Synthesis And Applications Of Selenomethionine And Its Schiff Base Metal Complexes

Selenomethionine(Se-Met), anα-amino acid containing selenium, is a reagent protecting human systems against oxidation, radiations, cancer, aging and related diseases, as well as a hopeful source of selenium in the diets of both animals and human. The synthesis and toxicity of Se-Met as well as the effect of its addition on performance in finishing pigs were investigated. Moreover, the Schiff base ligands derived from Se-Met and salicylaldehyde as well as 2-hydroxy-1-naphthaldehyde and their Co(II), Cu(II) and Zn(II) complexes were synthesized and characterized. The biological activity of these metal complexes was screened.Preparation ofα-amino-γ-butyrolactone hydrobromide started with amination of commercially availableα-bromo-γ-butyrolactone by ammonia water, followed by treatment with barium hydroxide and sulphuric acid. The amination ofα-bromo-γ-butyrolactone described here was a more effective and simple route for the synthesis ofα-amino-γ-butyrolactone hydrobromide in one step with 78.2 % yield. 3,6-Bis(2-hydroxyethy1)-2,5-diketopiperazine was readily produced fromα-amino-γ-butyrolactone hydrobromide by treatment with CH3COOK in absolute alcohol solution with 70.0 % yield. This route not only effectively protected carboxylic hydroxy and amino groups, but also prevented deprotection process through formation of two amide bonds in diketopiperazine. 3,6-Bis(2-hydroxyethy1)-2,5-diketopiperazine treated with thionyl chloride gave 3,6-bis(-2chloroethyl)-2,5-diketopiperazine in 80.1 % yield.A vital procedure for preparation of Se-Met is introduction of methylselenide. Hydrazine hydrate was used as reduction on selenium to give diselenide anion in water. Subsequently, addition of tetrabutyl ammonium bromide and dimethyl sulfate to above solution smoothly provided dimethyl diselenide in 90.0 % yield. The reduction of dimethyl diselenide was performed using hydrazine hydrate in DMSO in the presence of potassium carbonate. The nucleophilic methylselenide anions were not isolated and reacted directly with 3,6-bis(-2chloroethyl)-2,5-diketopiperazine to give 3,6-bis(β-methylselenoethyl)-2,5- diketopiperazine intermediate in a one-pot procedure. Followed by treatment with aqueous HCl and neutralization with triethylamine at pH= 6-7, Se-Met was obtained as white solid in 60.1 % yield. Se-Met was characterized by elemental analysis, mass spectrum, IR, NMR and COSPY spectra.The toxicity of Se-Met was evaluated through death rate, body weight, liver, lung and body organs change of rats when rats were fed with basal diets containing different concentration of Se-Met and sodium selenite (SS). Results showed that the toxicity of Se-Met was lower than that of SS at same level of dietary Se when the rats were fed with more than 4.20 mg/kg diet of Se. The data of LD50 were 7.85 for SS and 16.57 for Se-Met, respectively. This indicated that the toxicity of Se-Met was lower than that of SS.Finishing pigs were slaughtered to investigate the effects of Se-Met addition on performance, carcass traits, pork quality, and muscle antioxidant capacity in finishing pigs. A SS group was used as a standard of comparison in a control experiment. Results showed that①there was no significant differences in average daily gain, average daily feed intake and feed, back-fat thickness among all groups (P>0.05). However, addition of 0.30 mg/kg Se significantly improved eye muscle area compared to that of 0.15 mg/kg Se and SS added groups (P<0.05);②there was no significant differences in muscle fiber density among all groups (P>0.05). Addition of 0.30mg/kg Se significantly increased muscle fiber diameter of longissimus muscle (P<0.05);③meat color L* value was significantly decreased and a* value was significantly improved at 12 h, 24 h, 48 h post-slaughter in all Se-added groups in contrast with the control (P<0.05), also 0.15 mg/kg Se supplementation significantly decreased meat b* value at 12 h post-slaughter (P<0.05);④marbling score, shear force, drip loss and intramuscular fat content of porcine Longissimus muscle were not affected by Se addition. All Se-added groups presented significantly higher pH value at 12 h post-slaughter than the control (P<0.05).Amino acid Schiff bases are an important class of ligands containing electron-rich oxygen and nitrogen atoms, showing strong coordination ability and various coordination behavior. Se-Met, anα-amino acid containing selenium, is a potential source of selenium in the diets. On the other hand, cobalt, copper and zinc are necessary nutritious trace elements. Thus, we designed novel molecules which contained Se-Met, Schiff bases and nutritional metal elements, expecting their special biological activity. Certain problem of instability of the Se-Met Schiff base was encountered, which was resolved by making an equimolar potassium salt of the Schiff base ligand [K(HL)]. The synthesis of metal complexes proved to be straightforward in simple by one-pot reactions of Se-Met, salicylaldehyde and metal(II) acetate monohydrate. New cobalt(II), copper(II) and zinc(II) complexes of Schiff base derived from Se-Met and salicylaldehyde were characterized by elemental analysis, IR, NMR, electronic spectra, conductance magnetic measurements and powder XRD. The analytical data showed that the Schiff base ligand acted as tridentate towards divalent metal ions (cobalt, copper, zinc) via the azomethine-N, carboxylate oxygen and phenolato oxygen by a stoichiometric reaction of M:L (1:1) to form metal complexes [ML(H2O)], where L was the Schiff base ligand derived from Se-Met and salicylaldehyde, M = Co(II), Cu(II) and Zn(II). The proposed structures of metal complex were square planar geometry for Cu(II) complex and tetrahedral geometry for the Co(II) complex.2-Hydroxy-1-naphthaldehyde shows special property due to its high conjugation and steric hindrance. In the same way , due to instability of Schiff base of Se-Met and 2-hydroxy-1-naphthaldehyde, it was made an equimolar lithium salt of the Schiff base ligand [Li(HL)]. The novel zinc(II), copper(II), and cobalt(II) complexes of the Schiff base derived from 2-hydroxy-1-naphthaldehyde and Se-Met were synthesized by one-pot reactions and characterized by elemental analysis, IR, electronic spectra, conductance measurements, powder XRD, NMR and magnetic measurements. The analytical data displayed the composition of the metal complex to be ML(H2O), where L was the Schiff base ligand and M = Co(II), Cu(II) and Zn(II). The proposed structures of metal complex were square planar geometry for Cu(II) complex and tetrahedral geometry for the Co(II) complex.The ligands salts derived from Se-Met and salicylaldehyde as well as 2-hydroxy-1-naphthaldehyde and their metal complexes had been screened for their antibacterial activities. All the metal complexes were more potent bactericides than the ligand. This enhancement of metal complexes in the activity can be explained on the basis of chelation theory. Chelation reduces the polarity of the metal atom mainly because of partial sharing of its positive charge with the donor groups and possibleπelectron delocalization within the whole chalete ring. Such a chelation also enhances the lipophililic character of the central metal atom, which subsequently favors its permeation through the lipid layers of cell membrane and blocking the metal binding sites on enzymes of microorganism. Co(II) and Zn(II) complexes are much less microbial active than the Cu(II) complex.