Synthesis, Characterization And Preliminary Application Of Several Organic Chromium Complexes

Trivalent chromium is an essential element required for normal carbohydrate, lipid and protein metabolism in humans. Trivalent chromium obviously influences the structure, function and target tissue cells state of insulin. Trivalent chromium deficiency has been associated with such diseases as metabolic disorder, diabetes mellitus and hyperlipemia, et al. Different forms of Crare not necessarily absorbed equally because of extent of binding, the absorption and utilization efficiency of inorganic chromium with toxicity is low, organic chromium is absorbed quickly and safe. Cr-containing biologically active substances will be important to develop medicine of anti-hyperglycemia and functional food. Therefore, organic chromium as a potential therapy medicine of diabetes mellitus has been paid great attention by people. Nowadays, The search for Cr-containing biologically active substances has identified several products which composed of nicotinic acid chromium, picolinic acid chromium and baicalin chromium complexes. No study on synthesis and characterization of folic acid chromium complex and the preliminary anti-hyperglycemia study of citric acid chromium complexes has been carried out.Four chromium complexes with the natural compounds(rutin, quercetin, citric acid, folic acid) were synthesized. The citric acid chromium complex anti-hyperglycemia of alloxan-inductioned diabetic mice was studied by pharmacology experiment. The citric acid chromium complex acute toxicity was studied by one time most limited amount administration method.The formation of rutin and quercetin chroumium complexes are as followes: the ligands(rutin and quercetin) was dissolved in the solvent of ethanol, then Cr³⁺ added, the complexes in the form of precipitation appear after sodium hydroxide was added and pH value was adjusted to 7-8.The precipitate was filtered off, washed several times by ethanol and water and dried under vacuo. The formation of citric acid chromium complex was as followes: Citric acid was dissolved in the distilled water, then the Cr³⁺ added and titrated against aqueous sodium hydroxide to adjust pH at 4-5, after that the mixture was warmed and stired at about 60℃for 6-8 h, the colour of aqueous solution become violet. The complex in the form of precipitation appears when added 4 folds ethanol after the aqueous solution has been concentrated, then the precipitate was filtered off, washed several times by aqueous and dried under vacuo. The formation of folic acid chromium complex was as followes: (1) was dissolved in the distilled water, then the aqueous solution was heated and stired reaction with 80℃for 8h. It was Named A solution. (2) Folic acid was dissolved in the warm distilled water, then sodium hydroxide was added dropwise several drops in order to make folic acid completely dissolved, then the CrCl₃·6H₂O solution added and the brown precipitation appear after titrated against aqueous sodium hydroxide to adjust pH at 5-6. The precipitate was filtered off, washed several times by pyridine, DMSO and water and dried under vacuo.Synthesized complexes were characterized by IR spectroscopy, UV-visible spectroscopy, elemental analysis, AAS, TG analysis and XRD. The results showed that the potential coordinatin sites of rutin chromium complex, quercetin chromium complex, citric acid chromium complex and folic acid chromium complex are hydroxyl groups, 4-C=O and 5-OH, three carbonyl groups and two carbonyl groups, respectively. The molecular formulas are Cr₃C₅₄H₅₈O₃₂Cl₁₅·21H₂O for rutin chromium complex, CrC₁₅H₈O₇Cl₂·6 H₂O for quercetin chromium complex,CrC₆H₅O₇·4H₂O for citric acid chromium complex and Cr₂(C₁₉H₁₇N₇O₆)₃·18H₂O for folic acid chromium complex, respectively. A preliminary study of citric acid chromium complex anti-hyperglycemia of alloxan-inductioned diabetic mice by pharmacology experiment was carried out. The dosage of medicine administration were divided into three grades:low, middle and high dosage. After 21d administration to diabetic mice, the results showed that the efficiency of anti-hyperglycemia of the citric acid chromium complex display is better than that of CrCl₃,It showed a dosage dependent relation. The blood glucose (BG) of the mice in the low, middle and high dosage groups of the citric acid chromium complex all reduce compared with that of the mice before administration. No significant difference can be observed between the complex groups and the modeled mice. The citric acid chromium complex and CrCl₃ have the activity of adjustment triglyceride and total cholesterol. The citric acid chromium complex and CrCl₃ have the activity of inhibition decomposition of liver glycogen, and the middle and high dosage groups of the citric acid chromium complex and CrCl₃ group display significantly activity. It was found that trivalent chromium of citric acid chromium complex can be better absorbed by diabetic mice than that of CrCl₃ .Acute toxicity of citric acid complex was studied by one time most limited amount administration method. After observing 7d, the result indicated that no experimental mice died or unusal, and autopsy was not unusal. LD₅₀ of male and female mice by mouth is more than 15000mg/kg, The citric acid chromium complex can be considered safe. The cell parenchymatous degeneration, cellular necrosis was not observed of the tissue section of cordis, liver and kidney, and tissue structure was no changed. LD₅₀ of male and female mice by mouth is 2143.3mg/kg according to the Document, CrCl₃ can be considered low toxic, the toxicity of citric acid chromium complex is much lower than that of CrCl₃.