The absorption efficiency of any drug in blood is of prime importance. Compounds having the general formula:
Folic acid as reported in the figure, N-(4
Structure of folic acid.
It has been shown that folic acid supplementation can significantly reduce the risk of these disorders [
All chemicals used in the present study are reagent grade,
Folic acid, Adwic
The following metal basic carbonates were used in preparing the solid folate complexes after determining their metal content after dissolution in the least amount of dilute nitric acid, by atomic absorption spectrometry
C, H, and N were determined at the microanalytical laboratory, Cairo and Ain Shams Universities using a Perkin Elmer 2400 CHN elemental analyzer. Copper and iron were determined by atomic absorption spectrometry (AAS), using Perkin Elmer AAS 3100. A given weight of the complex was heated with concentrated nitric acid nearly to dryness. The resulting metal nitrate was dissolved in distilled water and the solution made to volume in a measuring flask. Standard metal solution series is prepared by diluting calculated volumes of a standard stock solution of the metal to the mark in a volumetric flask. The hollow cathode lamp of our metals concerned are used, the current adjusted to the recommended value and the metal line. (
Thermogravimetric analysis was carried out using a Perkin-Elmer 7 Series thermal analyzer. The measurements were carried out under nitrogen atmosphere at a heating rate 10
Polarimetric measurement was recorded on a Courtesy Messrs, Hilgher and Watts, Ltd., London polarimeter. The field of view appears dark (which occurs when the axes of the two prisms are at right angles to each other).
I.R. spectra of the solid complexes were recorded on a Perkin-Elmer spectrometer Model Jasco FTIR-300E Fourier Transform Infrared Spectrometer, using KBr discs in the range 400–4000
The solubility of the prepared complexes was determined by shaking few milligrams of the complex with about 25 mL of aliquots of distilled water in a water thermostat at 25
Elemental analysis and solubility of the complexes.
Metal complexes | Solubility (g/L) | Metal | C | H | N | ||||
Cal % | Found % | Cal % | Found % | Cal % | Found % | Cal % | Found % | ||
2.18 g/L | 5.83 | 6.09 | 41.85 | 41.08 | 3.67 | 3.27 | 17.99 | 16.30 | |
1.67 g/L | 5.47 | 4.87 | 42.98 | 42.29 | 3.83 | 3.36 | 18.47 | 17.91 |
All animal experimental procedures had full approval from the Animal Ethics Committee of Menoufia University.
White albino mice were obtained from the experimental animal house of the Genetic Engineering & Biotechnology Institute, Menoufia University.
All mice had free access to commercial pelleted food and tap water. The mice were maintained at an ambient temperature of 22
A group of male mice was given orally 100 mg/kg body weight of folic acid or its complexes (copper-folate and iron-folate), all preparations are dissolved and suspended in distilled water, five individuals were used for each treatment of folic acid and its complexes. Two hours after treatment mice were killed and plasma collected for investigations.
Results of elemental analysis and some physical characteristics of the obtained complexes are shown in Table
The polarimeter consists of a monochromatic light source, a polarizer, a sample cell, a second polarizer, which is called the analyzer, and a light detector. The analyzer is oriented
Polarimetric measurements on solutions of the two complexes showed that both complexes possess no angle of rotation (
The expected structure of the two complexes
I.R. Spectrum of iron folate complex.
The essential infrared data are summarized in Table
IR frequencies (Cm1 ) of folic acid (FO) and its metal complexes.
Assignments | Compounds | ||
Folic acid | Fe-folate complex | Cu-folate complex | |
34213415 | 3381 | 3388 | |
3230 | 3175 | 3220 | |
31062926 | 30902930 | 30302930 | |
2840 | 28202770 | 28302805 | |
1652 | 1658 | 1655 | |
1718 | — | — | |
1569 | 1613 | 1603 | |
14831413 | 14481401 | 14451400 | |
1453 | 1369 | 1350 | |
1528 | 1520 | 1532 | |
1323 | 1303 | 1300 | |
123011911106 | 11851106 | 11861102 | |
971 | 980 | 955 | |
764 | 767 | 766 | |
— | 587520 | 585521 |
The direction of the frequency shift of the
Asymmetric and Symmetric Stretching Vibrations of the Carboxylate group.
Compound | Bonding mode | |||
---|---|---|---|---|
Folic acid | 1569 | 1453 | 116 | — |
1631 | 1369 | 262 | Mono dentate | |
1603 | 1350 | 253 | Mono dentate |
Thermal analysis curves (TG
TG and DTG of copper complex.
The thermal decomposition of iron folate complex, occurs completely in four steps. The first step in the range 50.7
Atomic absorption data (Tables
The concentration of Cu and Fe elements in mice blood serum in case of folic acid and folic acid metal complex.
Elements | Cu (mg/L) (After inject of folic acid) | Cu (mg/L) (after inject complex) | Fe (mg/L) (after inject of folic acid) | Fe (mg/L)(after inject complex) |
---|---|---|---|---|
Mice 1 | 5.1 | 6.4 | 7.9 | 12.4 |
Mice 2 | 4.8 | 6.9 | 8.3 | 13.2 |
Mice 3 | 4.9 | 7.6 | 7.7 | 11.8 |
Mice 4 | 5.1 | 7.2 | 9.2 | 14.7 |
Mice 5 | 5.1 | 6.9 | 10.2 | 16.9 |
Comparison between the normal, folic acid case and folic acid metal complex case percentage of Cu and Fe elements in the serum of mice.
Metal ion | Normal concentration in the blood mg/L | After inject of folic acid mg/L | After inject complex mg /L |
---|---|---|---|
Cu (mg/L) | 1.18 | 5.00 | 7 |
Fe (mg/L) | 2.1 | 9.2 | 13.8 |
Inspection of the results shown in Table
This may be explained as being due to the high solubility differences between folic acid which is considered as an insoluble material, and its copper and iron complexes are shown in Table
The complexation between transition metal ions as (Fe(