Functionalized BODIPY derivatives as potential fluorescent labels

Labels can be attached to proteins, for example antibodies, which accumulate in specific organs for imaging in animals and human subjects. However, there is a growing realization that imaging events in cells and whole organisms by fluorescence is limited by the accessible probes. 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes tend to be strongly UV-absorbing small molecules that emit relatively sharp fluorescence peaks with high quantum yields. They are relatively insensitive to the polarity and pH of their environment and are reasonably stable to physiological conditions. Moreover, small modifications to their structures enable tuning of their fluorescence characteristics. Therefore, these dyes are widely used to label proteins and DNA, among others. Consequently, there is the potential that modifications to the BODIPY framework will lead to probes that can be used more effectively for imaging in living cells and whole organisms, but that it is still largely unrealized. Having in mind earlier studies, by other groups, and also the research developed recently by our group, we report in this work the synthesis and evaluation of the optical properties of BODIPY derivatives having in mind their potential application as novel fluorescent probes for the detection of a wide range of analytes, such as neutral molecules and ions, as well for bio-imaging in living cells.Thank are due to Fundação para a Ciência e Tecnologia (Portugal) and FEDER COMPETE for financial support through Centro de Química (UID/ QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT.info:eu-repo/semantics/publishedVersio

Functionalized BODIPY derivatives as potential fluorescent labels

BODIPY derivatives 1 and 2 were obtained with 16 % and 33 % yield by a two-step reaction: condensation of a pyrrole with the corresponding aldehyde followed by oxidation with DDQ in the presence of BF3OEt2. The two compounds were characterized by the usual spectroscopic techniques and a detailed photophysical study was undertaken. The compounds exhibited intense absorption bands at 502 nm and 497 nm, respectively. Emission studies of the compounds 1 and 2 showed emission bands with maximum wavelength at 518 nm and 519 nm, respectively.Thank are due to Fundação para a Ciência e Tecnologia (Portugal) and FEDER-COMPETE for financial support through Centro de Química (UID/QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT.info:eu-repo/semantics/publishedVersio

Anion dual mode fluoro-chromogenic chemosensor based on a BODIPY core

Herein, we report the synthesis and chromo-fluorogenic behaviour of a BODIPY derivative. The BODIPY core was functionalized with a phenyl group at meso-position and a formyl group at 2-postion introduced through the Vilsmeier Haack reaction. The compound showed an absorption band at 492 nm and an emission band at 508 nm, with a ФF = 0.84. The evaluation of the chemosensing ability of the BODIPY was investigated in the presence of several anions with environmental and biomedical relevance and a simultaneous colorimetric and fluorimetric response was observed for cyanide and fluoride anions.The authors acknowledge Fundação para a Ciência e Tecnologia—FCT (Portugal) for funding through CQUM (UID/QUI/00686/2020) and a Ph.D. grant to. R. C. R. Gonçalves (SFRH/BD/05278/2020). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT

A dual channel naphthyl-BODIPY probe for the detection of cations in mixed aqueous solution

The development of chemosensors for the sensing of metal ions is one of the most active research fields with great potential for environmental, physiological and medicinal applications, especially in the case of Pd2+, Hg2+ and the trivalent cations Fe3+ and Al3+. For example, mercury is one of the most toxic metal ions, even at very low concentrations. Accumulation of mercury over time in humans leads to cognitive and motion disorders and Minamata disease. On the other hand, trivalent metal cations such as Fe3+ and Al3+ play crucial roles in physiological processes and its abnormal levels in human tissues and cells could induce anemia, diabetes, Alzheimer´s and Parkinson’s diseases. Therefore, the efficient detection of these cations is a timeless topic in several areas of investigation. We report herein the chromo-fluorogenic behavior toward metal cations of a new BODIPY probe bearing a 4-N,N-dimethylnaphthyl group attached to the meso position of the BODIPY core and a formyl group in position 2. This receptor is a dual channel probe that can be used for the chromogenic and fluorogenic detection, in mixed aqueous solutions, of trivalent (Fe3+and Al3+) and divalent cations (Hg2+and Pd2+) with biological and medicinal relevance.The authors acknowledge Fundação para a Ciência e Tecnologia (Portugal) for funding through CQUM (Pest-C/QUI/UI0686/2019) and project PTDC/QUI COL/28052/2017. The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network (REDE/1517/RMN/2005)

Synthesis and characterization of aryl-substituted BODIPY dyes displaying distinct solvatochromic singlet oxygen photosensitization efficiencies

Three BODIPY derivatives substituted at meso position by aryl (phenyl or N,N-dimethylaminonaphthyl) groups and functionalized at position 2 with electron-withdrawing formyl or electron deficient benzimidazole heterocycle were synthesized and completely characterized by the usual spectroscopic techniques. A comprehensive photophysical study showed a remarkable enhancement of the singlet oxygen sensitization quantum yield for meso-substituted dimethylaminonaphthyl BODIPY with the decrease of the dielectric constant of the solvent (0.02–0.04 for dimethylsulfoxide vs. 0.84 in toluene). In toluene the triplet state formation for the aminonaphthyl substituted BODIPY's was found to be mediated by the intramolecular charge transfer state (ICT), whereas in polar solvents triplet state formation is hindered by fast recombination of the ICT state. Pump-probe transient absorption spectroscopy was used to characterize the photoinduced dynamics of the BODIPY derivatives from the femtosecond to the nanosecond time scale.FCT - Laserlab-Europe(REDE/1517/RMN/2005)This work was supported by the Fundação para a Ciˆencia e a Tec nologia (FCT), Portuguese Agency for Scientific Research, through the Coimbra Chemistry Centre projects UIDB/00313/2020 and UIDP/ 00313/2020 and through the Centro de Química (CQUM), project UID/ QUI/00686/2020. The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Reequipment, contract REDE/ 1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. Raquel C. R. Gonçalves acknowledges FCT for funding (SFRH/BD/ 05278/2020). The research leading to these results has received funding from Laserlab-Europe (grant agreement no. 284464, EC’s Seventh Framework Programme)

Crown ether benzoxazolyl-alanines as fluorimetric chemosensors for the detection of palladium in aqueous environment

Palladium (Pd) is a widely applied transition metal, for example in dental restorations, chemical catalysts, jewellery, electronic equipment, automobile industry, among others. As a consequence of its wide application, high levels of palladium in the environment have been reported, representing a risk to human health. So far, a variety of small fluorescence probes have been successfully developed for palladium detection, but there is an interest to design improved water-soluble probes for recognition of this metal in biological and environmental systems. Considering the research group´s experience on fluorescent chemosensors based on unnatural amino acid derivatives containing heterocyclic fluorescent and/or coordination units at the side chain,8,9,10,11 we report herein the evaluation of two benzoxazolyl-alanine derivatives bearing a crown ether moiety as potential fluorimetric chemosensors for palladium detection in aqueous media. Preliminary chemosensory studies for these unnatural amino acids in the presence of selected metal cations, with biological and environmental relevance, were performed in acetonitrile solution and in aqueous mixtures of sodium dodecyl sulfate (SDS, 20 mM, pH 7.5) solution with acetonitrile, 90:10 v/v. As expected, these probes had a fluorescence response for different cations in acetonitrile solutions but, most importantly, in aqueous solutions both benzoxazolyl-alanine derivatives displayed a selective fluorescence response in the presence of palladium.Acknowledgments: The authors acknowledge Fundação para a Ciência e Tecnologia—FCT (Portugal) for funding through CQUM (UIDB/00686/2020)

Synthesis and evaluation of heterocyclic pyrrolidene imines as optical chemosensors

Imine derivatives are an important class of compounds due their biological and optical properties making them suitable for several applications such as chemosensor, photochromic, and others.[1,2] In recent years the search for new colorimetric chemosensors for anions has been of great interest because of the role that ions play in chemical and biological processes.[3] In this context and as part of an on-going research to develop efficient heterocyclic systems for photochromic and chemosensor applications [4] we report in this communication the synthesis, the photophysical characterization and the chemosensor ability of pyrrolidene heterocyclic imines functionalized with aryl or naphthyl moieties.Thanks are due to Fundacao para a Ciencia e Tecnologia (FCT-Portugal) and FEDER-COMPETE for financial support through Centro de Quimica [PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302)], PhD grants to M.C.R. Castro (SFRH/BD/78037/2011) and R.C.M. Ferreira (SFRH/BD/86408/2012). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER. We are also grateful to the Instituto da Educação of Universidade do Minho for providing the laboratory infrastructure necessary for the development of this work

BODIPY derivatives: synthesis and evaluation of their optical properties

3-Difluoroborodipyrromethene, commonly known as BODIPY has been used in many innovative applications such as biological fluorescent labelling, electroluminescent devices, tunable laser dyes, components for solid state solar cells, photodynamic therapy and optical sensors (fluorimetric or colorimetric). The numerous desirable properties of BODIPY explain its growing success over recent years. It is endowed with chemical, structural and photochemical stability, both in solution and in solid state. Furthermore, it possesses a high coefficient of molar absorptivity, high quantum yield of fluorescence, negligible triplet formation and narrow band emission with high intensity peaks. Furthermore, its photophysical properties can be tuned/improved introducing groups at suitable positions in the BODIPY core. In continuation of the work developed in our research group, we report in this communication the synthesis, characterization and evaluation of the optical properties of BODIPY derivatives having in mind their potential application as novel chromofluorogenic sensors and/or fluorescent probes for the detection of molecules, cations and anions with biological and medicinal relevance.Thank are due to Fundação para a Ciência e Tecnologia (Portugal) and FEDERCOMPETE for financial support through Centro de Química (UID/ QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT.info:eu-repo/semantics/publishedVersio

New fluorescent heterocyclic materials: Synthesis, solvatochromic and fluorescence properties

Thienyl- and bithienyl-1,3-benzothiazoles 1 and 2 were synthesised by reacting various formyl thienyl and bithienyl derivatives with o-aminobenzenethiol in moderate to excellent yields. Evaluation of the solvatochromic and fluorescence properties of these compounds was carried out. Due to their strong fluorescence and also the strong push-pull character, benzothiazole derivatives 1 and 2 can be used as potential NLO materials or as fluorescent markers.Fundação para a Ciência e Tecnologia (FCT

Cartilage tissue engineering using electrospun PCL nanofiber meshes and MSCs

Mesenchymal stem cells (MSCs) have been recognized for their ability to differentiate into cells of different tissues such as bone, cartilage, or adipose tissue, and therefore are of great interest for potential therapeutic strategies. Adherent, colony-forming, fibroblastic cells were isolated from human bone marrow aspirates, from patients undergoing knee arthroplasties, and the MSCs phenotype characterized by flow cytometry. Afterward, cells were seeded onto electrospun polycaprolactone nanofiber meshes and cultured in a multichamber flow perfusion bioreactor to determine their ability to produce cartilagineous extracellular matrix. Results indicate that the flow perfusion bioreactor increased the chondrogenic differentiation of hBM-MSCs, as confirmed either by morphological and RT-PCR analysis. Cartilage-related genes such as aggrecan, collagen type II, and Sox9 were expressed. ECM deposition was also detected by histological procedures. Collagen type II was present in the samples, as well as collagen type I. Despite no statistically significant values being obtained for gene expression, the other results support the choice of the bioreactor for this type of culture.M. Alves da Silva would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for her grant (SFRH/BD/28708/2006). The authors would like to acknowledge the patients of Hospital de S. Marcos, Braga, Portugal, for the donation of the biological samples, as well to its medical staff. The authors would also like to thank the Institute for Health and Life Sciences (ICVS), University of Minho, Braga, Portugal, for allowing the use of their research facilities. Authors would like specially to acknowledge Luis Martins for his valuable help with the histological procedures and Goreti Pinto for the aid in the microscopy. We thank Ana M. Frias for the important help with the FACS procedure. Finally, we would like to acknowledge the European NoE EXPERTISSUES (NMP3-CT-2004-500283). This work was partially supported by the European FP7 Project Find and Bind (NMP4-SL-2009-229292)