CN105601670A - Chromium (III) complex as well as preparation method and application thereof - Google Patents

Chromium (III) complex as well as preparation method and application thereof Download PDF

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Publication number
CN105601670A
CN105601670A CN201610146067.5A CN201610146067A CN105601670A CN 105601670 A CN105601670 A CN 105601670A CN 201610146067 A CN201610146067 A CN 201610146067A CN 105601670 A CN105601670 A CN 105601670A
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chromium
iii
complex
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CN105601670B (en
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刘斌
周海乐
董金龙
杨斌盛
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Shanxi University
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Shanxi University
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F11/00Compounds containing elements of Groups 6 or 16 of the Periodic Table
    • C07F11/005Compounds containing elements of Groups 6 or 16 of the Periodic Table compounds without a metal-carbon linkage
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention provides a chromium (III) complex as well as a preparation method and application thereof. According to the chromium (III) complex, the molecular formula is CrC14H26N4O4Cl, the molecular weight is 402, the crystal structure belongs to a triclinic crystal system, the spatial point group is P-1, a is equal to 7.8880(6), b is equal to 9.8380(7), c is equal to 14.4490(12) angstroms, alpha is equal to 70.4550(10), beta is equal to 85.729(2), gamma is equal to 82.0880(10) degrees, V is equal to 1046.12(14) cubic angstroms, and Z is equal to 2. The preparation method comprises the steps of dissolving chromium (III) and 3-methyl-salicylic acid by virtue of an organic solvent, feeding a small amount of zinc granules, carrying out heating reflux, then dropwise adding triethylene tetramine, continuing to carry out reflux for a period of time, stopping reaction, cooling, filtering, standing obtained filtrate, and naturally volatilizing at the normal temperature, so as to obtain purple red crystals. The chromium (III) complex can be applied to the preparation of sugar-reducing medicines.

Description

A kind of chromium (III) complex and its preparation method and application
Technical field:
The present invention relates to metal complex, being specially a kind of is the chromium (III) of mixture part based on 3-methyl-salicylic acid and triethylene tetramineComplex and its preparation method and application.
Background technology:
Chromium is the trace element of needed by human. Trivalent chromium is the element useful to human body, and still, the physiological function of chromium is and otherThe material of controlling metabolism coordinates and works together, as the genetic stew of hormone, insulin, various enzyme, cell (DNA and RNA)Deng. Research shows, diabetic's chromium obviously lowers, and chromium level and blood sugar are negative correlation. Chromium (III) content in human body along withThe increase at age reduces gradually, lacks chromium (III) and can make the Reduced susceptibility of tissue to insulin, easily suffers from diabetes and AtherosclerosisChange. Can strengthen the effect of insulin to the supplementary appropriate chromium (III) of diabetes patient, the glucose tolerance that slowly-releasing human body is impaired, reduces bloodSugar level and cholesterol in serum content. At present, the chromium supplementing agent of selling on market has nicotinate chromium, amino acid chromium and chromium picolinateDeng commodity, wherein chromium picolinate is current the most salable nutrition chromium supplementing agent. But related documents report in the recent period: chromium picolinateMay cause chromosome damage, DNA mutation and cancer, and intestinal absorption rate low (< 3%), its use causes people graduallyQuery. Therefore, the substitute of finding more effective chromium picolinate becomes study hotspot, synthesizing efficient, easy absorption, low toxicityNovel Organic Chromium (III) complex significant.
Summary of the invention:
The object of the present invention is to provide a kind of preparation method and this complex of chromium (III) complex with hypoglycemic weight losing functionIn the application of preparing in hypoglycemic slimming medicine.
A kind of chromium provided by the invention (III) complex, its molecular structural formula is:
The preparation method of a kind of chromium provided by the invention (III) complex, reaction equation:
Preparation process comprises:
1) by chromic salts and 3-methyl-salicylic acid organic solvent dissolution, drop into zinc granule, add hot reflux 1~3 hour, then splash intoTriethylene tetramine, continues to reflux at least 1~2 hours, stops reaction, cooling, filters;
2) filtrate obtaining is left standstill, under normal temperature, volatilization naturally, obtained aubergine crystal after three days.
Step 1) described chromic salts is chromium chloride, chromic nitrate or chromium sulfate.
Step 1) the amount of substance ratio of described chromic salts, 3-methyl-salicylic acid and zinc granule is 1: 1: 0.5~1.65.
Step 1) described chromic salts and the amount of substance ratio of triethylene tetramine be 1: 50~100.
Step 1) described zinc granule is 20~50 object arsenic-free zinc granules.
Step 1) described organic solvent is methyl alcohol or ethanol.
Chromium (III) complex good water solubility prepared by the present invention, stability is moderate, and it is peculiar to take full advantage of 3-methyl-salicylic acid selfBiologically active and the blood sugar reducing function of chromic salts, play the collaborative biological effect of biological hypoglycemic. Animal hypoglycemic fat-reducing activity experimentShow, compared with nutritional agents chromium picolinate, this complex has remarkable effect at control animal blood glucose lipid aspects, and hasWish to apply preparing in hypoglycemic slimming medicine.
Brief description of the drawings
The crystal x-ray diffraction pattern of Fig. 1 chromium of the present invention (III) complex
The uv-visible absorption spectra of Fig. 2 chromium of the present invention (III) complex
Fluorescence spectrum (the λ of Fig. 3 chromium of the present invention (III) complexex=300nm)
Detailed description of the invention:
Embodiment 1: preparation and the structural characterization of chromium (III) complex
Take 2.67g (10.0mmol) CrCl3·6H2O and 1.52g (10.0mmol) 3-methyl-salicylic acid (3-CH3-SA), be placed inIn 100mL round-bottomed flask, add 50mL methyl alcohol to dissolve, then add 0.30g without arsenic Zn grain, add hot reflux 1 hour,Then slowly add 0.5mL triethylene tetramine (Trientine), treat that the color of solution slowly becomes redness from green, continue reaction 1Individual hour, cooling, suction filtration, filtrate normal temperature volatilizees naturally, after three days, obtains red crystals, and productive rate is 60%.
Determination of elemental analysis result, by molecular formula CrC14H26N4O4Cl theoretical value (%): C, 41.79; H, 6.47; N,13.93; Experiment value (%): C, 41.55; H, 6.69; N, 13.88.
Crystal structure determination result (seeing accompanying drawing 1): complex molecule formula is CrC14H26N4O4Cl, molecular weight is 402, three oblique crystalline substancesSystem, space group is P-1, a=7.8880 (6), b=9.8380 (7),α=70.4550(10),β=85.729(2),γ=82.0880(10)°,Z=2. The interior boundary of complex is by chromium ion, 1 3-firstBase-salicylate and 1 triethylene tetramine form hexa-coordinate octahedral structure; The external world is made up of 1 chlorion and 1 hydrone.Complex part bond distanceAnd bond angle (°) in table 1.
Table 1 complex part bond distanceAnd bond angle (°)
Uv-visible absorption spectra (seeing accompanying drawing 2): part 239 and 308nm place have characteristic absorption peak (curve a), with Cr3+Joinπ-the π of its phenyl ring behind position*Absworption peak respectively red shift to 285 and 338nm (curve b), illustrate electron cloud in pi-conjugated system toCr3+Empty d track shift; Complex is Cr in the absworption peak of 549nm appearance is attributed to complex3+D-d transition peak.
Near fluorescence spectrum (seeing accompanying drawing 3): part has strong fluorescence (curve a), as itself and Cr 420nm3+Form complex(curve b) by serious cancellation near fluorescence rear 420nm.
Embodiment 2: the preparation of chromium (III) complex
Take 2.67g (10.0mmol) CrCl3·6H2O and 1.52g (10.0mmol) 3-methyl-salicylic acid is placed in 100mL round bottomIn flask, add 50mL ethanol, then add 1.0g arsenic-free zinc granule, agitating heating refluxes 2 hours, slowly adds 1mLTriethylene tetramine, the color of solution slowly becomes redness from green, continues agitating heating back flow reaction about 2 hours, cooling,Normal temperature volatilizees naturally, after 3 days, obtains red crystals, and productive rate is 75%.
Embodiment 3: the active application of hypoglycemic fat-reducing of chromium (III) complex
Test to verify that by feeding small white mouse the hypoglycemic fat-reducing of chromium (III) complex is active. Test small white mouse used by Shanxi Province's traditional Chinese medical scienceMedicine research institute Experimental Animal Center provides. We choose 48 of Kunming mouses, wherein male half and half, weight range 12~15g;15~25 DEG C of room temperature conditions, relative humidity 30%~40%, natural lighting, allows ad lib and drinking-water. Normal diet is by northJing Suolaibao Science and Technology Ltd. provides. High lipid food formula: general food 66.5%, sucrose 20%, lard 10%, cholesterol 2.5%With sodium taurocholate 1%. By body weight, mouse is divided into 4 groups at random, wherein 12 of normal group, 12 of model group, positive controls12,12 of administration groups. From experiment at the beginning, give normal group mouse normal diet, all the other respectively organize equal feeding high lipid food,Last 50 days, modeling success. Then start administration, wherein normal group and model group adopt physiological saline in contrast, positive rightAdopt Cr (Pic) according to group3The aqueous solution, Cr (Pic)3Dosage is 50mg/kg, and administration group adopts the aqueous solution of this chromic compound, dosageFor 60mg/kg, every morning 9:00 point gavage 1 time, Therapy lasted 9 weeks. In experimentation, there are indivedual animal injuries, finalEvery group of unification chosen 10 and added up. After experiment finishes, make mouse fasting 20 hours, point its body weight of another name, from eye socket veinGet blood, utilize related kit to measure every biochemical indicator. Each group data acquisition carries out statistical analysis with SPSS17.0, all dataAll withRepresent, group difference adopt one-way analysis of variance, with P < 0.05 for there being significant difference. Specific experiment resultStatistics is referring to table 2.
The every physiological and biochemical index of table 2 (n=10)
With normal group comparison, ▲ P < 0.05, ▲ ▲ p < 0.01; With model group comparison, * P ﹤ 0.05, * * P ﹤ 0.01
From table 2:
(1) there is significant difference in the indices of normal group compared with model group, illustrates that the high confectionery thing of high fat has caused mouse blood sugarSerum lipid concentrations obviously raises, and ldl concn improves, and high-density lipoprotein concentration reduces, and body weight increases;
(2) compared with model group, positive controls Cr (Pic)3Fat-reducing effect unsatisfactory. Except body weight slightly lowers,All there were significant differences for all the other indexs;
(3) and compared with model group, the blood sugar of administration group reduces, and T-CHOL and triglycerides all obviously reduce, high density fatAlbumen raises, and body weight obviously reduces.
Cr(Pic)3It is current general hypoglycemic slimming medicine in the world. In this experiment, compare and positive controls compoundCr(Pic)3, the novel chromic compound [Cr (3-CH of synthesized3-SA)(Trientine)]Cl·H2O has good physiology hypoglycemicFat-reducing is active. This may be due to: 1) from chemical bond bond distance, the bond distance of boundary sum is than Cr (Pic) in this complex3To grow,Illustrate that this complexes stability is compared with Cr (Pic)3A little less than, in metabolic process, be easy to dissociate, chromium transport protein in the easy body of chromium ionTranshipment, makes bioavailability high; 2) the 3-methyl-salicylic acid structure in this complex molecule is similar to aspirin, hasThe effect of inhibition platelet aggregation etc.; 3) this complex is NaCl type, good water solubility, and bio-absorbable utilization rate is high.

Claims (9)

1. chromium (III) complex, is characterized in that, structural formula is:
2. the preparation method of a kind of chromium as claimed in claim 1 (III) complex, is characterized in that, comprises the steps:
1) by chromic salts and 3-methyl-salicylic acid organic solvent dissolution, drop into zinc granule, add hot reflux 1~3 hour, then splash intoTriethylene tetramine, continues to reflux at least 1~2 hours, stops reaction, cooling, filters;
2) filtrate obtaining is left standstill, under normal temperature, volatilization naturally, obtained aubergine crystal after three days.
3. the preparation method of chromium as claimed in claim 2 (III) complex, is characterized in that step 1) described chromic salts isChromium chloride, chromic nitrate or chromium sulfate.
4. the preparation method of chromium as claimed in claim 2 (III) complex, is characterized in that step 1) described chromic salts,The amount of substance ratio of 3-methyl-salicylic acid and zinc granule is 1: 1: 0.5~1.65.
5. the preparation method of chromium as claimed in claim 2 (III) complex, is characterized in that step 1) described chromic salts andThe amount of substance of triethylene tetramine is than being 1:50~100.
6. by the preparation method of chromium claimed in claim 2 (III) compound, it is characterized in that step 1) described zinc granule is20~50 object arsenic-free zinc granules.
7. the preparation method of chromium as claimed in claim 2 (III) complex, is characterized in that step 1) described organic solventFor methyl alcohol or ethanol.
8. chromium as claimed in claim 1 (III) complex is in the application of preparing in hypoglycemic medicine.
9. chromium as claimed in claim 1 (III) complex is in the application of preparing in slimming medicine.
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CN106220556A (en) * 2016-07-21 2016-12-14 太原师范学院 A kind of metformin pyridinedicarboxylic acid closes Cr (III) coordination compound and preparation method
CN108658849A (en) * 2018-06-21 2018-10-16 太原师范学院 A kind of Cr (III) complex and its preparation method and application

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Cited By (4)

* Cited by examiner, † Cited by third party
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CN106220556A (en) * 2016-07-21 2016-12-14 太原师范学院 A kind of metformin pyridinedicarboxylic acid closes Cr (III) coordination compound and preparation method
CN106220556B (en) * 2016-07-21 2019-07-05 太原师范学院 A kind of melbine pyridinedicarboxylic acid closes Cr (III) complex and preparation method
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CN108658849B (en) * 2018-06-21 2021-08-13 太原师范学院 Cr (III) complex and preparation method and application thereof

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