Expanding manganese(IV) aqueous chemistry: unusually stable water-soluble hexahydrazide clathrochelate complexes

Mn cage complexes are rare, and the ones successfully isolated in the solid state are not stable in water and organic solvents. Herein, we present the first report of mononuclear...

Research antianemic action of the iron (IV) clathrochelate complexes on the sickling piglets

A lot of antianemic drugs for animals are presented on the modern pharmaceutical market of veterinary medicine, but they have several drawbacks. So finding new drugs with goal to treat ill animals by anemia and to prevent the iron deficiency anemia is a pressing issue. We previously reported the results of preclinical studies of iron in rare high valence IV. This allowed us to determine, supplement, and generalize the data on clinical studies of the new drugs with the active substance iron (IV) clathrochelate. Therefore, the article presents the results of studies of its antianemic effect on sickling piglets. Experiments were carried out on piglets-analogues neonates, which were divided into three groups: control and two experimental groups. Piglets were kept with sows on suckling. For the purpose of prevention iron deficiency anemia the traditional solution of iron dextran was administered once intramuscularly to piglets of I control group. The aqueous solution of iron (IV) clathrochelate complexes was administered once intramuscularly to piglets of II experimental group. Iron (IV) clathrochelate complexes was dissolved in a solvent of rheopolyglucin and administered once intramuscularly to piglets of III experimental group. 1 mL of test solutions contained 100 mg of active substance. The investigative material were the samples of blood and serum of piglets, their liver and spleen. The experiment lasted during a 30-day period since birth of piglets. According to the results of the experiments, iron (IV) clatrochelate complexes which was dissolved in a water for injection and rheopolyglucin had higher antianemic activity compared to the control. This is evidenced by the dynamics of probable changes in the number of erythrocytes, hemoglobin content and hematocrit, Iron content in serum and its mass fraction in the blood, liver and spleen of piglets. The effectiveness of the action of iron (IV) clatrochelate complexes is explained by the full supply of piglets with iron and its higher bioavailability.

Antianemic action of the iron (IV) clathrochelate complexes

Anemia is one of the most common non-contagious diseases of pigs. Modern antianemic drugs have several drawbacks, so finding new drugs is a pressing issue. We previously reported the results of preclinical studies of iron in rare high valence IV. This allowed us to determine, supplement, and generalize the data on clinical studies of the new drugs with the active substance iron (IV) clathrochelate. Therefore, we studied its antianemic effect on piglets. Experiments were carried out on piglets-analogues neonates, which were divided into three groups: control and two experimental groups. Piglets were kept with sows on suckling. For the purpose of prevention of iron deficiency anemia, the traditional solution of iron dextran was administered once intramuscularly to piglets of I control group. The aqueous solution of iron (IV) clathrochelate complexes was administered once intramuscularly to piglets of II experimental group. Iron (IV) clathrochelate complexes were dissolved in a solvent of rheopolyglucin and administered once intramuscularly to piglets of III experimental group. 1 mL of test solutions contained 100 mg of active substance. The investigative material were the samples of blood and serum of piglets, their liver and spleen. The experiment lasted during a 30-day period since the birth of the piglets. According to the results of the experiments, iron (IV) clatrochelate complexes which were dissolved in water for injection and rheopolyglucin had higher antianemic activity compared to the control. This is evidenced by the dynamics of probable changes in the number of erythrocytes, hemoglobin content and hematocrit, iron content in serum and its mass fraction in the blood, liver and spleen of piglets. The effectiveness of the action of iron (IV) clatrochelate complexes is demonstrated by the full supply of piglets with iron and its higher bioavailability.

Investigation of the irritant effects and allergenic properties of the Iron(IV) clathrochelate complexes

During the preclinical studies of new drugs, the study of the degree of manifestation of their irritant and allergenic effects affects subsequent clinical studies, for example the routes of administration, the need to add excipients to reduce irritation. The article presents the results of studies of the irritant effects and allergenic properties of the Iron in rare unconventional valence – IV. The irritant effect of the Iron(IV) clathrochelate complexes on the skin was studied comprehensively. 20 rabbits were divided into 4 groups (control and three experimental), 5 animals each. The ointment on the vaseline and aqueous solution of the Iron(IV) clathrochelate complexes was applied to the skin of rabbits of the experimental groups. Also this solution was introduced subcutaneously. The investigated dosage forms were used at a dose of 1 ml/kg body weight (based on the active ingredient 500 mg/kg body weight of the laboratory animal). The results of the studies showed that of the Iron(IV) clathrochelate complexes has no irritant properties when used externally and is characterized by a lack of local reaction by subcutaneous injection. Determination of allergenic properties was performed by detecting itching and swelling in the guinea pigs in animals which were sensitized with this substance. In addition, in order to assess the severity of the inflammatory reaction, the skin temperature was determined before the experiment and on the 20th day of the experiment, and the skin fold thickness was measured using a caliper. The results of the studies showed that there is no allergic action of the Iron(IV) clathrochelate complexes. The results of the ophthalmic test on laboratory animals confirmed the data obtained.Therefore, comprehensive studies of the irritant and allergenic effects of the Iron(IV) clathrochelate complexes were performed for the first time. The Iron(IV) clathrochelate complexes in the form of ointment and solution does not irritate the skin and mucous membranes and has no allergenic properties to the body of the laboratory animals.

Chronic toxicity of the Iron (IV) clathrochelate complexes for white rats

The article presents the results of studies of chronic toxicity of the Iron in the rare unconventional valence – IV. During long-term use of the Iron(IV) clathrochelate complexes for white rats we have established the dynamics of the body weight of rats, the relative coefficients of mass of the internal organs, the content of hemoglobin and morphological parameters of blood, biochemical parameters of blood serum of animals of this species. The daily drinking of solution of the Iron(IV) clathrochelate complexes at the doses of 500 and 1000 mg/kg b. w. resulted in a decrease in body weight, an increase in the relative indices of masses of liver and kidney, and a decrease in the relative indices of masses of spleen and heart on 30th day. The hemoglobin content in the blood of rats of the experimental group was less than the control indicator by 3–47% (P < 0.05), which is evidence of inhibition of its synthesis under the influence of the Iron (IV) clathrochelatе. Changes in the morphological composition of the blood were characterized by marked leukocytopenia. The use of rats of a solution of the Iron (IV) clathrochelate complexes at doses of 500 and 1000 mg/kg b. w. caused the development of hypoproteinemia, hypercreatinemia and hyperurinemia. Iron(IV) clathrochelate complexes reduced alaninaminotransferase activity in the serum of rats of both experimental groups by 15–80% (P < 0.05); aspartataminotransferase activity increased significantly by day 10 and decreased by day 30; the activity of alkaline phosphatase was independent of the doses of the drug during the experimental period. The content of Calcium total, Phosphor inorganic and Iron in the serum of rats of the experimental groups was at the level of indicators in the animals of the control group. Consequently, comprehensive studies of the effects of solution of the Iron (IV) clathrochelate complexes at doses of 500 and 1000 mg/kg b. w. were performed for the first time with long-term administration to white rats, which revealed the main patterns of metabolic disorders and physiological functions.

Influence of iron (IV) clathrochelate complexon quail blood parameters and weight characteristics

We studied the chronic toxicity of the compounds of Iron(iv). We monitored the dynamics of the body weight, relative weight coefficients of the internal organs, the content of the hemoglobin, the morphological parameters of blood, and biochemical parameters of serum of blood of quails after use of Iron(IV) clathrochelate complexes at the doses 1/10 and 1/5 DL50 them for 30 days. Daily drinking of quails of experimental groups of solution of Iron(IV) clathrochelate complexes3 at the doses 76.43 and 152.86 mg/kg of body weight caused the reduction of body weight by 3 and 5% respectively on the thirtieth day. A tendency to increase the relative weight of the kidneys and to decrease the relative weight of the liver, heart and spleen showed an excessive load of Iron(IV) clathrochelate complexes on the internal organs of quails. Hemoglobin in the blood of the quails of the experimental groups was less by 2-34% (P 0.05) than the control indicator but the indicator of the number of erythrocytes in the quails of the control and experimental groups for 30 days was within the physiological values. The use of Iron(IV) clathrochelate complexes caused the development of hypoproteinemia, hypoalbuminemia, and short-term hypoglycemia in the serum of the blood of the quails of the experimental groups. Changes in an activity of alanine aminotransferase and aspartate aminotransferase for 30 days were not expressed, but the activity of alkaline phosphatase was significantly higher compared to the control indicators during the experimental period. Drinking the solution of Iron(IV) clathrochelate complexes caused hypercreatinemia and hyperuricemia, which indicates a decrease in the filtration capacity of the kidney glomeruli. We have seen an increase in the levels total Calcium and inorganic Phosphorus.

Acute toxicity of the iron clathrochelate complexes

A new class of highly valent iron compounds is formed by atmospheric oxidation in aqueous media and it is extremely stable both in solid and soluble conditions and may exist indefinitely in a medium without signs of degradation. The first clathrochelate complexes of iron (IV) are infinitely stable in water and readily available from simple, commercially available, inexpensive source materials with surprisingly mild reaction conditions. To create new drugs on their bases, research on their toxicity is required. In this study, the results of preclinical studies of a new iron clathrochelates drug are presented. Experiments were carried out on white rats and quails, which in the previous experiment were divided into five experimental and two control groups. The solution of iron clathrochelate complexes was administered intragastrically in doses 50, 500, 1000, 2000 and 5000 mg/kg, respectively. Our results have shown that there were no grounds for using rats in the advanced experiment because the conducted research has established that iron clathrochelate is non toxic to rats. Thus, the minimum dose of iron clathrochelate complexes did not cause death of quails, and the largest dose caused 100% mortality. The basic experiment was conducted on 6 groups of birds, each consisting of 7 quails. The drug was administered in the following doses: 500, 600, 700, 800, 900, 1000 mg/kg. The monitoring observation of the laboratory birds lasted for 14 days. It has been established that the average lethal dose of clathrochelate of the investigated drug for internal administration in quails is 764 ± 33 mg/kg. According to the classification of chemicals by the degree of danger (State ST 12.1.007-76), iron (IV) clathrochelate complexes correspond to the third class of hazard, and according to the classification of substances for toxicity they are classified as category 4 (low toxicity substances). The prospect of further research is to investigate the pharmacological and toxicological properties of iron (IV) clathrochelate for chronic toxicity.

Porous networks based on iron(ii) clathrochelate complexes

Iron clathrochelate complexes were used for the preparation of microporous polymers. The networks display permanent porosity with apparent Brunauer–Emmett–Teller surface areas of up to SABET = 593 m2 g−1, and they are not susceptible to hydrolytic degradation.