Unraveling the binding mechanism of an Oxovanadium(IV) – Curcumin complex on albumin, DNA and DNA gyrase by in vitro and in silico studies and evaluation of its hemocompatibility

An oxovanadium(IV) – curcumin based complex, viz. [VO(cur)(2,2´-bipy)(H2O)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (Kb) was calculated to be 2.56 x 105 M-1, whereas a single great-affinity binding site was revealed. Moreover, the hemocompatibility test demonstrated that the complex presented low hemolytic fraction (mostly below 1%), in all concentrations tested (0-250 μΜ of complex, 5% DMSO) assuring a safe application in interaction with blood. The binding of the complex to DNA was also investigated using absorption, fluorescence, and viscometry methods indicating a binding through a minor groove mode. From competitive studies with ethidium bromide the apparent binding constant value to DNA was estimated to be 4.82 x 106 M-1. Stern-Volmer quenching phenomenon gave a ΚSV constant [1.92 (± 0.05) x 104 M-1] and kq constant [8.33 (± 0.2) x 1011 M-1s-1]. Molecular docking simulations on the crystal structure of BSA, calf thymus DNA, and DNA gyrase, as well as pharmacophore analysis for BSA target, were also employed to study in silico the ability of [VO(cur)(2,2´-bipy)(H2O)] to bind to these target bio-macromolecules and explain the observed in vitro activity. © 2021 Elsevier Inc

In vitro and in silico evaluation of the inhibitory effect of a curcumin-based oxovanadium (IV) complex on alkaline phosphatase activity and bacterial biofilm formation

Abstract: The scientific interest in the development of novel metal-based compounds as inhibitors of bacterial biofilm-related infections and alkaline phosphatase (ALP) deregulating effects is continuous and rising. In the current study, a novel crystallographically defined heteroleptic V(IV)-curcumin-bipyridine (V-Cur) complex with proven bio-activity was studied as a potential inhibitor of ALP activity and bacterial biofilm. The inhibitory effect of V-Cur was evaluated on bovine ALP, with two different substrates: para-nitrophenyl phosphate (pNPP) and adenosine triphosphate (ATP). The obtained results suggested that V-Cur inhibited the ALP activity in a dose-dependent manner (IC50 = 26.91 ± 1.61 μM for ATP, IC50 = 2.42 ± 0.12 μM for pNPP) exhibiting a mixed/competitive type of inhibition with both substrates tested. The evaluation of the potential V-Cur inhibitory effect on bacterial biofilm formation was performed on Gram (+) bacteria Staphylococcus aureus (S. aureus) and Gram (−) Escherichia coli (E. coli) cultures, and it positively correlated with inhibition of bacterial ALP activity. In silico study proved the binding of V-Cur at eukaryotic and bacterial ALP, and its interaction with crucial amino acids of the active sites, verifying complex’s inhibitory potential. The findings suggested a specific anti-biofilm activity of V-Cur, offering a further dimension in the importance of metal complexes, with naturally derived products as biological ligands, as therapeutic agents against bacterial infections and ALP-associated diseases. Key points: • V-Cur inhibits bovine and bacterial alkaline phosphatases and bacterial biofilm formation. • Alkaline phosphatase activity correlates with biofilm formation. • In silico studies prove binding of the complex on alkaline phosphatase. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

A unique ternary Ce(III)-quercetin-phenanthroline assembly with antioxidant and anti-inflammatory properties.

From PubMed via Jisc Publications RouterHistory: received 2022-06-19, revised 2022-07-15, accepted 2022-07-24Publication status: ppublishQuercetin is one of the most bioactive and common dietary flavonoids, with a significant repertoire of biological and pharmacological properties. The biological activity of quercetin, however, is influenced by its limited solubility and bioavailability. Driven by the need to enhance quercetin bioavailability and bioactivity through metal ion complexation, synthetic efforts led to a unique ternary Ce(III)-quercetin-(1,10-phenanthroline) (1) compound. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetric analysis (TGA), UV-Visible, NMR, Electron Spray Ionization-Mass Spectrometry (ESI-MS), Fluorescence, X-rays) revealed its solid-state and solution properties, with significant information emanating from the coordination sphere composition of Ce(III). The experimental data justified further entry of 1 in biological studies involving toxicity, (Reactive Oxygen Species, ROS)-suppressing potential, cell metabolism inhibition in Saccharomyces cerevisiae (S. cerevisiae) cultures, and plasmid DNA degradation. DFT calculations revealed its electronic structure profile, with in silico studies showing binding to DNA, DNA gyrase, and glutathione S-transferase, thus providing useful complementary insight into the elucidation of the mechanism of action of 1 at the molecular level and interpretation of its bio-activity. The collective work projects the importance of physicochemically supported bio-activity profile of well-defined Ce(III)-flavonoid compounds, thereby justifying focused pursuit of new hybrid metal-organic materials, effectively enhancing the role of naturally-occurring flavonoids in physiology and disease. [Abstract copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

A unique ternary Ce(III)-quercetin-phenanthroline assembly with antioxidant and anti-inflammatory properties

Quercetin is one of the most bioactive and common dietary flavonoids, with a significant repertoire of biological and pharmacological properties. The biological activity of quercetin, however, is influenced by its limited solubility and bioavailability. Driven by the need to enhance quercetin bioavailability and bioactivity through metal ion complexation, synthetic efforts led to a unique ternary Ce(III)-quercetin-(1,10-phenanthroline) (1) compound. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetric analysis (TGA), UV–Visible, NMR, Electron Spray Ionization-Mass Spectrometry (ESI-MS), Fluorescence, X-rays) revealed its solid-state and solution properties, with significant information emanating from the coordination sphere composition of Ce(III). The experimental data justified further entry of 1 in biological studies involving toxicity, (Reactive Oxygen Species, ROS)-suppressing potential, cell metabolism inhibition in Saccharomyces cerevisiae (S. cerevisiae) cultures, and plasmid DNA degradation. DFT calculations revealed its electronic structure profile, with in silico studies showing binding to DNA, DNA gyrase, and glutathione S-transferase, thus providing useful complementary insight into the elucidation of the mechanism of action of 1 at the molecular level and interpretation of its bio-activity. The collective work projects the importance of physicochemically supported bio-activity profile of well-defined Ce(III)-flavonoid compounds, thereby justifying focused pursuit of new hybrid metal-organic materials, effectively enhancing the role of naturally-occurring flavonoids in physiology and disease

Structure Lattice-Dimensionality and Spectroscopic Property Correlations in Novel Binary and Ternary Materials of Group 13 Elements with α‑Hydroxycarboxylic Benzilic Acid and Phenanthroline

To probe and understand the structural and coordinative flexibility of Group 13 ions with α-hydroxycarboxylic acids, leading to crystalline inorganic–organic hybrid materials with distinct lattice architecture, dimensionality, and spectroscopic properties, the systematic synthesis and physicochemical properties of binary and ternary B­(III), Al­(III), Ga­(III), In­(III), and Tl­(I)-benzilic acid-(phenanthroline) systems were investigated in water–alcohol mixtures. Stoichiometric reactions of Group 13 ions with benzilic acid and phenanthroline (phen) afforded the new materials [B­(C₁₄H₁₀O₃)₂]­(C₃H₅N₂)­·H₂O (<b>1</b>), [Al­(C₁₄H₁₁O₃)₃]­·0.5C₂H₅OH­·4.5H₂O (<b>2</b>), [Ga­(C₁₄H₁₁O₃)₃]­·CH₃OH­·3H₂O (<b>3</b>), [In­(C₁₄H₁₁O₃)₄]­·C₃H₅N₂­·C₂H₅OH­·H₂O (<b>4</b>), [Tl­(C₁₄H₁₁O₃)]_<i>n</i> (<b>5</b>), [Tl₂(C₁₄H₁₁O₃)₂­(phen)₂] (<b>6</b>), and [Tl­(C₁₄H₁₁O₃)­(phen)­(H₂O)]­(C₁₄H₁₂O₃)­(phen) (<b>7</b>). All materials were characterized by elemental analysis, Fourier transform infrared spectroscopy, ¹³C, ¹¹B, ²⁷Al, ⁷¹Ga, and ²⁰⁵Tl cross-polarization/magic-angle spinning NMR, thermogravimetric analysis, luminescence, and single crystal X-ray diffraction. The nature of the benzilate ligand and phenanthroline in the chemical reaction mixtures with Group 13 ions led to the emergence of distinct lattice composition-dimensionality (1D-2D) correlations at the binary-ternary level, providing spectroscopic fingerprint identity to M­(I,III)-coordination and luminescence activity. The interplay between the benzilate ligand, phenanthroline, and Group 13 ions, (a) reveals well-defined contributions of the chemical and structural factors influencing the arising binary and ternary interactions at the M­(I) and M­(III) oxidation levels, and (b) clarifies correlations between crystal-lattice architecture and dimensionality with unique heteronuclear solid-state NMR and optical property signatures in inorganic–organic hybrid materials

Structure Lattice-Dimensionality and Spectroscopic Property Correlations in Novel Binary and Ternary Materials of Group 13 Elements with α‑Hydroxycarboxylic Benzilic Acid and Phenanthroline

To probe and understand the structural and coordinative flexibility of Group 13 ions with α-hydroxycarboxylic acids, leading to crystalline inorganic–organic hybrid materials with distinct lattice architecture, dimensionality, and spectroscopic properties, the systematic synthesis and physicochemical properties of binary and ternary B­(III), Al­(III), Ga­(III), In­(III), and Tl­(I)-benzilic acid-(phenanthroline) systems were investigated in water–alcohol mixtures. Stoichiometric reactions of Group 13 ions with benzilic acid and phenanthroline (phen) afforded the new materials [B­(C₁₄H₁₀O₃)₂]­(C₃H₅N₂)­·H₂O (<b>1</b>), [Al­(C₁₄H₁₁O₃)₃]­·0.5C₂H₅OH­·4.5H₂O (<b>2</b>), [Ga­(C₁₄H₁₁O₃)₃]­·CH₃OH­·3H₂O (<b>3</b>), [In­(C₁₄H₁₁O₃)₄]­·C₃H₅N₂­·C₂H₅OH­·H₂O (<b>4</b>), [Tl­(C₁₄H₁₁O₃)]_<i>n</i> (<b>5</b>), [Tl₂(C₁₄H₁₁O₃)₂­(phen)₂] (<b>6</b>), and [Tl­(C₁₄H₁₁O₃)­(phen)­(H₂O)]­(C₁₄H₁₂O₃)­(phen) (<b>7</b>). All materials were characterized by elemental analysis, Fourier transform infrared spectroscopy, ¹³C, ¹¹B, ²⁷Al, ⁷¹Ga, and ²⁰⁵Tl cross-polarization/magic-angle spinning NMR, thermogravimetric analysis, luminescence, and single crystal X-ray diffraction. The nature of the benzilate ligand and phenanthroline in the chemical reaction mixtures with Group 13 ions led to the emergence of distinct lattice composition-dimensionality (1D-2D) correlations at the binary-ternary level, providing spectroscopic fingerprint identity to M­(I,III)-coordination and luminescence activity. The interplay between the benzilate ligand, phenanthroline, and Group 13 ions, (a) reveals well-defined contributions of the chemical and structural factors influencing the arising binary and ternary interactions at the M­(I) and M­(III) oxidation levels, and (b) clarifies correlations between crystal-lattice architecture and dimensionality with unique heteronuclear solid-state NMR and optical property signatures in inorganic–organic hybrid materials

Structure Lattice-Dimensionality and Spectroscopic Property Correlations in Novel Binary and Ternary Materials of Group 13 Elements with α‑Hydroxycarboxylic Benzilic Acid and Phenanthroline

To probe and understand the structural and coordinative flexibility of Group 13 ions with α-hydroxycarboxylic acids, leading to crystalline inorganic–organic hybrid materials with distinct lattice architecture, dimensionality, and spectroscopic properties, the systematic synthesis and physicochemical properties of binary and ternary B­(III), Al­(III), Ga­(III), In­(III), and Tl­(I)-benzilic acid-(phenanthroline) systems were investigated in water–alcohol mixtures. Stoichiometric reactions of Group 13 ions with benzilic acid and phenanthroline (phen) afforded the new materials [B­(C₁₄H₁₀O₃)₂]­(C₃H₅N₂)­·H₂O (<b>1</b>), [Al­(C₁₄H₁₁O₃)₃]­·0.5C₂H₅OH­·4.5H₂O (<b>2</b>), [Ga­(C₁₄H₁₁O₃)₃]­·CH₃OH­·3H₂O (<b>3</b>), [In­(C₁₄H₁₁O₃)₄]­·C₃H₅N₂­·C₂H₅OH­·H₂O (<b>4</b>), [Tl­(C₁₄H₁₁O₃)]_<i>n</i> (<b>5</b>), [Tl₂(C₁₄H₁₁O₃)₂­(phen)₂] (<b>6</b>), and [Tl­(C₁₄H₁₁O₃)­(phen)­(H₂O)]­(C₁₄H₁₂O₃)­(phen) (<b>7</b>). All materials were characterized by elemental analysis, Fourier transform infrared spectroscopy, ¹³C, ¹¹B, ²⁷Al, ⁷¹Ga, and ²⁰⁵Tl cross-polarization/magic-angle spinning NMR, thermogravimetric analysis, luminescence, and single crystal X-ray diffraction. The nature of the benzilate ligand and phenanthroline in the chemical reaction mixtures with Group 13 ions led to the emergence of distinct lattice composition-dimensionality (1D-2D) correlations at the binary-ternary level, providing spectroscopic fingerprint identity to M­(I,III)-coordination and luminescence activity. The interplay between the benzilate ligand, phenanthroline, and Group 13 ions, (a) reveals well-defined contributions of the chemical and structural factors influencing the arising binary and ternary interactions at the M­(I) and M­(III) oxidation levels, and (b) clarifies correlations between crystal-lattice architecture and dimensionality with unique heteronuclear solid-state NMR and optical property signatures in inorganic–organic hybrid materials