Synthesis, Characterization And Hypoglycemic Activity Of Bisalicylic Acid Chromium Complexes

Diabetes is a kind of common disease, and it can lead to organ damage and dysfunction. The scale of diabetes is growing, so we have to prevent it. Science demonstrates that chromium has close relationship with insulin.At present, we classify the chromium products according to their ligands: chromium nicotinate, chromium picolinate and chromium amino acid. Although these complexes have been used in dietary, there are still some defects. Firstly, chromium complexes can enhance improve glucose uptake, but the bioavailability of inorganic chromium complexes is low, which is less than 1%. Secondly, the biological activity of chromium amino acid is bad. Chromium nicotinate and chromium picolinate have been approved by China as therapy for diabetes. Thirdly, biological activity and toxicity of these chromium compounds are different. Fourthly, many chromium complexes are inadequate or poorly characterized.In this paper salicylic acid and derivatives were choosen as first ligands, en and 1,3-PDA respectively as second ligands, chromium(III) as the center ion, six chromium(III) complexes were synthesized and studied, and we hope to receive efficient, low-toxic of glucose-lowering drugs or chromium reagents.1. The different substituting group salicylic acid was selected to reacted with chromium(III) to synthesize the chromium complexes. Some of them were characterized by mean of single crystal X-ray diffraction UV-vis spectra, fluorescence spectra, IR and element analysis.2. The transfer manner of Cr(III) from the complex to EDTA and apoOTf were studied by mean of UV-Vis absorption and fluorescence spectra. The second order rate constants were obtained. There were abvious differences in the reaction of chromium complexes with EDTA and apoOTf. The rate constant of TBA-[Cr(SA)2(en)] is bigger than the rate constant of [Cr(SA)(en)2]-Br, and it indicating that TBA-[Cr(SA)2(en)] is stable than [Cr(SA)(en)2]-Br. Fluorescence spectroscopy were used to study the four chromium(III) complexes on its ability to bind to human serum albumin. It indicates the intermolecular force between HSA and bisalicylic chromium complex is stonger than the intermolecular force between HSA and salicylic chromium complex.3. Potochemistry of complexes TBA·[Cr(SA)2(en)], [Cr(SA)(en)2]·Br, TBA·[Cr(5-ClSA)2(en)], K-[Cr(5-BrSA)2(en)] and Na·[Cr(SA)2(1,3-PDA)] were discussed by means of UV-Visible, conductivity mensuration. The first order rate constants were obtained. We got the conclusion that the rate sequence is Na·[Cr(SA)2(1,3-PDA)]> [Cr(SA)(en)2]·Br>TBA·[Cr(SA)2(en)] >TBA·[Cr(5-ClSA)2(en)]>K·[Cr(5-BrSA)2(en)]. The potochemical reaction of bisalicylic acid chromium complexes is reversible in methanol, and it is irreversible in water and Tris-HCl buffer.4. Gel electrophoresis experiment was adopted to study two different chromium complexes and pBR322DNA interaction. Experimental results show that the complex [Cr(SA)(en)2]-Br can cleavage pBR322DNA, complex TBA·[Cr(SA)2(en)] can not cleavage pBR322DNA. Hydroxyl radicals are generated through Fenton systems. Chromium picolinate induced an obvious increase over control in hydroxyl radical production. In contrast, complexes TBA·[Cr(SA)2(en)], [Cr(SA)(en)2]·Br, TBA·[Cr(5-ClSA)2(en)], K·[Cr(5-BrSA)2(en)] failed to cause any degradation of deoxyribose, and it suggesting that this kind of compound may not generate hydroxyl radicals under the conditions tested.5.Animal experiments shows that TBA·[Cr(SA)2(en)] can lead to the reducing of blood glucose, lipid-decreasing and cholesterol-reducing.