3100C 70% Antimicrobial Activity The newly synthesized hydroxamic acid 3 and its metal chelates 4a-d were tested for their antimicrobial activity against two bacteria Staphylococcus aureus and Escherichia Coli and two fungi Aspergillus niger and Aspergillus flavus. The experimental results of MIC values (Table 3) show moderate activity of all the compounds against both bacteria and fungi. Further, it has been found that the metal complexes were more active than hydroxamic acid. This increased antimicrobial activity of the complexes as compared to the hydroxamic acid is probably due to the fact that chelation increases the lipophilicity of the complexes, which subsequently enhances the penetration through the lipid layer of cell membrane and restricts further multiplicity of the microorganism à ¯Ã‚ †º46à ¯Ã‚  . Among the metal complexes, Cu (II) complex 4a was found most active against both bacteria and fungi. The higher antimicrobial activity of Cu (II) complex may be due to higher stability constant of copper complexes. Table 3. The minimum inhibitory concentration ( µg/ml) MIC values of hydroxamic acid 3 and their metal complexes 4a-d. S.No. Compound Bacteria Fungi Staphylococcus aureus Escherichia coli Aspergillus niger Aspergillus flavus 1 3 325 325 250 325 2 4a 125 125 250 250 3 4b 325 500 500 325 4 4c 500 250 250 325 5 4d 500 250 250 250 CONCLUSION Four new metal chelates, 4a-d with ligand 3 have been synthesized and characterized. Octahedral geometries were proposed for the prepared metal complexes. All the synthesized hydoxamic acids and their metal chelates were screened for antimicrobial activity. A comparative study of the MIC values of the ligand and its complexes show that complexes exhibit higher antimicrobial activity than free ligand. Among the metal complexes, Cu (II) complex 4a was found most active against both bacteria and fungi. ACKNOWLEDGEMENT One of the authors Ms. Rashmi Tomar is grateful to UGC, Bahadur Shah Zafar Marg, New Delhi, for providing fellowship. REFERENCES à ¯Ã‚ †º1à ¯Ã‚  AE Fazary; MM Khalil; AFahmy; TA Tantawy, Medical Journal of Islamic Academy of Science, 2001, 14(3), 109-116. à ¯Ã‚ †º2à ¯Ã‚  D Kumar; R Tomar, J. Inst. Chem. Ind., 2010, 82(1), 21-25. à ¯Ã‚ †º3à ¯Ã‚  H Jahangirian; J Harson; S Silong; NZ Yusof; K Shameli; S Eissazadeh; RR Moghaddam; B Mahdavi; M Jafarzade, Journal of Medicinal plants Research, 2011 5(19) 4826-4831. à ¯Ã‚ †º4à ¯Ã‚  H Agarwal; O P Agarwal; R Karnawat; IK Sharma; PS Verma, International Journal of Applied Biology and Pharmaceutical Technology, 2010, I(3), 1293-1299. à ¯Ã‚ †º5à ¯Ã‚  AO Aliyu; JN Wabueze, International J. of Physical Science, 2008, 2 (7), 167-172. à ¯Ã‚ †º6à ¯Ã‚  S Sonika; S Neeraj, Der Chemica Sinica, 2013, 4(3), 108-119. à ¯Ã‚ †º7à ¯Ã‚  MJ Miller, Chem. Rev., 1989, 89, 1563-1590. à ¯Ã‚ †º8à ¯Ã‚  HL Elford; GL Wampler; BV Riet, Cancer Res. 1979,39, 844-851. à ¯Ã‚ †º9à ¯Ã‚  Naqeebullah; F Yang; MC Kok; KM Lo; FR Nor; CO Theng, Molecules, 2013,18, 8696- 8711. à ¯Ã‚ †º10à ¯Ã‚  D Pal; S Saha, Review article, J. Adv. Pharm. Tech. Res. 2012, 3(2) 92-99. à ¯Ã‚ †º11à ¯Ã‚  CJ Marmion; T Murphy; JR Docherty; KB Nolan, Chem.. Commun., 2000, 1153-1154. à ¯Ã‚ †º12à ¯Ã‚  D veale; J Carmichael; BM Cantwell; HL Elford; R Blackie; DJ Kerr; SB Kaye; AL Harris, Br. J. Cancer, 1988, 58(1) 70-72. à ¯Ã‚ †º13à ¯Ã‚  PJ Loll; CT Sharkey; SJ O’connor; CM Dooley; E O’brien; M Devocelle; KB Nolan; BS Selinsky; DJ Fitzgerald, Molecular Pharmacology, 2001, 60(6), 1407-1413. à ¯Ã‚ †º14à ¯Ã‚  SSC Tam, DHS Lee, EY Wang, DG Munroe; CY Lau, J. Biol. Chem., 1995, 270 13948-13955. à ¯Ã‚ †º15à ¯Ã‚  M Arnold; DA Brown; O Deeg; W Errington; W Haase; K Herlihy; TJ Kemp; H Nimir; R Wemer, Inorg. Chem., 1998, 37, 2920-2928. à ¯Ã‚ †º16à ¯Ã‚  I Botos; L Scapozza; D Zhang; LA Liotta; EF Meyer, Proc. Nat. Acad. Sci. USA, 1996, 93, 2749-2754. à ¯Ã‚ †º17à ¯Ã‚  JP Demers; VM William, U.S. Patent Appl. pat. No. 4,820,828, 1989. à ¯Ã‚ †º18à ¯Ã‚  IK Larsen; BM Sjberg; L Thelander, Eur. J. Biochem., 1982,125, 75. à ¯Ã‚ †º19à ¯Ã‚  HM Niemeyer, J. Agric. Food Chem., 2009, 57, 1677-1696. à ¯Ã‚ †º20à ¯Ã‚  MZ Koncic; M Barbaric; V Perkovic; B Zorc, Molecules, 2011, 16(8), 6232-6242. à ¯Ã‚ †º21à ¯Ã‚  G Borland; G Murphy; A Ager, J. Bio-Chem, 1999, 274, 2810-2815. à ¯Ã‚ †º23à ¯Ã‚  KM Bttomley; WH Johnson; DS Waltor, J. Enzy. Inhibition, 1998, 13(2), 79-101. à ¯Ã‚ †º23à ¯Ã‚  KW Vogel; DG Druckhammer, J. Am. Chem. Soc., 1998, 120, 3275-3283. à ¯Ã‚ †º24à ¯Ã‚  KK Ghosh; P Tamrakar Indian J. Chem,. 2001, 40(A), 524-527. à ¯Ã‚ †º25à ¯Ã‚  BA Holmen; MI Tejedor; WH Casey, Langmuir, 1997, 13, 2197-2206. à ¯Ã‚ †º26à ¯Ã‚  KN Raymond, Coord. Chem. Rev., 1990, 105, 135-153. à ¯Ã‚ †º27à ¯Ã‚  AL Crumbliss, Handbook of Microbial Iron Chelate; Ed. G. Winkelmann, CRC Press, New York, 1991 à ¯Ã‚ †º28à ¯Ã‚  AMA Gary; AL Crumbliss, Metal Ions in Biological Systems; Marcel Dekker, New York, 1998, 35, 239–327. à ¯Ã‚ †º29à ¯Ã‚  JB Neilands, J. Biol. Chem., 1995, 270, 26723-26726. à ¯Ã‚ †º30à ¯Ã‚  MC Fernandes; EB Paniago; S Carvalho, J. Braz. Chem. Soc., 1997, 8(5), 537-548. à ¯Ã‚ †º31à ¯Ã‚  M Kuhne, JJ Gallay, U.S. Patent Appl. No.4,670,441, 1987. à ¯Ã‚ †º32à ¯Ã‚  D Griffith; K Lyssenko; P Jensen; PE Kruger; CJ Marmion, J. Chem. Soc., Dalton Trans., 2005, 956-961. à ¯Ã‚ †º33à ¯Ã‚  F Mathis, Bull. Soc. Chem., 1953, D9-D22 à ¯Ã‚ †º34à ¯Ã‚  S Pinchas; I Lavtichat, Infra red spectra of Labelled compounds, Academic Press, New York, 1971. à ¯Ã‚ †º35à ¯Ã‚  FF Bentley; LD Somothsen; AL Rojek, Infra red spectra and characteristic Frequencies 700-300 cm-1, Inter science Publisher, London, 1968. à ¯Ã‚ †º36à ¯Ã‚  AO Aliyu; Current Res. Chem., 2010, (2) 2, 39-42. à ¯Ã‚ †º37à ¯Ã‚  S Mikhaylinchenko, Eur. J. Chem., 2010, 1(4), 302-306. à ¯Ã‚ †º38à ¯Ã‚  RL Carlin; Trans. Met. Chem., 1968, 4, 199-211. à ¯Ã‚ †º39à ¯Ã‚  GC Saxena; VS Srivastava, J. Ind. Chem. Soc., 1987, 64, 633-636. à ¯Ã‚ †º40à ¯Ã‚  ABP Lever; E Mantovani. Inorg. Chem., 1971, 10, 817-826. à ¯Ã‚ †º41à ¯Ã‚  RL Carlin, Trans. Met. Chem., 1968, 4, 211. à ¯Ã‚ †º42à ¯Ã‚  RK Patel; RN Patel, J. Ind. Chem. Soc., 1990, 67, 238. à ¯Ã‚ †º43à ¯Ã‚  R Poppalardo, Phill. Mag., 1959, 4, 219. [44]ABP Lever. Inorganic Electronic Spectroscopy, Elsevier, Amsterdam , 1968. à ¯Ã‚ †º45à ¯Ã‚  KI Burden, Introduction to microbiology, Mc Millan, New York, 1968. à ¯Ã‚ †º46à ¯Ã‚  RC Sharma; PP Giri; D Kumar; Neelam, J. Chem. Pharm. Res., 2012, 4(4), 1969-1973.
Monday, January 20, 2020
Essay on Picture of Dorian Gray: A Jungian Analysis :: Picture Dorian Gray Essays
 The Picture of Dorian Gray begins with Basil describing his fascination with Dorian, and ends with his masterpiece reverting to its original splendour. He describes his reaction to Dorian in these words: "When our eyes met, I felt I was growing pale. A curious sensation of terror came over me. I knew that I had come face to face with some one whose mere personality was so fascinating that, if I allowed it to do so, it would absorb my whole nature, my whole soul, my very art itself." (6) Such a reaction is not a reaction to another human being. It signals an intimation of something super-human. The word "fascinating" comes from fascinum, which means "spell." A fascination is caused by unconscious factors. It grips us; it holds us in its power; it acts upon us. The expression "face to face" suggests an image of a "god" -- cf. Jacob's experience at Peniel (Gen. 32.30) or Moses in the Tabernacle (Ex. 33.11). Dorian as both Dionysos and Apollo corresponds to both Jung's definitions of the Self: "a god-image in the psyche," and a "complexio oppositorum" (Vol. 9.ii; par. 73; also CW 11.283). For Jung held that a god-image must be a mixture of opposites "if it is to represent any kind of totality" (CW 13.289). According to Jung, the Self is an autonomous archetypal image, which symbolizes something towards which the individual is striving. An experience of the Self thus represents an intimation of a meaning which the individual has not yet assimilated. The individual's task is to integrate the meaning implicit in his or her particular experience, but not to identify with it, for this would signal psychological inflation. Basil lives only for his art (56). He is afraid of life, because it is capable of exerting an influence over him which he feels as threatening. He is afraid of Dorian, because Dorian personifies the Dionysian side of his own personality which he has repressed. Thus he needs Dorian, because only through Dorian can he feel that he is alive. The contrast between them is suggestive. Basil is fascinated by what he himself is not. The attributes which he finds so fascinating stand in "compensatory" relation to him. But, instead of seeing his fascination as symbolic of a need to develop the Dionysian side of his own personality, he seeks to perpetuate his experience through art.
Saturday, January 11, 2020
Intention Letter Exchange Program Essay
With this letter my intention is to express the reasons for why an academic exchange is of interest to me, especially one for the ISC Paris. I am a Business Administration student at â€Å"Universidad La Salle†, I find my career very interesting and I really enjoy being a part of it, that’s why it developed great interest in me to know that the ISC was a school specialized in Administration committed to train students to become first class business people. In Mexico, we do not have a reputable University or Institute focused in Administrative Sciences, which is why from that moment, I knew that the ISC was the educational option that I was looking for. I researched more about the Institute and I realized that it is part of the prestigious French system â€Å"Grandes Ecoles†which immediately makes it an excellent choice in education and an institution that will be very important to my profession, boosting my career as well. I think France is a beautiful country that has too much to offer: from culture, food, landscapes, people, modernity, to its geographic location and boundaries with other major countries. Speaking of its capital, I believe Paris is one of the most exciting and dynamic cities in the world and it would be an honor to be a part of its student population, I think it will have a very good influence in me, studying in the city where most major French multinational corporations are located, where professional forums, conferences and fairs also take place, not mentioning it is full of culture and history to acknowledge and admire. I consider that this exchange is an ideal opportunity to relate and learn influenced by a vast diversity of cultures that will form a new international perspective in me. It will be a different experience in which I will be interacting in foreign languages such as English and French, something that will be invaluable in my future life. I’m sure ISC Paris is the right place for me, and it would be an honor to me to contribute with my knowledge and skills being part of the student community.
Friday, January 3, 2020
Ethics in Business - Free Essay Example
Sample details Pages: 8 Words: 2343 Downloads: 9 Date added: 2017/06/26 Category Ethics Essay Type Narrative essay Did you like this example? à ¢Ã¢â€š ¬Ã…“Business ethics (also known as corporate ethics) is a form of applied ethics or professional ethics that examines ethical principles and moral or ethical problems that arise in a business environment. It applies to all aspects of business conduct and is relevant to the conduct of individuals and business organizations as a wholeà ¢Ã¢â€š ¬Ã‚ . (www.wikipedia.org) à ¢Ã¢â€š ¬Ã…“Business ethics comprises the principles and standards that guide behaviour in the world of business. Investors, employees, customers, interest groups, the legal system, and the community often determine whether a specific action is right or wrong, ethical or unethical.à ¢Ã¢â€š ¬Ã‚ (Ferrell. Fraedrich. Ferrell. 2008, p. 6) à ¢Ã¢â€š ¬Ã‹Å"Aristotle said, The end and purpose of the polis is the good life. Adam Smith categorized the good life in terms of material goods and intellectual and moral excellences of character. Smith in his The Wealth of Nations commented, All for ourselves, and nothing for other people, seems, in every age of the world, to have been the vile maxim of the masters of mankind.à ¢Ã¢â€š ¬Ã¢â€ž ¢ (www.wikipedia.org). Ethical misconduct has become a key concern in business today. Ethics is the main area of corporate governance, and management must take responsibility for their actions on global community scale. Ethics in business and shareholders desires for profitability are not always put on the same pedestal, and it is the responsibility of the executive management to ensure ethics surpass profitability. The 2008 financial crisis initiated critics to inquire about the ethics of the executives who were put in charge of large financial institutions around the world and financial regulatory bodies. Finance ethics is usually not looked into because issues in finance are often seen as matters of law rather than ethics. In the simplest way corporate ethics is a lawful matter. Laws such as protecting workersà ¢Ã¢â€š ¬Ã¢â€ž ¢ rig hts and suitable compensations must be top priority for management. Ethics becomes more difficult with the way things are done in particular practices, which makes it important to be aware of how certain steps may affect the community in a bad way. Managers are the key decision-makers, which is why they must be held responsible for the way the business is run and the affect it will have on shareholders, employees and the community in which it operates. Business ethical customs reflect the customs of each historic period. As time passes customs evolve, causing accepted behaviours to become intolerable. Business ethics and the subsequent behaviour evolved as well. Business was involved in what drove slavery, colonialism, and the cold war. Before 1960, the United States went through several difficult phases of wondering what the concept of capitalism was. In the 1930à ¢Ã¢â€š ¬Ã¢â€ž ¢s came the New Deal, which blamed businesses for the countryà ¢Ã¢â€š ¬Ã¢â€ž ¢s fiscal woes. Busines ses were asked to work more thoroughly with the government to help increase family income. Through the 1950s, the New Deal advanced into the Fair Deal which was an ambitious set of proposals put forward by President Harry S Truman. This program made clear matters such as civil rights and environmental responsibility as ethical issues that needed to be addressed by businesses. Up until the 1960s ethical issues associated to business were often discussed within the field of theology or philosophy. Moral issues that were related to business were now addressed in churches and mosques. Religious leaders started to speak out about fair wages, labour practices, and the morality of capitalism. During the 1960s, the American society turned to causes about social issues. Antibusiness attitude developed as people attacked the individuals in power that got benefits from the economic and political sides of society that they controlled. The 1960s saw the deterioration of inner cities and the b eginning of ecological problems such as pollution and the disposal of toxic and nuclear wastes. This era also saw the rise of consumerism. The word à ¢Ã¢â€š ¬Ã‹Å"business ethicsà ¢Ã¢â€š ¬Ã¢â€ž ¢ came into common use in the early 1970s in the United States. It was developed as a course to study in the 1970s. The foundation that certain principles could be applied to business activities which were laid down by theologians and philosophers led to business lecturers start teaching and writing about corporate social responsibility (CSR) which can be defined as à ¢Ã¢â€š ¬Ã…“a form of corporate self-regulation integrated into a business model.à ¢Ã¢â€š ¬Ã‚ (www.wikipedia.org). Philosophers increased their participation, putting together ethical theory that will help to build the discipline of business ethics. à ¢Ã¢â€š ¬Ã…“Companies became more concerned with their public images and as social demands grew, many businesses realized that they had to address ethical issues more di rectly.à ¢Ã¢â€š ¬Ã‚ (Ferrell, pg. 13). Conferences where scheduled to discuss the responsibilities that businesses had socially and also ethical aspect of business. By the end of the 1970s, key ethical issues such as bribery, misleading advertising and price collusion had formed in the business. Business ethics became a common expression thanks to the media and it was no longer considered as an oxymoron. Limited efforts were made to explain the way the ethical decision-making process would work and also the things that would influence this process in organisations. Firms started emphasizing their ethical standing in the late 1980s and early 1990s, probably trying to distance themselves from the business scandals of the day. Academics and practitioners started to acknowledge à ¢Ã¢â€š ¬Ã‹Å"business ethicsà ¢Ã¢â€š ¬Ã¢â€ž ¢ as a field of study. In the 1980s, the Defence Industry Initiative on Business Ethics and Conduct (DII) which was developed to give a guide to organisations about support for ethical conduct. This era was the Reagan-Bush era where the belief of self-regulation was seen to be in the publicà ¢Ã¢â€š ¬Ã¢â€ž ¢s interest. In the 90s it was all about the institutionalization of business ethics. President Bill Clinton and his administration continued to show support for self-regulation and free trade. Unprecedented actions such as teenage smoking were dealt with by the government. Proposals included prohibition of cigarette advertising, and stopping sports events from using cigarette logos during advertisement. President Clinton chose Arthur Levitt to be the chairman of the Securities and Exchange Commission in 1993. Levitt who ineffectively pushed many reforms which could have prevented the accounting ethics scandals demonstrated by Enron and WorldCom. The 2000s had a new focus on business ethics. This era brought in the many scandals that shook the business world to this day. Although business ethics was seen to have become more instit utionalized in the 1990s, in the 2000s evidence came out that more than a few business executives and managers had not been compiling with the publicà ¢Ã¢â€š ¬Ã¢â€ž ¢s desire for high ethical standards. For example, the former CEO of Tyco Dennis Kozlowski was indicted on thirty-eight counts of misappropriating $170 million of Tyco funds and netting $430 million from inappropriate sales of stock. Dennis Kozlowski pleaded not guilty to all the charges. He allegedly used the funds to purchase personal luxuries such as art for $14.725 million, also throw his wife a $2 million birthday party and also bought a $30 million apartment in New York City. He was found guilty and sentenced to serve eight years and four months to twenty-five years in prison for his role in the scandal. Arthur Andersen, which was a holding company and formerly one of the à ¢Ã¢â€š ¬Ã…“Big Fiveà ¢Ã¢â€š ¬Ã‚ accounting firm. In its role as Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s auditor, they were responsible for make sure that Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s financial statements and internal bookkeeping were accurate. The firm after been found guilty of criminal charges in the way the auditing of Enron was conducted gave up their licenses to practice in the US. The reputation of the accounting firm disappeared over night, also most of its clients left, and the firm went out of business, but it still exists in a small way today. The verdict was overruled by the Supreme Court of the United States. Most of the other accounting firms bought most of the practices of Arthur Andersen. Other companies such as Halliburton, WorldCom, Dynegy and Sunbeam where faced with charges about employing certain accounting practices and they were also audited by Arthur Andersen. One of the few revenue-generating assets that the Andersen firm still has is Q Centre, which is a conference and training facility outside of Chicago. Accenture which is a consultancy firm separated from the accountancy side of Arthur Andersen in 1987 a nd renamed themselves after splitting in 2000, still continues to operate and it is one of the largest multinational corporations in the world. These accounting scandals really confirmed to the public that falsifying financial reports and reaping questionable benefits had become part of the culture of many companies. Firms outside the United States such as Royal Ahold in the Netherlands and Parmalat in Italy, also were caught out in practicing accounting misconducts from a global perspective. Such scandals increased public and political demands for accountability and to also improve ethical standards in business. The Enron Corporation was created in 1985 out a merger of two major gas pipeline companies. Through its subsidiaries the company provided products and services associated with natural gas, electricity, and communications for its wholesale and retail customers. It was based in Houston, Texas. It generated, transmitted and distributed electricity to the north-western Unite d States and marketed other commodities such as natural gas globally. It was also involved in the growth, construction, and operation of plants, pipelines, and other energy-related projects all over the world. Throughout the 1990s, Chairman Kenneth Lay, chief executive officer (CEO) Jeffrey Skilling, and chief financial officer (CFO) Andrew Fastow transformed Enron from an old-style electricity and gas company into a $150 billion energy company and Wall Street favourite that traded power contracts in the investment markets. From 1998 to 2000, Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s revenues grew from about $31 billion to more than $100 billion, making it the seventh-largest company of the Fortune 500. The wholesale energy income represented about 93 percent of 2000 revenues for Enron, with another 4 percent coming from natural gas and electricity. The remaining 3 percent came from broadband services and exploration. The companyà ¢Ã¢â€š ¬Ã¢â€ž ¢s worldwide internet trading platform Enron Online co mpleted on average over five thousand transactions per day, buying and selling over eighteen hundred separate products online that brought in over $2.5 billion in business every day. For the third quarter of 2001, Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s whole-sale business generated a potential $754 million of earnings (before interest and tax). This was an increase of 35 percent from the previous year. This represented over 80 percent of Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s worldwide sales. There was no reason to doubt that Enron was not financially stable in the third quarter of 2001 but it was later reported after a bankruptcy examiner examined their financial reports that there was a discrepancy in their net income and cash flow accounts. On October 22, 2001 Enron announces that the Securities and Exchange Commission (SEC) has launched a formal investigation into its related partyà ¢Ã¢â€š ¬Ã¢â€ž ¢s transactions. Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s corporate culture was described by people using words such as arr ogant or prideful. Enron only employed competent, creative and hardworking employees who were the best and brightest graduates and they were recruited from top universities. Enron employees had thus belief that competitors had no chance against it. There was an overwhelming confidence among Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s people that they could handle the increasing risk and pressure that came with the job. The culture of Enron was about a focus on how much money could be made for the people at the top, at many levels, that shared in a stock option incentive program. Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s aggressive employee culture was motivated by the desire to improve their financial position. Skilling brought in a system where employees were appraised every six months and if the employees ranked in the bottom 20 percent they were let go. This system called the à ¢Ã¢â€š ¬Ã‹Å"rand-and-yankà ¢Ã¢â€š ¬Ã¢â€ž ¢ helped create a fierce environment in which employees didnà ¢Ã¢â€š ¬Ã¢â€ž ¢t only compete with rivals outside the company but also the rivals at the next desk to them. Problems in the trading operation were covered up and not told to management because of the fear of losing their jobs. Lay who was the chairman always maintained that he was concerned with ethics. In his indictment the business ethics issue was that he lied about the financial conditions of Enron, but he maintained that he openly dealt with all issues that were brought to his attention. During 2001, when a series of revelations were revealed involving improper accounting procedures bordering on fraud committed throughout the 1990s involving Enron and its accounting company Arthur Andersen, Enron suffered the largest bankruptcy in history which has been surpassed by those of WorldCom during 2002 and Lehman Brothers during 2008. Off-balance-sheet financing called à ¢Ã¢â€š ¬Ã‹Å"special-purpose entitiesà ¢Ã¢â€š ¬Ã¢â€ž ¢ (SPEs) which were the write-offs and the losses not disclosed were the main thing that turned Enron into a disaster. Fastow the companyà ¢Ã¢â€š ¬Ã¢â€ž ¢s then CFO said that Enron established the SPEs to help in the moving of assets and debt off its balance sheet so as to increase cash flow by showing that funds were flowing through its books when it sold assets, while in a meeting with Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s lawyers in August 2001. Critics believed they might constitute fraudulent financial reporting because they didnà ¢Ã¢â€š ¬Ã¢â€ž ¢t accurately represent the companyà ¢Ã¢â€š ¬Ã¢â€ž ¢s true financial condition. Most of the SPEs at Enron were alleged to be entities in name only, and that Enron funded them with its own stock and maintained control over them. After the crash of Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s stock price, assets that were associated with the SPE system had to be written off. This cost Enron over $1.2 billion in equity in late 2001. Enron filed for bankruptcy and faced twenty-two thousand claims totalling $400 billion. For some time it appeared that Dyn egy might save the day by providing $1.5 billion in cash but when Standard Poor downgraded Enronà ¢Ã¢â€š ¬Ã¢â€ž ¢s debt below investment grade on November 28, $4 billion in off-balance-sheet debt came due and Enron didnà ¢Ã¢â€š ¬Ã¢â€ž ¢t have the resources to pay. Dynegy terminated the deal. Fastow and his wife, Lea, both pleaded guilty to charges against them. Fastow pleaded guilty to two charges of conspiracy and was sentenced to ten years with no parole in a plea bargain to testify against Lay and Skilling. Lea was indicted on six felony charges, but prosecutors later dismissed them in favour of a single misdemeanour tax charge. Lea was sentenced to one year for helping her husband hide income from the government. Don’t waste time! Our writers will create an original "Ethics in Business" essay for you Create order
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