Iron chelates in the anticancer therapy

Iron plays a significant role in the metabolism of cancer cells. In comparison with normal cells, neoplastic ones exhibit enhanced vulnerability to iron. Ferric ions target tumor via the ferroptotic death pathway—a process involving the iron-mediated lipid oxidation. Ferric ion occurs in complex forms in the physiological conditions. Apart from iron, ligands are the other factors to affect the biological activity of the iron complexes. In recent decades the role of iron chelates in targeting the growth of the tumor was extensively examined. The ligand may possess a standalone activity to restrict cancer’s growth. However, a wrong choice of the ligand might lead to the enhanced cancer cell’s growth in in vitro studies. The paper aims to review the role of iron complex compounds in the anticancer therapy both in the experimental and clinical applications. The anticancer properties of the iron complex rely both on the stability constant of the complex and the ligand composition. When the stability constant is high, the properties of the drug are unique. However, when the stability constant remains low, both components—ferric ions and ligands, act separately on the cells. In the paper we show how the difference in complex stability implies the action of ligand and ferric ions in the cancer cell. Iron complexation strategy is an interesting attempt to transport the anticancer Fe2+/3+ ions throughout the cell membrane and release it when the pH of the microenvironment changes. Last part of the paper summarizes the results of clinical trials and in vitro studies of novel iron chelates such as: PRLX 93,936, Ferumoxytol, Talactoferrin, DPC, Triapine, VLX600, Tachypyridine, Ciclopiroxamine, Thiosemicarbazone, Deferoxamine and Deferasirox.

EXTRACTION CONCENTRATING OF SCANDIUM (III) IN COMPLEX FORM WITH 2-HYDROXY-5-T-BUTYLPHENOL-4-METOXYAZOBENZENE AND ITS DETERMINATION BY ATOMIC-ABSORPTION SPECTROMETRY

Complexation of scandium 2-hydroxy-5-T-butylphenol-4-metoxyazobenzene (HR) was studied by atomic-absorption and spectrophotometric methods. Optimum conditions of formation and extraction of the complex were found. Maximum light absorbance of a complex in n-butanol is in the range of 470÷480 nm. Molar absorption coefficient equals to (2.2–3.0).104. Stability constant of scandium in n-butanol is л=2.8·1010. Selective and sensitive techniques of extraction-atomic absorption determination of scandium in soils were developed

SYNTHESIS OF NEW SUBSTITUTED PROCAINE HYDROCHLORIDE COMPOUNDS AND THEIR USE IN SPECTROPHOTOMETRIC DETERMINATION OF TETRACYCLINE HYDROCHLORIDE THROUGH DIAZOTIZATION-COUPLING REACTIONS

Background: Tetracycline is one of the most important antibiotics. It is used to treat many different bacterial infections. It is often used in treating severe acne, or sexually transmitted diseases such as syphilis, gonorrhea, or chlamydia. In some cases, tetracycline is used when penicillin or another antibiotic cannot be used to treat serious infections such as the ones caused by Bacillus anthracis, Listeria, Clostridium, Actinomyces. Aim: synthesized a new novel reagent used to determine TCH spectrophotometrically by using diazonium and coupling reaction. Methods: Four new substituted procaine derivatives were prepared by simple organic methods using aniline derivatives. A spectrophotometric approach was established for the micro-determination of TCH. The stoichiometry was investigated using mole ratio and continuous variation methods, and the stability constant was also estimated. The ΔG, ΔH, and ΔS were determined as thermodynamic parameters for evaluating the effect of temperature on the reaction. Results: Substituted procaine derivatives were prepared, and o-hydroxy procaine seems to be the best reagent used to determine TCH by diazotization and coupling reaction. The result was a yellow water-soluble dye with a maximum absorbance of 380 nm. The reaction conditions were studied and optimized. Beers law was obeyed over a concentration range (2.5–50) μg.mL-1 for TCH. The molar absorptivity was (14.4669.103) L.mol-1.cm-1, and the detection limit was (0.5052) μg.mL-1. The stoichiometry of the formed product was found 1:1 (o-hydroxyprocaine: TCH). The stability constant indicated that the product formed was stable, and the thermodynamic parameters showed that the diazonium salt reaction was preferred to occur at a low temperature. Conclusions: a simple, accurate, and fast method was developed to determine TCH in pure form and pharmaceuticals by coupling the TCH with a newly synthesized procaine derivative reagent (o-hydroxy procaine) in a basic medium.

Uranium migration through the Swiss Opalinus Clay varies on the metre scale in response to differences of the stability constant of the aqueous, ternary uranyl complex Ca₂UO₂(CO₃)₃

The simulation of uranium migration through the Swiss Opalinus Clay is used as an example to quantify the influence of varying values of a stability constant in the underlying thermodynamic database on the migration lengths for the repository scale. Values for the stability constant of the neutral, ternary uranyl complex Ca2UO2(CO3)3 differ in literature by up to one order of magnitude. Within the studied geochemical system, either the neutral or the anionic complex CaUO2(CO3)32- is the predominant one, depending on the chosen value for the neutral complex. This leads to a changed interaction with the diffuse double layers (DDL) enveloping the clay minerals and thus can potentially influence the diffusive transport of uranium. Hence, two identical scenarios only differing in the value for the stability constant of the Ca2UO2(CO3)3 complex were applied in order to quantify and compare the migration lengths of uranium on the host rock scale (50 m) after a simulation time of one million years. We ran multi-component diffusion simulations for the shaly and sandy facies in the Opalinus Clay. A difference in the stability constant of 1.33 log units changes the migration lengths by 5 to 7 m for the sandy and shaly facies, respectively. The deviation is caused by the anion exclusion effect. However, with a maximum diffusion distance of 22 m, the influence of the stability constant of the Ca2UO2(CO3)3 complex on uranium migration in the Opalinus Clay is negligible on the host rock scale.

Synthesis and study of complexes of the novel Russian antiviral drug Camphecene with Plant’s Flavonoids

Traditionally, glycyrrhizic acid has been used to form polydentate complexes. For the first time in the presented paper, the complexation of the Plant’s Flavonoids (Quercetin (Qu) and its glycoside - Rutin (Rut)) with the novel Russian antiviral drug Camphecene (Camph) was investigated. The complexes obtained at different molar ratios were studied using UV/Vis spectroscopy. Formation of the host: guest complexes were registered: Qu and Rut molecular complexes (Camph+2Qu; Camph+2Rut) with a stability constant K = 3.3·108 M-2. Comparison of the binding constants of the obtained complexes shows that the efficiency of Camphecene complexation with the participation of flavonoids is more efficient than with the participation of triterpenoids. Besides, it was found that the complexes of Camphecene with the quercetin and rutin are soluble in water, in contrast to the complexes with triterpenoids, which makes it possible to increase the bioavailability of both Camphecene and flavonoids. The obtained results demonstrate the high potential of flavonoids Qu and Rut to the development of novel pharmaceutical forms using the example of Camphecene in the form of molecular complexes, as the novel forms of delivery.

Synthesis, Complexation Properties, and Evaluation of New Aminodiphosphonic Acids as Vector Molecules for 68Ga Radiopharmaceuticals

Two new aminodiphosphonic acids derived from salicylic acid and its phosphonic analogue were prepared through a simple and efficient synthesis. 2-[(2-Amino-2,2-diphosphono)ethyloxy]-benzoic acid 8 and 2-[(2-amino-2,2-diphosphono)ethyloxy]-5-ethyl-phenylphosphonic acid 9 were evaluated for their applicability as 68Ga binding bone-seeking agents. Protonation constants of 8 and 9 and stability constants of the Ga3+ complexes with 8 and 9 in water were determined. The stability constant of Ga3+ complex with fully phosphorylated acid 9 (logKGaL = 31.92 ± 0.32) significantly exceeds stability constant of Ga3+ complex with 8 (logKGaL = 26.63 ± 0.24). Ligands 8 and 9 are as effective for Ga3+ cation binding as ethylenediamine-N,N’-diacetic-N,N’-bis(methy1enephosphonic) acid and ethylenediamine-N,N,N’,N’-tetrakis(methylenephosphonic) acid, respectively. The labelling process and stability of [68Ga]Ga-8 and [68Ga]Ga-9 were studied. Both 8 and 9 readily form 68Ga-complexes stable to ten-fold dilution with saline. However, in fetal bovine serum, only [68Ga]Ga-9 was stable enough to be subject to biological evaluation. It was injected into rats with bone pathology and aseptic inflammation of soft tissues. For [68Ga]Ga-9 in animals with a bone pathology model in 60 and 120 min after injection, a slight accumulation in the pathology site, stable blood percentage level, and moderate accumulation in the liver were observed. For animals with an aseptic inflammation, the accumulation of [68Ga]Ga-9 in the pathology site was higher than that in animals with bone pathology. Moreover, the accumulation of [68Ga]Ga-9 in inflammation sites was more stable than that for [68Ga]Ga-citrate. The percentage of [68Ga]Ga-9 in the blood decreased from 3.1% ID/g (60 min) to 1.5% ID/g (120 min). Accumulation in the liver was comparable to that obtained for [68Ga]Ga-citrate.

Does a stability constant decide on a repository permit?

<p>Safety of a nuclear waste repository is based to a large extent on the isolation of the radioactive waste within a suitable host rock. Clay rocks provide an option due to their very low hydraulic conductivity only allowing diffusive transport. Diffusion processes in clay formations are complex due to the diffuse double layers (DDL) enveloping the clay minerals to compensate their net surface charge and the associated different migration behaviour for cationic, anionic and neutral species. Therefore, determination of the speciation of an element in the porewater is essential to quantify migration lengths precisely. Safety assessments are based on numerical simulations to cover time periods of up to one million years and thus the predominant species of a radionuclide, dependent on the stability constants within the law of mass action, might be signififcant.</p><p>In the present study, we use uranium, one of the main components in spent fuel, as an example for the diffusion in the Swiss Opalinus Clay, a potential host rock for the storage of nuclear waste. In the geochemical system, uranium is mainly present as U(VI) in ternary uranyl complexes with calcium and carbonate, whereby speciation depends on the selected thermodynamic data (Hennig et al., 2020). For instance, the stability constants for the neutral uranyl complex Ca<sub>2</sub>UO<sub>2</sub>(CO<sub>3</sub>)<sub>3</sub> differ slightly in literature. Depending on the selected one, either the neutral or the anionic complex CaUO<sub>2</sub>(CO<sub>3</sub>)<sub>3</sub><sup>2-</sup> is the predominant species in the system with an associated varying interaction with the DDL of the clay minerals. With our one-dimensional, multi-component diffusion models we quantified the effect of the selected stability constant on the diffusion length for the host rock scale.</p><p>The chemistry in the porewater of the three facies of the Opalinus Clay, shaly, sandy and carbonate-rich, plays a key role for the sorption processes (Hennig et al., 2020) as well as for the composition and thickness of the DDL and therewith the diffusive transport. Based on our results, we show, that the influence of the predominant uranium species on the migration lengths varies between the individual facies, but is overall negligible for the host rock scale. Consequently, a stability constant is not decisive for the required thickness of the host rock as geological barrier.</p><p> </p><p>Hennig, T.; Stockmann, M.; Kühn, M. Simulation of diffusive uranium transport and sorption processes in the Opalinus Clay. Applied Geochemistry 2020, 123. doi:10.1016/j.apgeochem.2020.104777.</p>

Nano Synthesis and Characterization of Complex Derived from Silver Metal Conjugated with Midodrine Hydrochloride

The stability constant Kf for the complexation of Ag(Ⅰ) metal ion with Midodrine hydrochloride were determinedby spectrophotometric method at room temperature .The colored complexes were measured at 300 nm. The stability constant of the complexes were found to be 5.47 by mole ratio method. The stoichiometry of the complexes formed between the Midodrine drug and Ag (Ⅰ) metal ion are 1:1 M/L ratio. Silver conjugated Midodrine hydrochloride Nano synthesized and characterized by UV/Visible spectroscopy, SEM, XRD and FT-IR. The UV/Visible spectra of Midodrine –Ag nanoparticle in the range of 322 nm. XRD conformThe crystallite size of Midodrine - Ag (Ⅰ) nanoparticles are found to be 64.5 nmfrom Debye Scherer formula.Thecrystallinity of nanoparticles is Face centered cubic structure. SEM conform of particle size and surface morphology, FTIR analyzed involvement of -NH2 group in Midodrine is the stabilized of silver nanoparticle. This research is focuses on complexation, Nano synthesis and characterization of Drug-silver nanoparticle for antihypotention therapy.