Niobium oligomer-based nanostructured hybrid materials, preparation methods and uses

Abstract

This technology describes a method for obtaining materials containing nanostructured active molecules based on niobium compounds, the products obtained thereby, and their use as a chemical / biological barrier on surfaces. The nanostructured hybrid materials can be used as components of cosmetic products to enhance their effectiveness and duration of action. In addition, it can be introduced onto different surfaces (including fabrics) to maintain its action against bacteria and viruses. It can also be applied in the form of a gel or a liquid spray. Niobium nanoparticles combined with quaternary ammonium compounds are used in sprays, and combined with methylene blue dye to form a disinfection gel, showing highly efficient inactivation of coronaviruses, with stability and long-term activity.

Description

[0001] The present technology describes methods for obtaining materials containing nanostructured active molecules based on niobium compounds, the products obtained and their use as chemical / biological barriers on surfaces. The nanostructured hybrid material can be used as a component of cosmetic products, enhancing their effectiveness and duration of action. In addition, it can be introduced into different surfaces (including fabrics) to maintain its action against bacteria and viruses. It can also be applied in the form of a gel or liquid spray. Niobium nanoparticles combined with quaternary ammonium compounds for sprays, as well as with methylene blue dye to form disinfectant gels, show high efficiency in inactivating coronaviruses, with stability and long-term activity.

[0002] Brazil has more than 90% of the world's recoverable reserves of niobium and remains the largest producer and exporter of niobium. In this way, the development of new products for different industrial sectors can become a topic of strategic importance not only for the development of Minas Gerais, but also for the country. This development can mean technological improvement of products produced from Brazilian ores, meaning an increase in added value and the consequent generation of jobs in the country.

[0003] In the context of technological development, it has been observed that niobium-based systems have played an important role in several reactions, being able to act as active phase, dopant and also as reaction support. Specific characteristics, such as redox properties, photosensitivity, high acidity and strong metal-support interactions, have made these systems, in particular niobium oxyhydroxides, oxides, phosphates and pentoxides, show high performance in the most different types of reactions. To increase its activity, many studies have reported the modification of Nb2O5 with phosphoric acid, obtaining niobium phosphates. In some cases, NbCl5 has also been used as a precursor. Several studies have also been reported in the scientific literature, highlighting the use of niobium compounds in oxidation reactions, including organic pollutants present in industrial wastewaters, or in glycerol cracking reactions.

[0004] Quaternary ammonium compounds, such as cetrimonium bromide (CTAB), are membrane activators, i.e., the main site of action is the cytoplasmic membrane of bacteria or the plasma membrane of yeast. Surfactants or surface-active agents have two regions in their molecular structure: a hydrophobic (supporting) group and a hydrophilic (polar) group. Cationic agents, such as quaternary ammonium compounds, are the most useful preservatives and disinfectants and are also known as cationic surfactants. CTAB acts as an important surfactant in DNA extraction buffer systems to remove membrane lipids and promote cell lysis. CTAB has shown potential use as an anticancer agent, promoting apoptosis of tumor cells from head and neck cancer (Emma Ito, Kenneth W. Yip, David Katz, Sonali B. Fonseca, David W. Hedley, Sue Chow, G. Wei Xu, Tabitha E. Wood, Carlo Bastianutto, Aaron D. Schimmer, Shana O. Kelley, Fei-Fei Liu. Potential Use of Cetrimonium Bromide as an Apoptosis-Promoting Anticancer Agent for Head and Neck Cancer. Molecular Pharmacology, 76, 2009, 969–983).

[0005] Quaternary ammonium salts have known antibacterial properties, and their hydrophobic carbon chains can inactivate viruses by reacting with the lipid barrier of bacteria. Their activity has been demonstrated in inactivating coronaviruses (Franklin Dexter, FASA, Michelle C. Parra, Jeremiah R. Brown, Randy W. Loftus. Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management, Anesthesia & Analgesia, 2020) (Nancy Baker, Antony J. Williams, Alexander Tropsha, Sean Ekins. Repurposing Quaternary Ammonium Compounds as Potential Treatments for COVID-19, Pharm Res, 37, 2020, 104) (Maria L. S. O. Lima, Ramon K. S. Almeida, Francine S. A. da Fonseca, Caroline C. S The chemistry of disinfectants in the time of COVID-19. Do you know how it works? Quim. Nova, 43, 2020, 668-678).

[0006] The patent document US8,337,872 titled "Method for Inhibiting the Spread of Influenza Virus" from 2006 relates to a method for inhibiting the spread of influenza virus. An antibacterial composition with rapid and persistent antiviral efficacy against influenza viruses (including avian influenza viruses) is disclosed. The antibacterial composition contains disinfecting alcohol, organic acid, and water, where the composition has a pH value of about 5 or lower, and the non-volatile components of the composition can form a barrier film or layer on the treated surface.

[0007] The patent US 9,549,949 titled "Antiviral Agent" from 2008 describes an antiviral agent that contains at least one particle of an iodide composed of iodine and an element shown in Periods 4 to 6 and Groups 8 to 15 of the periodic table or at least one particle of a monovalent copper compound as an active ingredient. The antiviral agent can be introduced into various products. Although niobium is in Group 5 of the periodic table, this document presents iodides or iodine compounds in its composition, without referring to quaternary ammonium salts.

[0008] This technology describes a product with a combined effect between a niobium compound and a quaternary ammonium salt, acting as a chemical / biological barrier on the surface. The material can be used in the product in liquid form to protect the surface and effectively inactivate coronaviruses in an enhanced manner. The mechanism of action of the nanostructured hybrid material proposed in this technology includes: chemically binding a niobium compound with a high negative charge, accumulating several groups of quaternary ammonium salts around the compound, and promoting its enhanced effect in inactivating, for example, coronaviruses. This is because the compound formed by the chemical bond established between niobium and the quaternary ammonium salt concentrates the hydrophobic groups responsible for virus inactivation, generating a protective layer on the surface where it is deposited. The synergistic effect obtained between the niobium compound and CTAB in the results of coronavirus inactivation studies is evident, where the efficiency of individual species is far lower than that of the nanostructured hybrid material containing Nb-CTAB.

[0009] This technology also describes a product formed by the combination between a niobium-based nanostructured hybrid material and methylene blue dye, in gel form, obtained by introducing it into a commercially available alcohol gel. This product shows excellent performance in reducing the viral load. The antiviral effect of this product occurs due to the semiconductor properties of the niobium compound, which has the ability to act through photocatalytic effects. This makes it possible to use only 0.5% of the Nb-CTAB gel in combination with a commercially available alcohol gel to be very effective in inactivating coronaviruses. A greater reduction in the viral load was observed compared to pure alcohol gel. In addition, the new molecule Nb-methylene blue remains active even after the evaporation of the commercially available alcohol, providing a long-term effect for the proposed product.

[0010] The products of this technology have the potential to be used as chemical / biological barriers due to their introduction into different surfaces. Hybrid materials containing inorganic materials (niobium) and organic materials (CTAB and / or dyes), with nanostructured structural dimensions, can be used as components of cosmetic products, enhancing their effectiveness and duration of action. In addition, it can be introduced into different fabric surfaces, maintaining its action against bacteria and viruses. It can also be applied in the form of a gel or a liquid spray, showing a synergistic effect with other disinfection products, especially such as alcohol and disinfectants. Description of the Drawings

[0011] Figure 1 Photographs of the products in the form of gel (A) and liquid (B) from niobium oxide are shown.

[0012] Figure 2 The CTAB nuclear magnetic resonance spectrum of the new Nb-CTAB molecule (A) and the model (B) created for the protection generated on the surface are shown.

[0013] Figure 3Survival ability studies of Enterococcus faecalis (Ef), Escherichia coli (Ec), and Eikenella corrodens (Ek) bacteria using niobium compounds (A = niobium spray / CTAB; B = niobium spray / CTAB / methylene blue; C = niobium gel / methylene blue) are shown.

[0014] Figure 4 Viral load reduction studies of different samples and their respective controls are shown. In (A), the control samples of the spray are denoted by s1 - s12 and s13, and the control samples of the gel are denoted by g1 and g2, g4 - g6. (B) and (C) show studies on the long - term viral load reduction effects of liquid and gel materials (S12 = niobium spray / CTAB; g3 = niobium spray / CTAB / methylene blue; g7 = niobium gel / methylene blue). The red arrow indicates the result of the g7 sample, which inactivated all viruses. Detailed Description

[0015] This technology describes a method for obtaining materials containing nanostructured active molecules based on niobium compounds, the obtained products, and their use as chemical / biological barriers on surfaces. The nanostructured hybrid materials can be used as components of cosmetic products, enhancing their effectiveness and duration of action. In addition, it can be introduced into different surfaces (including fabrics), maintaining its action against bacteria and viruses. It can also be applied in the form of a gel or a liquid spray. The combination of niobium nanoparticles with quaternary ammonium compounds for sprays and with methylene blue dye to form a disinfectant gel shows high efficiency in inactivating coronaviruses, with stability and long - term activity.

[0016] The nanostructured hybrid material based on niobium oligomers contains negatively charged niobium oligomers and organic cations, where the cations are selected from quaternary ammonium salts of the didodecyldimethylammonium chloride type, cetyltrimethylammonium bromide (CTAB), methylene blue, gentian violet, and / or fuchsin dyes, with a quaternary ammonium concentration of 10 to 2000 mg / L and a niobium concentration of 100 to 3000 mg / L.

[0017] The negatively charged niobium oligomers can be obtained from niobium oxide, niobium pentoxide, niobic acid, and niobium phosphate.

[0018] The nanostructured hybrid material based on niobium oligomers can be introduced into an alcohol gel at a proportion of 0.1 - 10% by mass of the niobium compound in 10 - 70% m / m alcohol gel.

[0019] The method for obtaining a nanostructured hybrid material based on niobium oligomers includes the following steps:

[0020] a. Dissolve a niobium compound containing 1 to 5 g / L of niobium in oxalic acid or hydrogen peroxide at a concentration of 10 to 50% m / m;

[0021] b. Add quaternary ammonium salts at 10 to 1000 mg / L and / or cationic dyes at 500 to 20000 mg / L to the niobium oligomers obtained in step "a";

[0022] c. At room temperature, stir the solution obtained in step "b" at 10 to 100 rpm for a period of 5 to 30 minutes.

[0023] The niobium compounds described in step "a" are selected from their oxides, which are niobium oxide, niobium pentoxide, niobic acid, and niobium phosphate.

[0024] The quaternary ammonium described in step "b" is selected from didecyldimethylammonium chloride or cetyltrimethylammonium bromide (CTAB), and the cationic dye is selected from methylene blue, gentian violet, or magenta dyes, which can be added to 10 to 70% m / m alcohol gel at 0.1 to 5% m / m after step "c".

[0025] The nanostructured hybrid material based on niobium oligomers can be used to produce disinfection compounds with bactericidal and antiviral activities, preferably against coronaviruses.

[0026] The following examples describe aspects of the present technology and should not be considered restrictive.

[0027] Example 1 - Obtaining and using a nanostructured hybrid material based on niobium oligomers for inactivating coronaviruses.

[0028] The compound in spray form is obtained by reacting niobium oligomers containing 2000 mg / L niobium with 100 mg / L of quaternary ammonium (CTAB). CTAB is dropped into the oligomer solution until micelles containing chemically bonded niobium and CTAB are formed to form Nb-CTAB. Importantly, it should be noted that the micelle point is obtained before the solution gels, so stirring must be observed and gelation of the medium should be avoided. The resulting micelles should be kept under gentle stirring at 100 rpm for 10 minutes.

[0029] The disinfection gel is obtained from the reaction of methylene blue dye and niobium compound using equal volumes of the compound, with a dye concentration of 1000 mg / L and a niobium compound concentration of 2,000 mg / L. This material has good disinfection properties, especially when combined with 70% m / m alcohol gel. In the mixture with 70% m / m alcohol gel, a disinfection gel with a mass ratio of 0.5% formed by Nb-methylene blue was prepared.

[0030] Figure 1 Photos showing the final gel containing 0.5% methylene blue dye in 70% alcohol gel and the spray containing 10 mg / L CTAB quaternary ammonium salt in aqueous niobium compound are presented.

[0031] Strong evidence of the chemical interaction established between CTAB and the negatively charged species of niobium was obtained through Raman spectra, in which the shifts indicating the established chemical interaction were clearly observed, such as Figure 2 shown in a. The model of the newly formed structure and its role as a protective layer on the skin surface is presented in Figure 2 b. Therefore, based on the analysis of the 1 1H NMR spectra of both the surfactant CTAB and the mixture containing niobium compounds and CTAB in D2O, it can be inferred that there is an interaction between the species, and this synergistic effect enhances the activity of the sample against the virus causing COVID-19. Niobium compounds have a high negative surface charge. When they interact with the positive part of the surfactant, they transfer electron density, making the hydrogen in the molecule more shielded, resulting in a significant difference in the chemical shifts of H. The hydrogen of the methyl group of CTAB exhibits a chemical shift (δ) of 3.16 ppm. However, when interacting with Nb, a shift of δ = 4.31 ppm is observed, which is due to the strong influence of the metal, presenting as an extended singlet and actually superimposed on the water signal. The hydrocarbon directly bonded to the N atom of CTAB has δ = 3.41 ppm; however, in the presence of Nb, the triplet corresponding to this H undergoes a shift of δ = 2.91 ppm. The chemical shifts of this compound clearly indicate the formation of a new chemical species established between Nb - CTAB.

[0032] Example 2 - Bacterial Inactivation Study

[0033] The product was tested in the viability studies of Enterococcus faecalis (Ef), Escherichia coli (Ec), and Eikenella corrodens (Ek) bacteria. In the study, 100 μL of BHI medium and 100 μL of sterile distilled water were added to each well of the sterile control plate of the medium. The microplate was incubated in an oven at 37 °C, and the first test reading was taken in a microplate reader after 24 hours. After 48 hours, a new reading should be taken to end the test. The readings were taken at a fixed wavelength of 492 nm. Figure 3 The study in

[0034] shows the ability of this material to promote the inactivation of three types of bacteria. In the study conducted, a silver plate of 1.0 x 0.5 cm was polished successively with 1500, 2000, and 2500 - mesh SiC sandpaper and commercially available polishing paste before the cleaning bath. This procedure is optional and not recommended for objects with details such as text and images on their surfaces.

[0035] For the viral load reduction studies directly using coronaviruses, 8 parts of the compound were conditioned to room temperature (RT) and mixed with 1 part of the virus suspension. After culturing for a defined time at room temperature, the mixture was immediately diluted 1:10. After culturing for 4 days at 37 °C in a CO2 incubator, after 10 minutes of contact of the virus with the niobium compound, the virus-specific cytopathic effect of the cells was examined by microscopy. All tests were performed in triplicate.

[0036] Initially, exploratory studies were carried out with different ratios of the compound and the material. Figure 4 (A) presents these data and clearly shows the enhancing effect of the new molecules formed by the reaction between the niobium compound and CTAB. In fact, the results of sample S10 (representing a solution containing pure CTAB dissolved in water) and S12 (a sample containing the same amount of CTAB reacted with niobium) clearly demonstrate the enhancing effect of the Nb-CTAB species.

[0037] CTAB only promotes a viral load reduction of about 30%, while the new molecule Nb-CTAB promotes a viral load reduction of 90%. This result clearly shows that, according to the model generated in the present technology, the action of the new hybrid molecules formed by the reaction between CTAB and the negatively charged species of niobium is enhanced.

[0038] Another result worth emphasizing is the data on the combination of niobium gel containing niobium-methylene blue and alcohol gel. According to Figure 4 the results of sample g7 in (A), the presence of niobium gel promotes a viral load reduction of 100%. In turn, the alcohol gel without the Nb-methylene blue compound (sample g1) shows a viral load reduction of only 15%.

[0039] Figure 4 Two ways of evaluating the reduction of viral load using the niobium hybrid products developed in the present technology are also presented. Figure B shows that for values below 1, a viral load reduction was observed in the presence of the niobium compound. Figure C shows the same results but in a quantitative linear form. The results also show that these products have a long-term effect, as these materials are deposited on the glass surface and the virus is deposited after 1, 4, and 24 hours. After this time on the surface, the virus is deposited and the viral load is analyzed 10 minutes later. The material labeled g7 in the figure shows 100% virus clearance at all times studied, demonstrating its efficiency and, moreover, its ability to remain active 24 h after being applied to the surface. The material labeled g7 is a niobium gel containing methylene blue chemically bonded to niobium oligomers. As Figure 4(A) As can be seen, under experimental conditions, pure alcohol does not show high efficiency; however, compared to pure commercially available alcohol gels, niobium compounds act for a longer time and with higher efficiency in inactivating coronaviruses. The data show that in the niobium compound-containing formulation, only 0.5% of niobium is dispersed in the commercially available alcohol gel, promoting a 100% reduction in viral load after 24 hours of deposition on the surface. These results demonstrate the efficiency of the new species formed between niobium compounds and methylene blue dye, which forms a semiconductor gel capable of photocatalytically acting on coronavirus inactivation in an unprecedented way, allowing the formation of materials with the ability to act in a long-term manner on different surfaces. It should be clear that pure alcohol loses its activity with natural evaporation, but the niobium species remain active, making this new compound unique in the fight against coronaviruses.

[0040] Materials g3 and S12, which are sprays containing hybrid niobium compounds in liquid form, also show the ability to inactivate coronaviruses, although with lower efficiency when compared to material g7. These compounds in liquid form also show long-lasting efficiency and remain active even after 6 hours of deposition on the surface.

[0041] The results obtained indicate that the materials described in the present invention have high potential for use against coronaviruses and can be used as disinfectants in the form of sprays and gels and as components of alcohol gels.

Claims

1. Niobium oligomer-based nanostructured hybrid material, It is characterized in that which comprises negatively charged niobium oligomers and organic cations, the negatively charged niobium oligomers being obtained from niobium oxide, niobium pentoxide, niobic acid and niobium phosphate, the organic cations being selected from quaternary ammonium salts and / or methylene blue, the concentration of the quaternary ammonium salt being 10 to 2000 mg / L and the concentration of niobium being 100 to 3000 mg / L, wherein the quaternary ammonium salt is cetyltrimethylammonium bromide, The method for obtaining the niobium oligomer-based nanostructured hybrid material comprises the following steps: a. Dissolving niobium oxide, niobium pentoxide, niobic acid or niobium phosphate containing 1 to 5 g / L of niobium in oxalic acid or hydrogen peroxide at a concentration of 10 to 50% m / m to obtain negatively charged niobium oligomers; b. Adding 10 to 1000 mg / L of quaternary ammonium salt and / or 500 to 20000 mg / L of methylene blue to the negatively charged niobium oligomers obtained in step "a" to obtain a solution; c. At room temperature, stirring the solution obtained in step "b" at 10 to 100 rpm for a period of 5 to 30 minutes.

2. Use of the nanostructured hybrid material based on niobium oligomers according to claim 1, characterized in that For the production of disinfection compounds with bactericidal and antiviral activities.

3. Use of the nanostructured hybrid material based on niobium oligomers according to claim 1, characterized in that For the production of disinfection compounds against coronaviruses.

4. Use of the nanostructured hybrid material based on niobium oligomers according to claim 1, characterized in that The niobium oligomer-based nanostructured hybrid material is introduced into an alcohol gel at 10-70% m / m.

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