Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action

The complexation of biogenic molecules with metals is the widespread strategy in screening for new pharmaceuticals with improved therapeutic and physicochemical properties. This paper demonstrates the possibility of using simple QSAR modeling based on topological descriptors for chelates study. The presence of a relationship between the structure (J) and lipophilic properties (logP) of zinc complexes with amino acids, where two molecules coordinate the central atom through carboxyl oxygen and amino group nitrogen, and thus form a double ring structure, was predicted. Using a cellular biosensor model for Gly, Ala, Met, Val, Phe and their complexes Zn(AA)2, we experimentally confirmed the existence of a direct relationship between logP and biological activity (Ea). The results obtained using topological analysis, Spirotox method and microbiological testing allowed us to assume and prove that the chelate complex of zinc with methionine has the highest activity of inhibiting bacterial biofilms, while in aqueous solutions it does not reveal direct antibacterial effect

Comparative Analysis of Physical and Chemical Properties of Differently Obtained Zn—Methionine Chelate with Proved Antibiofilm Properties (Part II)

The previously demonstrated activity of aqueous solutions of methionine and zinc salts against biofilms of uropathogenic bacteria prompted us to investigate the structure and properties of zinc methionine complex obtained from such solutions. The paper presents the analysis results of zinc coordination complexes with methionine obtained by synthesis (0.034 mol of L-methionine, 0.034 mol of NaOH, 40 mL of H2O, 0.017 mol ZnSO4, 60 °C) and simple crystallization from water solution (25 mL of a solution containing 134 mmol/L L-methionine, 67 mmol/L ZnSO4, pH = 5.74, I = 0.37 mmol/L, crystallization at room temperature during more than two weeks). IR spectral analysis and X-ray diffraction showed the structural similarity of the substances to each other, in agreement with the data described in the literature. DSC confirmed the formation of a thermally stable (in the range from −30 °C to 180 °C) chelate compound in both cases and indicated the possible retention of the polymorphic two-dimensional structure inherent in L-methionine with the temperature of phase transition 320 K. The crystallized complex had better solubility in water (100 to 1000 mL per 1.0 g) contra the synthesized analog, which was practically insoluble (more than 10 000 mL per 1.0 g). The results of the solubility assessment, supplemented by the results of the dispersion analysis of solutions by the dynamic light scattering method indicated the formation of zinc-containing nanoparticles (80 nm) in a saturated water solution of a crystallized substance, suggesting the crystallized substance may have higher bioavailability. We predicted a possibility of the equivalent existence of optically active cis and trans isomers in methionine-zinc solutions by the close values of formation enthalpy (−655 kJ/mol and −657 kJ/mol for cis and trans forms, respectively) and also illustrated by the polarimetry measurement results (∆α = 0.4°, pH = 5.74, C(Met) = 134 mmol/L; the concentration of metal ion gradually increased from 0 to 134 mmol/L). The obtained results allowed us to conclude that the compound isolated from the solution is a zinc-methionine chelate with the presence of sulfate groups and underline the role of the synthesis route for the biopharmaceutical characteristics of the resulting substance. We provided some quality indicators that it may be possible to include in the pharmacopeia monographs

Possible Mechanisms of Relations between the Thermal Neutrons Field and Biosphere

This paper proposes some results concerning the interaction of living matter of different organization levels (prokaryotes and eukaryotes) with the flux of thermal neutrons. The phenomenon of the virtual neutron trap was tested during the passage of thermalized neutrons from the Pu-Be couple through a flat layer of E. coli suspension. We have studied the metabolic characteristics of A. salina cysts before and after artificial neutron flux exposure. It has been demonstrated that the concentrations of some metals in samples of alive and dead cysts irradiated with an artificial flow of thermal neutrons are not equal. The content of Mn in alive A. salina samples has increased more than ten-fold after their interaction with neutron flux, while the amount of As decreased by a factor of two after exposure. Levels of other elements (Al, Cr, Ni, Cu, Cd, and Pb) did not show any significant difference. Trace element composition of cysts was assessed using the method of atomic absorption spectroscopy with electrothermal atomization and the Zeeman background correction

Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action

The complexation of biogenic molecules with metals is the widespread strategy in screening for new pharmaceuticals with improved therapeutic and physicochemical properties. This paper demonstrates the possibility of using simple QSAR modeling based on topological descriptors for chelates study. The presence of a relationship between the structure (J) and lipophilic properties (logP) of zinc complexes with amino acids, where two molecules coordinate the central atom through carboxyl oxygen and amino group nitrogen, and thus form a double ring structure, was predicted. Using a cellular biosensor model for Gly, Ala, Met, Val, Phe and their complexes Zn(AA)2, we experimentally confirmed the existence of a direct relationship between logP and biological activity (Ea). The results obtained using topological analysis, Spirotox method and microbiological testing allowed us to assume and prove that the chelate complex of zinc with methionine has the highest activity of inhibiting bacterial biofilms, while in aqueous solutions it does not reveal direct antibacterial effect

Optimization of Ethanolic Extraction of <i>Enantia chloranta</i> Bark, Phytochemical Composition, Green Synthesis of Silver Nanoparticles, and Antimicrobial Activity

In this study, using the Box–Behnken model, we optimized the ethanolic extraction of phytochemicals from Enantia chloranta bark for the first time, assessed the composition with HPLC-MS/MS, performed the green synthesis of silver nanoparticles (AgNPs) and characterized them with UV-Vis spectrophotometry, photon cross-correlation spectroscopy, energy-dispersive X-ray fluorescence spectrometry, and Fourier transform infrared spectroscopy. The antibacterial and antibiotic-resistance reversal properties of optimized extract (O-ECB) and AgNPs were assessed on various microorganisms (15 Gram−, 7 Gram+, and 2 fungi) using the well diffusion method and microbroth dilution assay. The mechanism of action was investigated on growth kinetic and proton pumps of Escherichia coli. The in vivo antimicrobial activity and toxicity were assessed on Galleria mellonella larvae. The optimal mass yield (14.3%) related to the highest antibacterial activity (31 mm vs. S. aureus ATCC 6538) was obtained with the following operating conditions: % EtOH—100%; ratio m/v—20 g/mL; and extraction time—6 h. All the compounds identified in O-ECB were alkaloids and the major constituents were palmatine (51.63%), columbamine +7,8-dihydro-8-hydroxypalmatine (19.21%), jatrorrhizine (11.02%), and pseudocolumbamine (6.33%). Among the minerals found in O-ECB (S, Si, Cl, K, Ca, Mn, Fe, Zn, and Br), Br, Fe, and Cl were the most abundant with mean fluorescence intensities of 4.6529, 3.485,4, and 2.5942 cps/uA, respectively. The synthesized AgNPs revealed a strong absorption plasmon band between 430 and 450 nm and an average hydrodynamic diameter ×50 of 59.74 nm, and the presence of Ag was confirmed by a characteristic peak in the spectrum at the silver Kα line of 22.105 keV. Both O-ECB and AgNPs displayed noteworthy and broad-spectrum antimicrobial activities against 20/24 and 24/24 studied microorganisms, respectively, with recorded minimal inhibitory concentrations (MICs) ranging from 8 to ≥1024 µg/mL and 2 to 64 µg/mL. O-ECB and AgNPs showed antibiofilm properties and significantly enhanced the efficacy of conventional antibiotics against selected multidrug-resistant bacteria, and the mechanistic investigations revealed their interference with bacterial growth kinetic and the inhibition of H+-ATPase proton pumps. LD50s were 40 mg/mL and 0.6 mg/mL for O-ECB and AgNPs, respectively. In conclusion, the current study provides a strong experimental baseline to consider Enantia chlorantha bark and their green synthetized AgNPs as potent antimicrobial compounds in this era of antimicrobial resistance