Enzymes as a platform for drug development

Polyoxometalates are negatively charged polyanions containing early transition metal ions in their high oxidation state surrounded by bridged oxygen. Firstly, these metal-based clusters were used as promising agents in electron-dense imaging, separations, catalysis, and analysis. In recent years, numerous studies in vitro and in vivo found that these nanocomplexes possess a variety of biological effects including antidiabetic, anticancer, and antibiotic actions. Despite these observed properties, the mechanism of their biological activities has not been completely elucidated so far. On the other hand, the results of enzymatic studies revealed their inhibiting influence on physiologically important extracellular enzymes such as phosphatases, esterases, and ecto-nucleotidases, which are considered target enzymes for the approved biological actions. Accordingly, the overview of the in vitro influence of selected polyoxo-vanadates, -tungstates, and – palladates on cholinesterase, ATPase, and phosphatase activities will be given in this presentation. Cholinesterases, enzymes located on the postsynaptic plasma membrane, have a key role in nerve impulse transmission and were confirmed as the targets of drugs for neurological diseases, which are regularly used in clinical practice. Moreover, ATPases and phosphatases were found to be included in the proliferation and migration of tumor cells, thus the inhibition of these enzymes was found as the mechanism of some anticancer drug actionSimpozijum „Stremljenja i novine u medicini“ Medicinskog fakulteta u Beogradu, Beograd, 04-08. decembra, 2023

Keggin Structure, Quō Vādis?

Working under the supervisor of William Lawrence Bragg at the University of Manchester and being under the direct personal and scientific influence by Linus Pauling, Dr. James Fargher Keggin some 85 years ago published a highly unique discovery—the structure of phosphotungstic acid (Nature 1933, 131, 908–909). This structure sparked the reports of other related polyanions from Keggin's contemporaries, marking the true beginnings of structural polyoxometalate chemistry. In this perspective article, we unveil some aspects and applications of Keggin's structure and discuss how it has shaped the course of our understanding of polyoxometalate chemistry and nanomolecular metal oxides/hydroxides in general

Poly[µ2-L-alanine-µ3-nitrato-sodium(I)]

The title compound, [Na(NO3)(C3H7NO2)](n), was obtained unintentionally as the product of an attempted reaction of sodium molybdate in aqueous solution and the amino acid L-alanine ( ala), in order to obtain a gamma-type octamolybdate, Na-4[Mo8O26(ala)(2)].18H(2)O, coordinated by L-alanine. The coordination geometry around the Na atom can be considered as trigonal-bipyramidal, with three bidentate nitrate anions coordinating through their O atoms and two L-alanine molecules each coordinating through one carboxylate O atom

Exploring polyoxometalates as non-destructive staining agents for contrast-enhanced computed tomography

Due to the high complexity and heterogeneous structure of biological tissues, imaging techniques that allow for precise and quantitative structural analyses of such materials are of high importance. These techniques could also advance clinical translation of regenerative medicine by providing better insights in tissue development and disease. The standard techniques for evaluating biological tissues such as histological sectioning and staining, have a high discriminative power, but allow assessment of the tissue distribution only in two dimensions. Due to restricted sectioning orientation and limited depth resolution, this leads to loss of information in three dimensions (3D), and therefore, more precise imaging of the 3D microstructure and spatial interrelationships of the different tissues within organs is crucial. MicroCT can provide full 3D structural information of mineralized tissues and dense biomaterials. However, the intrinsic low X-ray absorption of soft tissues requires contrast-enhancing staining agents (CESAs) to be used. We have shown that a range of polyoxometalate clusters (POMs) can be excellent non-destructive staining agents for high-resolution contrast-enhanced microCT (CE-CT) visualization of various tissues, of bone and its marrow vascularization and adiposity. A range of Wells-Dawson POMs, differing in structure and overall charge, has been synthesized and evaluated for their potential as soft tissue CESAs. We have shown that hafnium-substituted POM (Hf-POM) allows for simultaneous contrast-enhanced microCT (CE-CT) visualization of bone and its marrow vascularization and adiposity. Monolacunary Wells-Dawson POM (Mono-WD POM) showed similar soft tissue enhancement as Hf-WD POM and phosphotungstic acid (PTA), a frequently used but destructive CESA. However, compared to PTA, the POMs are much less destructive and show a better diffusion. The solubility of Mono-WD POM can be improved by simple addition of lithium chloride to the staining solution, leading to further enhancement of the soft tissue contrast. In vivo toxicity of Wells-Dawson POM has been also evaluated according to standard toxicological protocols using Wistar albino rats, which is the first and important step in evaluating side effects of these polyoxometalate nanoclusters that show large potential as therapeutics and contrast agents.Simpozijum „Stremljenja i novine u medicini“ Medicinskog fakulteta u Beogradu, Beograd, 04-08. decembra, 2023

In vitro cytotoxic activity of a monolacunary Wells-Dawson nanocluster against cervical carcinoma HeLa cells

The aim of this study was to assess in vitro cytotoxic activity of a monolacunary Wells- Dawson nanocluster, α2-K10P2W17O61.20H2O (lacunary WD) against cervical carcinoma HeLa cells as a commonly used model system for the evaluation of antitumor properties. After HeLa cells had been exposed to the investigated polyoxotungstate (the concentration range of 0.001 - 1 mM) for 24, 48, and 72 h, relative cell viability (expressed as a percentage of control) was determined. The obtained results showed that lacunary WD affected HeLa cell viability in a concentration- and time-dependent manner. IC50 values (in μM), calculated using sigmoidal fitting experimental plots, were as follows: 24.11 ± 9.95, 12.74 ± 0.096, and 11.48 ± 0.12 for 24, 48, and 72 hours treatment, respectively. In comparison with cisplatin, (positive control), IC50 values (μM) for 24 hours treatment were similar – 24.11 (lacunary WD) vs. 24.49 (cisplatin). However, after 48 and 72 hours IC50 obtained for cisplatin were found to be lower – 8.81 and 4.93 μM, respectively. Accordingly, the studied WD polyoxotungstate could not be regarded as a superior anticancer agent in comparison with the standard chemotherapeutic. Nevertheless, this studied nanocluster deserves attention as a promising antitumor therapeutic and as a good platform for the design of next-generation metal-based anticancer agents.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, 28-29 September 2023, Kragujevac, Serbi

The influence of Fe(III) incorporation on anti-cancer potential of a Wells-Dawson nanocluster

The objective of this study was to evaluate in vitro the antitumor properties of Fe(III)- substituted monolacunary Wells-Dawson polyoxotungstate, K7[FeIII(α2-P2W17O61)(H2O)] (FeWD) using cervical carcinoma HeLa cells as a model system. HeLa cells were exposed in vitro to FeWD within the concentration range from 0.001 to 1 mM, for 24, 48, and 72 hours. The studied Fe(III)- substituted polyoxotungstate affected HeLa cell viability in a concentration- and time-dependent manner. The obtained IC50 values (µM), as an indicator of the cytotoxic potential of FeWD, were: 16.64 ± 0.49, 10.75 ± 0.97, and 9.64 ± 0.19 for 24-, 48-, and 72-hour treatment, respectively. FeWD exhibited a stronger antitumor potential against HeLa cells than the structurally similar monolacunary Wells-Dawson polyoxotungstate, K10P2W17O61.20H2O (lacunary WD). Lacunary WD achieved IC50 at 24,11 µM after 24-hour exposure, which is about 44% higher concentration compared to the corresponding IC50 obtained for FeWD. This indicates that incorporating Fe(III) might be a new strategy for improving the antitumor efficacy of polyoxometalates as promising candidates for next-generation chemotherapeutics.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, 28-29 September 2023, Kragujevac, Serbi

Influence of 12-Tungstosilicic acid and 12-Tungstophosphoric acid on the activity and secondary structure of acetylcholinesterase

Inhibition of acetylcholinesterase (AChE) is presented as a promising strategy in the treatment of Alzheimer disease providing inspiration for new discoveries and investigations less toxic and more effective potential anti Alzheimer drugs. In this paper, it demonstrated that the activity of acetylcholinesterase can be effectively inhibited by polyoxometalates (POMs), 12-tungstosilicic acid (WSiA) and 12-tungstophosphoric acid (WPA) without significant changes on the secondary structure of this enzyme. The obtained values of partition coefficient implicated on smooth pass of these POMs trough cell membrane and satisfied necessary criteria for the drugs used in the treatment of the central nervous system disease. Based on these obtained results it is possible to conclude that POM could represent new generation of potential anti Alzheimer drugs.14th international conference on fundamental and applied aspects of physical chemistry; 24-28 September 2018, Belgrade, Serbia

Beneficial impact of lithium bis(oxalato)borate as electrolyte additive for high‐voltage nickel‐rich lithium‐battery cathodes

High-voltage nickel-rich layered cathodes possess the requisite, such as excellent discharge capacity and high energy density, to realize lithium batteries with higher energy density. However, such materials suffer from structural and interfacial instability at high voltages (>4.3 V). To reinforce the stability of these cathode materials at elevated voltages, lithium borate salts are investigated as electrolyte additives to generate a superior cathode-electrolyte interphase. Specifically, the use of lithium bis(oxalato)borate (LiBOB) leads to an enhanced cycling stability with a capacity retention of 81.7%. Importantly, almost no voltage hysteresis is detected after 200 cycles at 1C. This outstanding electrochemical performance is attributed to an enhanced structural and interfacial stability, which is attained by suppressing the generation of micro-cracks and the superficial structural degradation upon cycling. The improved stability stems from the formation of a fortified borate-containing interphase which protects the highly reactive cathode from parasitic reactions with the electrolyte. Finally, the decomposition process of LiBOB and the possible adsorption routes to the cathode surface are deduced and elucidated