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Publicação 67

Semi-synthesis and PDT activities of a new amphiphilic chlorin derivative. Photodiagnosis and Photodynamic Therapy.

Moritz, M. N. O ; Gonçalves, J. L.S. ; Linares, I. A. P ; Perussi, J. R ; De Oliveira, K. T. Semi-synthesis and PDT activities of a new amphiphilic chlorin derivative. Photodiagnosis and Photodynamic Therapy, v. 17, p. 39-47, 2017.

DOI:https://doi.org/10.1016/j.pdpdt.2016.10.005

Abstract

An amphiphilic chlorin derivative (CHL-T) was prepared from methylpheophorbide a (CHL) and 2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRISMA®). The new chlorin was compared to other dyes (CHL and Hypericin) in relation to photophysical and photobiological activities in tumor and non-tumor cell lines. Cytotoxicity and cell death target were determined to evaluate the CHL-T efficiency, comparing to the precursor CHL and to the well-known dye hypericin (HY). All of the studied compounds exhibited absorption bands in the therapeutic window and presented a small fluorescence quantum yield compared to the reference dye (rhodamine B). CHL-T was about three times more efficient on singlet oxygen generation than the others photosensitizers. The lipophilicity order of the photosensitizers was CHL > HY > CHL-T. The tumoral HeLa cells presented improved accumulation for CHL and CHL-T compared to HY. The phototoxicity presented by the CHL-T was about ten times higher than by CHL, as demonstrated by the MTT assay. CHL-T showed more cytotoxicity to tumoral cell, comparing to non-tumoral cell in short incubation time. The cell death rises proportionally with increasing PSs concentrations, mainly by necrosis. These findings suggest that CHL-T is a potential new photosensitizer for PDT.

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Publicação 66

Soluble and Non-aggregated Phthalocyanines: Synthesis, Mechanistic aspects and Their Main Building Blocks. Current Organic Synthesis.

Gobo, N ; Brocksom, T ; De Oliveira, K . Soluble and Non-aggregated Phthalocyanines: Synthesis, Mechanistic aspects and Their Main Building Blocks. Current Organic Synthesis, v. 14, p. 1-1, 2017.

DOI:10.2174/1570179414666170403115907 

Abstract:

An overview on phthalocyanine chemistry and the principal synthetic precursors is presented. Strategies developed for obtaining soluble and non-aggregated phthalocyanine dyes are also covered, with insights on the reaction mechanisms. The main synthetic methods are presented, and different approaches to symmetric and non-symmetric systems discussed.

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Publicação 65

The Chemistry of the Sesquiterpene Alkaloids.

Brocksom, T ; De Oliveira, K ; Desiderá, A . The Chemistry of the Sesquiterpene Alkaloids. J BRAZIL CHEM SOC, v. 28, p. 933-942, 2017.

DOI:http://dx.doi.org/10.21577/0103-5053.20170049

Abstract

We present the occurrence, structures, biological activities, biosynthesis, and syntheses of the sesquiterpene alkaloids.

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Publicação 64

Antimicrobial Photodynamic Therapy against Endodontic Enterococcus faecalis and Candida albicans Mono and Mixed Biofilms in the Presence of Photosensitizers: A Comparative Study with Classical Endodontic Irrigants. FRONTIERS IN MICROBIOLOGY.

Diogo, P. ; Fernandes, C. ; Caramelo, F. ; Mota, M. ; Miranda, I. M. ; Faustino, M. A. F. ; Neves, M. G. P. M. S. ; Uliana, M. P. ; de Oliveira, Kleber T. ; Santos, J. M. ; Gonçalves, T . Antimicrobial Photodynamic Therapy against Endodontic Enterococcus faecalis and Candida albicans Mono and Mixed Biofilms in the Presence of Photosensitizers: A Comparative Study with Classical Endodontic Irrigants. frontiers in microbiology, v. 8, p. 498, 2017.

DOI:https://doi.org/10.3389/fmicb.2017.00498

Abstract

Endodontic biofilms eradication from the infected root canal system remains as the primary focus in endodontic field. In this study, it was assessed the efficacy of antimicrobial Photodynamic Therapy (aPDT) with the Zn(II)chlorin e6 methyl ester (Zn(II)e6Me) activated by red light against monospecies and mixed biofilms of Enterococcus faecalis and Candida albicans. The results were compared with the ones obtained with Rose Bengal (RB), Toluidine Blue-O (TBO), the synthetic tetracationic porphyrin (TMPyP) as well as classical endodontic irrigants (3% NaOCl, 17% EDTA and 2% CHX). The antimicrobial efficacy of aPDT toward monospecies and mixed biofilms was quantified resorting to safranin red method. The changes of biofilm organization and of cellular ultrastructure were evaluated through several microscopy techniques (light, laser confocal and transmission electron microscopy). Zn(II)e6Me once activated with light for 60 or 90 s was able to remove around 60% of the biofilm’s biomass. It was more efficient than TBO and RB and showed similar efficiency to TMPyP and classical irrigants, CHX and EDTA. As desirable in a PS, Zn(II)e6Me in the dark showed smaller activity than TMPyP. Only NaOCl revealed higher efficiency, with 70–90% of the biofilm’s biomass removal. The organization of biofilms and the normal microbial cell ultrastructure were extensively damaged by the presence of Zn(II)e6Me. aPDT with Zn(II)e6Me showed to be an efficient antimicrobial strategy deserving further studies leading to a future clinical usage in endodontic disinfection.

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Publicação 63

Chlorin derivatives sterically-prevented from self-aggregation with high antitumor activity for photodynamic therapy.

Linares, I. A.P. ; de Oliveira, K.T ; Perussi, J. R . Chlorin derivatives sterically-prevented from self-aggregation with high antitumor activity for photodynamic therapy. Dyes and Pigments, v. x, p. x-x, 2017.

DOI:https://doi.org/10.1016/j.dyepig.2017.06.011

Abstract

In this study two new chlorin derivatives sterically prevented from aggregation were synthesised by the Diels-Alder reaction originated from protoporphyrin IX dimethyl ester and 1-(2-hydroxyethyl)maleimide. The compounds were fully characterised by 1H NMR, 13C NMR, UV-Vis and high-resolution mass spectroscopy (HRMS) and their photochemical properties such as singlet oxygen quantum yield (ϕ0), fluorescence quantum yield (ϕf) and photodegradation were also evaluated. Furthermore, the partition coefficient (log P) revealed that these compounds present amphiphilic properties. Studies of the photodynamic action in tumour cells (HEp-2 and HeLa) and non-tumour cells (Vero) were also performed in order to confirm the photodynamic therapy (PDT) activity that was indicated by the preliminary photophysical studies. Those phototoxicity results were 55–77% higher than the results obtained with the commercial photosensitiser verteporfin. Finally, cytotoxic assays were performed with the new photosensitiser candidates and cell death was determined using fluorescence microscopy, which provided information about the mechanisms of cell death. In general, we have obtained improved and accessible compounds for PDT studies, as highlighted by the research presented here.

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Publicação 62

Combining batch and continuous flow setups in the end-to-end synthesis of naturally occurring curcuminoids.

Carmona-Vargas, C. C ; Alvez, L. C ; Brocksom, T. J ; de Oliveira, K. T. Combining batch and continuous flow setups in the end-to-end synthesis of naturally occurring curcuminoids. React. Chem. Eng., v. 2, p. 366-374, 2017.

DOI:10.1039/C6RE00207B

Abstract

A successful end-to-end continuous flow synthesis of pure curcumin (1) and two other natural derivatives present in turmeric is described. Batch and continuous flow conditions were combined in order to develop the end-to-end process. Three operations were telescoped yielding the three different natural curcuminoids in a safe, gram-scale and reproducible manner.

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Publicação 61

Exploiting photooxygenations mediated by porphyrinoid photocatalysts under continuous flow conditions

de Oliveira, Kleber T.; Miller, L. Zane ; Mcquade, D. Tyler . Exploiting photooxygenations mediated by porphyrinoid photocatalysts under continuous flow conditions. RSC Adv, v. 6, p. 12717-12725, 2016.

DOI: 10.1039/C6RA00285D

Abstract

Photooxygenation reactions are a powerful synthetic tool to produce oxidized organic compounds; however, these reactions often exhibit experimental limitations including the production of complex mixtures that hinder desired product isolation and scale-up. Herein, we present a photocatalysed protocol under continuous flow conditions using a simple home built photoreactor and porphyrinoids as photocatalysts. Reaction conditions, long-term experiments, and scope demonstrate a protocol that is cost-effective, safe, reproducible and robust, thus allowing the production of relevant substituted naphthoquinones with interest in natural product synthesis and biological activity.

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Publicação 60

Porphyrins as Catalysts in Scalable Organic Reactions

Barona-Castaño, J.; Carmona-Vargas, C.; Brocksom, T.; de Oliveira, K.T. Porphyrins as Catalysts in Scalable Organic Reactions. Molecules, v. 21, p. 310-337, 2016.

DOI:10.3390/molecules21030310

Abstract

 Catalysis is a topic of continuous interest since it was discovered in chemistry centuries ago. Aiming at the advance of reactions for efficient processes, a number of approaches have been developed over the last 180 years, and more recently, porphyrins occupy an important role in this field. Porphyrins and metalloporphyrins are fascinating compounds which are involved in a number of synthetic transformations of great interest for industry and academy. The aim of this review is to cover the most recent progress in reactions catalysed by porphyrins in scalable procedures, thus presenting the state of the art in reactions of epoxidation, sulfoxidation, oxidation of alcohols to carbonyl compounds and C–H functionalization. In addition, the use of porphyrins as photocatalysts in continuous flow processes is covered.

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Publicação 59

High efficiency ruthenium(II) tris-heteroleptic dye containing 4,7-dicarbazole-1,10-phenanthroline for nanocrystalline solar cells

Müller, A.V.; Ramos, L.D.; Frin, K.; de Oliveira, K.T.; Polo, A.S. High efficiency ruthenium(II) tris-heteroleptic dye containing 4,7-dicarbazole-1,10-phenanthroline for nanocrystalline solar cells. RSC Adv, v. 6, p. 46487-46494, 2016.

DOI: 10.1039/C6RA08666G

Abstract

The tris-heteroleptic polypyridyl ruthenium(II) dye, cis-[Ru(cbz2-phen)(dcbH2)(NCS)2], cbz2-phen = 4,7-dicarbazole-1,10-phenanthroline and dcbH2 = 4,4′-dicarboxylic acid 2,2′-bipyridine, was designed, synthesized, purified via liquid chromatography and characterized using 1H NMR, FTIR, cyclic voltammetry, absorption and emission spectroscopy. The compound exhibits broad and intense MLCT bands that overlap the visible spectrum and it is capable of sensitizing TiO2 films. The energy levels of cis-[Ru(cbz2-phen)(dcbH2)(NCS)2] are adequate for its use in DSSCs. The solar cells prepared using this dye achieved a performance that surpasses N3 dye under the same conditions. The introduction of the extended π-conjugated carbazole substituent at the 4 and 7 positions of 1,10-phenanthroline increases the IPCE and the overall solar cell efficiency. The high performance is ascribed to the HOMO stabilization and to the increase in electron delocalization of the triplet excited state, which favors the electron injection via singlet and triplet pathways.

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Publicação 58

Contrasting photophysical properties of rhenium(I) tricarbonyl complexes having carbazole groups attached to the polypyridine ligand

Ramos, L. D.; Sampaio, R. N. ; de Assis, F. F. ; de Oliveira, K. T. ; Homem-de-Mello, P. ; Patrocinio, A. O.; Frin, K.. Contrasting photophysical properties of rhenium(I) tricarbonyl complexes having carbazole groups attached to the polypyridine ligand.. Dalton T, v. 45, p. 11688-11698, 2016.

DOI: 10.1039/C6DT01112H

Abstract

In the present work, new rhenium(I) polypyridyl compounds, fac-[Re(L)(CO)3(cbz2phen)]+/0 where cbz2phen = 4,7-di(9H-carbazol-9-yl)-1,10-phenanthroline and L = Cl−, pyridine (py) or 2-aminomethylpyridine (ampy) were synthesized and characterized by 1H NMR, UV-Vis and IR spectroscopy combined with theoretical calculations using time-dependent density functional theory (TD-DFT). Their photophysical properties were investigated by steady state and time-resolved emission spectroscopy. These compounds show a strong and broad absorption band around 350–500 nm that, also by TD-DFT, corresponds to the carbazol → phenanthroline intraligand charge transfer transition, 1ILCTcbz2phen, with some contribution of the Re(I) → phenanthroline metal-to-ligand charge transfer transition, 1MLCTRe→cbz2phen. In contrast to typical Re(I) polypyridyl complexes, cbz2phen-based Re(I) compounds exhibit two emission maxima in CH3CN solution and relatively low emission quantum yields, 10−3–10−2. Solution phase time-resolved photoluminescence and excited state quenching experiments provided meaningful information on the presence of multiple emitter states after light excitation, which were identified as an 1ILCTcbz2phen excited state deactivation at higher energies and a long-lived phosphorescence attributed to the 3MLCTRe→cbz2phen excited state. When embedded into a PMMA matrix, the radiative decay from the singlet state is inhibited and the contribution of both 3MLCT and 3ILCTcbz2phen to the luminescence is observed. The photophysics of these Re(I) compounds reported herein provide new insights into the understanding of substitutional groups on the polypyridyl ligands that are relevant to practical and fundamental development of photo-induced molecular devices.

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Publicação 57

One-pot Sequential Functionalizations of meso-Tetrathienylporphyrins via Heck-Mizoroki Cross-coupling Reactions

Donatoni, M. C. ; Vieira, Y. W. ; Brocksom, T. J. ; Rabelo, A. C. ; Leite, E. R. ; de Oliveira, K. T. . One-pot Sequential Functionalizations of meso-Tetrathienylporphyrins via Heck-Mizoroki Cross-coupling Reactions. Tetrahedron Lett, v. 57, p. 27-28, 2016.

DOI:10.1016/j.tetlet.2016.05.106

Abstract

Synthesis and sequential functionalizations of a new meso-tetraiodo(thien-2-yl)porphyrin and its Ni(II) derivative are described. The reactions for the preparation of these new porphyrins were optimized. Subsequently, four successive one-pot Heck–Mizoroki cross-coupling reactions were studied using two acrylates and varied reaction conditions. We describe an optimized protocol for the preparation of highly conjugated thienylporphyrins with the potential to be used as dyes in solar cell devices as demonstrated in our preliminary studies.

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Publicação 56

Basic Concepts and Applications of Porphyrins, Chlorins and Phthalocyanines as Photosensitizers in Photonic Therapies

Oliveira, K. T.; Souza, J. M.; Gobo, N. R. Silva; Assis, F. F.; Brocksom, T. J. Basic Concepts and Applications of Porphyrins, Chlorins and Phthalocyanines as Photosensitizers in Photonic Therapies. RVQ, v. 7, p. 310-335, 2015.

DOI: 10.5935/1984-6835.20150016

Abstract

Nesta revisão são descritas algumas aplicações da luz em terapias fotônicas, em particular, na terapia fotodinâmica (PDT) que envolve a combinação luz/fotossensibilizador/oxigênio. Foram selecionados e apresentados alguns exemplos mais relevantes dos derivados do tipo porfirina, clorina e ftalocianina que são atualmente comercializados como fotossensibilizadores para uso nesta terapia. O objetivo aqui não é cobrir todas as alternativas de fotossensibilizadores no mercado nem mesmo em fase de estudos acadêmicos, e sim, dar uma visão geral sobre fotossensibilizadores e PDT dentro da perspectiva de como ocorre a interação da luz com a matéria.

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Publicação 55

Co-Deposition of Gold Nanoparticles and Metalloporphyrin Using the Langmuir-Blodgett (LB) Technique for Surface-Enhanced Raman Scattering (SERS)

Camacho, S. A ; Aoki, P. H. B.; de Assis, F. F. ; Pires, A. M. ; de Oliveira, K. T. ; Aroca, R. F. ; Constantino, C. J. L. . Co-Deposition of Gold Nanoparticles and Metalloporphyrin Using the Langmuir-Blodgett (LB) Technique for Surface-Enhanced Raman Scattering (SERS). Appl Spectrosc, v. 69, p. 451-456, 2015.

DOI: 10.1366/14-07625

Abstract

The synergistic effect produced by metallic nanoparticles when incorporated into different systems empowers a research field that is growing rapidly. In addition, organometallic materials are at the center of intensive research with diverse applications such as light-emitting devices, transistors, solar cells, and sensors. The Langmuir-Blodgett (LB) technique has proven to be suitable to address challenges inherent to organic devices, since the film properties can be tuned at the molecular level. Here we report a strategy to incorporate gold nanoparticles (AuNPs) into the LB film by co-deposition in order to achieve surface-enhanced Raman scattering (SERS) of the zinc(II)-protoporphyrin (IX) dimethyl ester (ZnPPIX-DME). Prior to the LB co-deposition, the properties of the Langmuir monolayer of ZnPPIX-DME at the air-water interface, containing AuNPs in the subphase, are studied through the surface-pressure versus mean molecular area (π-A) isotherms. The ZnPPIX-DME+AuNPs π-A isotherm presented a significant shift to higher molecular area, suggesting an interaction between both ZnPPIX-DME molecules and AuNPs. Those interactions are a key factor allowing the co-deposition of both AuNPs and ZnPPIX-DME molecules onto a solid substrate, thus forming the LB film. SERS of ZnPPIX-DME was successfully attained, ensuring the spatial distribution of the AuNPs. Higher enhancement factors were found at AuNP aggregates, as a result of the intense local electromagnetic field found in the metal nanoparticle aggregates. The main vibrational bands observed in the SERS spectra suggest a physical adsorption of the ZnPPIX-DME onto the surface of AuNPs. The latter is not only in agreement with the interactions pointed out by the π-A isotherms but also suggests that this interaction is kept upon LB film co-deposition.

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Publicação 54

Selective Vilsmeier-Haack aryl-formylations of tetrathienylporphyrin and its Ni(II) complex. Journal of Porphyrins and Phthalocyanines

Momo, P. B. ; Sampaio, O. M. ; Brocksom, T. J. ; de Oliveira, K. T. Selective Vilsmeier-Haack aryl-formylations of tetrathienylporphyrin and its Ni(II) complex. J Porphyr Phthalocya, v. 19, p. 745-752, 2015.

DOI: http://dx.doi.org/10.1142/S1088424615500467

Abstract

Regioselective aryl-formylations of tetrathienylporphyrin and its Ni(II) complex were performed with the Vilsmeier–Haack reaction. We have studied different solvents and temperatures to obtain the mono, di, tri and tetra-formylated porphyrins, all at the α-position of the thienyl groups. No β-formylations were observed and the four different formylated products presented here are suitable intermediates for subsequent extended conjugation reactions.

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Publicação 53

The New Directions of Organic Synthesis

Brocksom, T. ; Desiderá, A. ; Carvalho Alves, L. ; Oliveira, K. . The New Directions of Organic Synthesis. Curr Org Synth, v. 12, p. 496-522, 2015.

DOI: 10.2174/157017941205150821121222 

Abstract:

This review deals with the important changes that have taken place in the last twenty to thirty years, on the directions and objectives of organic synthesis. Target oriented synthesis now competes with diversity oriented synthesis, and variations, in an attempt to occupy chemical space more completely. At the same time practicality, efficiency, scalability and robustness are once again the major goals to be associated with atom, step and function economies, within the context of sustainability.

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Publicação 52

Exploiting Novel Process Windows for the Synthesis of meso-Substituted Porphyrins under Continuous Flow Conditions

Momo, P. B.; Bellete, B. S ; Brocksom, T. J.; de Souza, R. O. M A ; de Oliveira, K. T. Exploiting Novel Process Windows for the Synthesis of meso-Substituted Porphyrins under Continuous Flow Conditions. RSC Adv, v. 5, p. 84350-84355, 2015.

DOI: 10.1039/C5RA16962C

Abstract

Porphyrin synthesis by classical methods frequently involves the use of high temperatures, toxic and dangerous reagents yielding the product in very low amounts and with poor scalability. Herein, we have studied the synthesis of meso-substituted porphyrins under continuous flow conditions, thus demonstrating scale-up for the porphyrin synthesis in a safe, cost-competitive, highly pure, reproducible and robust manner.

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Publicação 51

A Practical Deca-gram Scale Ring Expansion of (R)-(-)-carvone to (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1.

Alves, L. C.; Desiderá, A. L. ; de Oliveira, K. T. ; Newton, S.; Ley, S. V. ; Brocksom, T. J. A Practical Deca-gram Scale Ring Expansion of (R)-(-)-carvone to (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1. Org Biomol Chem, v. 13, p. 7633-7642, 2015.

DOI: 10.1039/C5OB00525F

Abstract

A route to enantiopure (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1, an intermediate for terpenoids, has been developed and includes a highly chemo- and regioselective Tiffeneau–Demjanov reaction. Starting from readily available (R)-(−)-carvone, this robust sequence is available on a deca-gram scale and uses flow chemistry for the initial epoxidation reaction. The stereochemistry of the addition of two nucleophiles to the carbonyl group of (R)-(−)-carvone has been determined by X-ray diffraction studies and chemical correlation.

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Publicação 50

Sensitive determination of 17β-estradiol in river water using a graphene based electrochemical sensor

Moraes, F. C. ; Rossi, B. ; Donatoni, M. C. ; de Oliveira, K. T. ; Pereira, E. C. . Sensitive determination of 17β-estradiol in river water using a graphene based electrochemical sensor. Anal Chim Acta, v. 881, p. 37-43, 2015.

DOI:10.1016/j.aca.2015.04.043

Abstract

In this study, a novel material for the electrochemical determination of 17β-estradiol using an electrode based on reduced graphene oxide and a metal complex porphyrin has been applied to environmental monitoring. The electrochemical profile of the proposed electrode was analyzed by differential pulse voltammetry, which showed a shift of the oxidation peak potential of 17β-estradiol to 150 mV in a less positive direction compared to the bare reduced graphene oxide electrode. DPV experiments were performed in PBS at pH 7.0 to determine 17β-estradiol without any previous step of extraction, cleanup, or derivatization, in the range of 0.1–1.0 μmol L−1 with a detection limit archived at 5.3 nmol L−1 (1.4 μg L−1). The proposed sensor was successfully applied in the determination of 17β-estradiol in a river water sample without any purification step and was successfully analyzed under the standard addition method. All the obtained results were in agreement with those from the HPLC procedure.

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Publicação 49

Editorial (Thematic Issue: Organic Synthesis in Brazil: Past, Present and Future (Part 1))

de Oliveira, K.; de Souza, R.. Editorial (Thematic Issue: Organic Synthesis in Brazil: Past, Present and Future (Part 1)). Curr Org Synth, v. 12, p. 495-495, 2015.

DOI: 10.2174/157017941205150821154542

Abstract

The Brazilian Meeting on Organic Synthesis (BMOS) is a biannual international event, which brings together researchers in the field of synthetic organic chemistry. The first meetings brought together the Brazilian synthetic organic chemistry community in the early 80’s, with about 100 participants. BMOS has grown from this modest beginning to be now the most important event on organic synthesis in the southern hemisphere, bringing together organic chemists from all over the world. The attendance has also grown steadily, now reaching more than 500 participants expected for the 16th edition, to be held in Buzios, Rio de Janeiro between the 15th and the 19th of November 2015. The official language of BMOS has been English for quite some time now. A large number of the participants are graduate students, and the contacts that they make during BMOS lead to many post-doctoral or sandwich PhD positions outside Brazil. BMOS have also given us the opportunity to establish research programs in collaboration with scientists from other countries, and to exchange knowledge at the forefront of basic and applied research in the field of organic synthesis. Several Nobel laureates have already come to BMOS, and this year we have selected a team of really top speakers to talk about their recent advances (www.bmos.com.br). This special issue of Current Organic Synthesis journal collects some of our best research groups, representing not only 11 Brazilian states, but also the diversity of our synthetic organic chemistry. The readers will be able to find reviews on total synthesis and methodology, including organocatalysis, biocatalysis and process development, as well as a concept article regarding strategies and directions of organic synthesis.

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Publicação 48

NIR Bacteriochlorin Chromophores Accessed by Heck and Sonogashira Cross-Coupling Reactions on a Tetrabromobacteriochlorin Derivative

De Assis, F. F.; Ferreira, M. A. B.; Brocksom, T. J.; de Oliveira, K. T.. NIR Bacteriochlorin Chromophores Accessed by Heck and Sonogashira Cross-Coupling Reactions on a Tetrabromobacteriochlorin Derivative. Org Biomol Chem, v. 14, p. 1402-1412, 2015.

DOI: 10.1039/C5OB02228B

Abstract

The synthesis of a new tetrabromobacteriochlorin BCBr4 is reported having the 3,4-dibromo-1H-pyrrole-2-carbaldehyde (10) as the major precursor. The BCBr4 was successfully employed in Pd cross-coupling reactions with methyl acrylate, phenyl acetylene and 4-ethynylanisole. In all three cases, the desired tetra-coupled products were obtained in good to excellent yields, and present a significant red shift in the UV-Vis bands above 800 nm. DFT and TD-DFT theoretical analyses of the NIR bacteriochlorin chromophores were performed in order to evaluate the effect of β substitution on their electronic structures.

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Publicação 47

Editorial (Thematic Issue: Organic Synthesis in Brazil: Past, Present and Future (Part 2))

De Oliveira, K.; de Souza, R.. Editorial (Thematic Issue: Organic Synthesis in Brazil: Past, Present and Future (Part 2)). Curr Org Synth, v. 12, p. 674-674, 2015.

DOI: 10.2174/157017941206150828114929

Abstract

As we mentioned in the editorial of the first volume of this special issue “Organic Synthesis in Brazil: Past, Present and Future”, we are celebrating our vibrant community in Organic Synthesis, by putting together 21 articles covering research groups from all over Brazil. It is important to mention that organic synthesis has assumed a very relevant position in the national scientific scenario, and attracted a broad audience due to the highly qualified synthetic and methodological studies developed over the years. In conclusion, we hope to have shown in this project our very enthusiastic community and how we are promoting excellent science covering the main questions of modern Organic Synthesis. We hope that all the readers of Current Organic Synthesis enjoy both issues and join us on this fascinating tour of Brazilian Organic Synthesis.

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Publicação 46

Supramolecular arrangements of an organometallic forming nanostructured films

Camacho, S. A.; Aoki, P. H. B.; de Assis, F. F.; Pires, A. M.; de Oliveira, K. T.; Constantino, C. J. L. Mater Res. 2014; 17, 1375-1383.

DOI: I: 10.1590/1516-1439.279014

Abstract

Organometallic materials have become subject of intensive research on distinct technological applications. The Langmuir-Blodgett (LB) and Langmuir-Schaefer (LS) techniques have proven to be suitable to address challenges inherent to organic devices, in which the film properties can be tuned at molecular level. Here, we report on the supramolecular arrangement of zinc(II)-protoporphyrin(IX) dimethyl ester (ZnPPIX-DME) using the Langmuir, LB and LS techniques, leading to nanostructured films. The π-A isotherms showed that π-π stacking interaction among ZnPPIX-DME molecules takes place at the air/water interface, favoring the formation of Langmuir films closely packed. The controlled growth of the LB and LS films was monitored via UV-Vis absorption spectroscopy, with the thickness per monolayer within 1.3 and 1.7 nm. The homogeneous topography found at microscale is no longer preserved at nanoscale, which is found rougher according to AFM data. The FTIR indicated that the ZnPPIX-DME is isotropically arranged on both LB and LS films.

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Publicação 45

Synthesis of New Chlorin - Trimethyl and Protoporphyrin IX Dimethyl Ester Derivatives and Their Photophysical and Electrochemical Characterizations.

Menezes, J.C. J. M. D. S.; Faustino, M.A.F.; de Oliveira, K.T.; Uliana, M.P.; Ferreira, V.F.; Hackbarth, S.; Röder, B.; Tasso, T.T.; Furuyama, T.; Kobayashi, N.; Silva, A.M.S.; Neves, M.G.P.M.S.; Cavaleiro, J.A.S., Chem-Eur J 2014, 20, 13644–13655

DOI: 10.1002/chem.201403214

Abstract

In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and ZnII complexes. The synthesis of these molecules linked at the β-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels–Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as ZnII complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one ZnII complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the ZnII complexes were also carried out to gain insights into their behavior for such applications.

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Publicação 44

The Diels–Alder reactions of para-benzoquinone nitrogen-derivatives: an experimental and theoretical study.

Ulianna, M.P.; Servilha, B.M.; Alexopoulosa, O.; de Oliveira, K.T.; Tormenab, C.F.; Ferreira, M.A.B.; Brocksom, T.J., Tetrahedron 201470,6963–6973.

DOI: 10.1016/j.tet.2014.07.088

Abstract

An experimental and theoretical study of the comparative reactivity and selectivity of the Diels–Alder reactions of para-benzoquinones and three nitrogen derivatives have been performed. The mono-oximes derivatives do not react under the tested reaction conditions, whereas the tosylated mono-oximes react slowly. However, the mono N-tosyl imines show excellent reactivity, and superior to the parent para-benzoquinones. DFT calculations support these experimental results.

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Publicação 43

Validation of Photodynamic Action via Photobleaching of a New Curcumin-Based Composite with Enhanced Water Solubility.

Rego-Filho, F.G.; de Araujo, M. T.; de Oliveira, K.T.; Bagnato, V.S., J. Fluoresc. 201424, 1407-1413.

DOI: 10.1007/s10895-014-1422-z

Abstract

Motivated by the photochemical and photophysical properties of curcumin-based composites, the characteristics of a new curcumin-based water-soluble salt were investigated via absorption and fluorescence spectroscopy. Photobleaching was investigated using a set of LEDs in three different wavelengths (405 nm, 450 nm and 470 nm) to illuminate an aqueous solution of curcumin, evaluating its degradation for five different exposure times (0, 5, 15, 45 and 105 minutes). The results were compared with equivalent measurements of dark degradation and illumination in the presence of a singlet-oxygen quencher. Three solution concentrations (50, 100 and 150 μg/ml) were studied. To measure the fluorescence, it was used low power 405 nm excitation laser source. Time dependent photodegradation of curcumin was observed, as compared to the natural degradation of samples maintained on a dark environment. Two main absorption peaks were detected and their relation responded to both concentration and wavelength of the illumination source. A spectral correlation between absorption of curcumin and the emission bands of the sources showed an optimal spectral overlap for the 450 nm LED. For this source, photobleaching showed a less intense degradation on the presence of singlet oxygen quencher. This last result confirmed singlet oxygen production in vitro, indicating a strong potential of this composite to be used as a blue-light-activated photosensitizer.

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Publicação 42

“Chemical Transformations and Photophysical Properties of meso-Tetrathienyl-Substituted Porphyrin Derivatives”

Momo, P. B.; Pavani, C.; Baptista, M. S.; Brocksom, T. J.;de Oliveira, K. T., Eur J Org Chem. 201420, 4536–4547.

DOI: 10.1002/ejoc.201402227

Abstract

The chemistry of meso-tetrathienyl-substituted porphyrin derivatives was explored, including synthesis and subsequent metalation, nitration and 1,3-dipolar cycloaddition reactions. Mono– and tetra-nitro-meso-tetrathienylporphyrins were prepared selectively under mild nitration conditions with NaNO2 and trifluoroacetic acid, and the corresponding chlorins and bacteriochlorins were also obtained by reaction with 1,3-dipoles. The products were characterized in detail and their preliminary photophysical properties were evaluated.

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Publicação 41

“Chlorins: Natural Sources, Synthetic Developments and Main Applications”

de Oliveira, K.T. ; Momo, P. B. ; de Assis, F. F. ; Ferreira, M. A. B. ; Brocksom, T. J.Curr. Org. Synth. 2014, 11, 42-58.

DOI: 10.2174/15701794113106660085

Abstract

Chlorin derivatives have attracted considerable attention over the last three decades in different scientific fields. These compounds are present in a large number of bacteria, fungi and in all plants found on Earth. Since the discovery of these pigments, chemists, biologists, medical professionals and materials scientists have devoted pronounced efforts in order to develop new synthetic methods and discover useful applications for these compounds. In this review we wish to cover the main natural chlorins, their natural sources, synthetic approaches to access these compounds, and the major applications.

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Publicação 40

“Photobiological characteristics of chlorophyll a derivatives as microbial PDT agents”

Uliana, M. P. ; Pires, L. ; Pratavieira, S. ; Brocksom, T. J. ; de Oliveira, K. T. ; Bagnato, V. S. ;Kurachi, C.Photoch. Photobio. Sci. 201413, 1137-1145

DOI: 10.1039/C3PP50376C

Abstract

Chlorin-e6 (chl-e6) and a hydrogenated derivative (chl-e6H) were semi-synthesized, and their photophysical properties and photodynamic activity against Escherichia coliStaphylococcus aureus and Candida albicans evaluated. Methyl pheophorbide-a (Mepheo-a) was obtained from S. maxima using methanolic extraction with acid catalysis (CH3OH–H2SO4). Chlorin-e6 was prepared from Mepheo-a by basic hydrolysis with H2O–acetone and NaOH. Hydrogenated Chlorin-e6 was synthesized by a similar procedure starting from the hydrogenated methyl pheophorbide-a (Mepheo-aH). Photophysical studies were performed in order to determine the singlet oxygen quantum yield of chl-e6H which is higher than that of chl-e6. The microorganism inactivation of chl-e6 and chl-e6H was investigated at two concentrations and three fluence levels. Both chl-e6 and chl-e6H showed microorganism inactivation against Gram-positive bacteria and a fungus.

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Publicação 39

“Unequivocal structural assignments of three cycloheptenoid intermediates for guaiane sesquiterpenes: an experimental and theoretical approach”

Barbosa, L. R. ; Vieira, Y. W. ; Lacerda, V. ; de Oliveira, K. T. ; Dos Santos, R. B. ; Greco, S. J. ; Neto, A. C. ; De Castro, E. V. R. ; Brocksom, T. J.Magn. Reson. Chem. 2014, 52, 318-328.

DOI: 10.1002/mrc.4057

Abstract

We present here a complete NMR assignment for three synthetic cycloheptenone intermediates (compounds 2, 3 and 4, Fig. 1). These studies were performed using 1D and 2D NMR techniques and compared with the theoretical predictions of the chemical shifts and coupling constants using DFT calculations. The results of the theoretical calculations are directly linked to the method selected.[23] Thus, one of the objectives of the present work is to verify which method (GIAO or CSGT) provides the best correlation with the experimental chemical shift (δ) data in the 1H and 13C NMR spectra for compounds 2, 3 and 4.

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Publicação 38

“Solvent-free Diels-Alder reactions catalyzed by FeCl3 on Aerosil silica”

Donatoni, M. C. ; Junior, G. A.B. ; de Oliveira, K. T. ; Ando, R. A. ; Brocksom, T. J. ; Dos Santos, A. A.Tetrahedron. 2014, 70, 3231-3238.

DOI: 10.1016/j.tet.2014.02.017

Abstract

A mild solvent-free protocol for the promotion of the Diels–Alder reactions of simple dienes and p-benzoquinones, catalyzed by a mixture of iron(III) chloride on Aerosil® silica is reported.

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Publicação 37

“Synthesis of non-aggregating chlorins and isobacteriochlorins from meso-tetrakis(pentafluorophenyl)porphyrin: a study using 1,3-dipolar cycloadditions under mild conditions”

De Souza, J. M. ; de Assis, F. F. ; Carvalho, C. M.B. ; Cavaleiro, J. A.S. ; Brocksom, T. J. ; de Oliveira, K. T., Tetrahedron Lett. 2014, 55, 1491-1495.

DOI: 10.1016/j.tetlet.2014.01.049

Abstract

The 1,3-dipolar cycloaddition of meso-tetrakis(pentafluorophenyl)porphyrin and its nickel complex, with the bulky azomethine ylide dipole was studied under mild conditions, and yielded chlorin and isobacteriochlorin derivatives self-prevented from aggregation. The reactions were performed at room temperature or 0 °C, and we were able to establish a set of reaction conditions to obtain only the chlorin or the isobacteriochlorin. These compounds were evaluated in solution, and no aggregation was observed at less than 25 mM (~30 mg mL-1) using 1H NMR experiments.

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Publicação 36

“Unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents”

Ud Din, Z. ; Fill, T. P. ; De Assis, F. F. ; Lazarin-Bidóia, D. ; Kaplum, V. ; Garcia, F. P. ; Nakamura, C. V. ; de Oliveira, K. T. ; Rodrigues-Filho, E.Bioorgan. Med. Chem. 2014, 22, 1121-1127.

DOI: 10.1016/j.bmc.2013.12.020

Abstract

In this work the synthesis and antiparasitical activity of new 1,5-diaryl-3-oxo-1,4-pentadienyl derivatives are described. First, compounds 1a, 1b, 1c and 1d were prepared by acid-catalyzed aldol reaction between 2-butanone and benzaldehyde, anisaldehyde, p-N,N-dimethylaminobenzaldehyde and p-nitrobenzaldehyde. Reacting each of the methyl ketones 1a, 1b, 1c and 1d with the p-substituted benzaldehydes under basic-catalyzed aldol reaction, we further prepared compounds 2a–2p. All twenty compounds were evaluated for antiproliferative activity, particularly for promastigote of Leishmania amazonensis and epimastigote of Trypanosoma cruzi. All compounds showed good activity while nitro compounds 2i and 2k showed inhibition activity at a few µM.

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Publicação 35

“Synthesis of the bicyclo[6.2.1]undecane ring system by a solvent-free Diels–Alder reaction”

Beatriz, A. ; Gomes, R. D. S. ; Constantino, M. G. ; Da Silva, G. V. J. ; de Oliveira, K. T.
Tetrahedron Lett. 2014, 55, 679-681.

DOI: 10.1016/j.tetlet.2013.11.114

Abstract

A bicyclo[6.2.1]undecane model compound of the core structure of the biologically active furanoheliangolide sesquiterpene was synthesized. This new and short route was developed by using a solvent-free Diels–Alder reaction between cyclopentadiene and 3-nitro-2-cyclohexenone, followed by simple transformations. Theoretical calculations were performed in order to understand reactivity aspects of the cycloaddition.

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