Obtaining crystalline films of maleate with copper(II) in a polymeric matrix and films obtained.

Description

Obtaining crystalline films of maleate with copper(II) in a polymeric matrix and films obtained. Field of invention

[001] This product is a film synthesized from powdered crystals of maleate and phenanthroline complexed with Cu(II) ions, coated with a polymeric mixture of alginate and cellulose, for application to pathogenic agents. Fundamentals of the invention

[002] Polymeric matrices are essential components, playing a crucial role in determining the overall properties of novel materials, as well as the impact resistance, toughness, and thermal stability of the material. They exhibit properties such as: stiffness, transparency, chemical stability, biocompatibility, and biodegradability. Polymeric matrices are fundamental in various applications, including medicine, drug delivery devices, and wound dressings, among many others. They offer a wide range of properties, making composite materials versatile and adaptable to the specific needs of each application (YOUSEFI, Mohammad et al. Polymeric nanocomposite materials: preparation and characterization of star-shaped PbS nanocrystals and their influence on the thermal stability of acrylonitrile—butadiene—styrene (ABS) copolymer. Polyhedron, v. 30, n. 6, p. 1055-1060, 2011). Petition 870250005138, dated 01 / 22 / 2025, page 7 / 22 2 / 10

[003] Several techniques are used to study the chemical composition of films. The advantages of using FT-IR and Raman spectroscopies, as well as X-ray diffraction, are that they are non-invasive, fast, and colorless methods for biofilm characterization, allowing the analysis of intact biological samples without the need for extensive preparation, making them valuable tools for the study of biofilms in a clinical context. These techniques allow the identification of components such as proteins, lipids, and carbohydrates in biofilms. They provide detailed information on the chemical composition and functional groups present in the biofilm matrix. (GIEROBA, Barbara et al. The FT-IR and Raman spectroscopies as tools for biofilm characterization created by cariogenic streptococci. International Journal of Molecular Sciences, v. 21, n. 11, p. 3811, 2020).

[004] Among the numerous applications in the field of medicine, the presence of copper ions complexed with organic molecules presents bactericidal, bacteriostatic, and fungistatic effects, being able to eliminate or inhibit microbial development, delaying the growth of bacteria and fungi harmful to human health. However, these activities can be potentiated and more significant if the complexed material is coated with a polymeric matrix, providing a larger surface area for interaction of the material with disease-causing microorganisms (OLIVEIRA NETO, Joao G. et al.) Petition 870250005138, dated 01 / 22 / 2025, page 8 / 22 3 / 10 al. Crystalline films of l-threonine complexed with copper (ii) dispersed in a galactomannan solution: a structural, vibrational, and thermal study. Polymer Engineering & Science, vol. 60, no. 1, p. 71-77, 2020).

[005] Copper(II) complexes have gained prominence due to studies suggesting their cytotoxic and pharmacological potential in microbiological systems. Copper plays a crucial role in biochemistry and interaction with biomolecules. Copper complexes exhibit antacid, anti-inflammatory, antiviral, and antitumor properties. They interact with proteins and nucleic acids by complexing the metal ion with amino acids, electron transport, and oxygen metabolism. Copper(II) complexes also stand out as promising cytotoxic agents, inhibiting the proliferation of diseased cells and exhibiting pharmacological effects (JA Eremina, et al. Mixed-ligand copper(II) complexes with tetrazole derivatives and 2,2'-bipyridine, 1,10-phenanthroline: Synthesis, structure and cytotoxic activity, Inorganica Chim Acta 487;2019).

[006] Cellulose is the most abundant natural polymer in the biosphere, consisting of linked β-D-glucopyranose monosaccharide units. It is found mainly in plant cells, but can also be produced by algae, fungi, and bacteria. Alginate is a linear anionic copolymer consisting of β-D-mannuronate (M) and α-L-guluronate units. Petition 870250005138, dated 01 / 22 / 2025, page 9 / 22 4 / 10 (G) linked by glycosidic bonds. The physicochemical and biological properties of alginates depend on their source. This polymer is usually extracted from brown algae and used in biomedical applications because its degradation products are biocompatible. Alginate and cellulose-based materials can be processed into different structures such as gels, polymer blends, films, sponges, and porous membranes, which have potential applications in bone regeneration, as dressings, and in the release of bioactive compounds such as drugs, enzymes, cells, and growth factors (BERNARDO, Marcela Piassi et al. Processing and application of polymeric biomaterials: recent advances and perspectives. Química Nova, v. 44, p. 1311-1327, 2021).

[007] Prior patent PI 102019010859-2, entitled “L-threonine crystalline film with copper(II) and galactomannan”, describes the production of a crystalline film with antimicrobial properties from the copper(II) complex coated with galactomannan, since the polymer increases the contact surface of the material and inactivates the presence of various pathogenic microorganisms due to interaction with the crystal.

[008] The prior art PI 102020002745-0, entitled “Biodegradable film with antitumor properties and its process for obtaining it” refers to the process used for the synthesis of a film with antitumor properties composed of a 1,10-phenanthroline crystal and serine. Petition 870250005138, dated 01 / 22 / 2025, page 10 / 22 5 / 10 complexed with Copper(II) dispersed in a gelatin solution. The film showed itself to be an antitumor agent, and the polymeric matrix increased the adhesion of the material, in addition to acting as a biomaterial.

[009] The prior art PI 102021016255-4, entitled “Crystalline film with biological properties” refers to biodegradable and biocompatible chitosan films with ternary copper(II) crystal containing 1,10-phenanthroline and L-proline that have high biological potential in antitumor activity.

[0010] Prior art PI 102022004728-6 A2, entitled “PROCESS FOR THE SYNTHESIS OF THE NICKEL(II), 1,10-PHENANTHROLINE AND MALEIC ACID CRYSTAL COMPLEX”, refers to the innovative process for the mechanical synthesis of the nickel(II), 1,10-phenanthroline and maleic acid crystalline complex. According to the authors, maleic acid, or maleate, plays a crucial role in the formation of the crystalline structure of the nickel(II) complex with 1,10-phenanthroline. Its importance includes the stability of the complex, the formation of the crystalline structure, and biological activity. Maleic acid acts as a ligand that coordinates with the metal ion (nickel(II)), contributing to the stability of the crystalline complex. The presence of bidentate ligands, such as maleic acid and 1,10-phenanthroline, generally results in more stable complexes due to stronger interactions with the central metal. Petition 870250005138, dated 01 / 22 / 2025, p. 11 / 22 6 / 10

[0011] The aforementioned prior art forms present significant differences in the production of semi-organic films, since these differences are related to coordination with the metal ion, structure, polymeric matrix, as well as efficiency in biological activity patterns.

[0012] In studies addressing materials previously mentioned in bibliographic references, alginate and cellulose stand out as natural biopolymers of great importance, widely used in various areas due to their favorable physicochemical properties, ease of handling, biocompatibility, biodegradability, and their ability to form three-dimensional structures. Films containing copper(II) and 1,10-phenanthroline exhibit biological activities and their potential use in skin wound care and bacterial skin infections due to pathogenic agents. Brief description of the drawings

[0013] The results obtained present the structural analysis of the crystalline films and bactericidal activity.

[0014] Figure 1 shows a photograph of crystalline films of copper(II), phenanthroline and maleate, in different concentrations (0.5%, 1% and 2%) of polycrystals, dispersed in a polymeric matrix of alginate and cellulose. Using the 0.5% concentration of polycrystals, nucleation in the form of frost is observed, and at the 1% concentration of polycrystals, nucleation within the polymeric matrix is ​​observed to be in the form of spheres (Figure 1). Petition 870250005138, dated 01 / 22 / 2025, page 12 / 22 7 / 10

[0015] Figure 2 shows the X-ray diffraction pattern of copper(II), phenanthroline, and maleate films in the angular range of 5 to 40°, 2θ. The diffractograms reveal that there were significant structural modifications. The main one was the change from the amorphous system to the crystalline system, since, with the polycrystals dispersed in the polymer, the diffractograms revealed the presence of several peaks, characteristic as the concentration of polycrystals increases. The absence of crystalline peaks at a concentration of 0.5% indicates that the material has an amorphous structure; in other words, the interaction between the polycrystals and the polymer does not provide long-range atomic order.

[0016] Figure 3 shows the antibacterial inhibition halos. A qualitative method was used to evaluate the bactericidal activity in the crystalline films coated with the polymeric matrix. Note that as the concentration of polycrystals in the polymeric matrix increases, the inhibition halos are much larger (Figure 3). Using a concentration of 2% polycrystals, the material is able to better eliminate the growth of these strains. Description of the invention

[0017] The invention can be better understood through the following detailed description, in accordance with the steps of the synthesis process from the preparation of copper(II), phenanthroline and maleate films. Petition 870250005138, dated 01 / 22 / 2025, page 13 / 22 8 / 10

[0018] One aspect of the present invention relates to the process for obtaining crystalline films, which comprises the following steps:

[0019] CRYSTAL SYNTHESIS: Initially, the masses of 1,10-phenanthroline (10 mmol), copper(II) nitrate trihydrate (10 mmol), and maleic acid (10 mmol) are determined and weighed to produce a saturated solution. Copper(II) nitrate trihydrate is dissolved in 40 mL of methanol under constant stirring at 400 rpm for 10 min. Then, it is slowly added to the 1,10-phenanthroline in the methanolic solution of copper(II) nitrate trihydrate, in which the mixture remains under constant stirring for about 1 hour at 348 K. Maleic acid is dissolved with 10 mL of H2O treated with NaOH (20 mmol) and slowly added to the reaction mixture above with continuous stirring for 30 min at 348 K. The resulting solution is filtered and subjected to slow solvent evaporation. The crystals are obtained over 30 days, after which they are macerated and then coated in a mixture of alginate and cellulose polymers.

[0020] PREPARATION OF POLYMERIC SOLUTIONS: Three solutions are prepared, comprising 0.3% (W / W) sodium carboxymethylcellulose and 0.3% (W / W) sodium alginate. The mixture of the two reagents results in a 1.2% (W / V) solution, which is kept under constant stirring at 300 RPM for 24 h. The mixture is prepared in triplicate. Petition 870250005138, dated 01 / 22 / 2025, page 14 / 22 9 / 10

[0021] FILM FORMATION: With the three polymer solutions prepared previously, 0.5, 1 and 2% (W / W) of the crystalline powder prepared in section

[0019] is added to each 1.2% (W / V) polymer solution, resulting in three solutions of 1.4% (W / V), 1.8% (W / V) and 2.4% (W / V), which remain under constant stirring at 300 RPM for 24 h. After this, the solutions are stored for 65 days to allow for slow evaporation at low temperatures.

[0022] Another aspect of the present invention features copper(II), phenanthroline and maleate films coated with polymers that are characterized by the following formulation: 1% to 2% sodium carboxymethylcellulose (CH2OCH2COONa) and sodium alginate (C6H7O6Na)x, preferably a mixture of 1.2% (CH2OCH2COONa) and (C6H7O6Na)x and 0.5%, 1% and 2% crystalline copper, 1,10-phenanthroline and maleate powder. Examples of how the invention can be implemented

[0023] Crystalline films were obtained in 65 days, with a strong blue coloration as the concentration of polycrystals increased (Figure 1).

[0024] Structural characterization (XRD at room temperature) was performed to analyze the amorphous phase belonging to the polymer mixture and the crystalline phase belonging to the polycrystals coated in the matrix (Figure 2). The diffractograms are observed at concentrations of 0.5%, 1% and 2% of copper(II), phenanthroline and maleate polycrystals, and as the crystallite concentration increases, a definition of the peaks is observed. Petition 870250005138, dated 01 / 22 / 2025, page 15 / 22 10 / 10 The crystalline phase exhibits a square pyramidal coordination structure around the transition metal.

[0025] Table 1 presents the statistical data related to bacterial inhibition. Table 1 - Diameters (mm) of the bacterial inhibition halos of crystalline copper(II), phenanthroline and maleate films coated with polymers, against Gram-positive and Gram-negative bacteria. Gram-positive 1.4% 1.8% 2.4% Staphylococcus aureus ATCC 6538 21.31 mm 22.28 mm 33.26 mm Enterococcus faecalis ATCC 29212 26.04 mm 29.84 mm 34.32 mm Gram-negative 1.4% 1.8% 2.4% Escherichia coli ATCC 25922 21.54 mm 25.24 mm 28.64 mm Pseudomonas aeruginosa ATCC 27853 20.87 mm 24.14 mm 26.94 mm

[0026] With these data, it is observed that coating polycrystals in polymeric matrices can significantly improve their solubility, making them more bioavailable for therapeutic use as an antibacterial agent. Since the films provide a protective environment for the Cu(II) polycrystals, increasing their stability and preventing degradation, this can improve overall efficacy.

Claims

CLAIMS 1. CRYSTALLINE FILMS, characterized by being prepared using a polymeric solution of alginate, cellulose and copper(II) polycrystals, 1,10-phenanthroline and maleic acid, wherein the formulation comprises: 1% to 2% sodium carboxymethylcellulose (CH2OCH2COONa) and sodium alginate (C6H7O6Na)x, preferably a mixture of 1.2% (CH2OCH2COONa) and (C6H7O6Na)x and 0.5%, 1% and 2% crystalline copper powder, 1,10-phenanthroline and maleate, ultimately forming three solutions of 1.4% (W / V), 1.8% (W / V) and 2.4% (W / V) of polymer and polycrystals.

2. PROCESS FOR OBTAINING CRYSTALLINE MALEATE FILMS WITH COPPER(II) IN A POLYMERIC MATRIX, defined in claim 1, characterized by the steps of: a) Crystal synthesis, wherein initially the masses of 1,10-phenanthroline (10 mmol), copper(II) nitrate trihydrate (10 mmol), maleic acid (10 mmol) are determined and weighed to produce a saturated solution; subsequently the copper(II) nitrate trihydrate is solubilized in 40 mL of methanol under constant stirring at 400 rpm for 10 min, then the 1,10-phenanthroline is slowly added to the methanolic solution of copper(II) nitrate trihydrate, in which the mixture remains under constant stirring for about 1 hour at 348 K; Maleic acid is solubilized with 10 mL of H2O treated with NaOH (20 mmol) and Petition 870250005138, dated 22 / 01 / 2025, page.19 / 22 2 / 2 is slowly added to the reaction mixture above with continuous stirring for 30 min at 348 K; then the resulting solution is filtered and subjected to slow solvent evaporation; crystals are obtained in 30 days, where they are macerated to be subsequently coated in the alginate and cellulose polymer mixture. b) Preparation of polymer solutions, where three solutions are prepared, comprising 0.3% (W / W) sodium carboxymethylcellulose and 0.3% (W / W) sodium alginate; the mixture of the two reagents comprises a 1.2% (W / V) solution, which remains under constant stirring at 300 RPM for 24 h. c) Film formation, where 0.5%, 1%, and 2% (W / W) of the crystalline powder prepared in item a) are added to the three polymer solutions prepared in item b), ultimately forming three solutions of 1.4% (W / V), 1.8% (W / V), and 2%.4% (W / V), which remain under constant stirring at 300 RPM for 24 h; then the solutions are stored for 65 days to allow slow evaporation at low temperatures.

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