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Bioinspired copper corrole and porphyrin catalysts for oxidation and hydrocarboxylation of alkanes
Publication . Santos, Carla I. M.; Rosa, Vitor; Neves, M. Graça P. M. S.; Kirillov, Alexander M.; Kirillova, Marina V.; LAQV@REQUIMTE; DQ - Departamento de Química; Elsevier BV
The development of novel bioinspired catalytic systems that are efficient in the mild oxidative transformation of alkanes remains an attractive research direction in the area of molecular catalysis. In the current study, three copper corrole/porphyrin complexes were synthesized, characterized, and evaluated as homogeneous catalysts in the oxidative transformation of cycloalkanes under mild conditions. New copper complexes of 5,10,15-tris(pentafluorophenyl)corrole and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin derivatives bearing a hydroxyethoxy unit were obtained via the controlled nucleophilic substitution of para fluorine atom with ethylene glycol. The model catalytic processes include: (i) the oxidation of cycloalkanes with H2O2 into a mixture of cyclic ketones and alcohols, and (ii) the hydrocarboxylation of cycloalkanes in the CO/S2O82−/H2O system to generate cycloalkanecarboxylic acids as main products. Both model reactions occur under mild conditions (50−60 °C). Selectivity features, substrate and oxidant scope, and the effects of various reaction parameters were studied and discussed. The best catalysts were the copper corrole derivatives, the performance of which is slightly influenced by the presence of the ethylene glycol moiety. In particular, the copper(III) complex of 5,10,15-tris(pentafluorophenyl)corrole is an efficient catalyst for the mild oxidation and carboxylation of cycloalkanes. This work widens the types of Cu-based corrole/porphyrin derivatives that can be used as bioinspired catalytic systems.
Mechanistic insights on ionic liquid and poly(ionic liquid) solutions for CO2 capture and cycloaddition reactions
Publication . Barrulas, Raquel V.; Barão, Rodrigo M.; Bernardes, Carlos E.S.; Zanatta, Marcileia; Corvo, Marta C.; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; Elsevier
This study explores the potential of ionic liquids (ILs) and poly(ionic liquid)s (PILs) for CO2 capture and conversion. Using molecular dynamics simulations in DMSO solutions, we found that ILs and PILs exhibit similar CO2 sorption, with the ILs [BMIM][OAc] and [P4,4,4,4][OAc] showing the highest capacities. Bromide-derived PILs enhance aqueous sorption through cage formation, unlike ILs. We also examined the catalytic efficiency of PILs P[VBA]Cl and P[VBP]Cl, and IL [BA]Cl in CO2 cycloaddition reactions. DMSO decreases IL catalytic activity but improves P[VBA]Cl's performance. These findings suggest that higher CO2 sorption in ILs does not always correlate with better catalytic results. In conclusion, IL and PIL solutions in DMSO demonstrate significant potential for the effective modulation of material properties.
How reliable is the evaluation of DNA binding constants?
Publication . Dömötör, Orsolya; Binacchi, Francesca; Ribeiro, Nádia; Busto, Natalia; Gonzalez-García, Jorge; Garcia-España, Enrique; Correia, Isabel; Enyedy, Éva A.; Hamacek, Josef; Terenzi, Alessio; Basílio, Nuno; Barone, Giampaolo; Cavaco, Isabel; Biver, Tarita; LAQV@REQUIMTE; DQ - Departamento de Química; Elsevier Science Publisher B.V.
In all experimental sciences, the precision and reliability of quantitative measurements are paramount. This is particularly true when examining the interactions between small molecules and biomolecules/polyelectrolytes, such as DNAs/RNAs, and yet it is overlooked in most publications of thermodynamic binding parameters. This paper presents findings from COST Action 18202 “Network for Equilibria and Chemical Thermodynamics Advanced Research,” which assessed the consistency of data derived from the interactions of calf-thymus DNA (CT-DNA) with the fluorescent intercalator ethidium bromide (EB) through spectrofluorimetric titrations. We first discuss critical experimental aspects and propose a reference experimental protocol which can be used to calibrate procedures for the determination of nucleic acid binding equilibrium constants. We then fit the experimental points according to different procedures and analyse the results focusing on the statistical dispersion of the data, aiming at enlightening the strong and weak points of different fitting procedures. The implications of this work are significant, demonstrating how the statistical dispersion of experimental data can influence the interpretation of biochemical coordination mechanisms. Our study reveals that, despite rigorous protocol standardization, the determination of binding parameters remains sensitive to the choice of data fitting method, with deviations in the logarithmic stability constant (logK) values not falling below 5 % relative standard deviation (RSD), or ± 0.5 logK units for 95 % confidence. This variability evidences the critical need for standardized best practices in data treatment as well as experimental procedures. Although our study focuses on the EB/CT-DNA system through fluorescence titrations, the broader implications for other methodologies across various biochemical systems highlight the importance of this first-of-its-kind inter-laboratory comparison in advancing our understanding of biochemical coordination processes.
Cyclam-based molybdenum carbonyl complexes as a novel class of cytotoxic agents
Publication . Teles, Tamara; Fernandes, Auguste; Ferreira, Maria João; Côrte-Real, Leonor; Marques, Fernanda; Correia, João D. G.; Alves, Luis G.; Faculdade de Ciências e Tecnologia (FCT); RSC - Royal Society of Chemistry
Cyclam-based molybdenum carbonyl complexes of formulae [(H2R2Cyclam)Mo(CO)3] (R = H, 4-tBuPhCH24-CF3PhCH2 and 3,5-MePhCH2) were prepared in high yields by the reaction of Mo(CO)6 with the appropriate ligand precursor under reflux in di-n-butyl ether. All complexes were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopy, thermogravimetry as well as single-crystal X-ray diffraction in the case of [(H4Cyclam)Mo(CO)3]. The cytotoxic effect of all compounds was examined on the human breast cancer cells MCF-7 and MDA-MB-231 revealing high antiproliferative activity.
Liposomal nanoformulations of novel copper-based complexes exhibiting antimelanoma activity – In vitro and in vivo validation
Publication . Coelho, Mariana P.; Farinha, Pedro F.; Côrte-Real, Leonor; Ribeiro, Nádia; Luiz, Hugo; Pinho, Jacinta O.; Noiva, Rute; Godinho-Santos, Catarina; Reis, Catarina Pinto; Correia, Isabel; Gaspar, Maria Manuela; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; Elsevier
Melanoma stands as the most aggressive form of skin cancer. The lack of effective and safe therapies has led to the investigation of innovative strategies. The present work validates the in vitro and in vivo antimelanoma activity of new copper complexes of 8-hydroxyquinoline (8HQ) derivatives in free or liposomal forms. Firstly, the cytotoxic properties of several copper-based complexes were screened towards human (A375) and murine (B16F10) melanoma cell lines and human dermal fibroblasts or keratinocytes (HaCaT) cell lines. All the complexes presented lower IC50 values (<20 μM) than dacarbazine (DTIC) and temozolomide (TMZ), the positive controls (>80 μM). Aiming to solve low specificity against tumor cells and enhance its targetability to affected sites three metal-based complexes were selected, based on their antiproliferative properties, and incorporated in long blood circulating liposomes. One of them, di-2-(((2-morpholinoethyl)imino)methyl)quinolin-8-olCopper(II), designated as LCR35, was selected for further studies due to the highest incorporation parameters and cytotoxic properties observed. The antiproliferative activity of LCR35 was preserved after its association to liposomes. Moreover, in B16F10 cells this effect was potentiated. Furthermore, cell cycle analysis studies in A375 and B16F10 cell lines were performed to elucidate the mechanism of action of copper-based complex formulations. A cell cycle arrest at G2/M and G0/G1 phases in A375 and B16F10 cells, respectively, both in free and liposomal forms were observed. To validate the therapeutic potential of LCR35 two murine melanoma models were carried out: subcutaneous and metastatic. Pre-clinical studies demonstrated the high therapeutic effect of LCR35, especially after incorporation in liposomes, compared to control group or animals that received LCR35 Free and DTIC. Overall, in vitro and in vivo studies highlight the potential antimelanoma properties of the copper-based complex, LCR35.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
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Concurso para Atribuição do Estatuto e Financiamento de Laboratórios Associados (LA)
Número da atribuição
LA/P/0056/2020