https://repositorio.ufpb.br/jspui/handle/tede/7029 PPGQ Tue, 14 Apr 2026 13:04:35 GMT 2026-04-14T13:04:35Z https://repositorio.ufpb.br/jspui/handle/123456789/37683 Título: Investigação do uso de solventes eutéticos profundos como co-catalisador na reação de Morita-Baylis-Hillman envolvendo derivados de isatina e ésteres acrílicos Autor(es): Andrade, Sandro Dutra de Orientador: Lima Junior, Claudio Gabriel Abstract: The search for greener synthetic protocols has been a challenge for Chemistry in recent decades. This work describes the use of Deep Eutectic Solvents (DES) as a substitute for volatile organic solvents and as a co-catalyst in the Morita-Baylis- Hillman Reaction (MBHR). We investigated some DES consisting of choline chloride (ChCl), glycerol (G), ethylene glycol (EG) and urea (U), applied in MBHR using as electrophiles, isatin, 5-chloroisatin, 5,7-dichloroisatin, 5- fluoroisatin, 5- nitro-isatin, 5-methyl-isatin and their respective N-alkylated derivatives. As Michael acceptors, acrylonitrile, methyl acrylate and 2-hydroxyethyl acrylate were used, and the experiments were conducted at room temperature, leading to obtaining twelve Morita-Baylis-Hillman adducts with yields that varied between 40 - 98%, in reactions lasting from 50 minutes to 30 hours, according to the type of DES and Michael acceptors used. The unpublished adducts derived from 2- hydroxyethyl acrylate (11 and 11a) were obtained during the investigations and completely characterized and elucidated by Infrared (IR) spectroscopic techniques, 1H and 13C Nuclear Magnetic Resonance and High Resolution Mass Spectrometry. We also sought to establish protocols reducing the amount of DABCO to catalytic proportions (15 mol%), in addition to a probable replacement with Hexamethylenetetramine (HMTA), which is less expensive and non- hygroscopic. In this case, even comparing their behavior by altering DES and Michael's acceptor, it was observed that the use of HMTA was not satisfactory in relation to DABCO. Throughout the investigation, we identified that the DES consisting of ChCl:EG (1:2) promoted a transesterification reaction with methyl acrylate, which made its use unfeasible as a solvent for reactions involving this Michael acceptor. New protocols were proposed for the synthesis of the adduct derived from 2-hydroxyethyl acrylate (11) using DESs constituted by ChCl:EG (1:2) and ChCl:U (1:2). The substitution of DES ChCl:EG (1:2) for ChCl:U (1:2) and the use of 50 mol% of DABCO proved to be a very promising methodology, reducing the reaction times (5 – 30h) in relation to other protocols established in the literature and satisfactory yields (45 - 95%). An investigation into the prototype reaction between N-methylisatin and methyl acrylate was carried out by Electrospray Mass Spectrometry (ESI(+)-MS), allowing to identify some reaction intermediates that are proposed in this work. The DES consisting of ChCl:U (1:2) was reused two more times, but the increased viscosity of the reaction medium proved to be a limiting factor to be overcome. Editor: Universidade Federal da Paraíba Tipo: Tese Fri, 10 Feb 2023 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/37683 2023-02-10T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37674 Título: Síntese, estudo in silico, elucidação teórica da estereoquímica e atividade antifúngica de novas imidas derivadas do safrol análogas à podofilotoxina Autor(es): Vilela, Raquel Finazzi Orientador: Athayde Filho, Petrônio Filgueiras de Abstract: Among nitrogenous compounds, imides represent important building blocks for the development of new drugs, considering that this class of compounds contains a wide range of biological activity, such as: antimicrobial, antitumor, anticonvulsant, antispamodic, analgesic, fungicide, bactericide, herbicide and more. In this sense, the aim of this study was to synthesize cyclic imide derivatives, from safrole, amino acid and aromatic amines substituted as podophyllotoxin analogues, which are substances known in the literature due to their extensive biological activity as antitumor, antiviral, antidepressant, among others, and that can be used in the microbiological combat of resistant strains, tumor cells and that present themselves as alternatives to commercial drugs, drugs available in the pharmaceutical market. In this research, ten molecules were synthesized, nine of which are new and characterized by Spectroscopy IV, 1H NMR, 13C NMR and High Resolution Mass Spectroscopy. In order to obtain the compounds, the isomerization of Safrol (1) was necessary, using Potassium Hydroxide (KOH), to obtain the Isosafrol isomer (2). After this step, isosafrole was reacted with maleic anhydride, to obtain the product (3). This was purified by means of a chromatographic column. After purification, compound (3) was used as an intermediate, subsequently reacting with p-substituted aromatic amines and two amino acids (glycine and p-aminobenzoic acid) to obtain the final products (4a- j) with yields around 60%. In silico studies showed that the compounds met Lipinski's parameters, suggesting good oral bioavailability, good absorption, moderate solubility, and drug-likeness values indicated that the compounds are frequently present in most drugs currently used in the OSIRIS Property program Explorer, showing strong to moderate antifungal activity against various strains of Candida and Cryptococcus. In the biological assay in particular, compounds 4b, 4c and 4h exhibited strong antifungal activity, with MICs between 0.17 - 0.73 μmol mL-1 . The compound 4j exhibited antifungal activity with MIC 1.28 μmol mL- 1 for all strains tested. In silico studies for the Lipinski's five rule have indicated that these compounds have potential candidates for new drugs. Oral bioavailability was assessed using these parameters. In addition, a computational study helped to attribute the stereochemistry of compound 4j, where the synthesized mixture is composed of two stereoisomers, 4j (SRR) and 4j (RSS). Editor: Universidade Federal da Paraíba Tipo: Tese Fri, 29 May 2020 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/37674 2020-05-29T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37239 Título: Desenvolvimento e aplicação de protocolos de solvatação baseados em uma abordagem híbrida multiescala sequencial Autor(es): Silva, Daniel Gabriel da Orientador: Santana, Otávio Luís de Abstract: Describing the solvated phase remains a significant challenge, especially when the system contains protic and polar solvents, such as water, directly impacting the accuracy in predicting the properties of interest. This work aims to develop protocols that account for the effect of explicit solvation in the calculation of thermodynamic properties (especially Gibbs’ free energies), with the goal of reproducing experimental data within chemical accuracy, defined as an absolute error below 1 kcal mol-1. To achieve this, a multiscale hybrid approach was employed, characterized by the combination of simulation methods at different resolution levels: quantum mechanics, molecular mechanics, and implicit solvation models. As an evaluation metric, both theoretical and experimental reduction potentials of a set of redox reactions were considered. Although conceptually simple, modeling reduction potentials presents high operational complexity, particularly when aiming to achieve chemical accuracy. The methodological development involved the following steps: (i) performing a benchmark of reduction potentials in water using 25 density functionals; (ii) inclusion of explicit water molecules forming hydrogen bonds with the solute, incorporated into the reduction potential calculations; and (iii) inclusion of explicit water molecules in a solute-solvent ratio corresponding to the standard concentration (1 mol kg 1). The study − enabled the development of tools capable of automatically selecting solvent molecules in the vicinity of the modeled systems, positioned through classical molecular dynamics simulation procedures. These applications compose the suite named Solvate Suite. The results showed absolute mean errors ranging from 4.78 kcal mol-1 to 27.98 kcal mol-1 for the reduction potentials. However, this same methodology was also applied to the calculation of chemical shifts of 13C for a set of molecules from different categories, for which mean errors below 1.5 ppm were obtained. This performance enabled a more accurate prediction of the order of the peaks in the NMR spectrum of two isomeric carbohydrates, overcoming several incorrect assignments associated with the use of the implicit solvation model C-PCM. Editor: Universidade Federal da Paraíba Tipo: Tese Mon, 30 Jun 2025 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/37239 2025-06-30T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37179 Título: Desenvolvimento de hidrogel injetável contendo nanopartículas de zeína para liberação simultânea de doxorrubicina e quercetina Autor(es): Nascimento, Sanierlly da Paz do Orientador: Souza, Antônia Lúcia de Abstract: Systemic toxicity is one of the major challenges of chemotherapy. Doxorubicin, a first- line drug for breast cancer treatment, is limited by severe adverse effects. The combined administration of chemotherapeutics, along with drug delivery systems for localized application in malignant tumors, may effectively reduce systemic toxicity. This study developed an injectable hydrogel based on oxidized sodium alginate (OSA) and gelatin (GEL), incorporating zein nanoparticles for the simultaneous release of doxorubicin (DOX) and quercetin (QUE), the latter encapsulated in nanoparticles. The study was structured into five stages: (1) functionalization of sodium alginate by oxidation with sodium periodate (OSA) and characterization using infrared spectroscopy (IR), proton nuclear magnetic resonance (1H NMR), and heteronuclear single quantum coherence (HSQC) correlation; (2) synthesis of hollow zein nanoparticles coated with chitosan using sodium carbonate as a sacrificial template (HNPs), followed by quercetin encapsulation (QNPs). HNPs were characterized in terms of size, zeta potential, X-ray diffraction (XRD), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The encapsulation of quercetin was analyzed via UV-vis spectroscopy; (3) preparation of the injectable hydrogel (OSAG) via Schiff base crosslinking with a 10% (w/v) OSA and 15% gelatin ratio, achieving a gelation time of 2.33 ± 0.03 minutes. The hydrogel was characterized for rheological, morphological, and swelling properties. After confirming the formation of a stable, porous, injectable, and self-healing network, DOX and QNPs were incorporated, resulting in the following systems: hydrogel containing DOX (OSAGX), hydrogel containing quercetin (OSAGQ), and the composite hydrogel containing both therapeutic agents (OSAGC); (4) in vitro release study of DOX and QUE from OSAGX, OSAGQ, and OSAGC; (5) cytotoxicity evaluation of OSAG, OSAGX, OSAGQ, and OSAGC in MCF-7 breast cancer cells. OSA was identified by absorption bands between 1730 and 1739 cm−1 in the IR spectrum, characteristic of aldehydes, further confirmed by the emergence of signals between 5.15 and 5.4 ppm in the 1H NMR spectrum. HNPs had an average size of 195 ± 0.44 nm, while QNPs measured 218.8 ± 2.77 nm, as confirmed by TEM and AFM, which also revealed the spherical morphology of HNPs. The nanoparticles exhibited an encapsulation capacity and efficiency of 4.78 ± 0.00% and 67.32 ± 0.06%, respectively. In vitro release tests of DOX and QUE at pH 6.8 and 7.4 showed distinct release profiles, with 81.2% and 9.7% released, respectively. Cytotoxicity assays revealed a 4.66-fold increase in cytotoxic action with OSAGX. The composite hydrogel OSAGC exhibited an even greater increase, enhancing cytotoxicity by 20.7 times compared to free DOX. Furthermore, the inclusion of QNPs reduced the IC50 of OSAGX from 0.071 ± 0.039 to 0.016 ± 0.014 μg/mL. These results highlight the cytotoxicity-enhancing effect of the hydrogel system, broadening the applications of oxidized alginate–gelatin hydrogels for dual drug delivery. Although localized administration requires further in vivo investigation, in vitro findings suggest strong potential for future therapeutic applications. Editor: Universidade Federal da Paraíba Tipo: Tese Wed, 18 Dec 2024 00:00:00 GMT https://repositorio.ufpb.br/jspui/handle/123456789/37179 2024-12-18T00:00:00Z