Sinteza, karakterizacija i ispitivanje mehanizma supstitucionih reakcija kompleksa nekih jona prelaznih metala

Sinteza novih kompleksnih jedinjenja jona prelaznih metala i njihova karakterizacija od velikog su značaja ne samo u koordinacionoj hemiji, već i u bioneorganskoj i medicinskoj hemiji. Primena kompleksa jona prelaznih metala u biologiji, farmaciji, medicini, poljoprivredi je predmet istraživanja mnogih naučnika. Neki joni metala su gradivni elementi biomolekula, dok neki ulaze u sastav mnogobrojnih lekova koji se već dugi niz godina koriste u medicini. Otkrićem antitumorskog dejstva cisplatine od strane B. Rozenberga 60-ih godina dvadesetog veka otpočela je prava revolucija u terapiji teških bolesti lekovima na bazi kompleksa jona prelaznih metala. Mnogobrojna istraživanja u ovoj oblasti dovela su do toga da se danas pored cisplatine i neki drugi kompleksi Pt(II), kao što su karboplatina i oksaliplatina, intenzivno koriste u hemoterapiji. Poslednjih 40 godina veliki broj drugih kompleksa platine sintetisan je sa ciljem da se postigne bolja aktivnost u odnosu na cisplatinu. Takođe, već duži niz godina predmet istraživanja mnogobrojnih naučnika su derivati pirazola i njihovi kompleksi sa prelaznim metalima. Pirazoli su vrlo pogodni za sintezu raznih organskih jedinjenja koja mogu imati različitu primenu. Od važnijih proizvoda mogu se istaći biološki aktivni molekuli koji se koriste u medicini kao aktivne komponente nekih komercijalnih lekova, dok se neki koriste u poljoprivredi kao pesticidi (herbicidi, fungicidi, insekticidi, itd.). Jedan od glavnih ciljeva bioneorganske hemije je razjašnjavanje mehanizama delovanja kompleksa jona metala u biološkim sistema. Za ispitivanje kinetike i mehanizma supstitucionih reakcija kompleksa Pt(II) kompleksi Pd(II) predstavljaju pogodne modele, uzimajući u obzir činjenicu da kompleksi Pd(II) reaguju 103-105 puta brže od analognih kompleksa Pt(II). Zbog velikog afiniteta prema sumpor- i azot- donorskim ligandima, kao i velike reaktivnosti, selektivnost kompleksa Pd(II) prema biomolekulima je mala, što ograničava upotrebu ovih jedinjenja kao antitumorskih agenasa. Međutim, poslednjih godina utvrđeno je da neki kompleksi Pd(II) ipak poseduju antitumorsku aktivnost.The synthesis of new complex compounds with transition metal ions and their characterization are of great importance, not only in coordination chemistry, but also in bioinorganic chemistry and medicinal chemistry. Application of transition metal complexes in biology, pharmacy, medicine, agriculture is subject of research of many scientists. Some of metal ions are building blocks of biomolecules, while some of them are part of many drugs that are already used for many years in medicine. Discovery of antitumor activity of cisplatin by B. Rosenberg during the 60’s of the twentieth century started a real revolution in treatment of severe disease drugs based on transition metal ion complexes. Most of results in this field have contributed that today, beside cisplatin, other complexes of Pt(II), such as carboplatin and oxaliplatin, are used extensively in chemotherapy. In the past 40 years a large number of other platinum complexes were synthesized in order to obtain a compound with better activity than cisplatin. Also, for many years, pyrazole based compounds and their transition metal complexes have attracted considerable research interest. The pyrazoles are very suitable for obtaining various organic compounds, which can have different applications. The most important products are biologically active molecules which are used in medicine as active components of some commercial drugs, while some are used in agriculture as pesticides (herbicides, fungicides, insecticides, etc.). One of the main aims of bioinorganic chemistry is to clarify the mechanism of interactions of metal complexes in biological systems. For the study of kinetics and mechanism of substitution reactions of Pt(II) complexes, Pd(II) complexes are very suitable models, taking into account the fact that Pd(II) complexes react 103-105 times faster than their Pt(II) analogous. Due to the very high affinity for sulfur and nitrogen donor ligands, as well as very high reactivity, the selectivity of Pd(II) complexes toward bio-molecules is small. In addition, these facts limit the application of Pd(II) complexes as antitumor agents. However, in recent years it was established that some complexes of Pd(II) possess antitumor activity

Ternary flower-structured nanoferrites with polyvalent cations for potential applications in electrochemical sensors and magnetic hyperthermia

Nanoferrites have been intensively studied because of the possibility of their use in the fields such as medicine, sensors, environmental, agriculture, weather, battery, etc. Often, they are used as modal systems in fundamental science to study physical and chemical phenomena at the nanoscale. Various pathways were applied for the synthesis of nanoferrites with the same composition were led to different microstructure and structure properties, which further influenced magnetic, electric, catalytic and other properties. Consequently, with a controlled synthesis, it is possible to tune the properties of nanoferrites important for applications. On the other side, properties can be controlled by changing chemical composition. In ternary nanoferrites often deviation of stoichiometry accompanied with cation polyvalence was found [1]. The main idea of our work was the application of the polyol-modified method developed for the synthesis of flower-structured iron oxides nanoparticles in the preparation of ternary ZnxMnyFezO4 samples to seek a correlation among chemical composition and microstructure with magnetic hyperthermia efficiency and electrochemical properties. A series of the samples ZnxMnyFezO4 was prepared by polyol process using a slightly modified procedure described in ref [2]. By elemental analysis performed using the ICP technique, the content of cations in the formula unit was determined as follow: Zn0.640Fe2.360O4, Zn0.394Mn0.138Fe2.468O4, Zn0.309Mn0.240Fe2.451O4, Zn0.182Mn0.344Fe2.474O4, Zn0.098Mn0.447Fe2.455O4, Mn0.624Fe2.376O4. The ICP results pointed to the presence of multivalent cations, Mn2+/Mn3+ and Fe3+/Fe2+. Zn has stable valence +2, while the oxidation state of +4 for Mn couldn’t be excluded. Different oxidation states of Mn and Fe and possible deviation of stoichiometry, can create physical effects [3] and make ZnxMnyFezO4 suitable material in practical applications, used for modification of working electrodesin electrochemical sensors. Consequently, we have performed basic electrochemical characterisation of nanoferrites. Cyclic voltammetry of 5 mM K3[Fe(CN)]6/K4[Fe(CN)]6 (1:1) in 0.1 M KCl at bare SPCE and ZnxMnyFezO4-modified SPCE showed that the highest peak current (Ip) was achieved using a Zn0.098Mn0.447Fe2.455O4/SPCE. The Ip was about 22% higher than the bare electrode. X-ray diffraction pattern showed the samples were single-phase crystallising in spinel structure type. Morphology and particle size of the samples were analysed from TEM micrographs. Particles (or crystallites) were agglomerated in a flower-like structure (Figure 1). The diameter of the flowers was around 50-60 nm. Superparamagnetic behaviour of the samples was found from magnetization versus field measurements (hysteresis loops). Prepared samples were in the form of stable colloids with hydrodynamic diameter in the range of 50-120 nm. The heating properties of the samples were analysed from the data of specific absorption rate (SAR), Figure 1b. The highest SAR value was found for Zn0.098Mn0.447Fe2.455O4. The best heating efficiency and electrochemical properties had the same sample. To correlate ZnxMnyFezO4 different efficiency in magnetic hyperthermia and electrochemical sensor applications with parameters like cation distribution in two non-equivalent spinel crystallographic sites (space group, Fd-3m), local distortion on cationic sites, crystallite size and defects, an integrated study of samples structure and microstructure is in progress

Exploring the Pharmacokinetic Properties of (NH4)4[Fe(idadtc)2]: In Silico Biological screening and ADMET analysis

Carbonic anhydrases (CA) have been identified in the early ‘50s as potential targets for the treatment of numerous diseases, including cancer, glaucoma, epilepsy, etc. Current inhibitors, i.e., treatment options, offer high efficacy coupled with a high probability of various side-effects. On the other hand, dithiocarbamates and their metal complexes are known for being good CA inhibitors. In this paper, a novel Fe (II) dithiocarbamato complex was investigated for its biological and pharmacological properties using a combination of different in silico methodologies. It was found that this water soluble, almost non-toxic (LD50 values around 4860 mg/kg), druglike compound shows high inhibitory potential towards CA II. However, it also shows slow gastro-intestinal absorption, which means that, if ever used as a pharmacological agent, in its present form cannot be orally administrated. Binding energies with the value of -7.8 kcal mol-1 indicate reversible binding to human serum albumin, which can serve as a delivery system for the investigated compound. Overall, the obtained results indicate a high potential of (NH4)4[Fe(idadtc)2] to be an effective CA II inhibitor.Publishe

Synthesis, crystal structure and biological activity of copper(II) complex with 4-nitro-3-pyrazolecarboxylic ligand

The reaction of 4-nitro-3-pyrazolecarboxylic acid and Cu(OAc)2⋅H2O in ethanol resulted in a new coordination compound [Cu2(4-nitro-3- -pzc)2(H2O)6]2H2O (4nitro-3pzc = 4-nitro-3-pyrazolecarboxylate). The compound was investigated by means of single-crystal X-ray diffraction and infrared spectroscopy. The biological activity of the complex was also tested. In the crystal structure of [Cu2(4nitro-3-pzc)2(H2O)6]2H2O, the Cu(II) ion is in a distorted [4+2] octahedral coordination due to the Jan–Teller effect. A survey of the Cambridge Structural Database showed that the octahedral coordination geometry is generally rare for pyrazole-bridged Cu(II) complexes. In the case of Cu(II) complexes with the 3-pyrazolecarboxylato ligands, no complexes with a similar octahedral coordination geometry have been reported. Biological research based on determination of the inhibition effect of the commercial fungicide Cabrio top and the newly synthesized complex on Ph. viticola were performed using the phytosanitary method

Superparamagnetic cobalt substituted iron oxide nanoparticles as heat source in magnetic hyperthermia: influence cobalt concentration on Specific Loss Power

When magnetic nanoparticles (MNPs) are placed in an alternating (ac) magnetic field, they absorb the energy of the field and convert it into heat, which causes a temperature change in the system. Consequently, it makes them suitable for cancer treatment with magnetic hyperthymia

The crystal structure of bis[4-bromo-2-(1H-pyrazol-3-yl) phenolato-κ2N,O] copper(II), C18H12Br2CuN4O2

C 18 H 12 Br 2 CuN 4 O 2 , monoclinic, P 2 1 / c (no. 14), a  = 11.5165(11) Å, b  = 5.4369(5) Å, c  = 14.4872(14) Å, V  = 873.52(14) Å 3 , Z  = 2, R gt ( F ) = 0.0232, wR ref ( F 2 ) = 0.0559, T  = 200 K

Crystal structure of ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate, C7H7F3N2O2

C7H7F3N2O2, monoclinic, P21/m (no. 11), a = 6.8088(8) Å, b = 6.7699(9) Å, c = 9.9351(12) Å, β = 105.416(3)°, V = 441.48(9) Å 3 , Z = 2, R gt ( F ) = 0.0398, wR ref ( F 2 ) = 0.1192, T = 200(2) K

Self-Heating Flower-like Nanoconstructs with Limited Incorporation of Yttrium in Maghemite: Effect of Chemical Composition on Heating Efficiency, Cytotoxicity and Genotoxicity

Partial cation substitution can significantly change the physical properties of parent compounds. By controlling the chemical composition and knowing the mutual relationship between composition and physical properties, it is possible to tailor the properties of materials to those that are superior for desired technological application. Using the polyol synthesis procedure, a series of yttrium-substituted iron oxide nanoconstructs, γ-Fe2−xYxO3 (YIONs), was prepared. It was found that Y3+ could substitute Fe3+ in the crystal structures of maghemite (γ-Fe2O3) up to a limited concentration of ~1.5% (γ-Fe1.969Y0.031O3). Analysis of TEM micrographs showed that crystallites or particles were aggregated in flower-like structures with diameters from 53.7 ± 6.2 nm to 97.3 ± 37.0 nm, depending on yttrium concentration. To be investigated for potential applications as magnetic hyperthermia agents, YIONs were tested twice: their heating efficiency was tested and their toxicity was investigated. The Specific Absorption Rate (SAR) values were in the range of 32.6 W/g to 513 W/g and significantly decreased with increased yttrium concentration in the samples. Intrinsic loss power (ILP) for γ-Fe2O3 and γ-Fe1.995Y0.005O3 were ~8–9 nH·m2/Kg, which pointed to their excellent heating efficiency. IC50 values of investigated samples against cancer (HeLa) and normal (MRC-5) cells decreased with increased yttrium concentration and were higher than ~300 μg/mL. The samples of γ-Fe2−xYxO3 did not show a genotoxic effect. The results of toxicity studies show that YIONs are suitable for further in vitro/in vivo studies toward to their potential medical applications, while results of heat generation point to their potential use in magnetic hyperthermia cancer treatment or use as self-heating systems for other technological applications such as catalysis

Kinetics and mechanism of the substitution reactions of some monofunctional Pd(II) complexes with different nitrogen-donor heterocycles

<div><p>Substitution reactions of five monofunctional Pd(II) complexes, [Pd(terpy)Cl]⁺ (terpy = 2,2′;6′,2″-terpyridine), [Pd(bpma)Cl]⁺ (bpma = bis(2-pyridylmethyl)amine), [Pd(dien)Cl]⁺ (dien = diethylenetriamine or 1,5-diamino-3-azapentane), [Pd(Me₄dien)Cl]⁺ (Me₄dien = 1,1,7,7-tetramethyldiethylenetriamine), and [Pd(Et₄dien)Cl]⁺ (Et₄dien = 1,1,7,7-tetraethyldiethylenetriamine), with unsaturated N-heterocycles such as 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr), 1,2,4-triazole, pyrazole, pyrazine, and imidazole were investigated in aqueous 0.10 M NaClO₄ in the presence of 10 mM NaCl using variable-temperature stopped-flow spectrophotometry. The second-order rate constants <i>k</i>₂ indicate that the reactivity of the Pd(II) complexes decrease in the order [Pd(terpy)Cl]⁺ > [Pd(bpma)Cl]⁺ > [Pd(dien)Cl]⁺ > [Pd(Me₄dien)Cl]⁺ > [Pd(Et₄dien)Cl]⁺. The most reactive nucleophile of the heterocycles is pyrazine, while the slowest reactivity is with pyrazole. Activation parameters were determined for all reactions and negative entropies of activation, Δ<i>S</i>^≠, supporting an associative mode of substitution. The reactions between [Pd(bpma)Cl]⁺ and 1,2,4-triazole, pzI, and pzBr were also investigated by ¹H NMR to define the manner of coordination. These results could be useful for better explanation of structure-reactivity relationships of Pd(II) complexes as well as for the prediction of potential targets of Pd(II) complexes toward common N-heterocycles, constituents of biomolecules and different N-bonding pharmaceutical agents.</p></div

First crystal structures of metal complexes with a 4-nitropyrazole-3-carboxylic acid ligand and the third crystal form of the ligand

Pyrazole (pz)-derived ligands can, besides exhibiting a strong coordination ability toward different metal ions, exhibit a great diversity in their coordination geometry and nuclearity, which can be achieved by varying the type and position of the pz substituents. The present study reports the synthesis and crystal structure of two binuclear complexes, namely bis(μ-4-nitro-1 H -imidazol-1-ide-5-carboxylato)-κ 3 N 1 , O : N 2 ;κ 3 N 2 : N 1 , O -bis[aqua(dimethylformamide-κ O )copper(II)], [Cu 2 (C 4 HN 3 O 4 ) 2 (C 3 H 7 NO) 2 (H 2 O) 2 ], (II), and bis(μ-4-nitro-1 H -imidazol-1-ide-5-carboxylato)-κ 2 N 1 , O : N 2 ;κ 2 N 2 : N 1 , O -bis[triaquacobalt(II)] dihydrate, [Co 2 (C 4 HN 3 O 4 ) 2 (H 2 O) 6 ]·2H 2 O, (III). These compounds represent rare examples of metal complexes comprising 3,4-substituted pz derivatives as a bridging ligand and also the first crystal structures of transition-metal complexes with ligands derived from 4-nitropyrazole-3-carboxylic acid. Recently, the crystal structures of the same ligand in the neutral and mixed neutral/anionic forms have been reported. We present here the third form of this ligand, where it is present in a fully deprotonated anionic form within a salt, i.e. ammonium 4-nitropyrazole-3-carboxylate, NH 4 + ·C 4 H 2 N 3 O 4 − , (I). Single-crystal X-ray diffraction revealed that in the present complexes, the Cu II and Co II centres adopt distorted square-pyramidal and octahedral geometries, respectively. In both cases, the N , N ′, O -coordinated pz ligand shows simultaneously chelating and bridging coordination modes, leading to the formation of a nearly planar six-membered M 2 N 4 metallocycle. In all three crystal structures, the supramolecular arrangement is controlled by strong hydrogen bonds which primarily engage the carboxylate O atoms as acceptors, while the nitro group adopts the role of an acceptor only in structures with an increased number of donors, as is the case with Co II complex (III). The electrostatic potential, as a descriptor of reactivity, was also calculated in order to examine the changes in ligand electrostatic preferences upon coordination to metal ions