Search

Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity and in vitro cellular toxicity of porphyrin- and chlorin-indomethacin conjugates (P2-Ind and C2-Ind). Both the conjugates were obtained in high yields and were characterized by 1H, 19F and 13C NMR as well as by high resolution mass spectrometry. The singlet oxygen generation properties were assessed by the 1,3-diphenylisobenzofuran singlet oxygen trap method, which showed that C2 and C2-Ind are the best singlet oxygen photosensitizers. In addition, it was found that the presence of indomethacin did not influence the singlet oxygen generation of porphyrin or chlorin. Cytotoxicity studies of the conjugate in human HEp2 cells revealed that the porphyrin- and chlorin-indomethacin conjugates have similar dark cytotoxicities, while chlorin C2 was shown to be the most phototoxic. Despite having lower cellular uptake than C2-Ind after 24 hours, chlorin C2 had a broad localization in HEp2 cells while the chlorin-indomethacin conjugate C2-Ind could be detected in the form of small aggregates. DFT calculations were performed to shed light on the reaction energy involved in the formation of the indomethacin conjugates and to compare the relative stability of selected isomers in solution. Moreover, the calculated energy of their first excited triplet state structures confirmed their use as suitable photosensitizers to generate singlet oxygen for PDT.

Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV–Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9−aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines., Financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project PTDC/QUI-QOR/29426/2017. The research team would like to thank the projects UIDB/50006/2020, PTDC/QUI-QIN/28142/2017 and Grant BU263P18 (from the Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo). F. M. -S. gratefully acknowledges FCT (Portugal’s Foundation for Science and Technology) within grant DFA/BD/9136/2020. A.M.G.S. and A.L. thank FCT for the program DL 57/2016 – Norma transitória.

The chemical composition and anatomy of the woody follicles of the hakea fruits are characterized here for the first time, aiming at an appraisal of their potential valorization. Hakea sericea Schrader is a woody shrub with evergreen needle-like leaves and fruits composed of woody follicles that surround the seed. The woody follicles have two dehiscent valves containing a primary and a secondary wood growth distinguished by dark and pale color respectively. H. sericea was introduced as an ornamental and hedge plant but it became a major problem due to its invasive character. The woody follicles of the hakea fruits had the following chemical composition (dry mass): ash 1.1%, total extractives 7.4% mainly corresponding to polar compounds soluble in ethanol and water, lignin 29.0% and 62.6% polysaccharides. The polysaccharides showed a predominance of xylose (43.2% of total monosaccharides) and glucose (40.5%). The mineral composition of the hakea fruit contains substantial amounts of potassium. The main lipophilic extractives are bilobol derivatives (23.9–41.8% of the extract), alkanols (15.5–26.5%) and saturated alkanoic acids (10.6–13.1%). The ethanol–water H. sericea fruit extract contains total phenolics (186.3 mg GAE/g extract), flavonoids (67.7 mg CE/g extract) and condensed tannins (84.9 mg CE/g extract). The antioxidant activity was weak compared to known antioxidants (271.7 mg Trolox/g extract). H. sericea fruits fracture easily with predominance of larger particles and little formation of fines (5.8% of the total mass). The chemical characterization of different granulometric fractions showed that extractives were present preferentially in the finest fractions, particularly with enrichment in ethanol soluble compounds, with the exception of bilobol derivatives that were present in higher amounts in fines. Most promising valorization routes for the hakea fruits include a fractionation process for hemicelluloses to yield potentially valuable xylo-oligosaccharides (XOS) and the recovery of bilobol derivatives from the lipophilic extract given the potential application of these compounds in medicine.

The shells of three important food nuts, walnut, almond, and pine nut, were studied in view of valorization as residues. The shells differed chemically: walnut shells had 10.6% extractives, 30.1% lignin, and 49.7% polysaccharides; almond shells 5.7% extractives, 28.9% lignin, and 56.1% polysaccharides; and pine nut shells 4.5% extractives, 40.5% lignin, and 48.7% polysaccharides. The polysaccharide composition also differed, e.g., glucose/xylose ratio of 1.12, 0.94, and 2.29 for walnut, almond, and pine nut shells, respectively. Walnut and almond shells have a SG lignin (S/G 1.6 and 1.0, respectively) and pine nut shell a G lignin. The lipophilic extracts contained mostly saturated and unsaturated alkanoic acids. The ethanol-water extracts contained total phenolics, flavonoids, and condensed tannins. The antioxidant activity was moderate (IC50 15.2, 7.9, and 8.2 μg/mL for walnut, almond, and pine nut). The three nut shells fractured easily with little formation of fines.

The development of straightforward reproducible methods for the preparation of new photoluminescent coordination polymers (CPs) is an important goal in luminescence and chemical sensing fields. Isophthalic acid derivatives have been reported for a wide range of applications, and in addition to their relatively low cost, have encouraged its use in the preparation of novel lanthanide-based coordination polymers (LnCPs). Considering that the photoluminescent properties of these CPs are highly dependent on the existence of water molecules in the crystal structure, our research efforts are now focused on the preparation of CP with the lowest water content possible, while considering a green chemistry approach. One- and two-dimensional (1D and 2D) LnCPs were prepared from 5-aminoisophthalic acid and Sm3+/Tb3+ using hydrothermal and/or microwave-assisted synthesis. The unprecedented LnCPs were characterized by single-crystal X-ray diffraction (SCRXD), powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM), and their photoluminescence (PL) properties were studied in the solid state, at room temperature, using the CPs as powders and encapsulated in poly(methyl methacrylate (PMMA) films, envisaging the potential preparation of devices for sensing. The materials revealed interesting PL properties that depend on the dimensionality, metal ion, co-ligand used and water content.

We describe the synthesis and characterization of a new N-methylpyrrolidine-fused meso-tetracarboxyphenylchlorin with highly emissive features. The synthetic approach to obtain the fluorescent chlorin involves the microwave-assisted synthesis of meso-tetrakis (4-methoxycarbonylphenyl)porphyrin, followed by a 1,3-dipolar cycloaddition reaction of this porphyrin with azomethine ylide and, finally, ester hydrolysis under basic conditions. The incorporation and anchoring of the chlorin to a nanostructured porous TiO2 matrix is achieved and optimized for its use as a fluorescent sensor. In particular, we found an efficient detection of the explosive triacetone triperoxide (TATP) in the gas phase. The optical response after analyte exposure is selective and fast, with response time t50 values of less than 10 min under exposure to TATP saturated vapours.

Luminescent metal–organic frameworks (LMOFs) are promising materials for lighting and sensing applications. Herein, exposure of the highly luminescent Zn2(bpdc)2(bpee) MOF (H2bpdc = 4,4′-biphenyldicarboxylic acid and bpee = 1,2-bipyridylethene) to subppm amine contents turns on a new absorption band unambiguously ascribed to free bpee molecules concomitant with the gradual appearance of a new photoluminescence band at shorter wavelengths. These findings combined with Fourier-transform infrared spectra, powder X-ray diffraction and thermogravimetric analysis of exposed LMOF powders confirm that bpee ligands are exchanged by amines and released inside the LMOF, triggering absorption and luminescence features which can be exploited for highly sensitive amine recognition. This principle was demonstrated in mixed matrix membranes (MMMs) prepared by a simple solvent-free method consisting of mixing Zn2(bpdc)2(bpee) with dimethylvinyl-terminated dimethylsiloxane and dimethylhydrogen siloxane. This method enabled...

Ionic liquids (ILs) were initially hailed as a green alternative to traditional solvents because of their almost non-existent vapor pressure as ecological replacement of most common volatile solvents in industrial processes for their damaging effects on the environment. It is common knowledge that they are not as green as desired, and more thought must be put into the biological consequences of their industrial use. Still, compared to the amount of research studying their physicochemical properties and potential applications in different areas, there is a scarcity of scientific papers regarding how these substances interact with different organisms. The intent of this review was to compile the information published in this area since 2015 to allow the reader to better understand how, for example, bacteria, plants, fish, etc., react to the presence of this family of liquids. In general, lipophilicity is one of the main drivers of toxicity and thus the type of cation. The anion tends to play a minor (but not negligible) role, but more research is needed since, owing to the very nature of ILs, except for the most common ones (imidazolium and ammonium-based), many of them are subject to only one or two articles.

Published data on the thermophysical properties of ionic liquids are normally in disagreement if results from different laboratories, using different samples and different measurement protocols, are compared. This fact was recognized years ago at the level of the International Union of Pure and Applied Chemistry (IUPAC), which established IUPAC Project 2002-005-1-100 (Thermodynamics of ionic liquids, ionic liquid mixtures, and the development of standardized systems), with the main objective of recommending a reference ionic liquid, making reference-quality measurements on selected thermophysical properties of both the pure ionic liquid and its mixtures, establishing recommended values for the properties measured, and providing recommendations on measurement methods. The ionic liquid chosen was 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C6mim][(CF3SO2)2N], because of its stability, low viscosity compared with that of most common ionic liquids, low water solubility, ease of preparation and purification, and commercial availability. Due to its hydrophobicity, it is capable of being obtained very pure, with water amounts as small as 20 ppm. This paper reports new results obtained with the sample of [C6mim][(CF3SO2)2N] synthesized in the IUPAC project, namely on density, speed of sound, surface tension, and refractive index, as well as thermal conductivity of a commercial sample at P = 0.1 MPa, as a function of temperature, and proposes reference data and reference data correlations for the density, speed of sound, heat capacity, surface tension, viscosity, electrical conductivity, thermal conductivity, refractive index, ion self-diffusion coefficient, and melting temperature of this ionic liquid at 0.1 MPa, as a function of temperature, using these and other data reported up to July 2020. Rheological measurements demonstrated that this ionic liquid is Newtonian.

We report the synthesis and physicochemical properties of a new tripodal hexadentate chelator ( catTHC ) synthesized by reaction of a flexible tripodal backbone with three bidentate catechol units. To improve the efficiency of the amide coupling reaction, classical conditions using two pairs of coupling reactants were tested, and a significant reduction in reaction time was achieved by using microwave irradiation with the reactants DCC/HOBt. Subsequent removal of the benzyl protecting groups using BCl 3 in dichloromethane provided the final chelator in good yield. The acid–base properties of catTHC in aqueous solution and the affinity of the ligand towards iron(III) were investigated at variable pH and in the presence of iron(III) using spectroscopic methods. The hexadentate ligand forms a 1:1 complex with iron(III) whose stability constant was determined by competition with EDTA. The values obtained for the stability constant and pFe 3+ are log β 110 = 36.70 and pFe 3+ = 26.7.

The design of fluorescent molecules with structural features for efficient immobilization in polymeric supports or binding matrixes is an active research topic, which aims to create materials with optical and mechanical properties suitable for sensing applications. Herein, we describe the synthesis and characterization of two new fluorescent ligands prepared by a combination of a rosamine platform and an isophthalate receptor using amine and amide linkages. In order to evaluate their potential application as fluorescence sensors, the photophysical properties of the ligands were accessed by UV-Vis and photoluminescence measurements in solution and after immobilization (infiltrated in TiO2 thin films). Furthermore, molecular and electronic structures of both ligands were rationalized by DFT and TD-DFT calculations. Interesting features were found for the ligand containing an amide bond, which has shown to be less prone to aggregation and has higher emission capacity, being a promising candidate in fluorescence sensor devices.

Recent efforts in using ionic liquids for the dissolution of wood constituents, including cellulose, concluded that 1-ethyl-3-methylimidazolium acetate ([emim][OAc]) is one of the most promising ionic liquids to dissolve cellulose. However, in order to make possible any industrial application, thermophysical properties of the pure liquid and of its mixtures with water are needed. In this study the influence of water on the thermophysical properties of [emim][OAc] is discussed. Density, speed of sound, viscosity, electrical conductivity, thermal conductivity, refractive index and infinite dilution diffusion coefficients were measured for mixtures of [emim][OAc] and water, in the temperature range 293.15–333.15 K, at 0.1 MPa, and full composition range. The rheological behaviour was also tested. The mixture was found to be completely miscible. Water free values for the properties of pure ionic liquid were extracted from mixture data, using new methodologies. Results show that the mixture is highly structured, dominated by hydrogen bonding interactions between the water molecules and the ionic liquid acetate anions. The values of the properties establish a consistent and accurate data set for chemical plant cellulose dissolution and other future applications of these mixtures.

A previously reported fluorescein-based dye containing a catechol unit showed high sensitivity to Fe(III) at physiological pH, but also undesirable pH sensitivity, mainly due to the lower pKa values of the phenolic hydroxyl groups of the fluorescein core. Aiming to synthesize compounds that interact with metal ions at physiological pH, exhibiting no pH sensitivity, we designed two novel fluorescent compounds by assembling, through amide linkage, a rhodamine fluorophore with two selected chelating moieties, catechol and 3-hydroxy-4-pyridinone, both possessing high affinity for Fe(III) but distinct pKa values. The fluorescent compounds were prepared using straightforward synthetic protocols and characterized by NMR, mass spectrometry and electronic spectroscopy (UV–Vis and fluorescence) and one of the compounds was also characterized by single crystal X-ray diffraction. The results reveal that, while the fluorescent 3-hydroxy-4-pyridinone derivative exhibits a significant dependence of fluorescence emission with increasing pH, due to the pKa values arising from the 3-hydroxy-4-pyridinone residue, the fluorescent catechol ligand responds mainly to interactions with metal ions, preferentially to Fe(III), showing less sensitivity to pH than the related ligands over the pH range 3–8, fact that is relevant concerning the application of this compound as an ion sensor in biological media.

The synthesis and sensing properties of a new fluorescent probe designed to have a 4-amino-1,8naphthalimide fluorescent platform functionalized with a 3-hydroxy-4-pyridinone bidentate chelating unit at the 4-position and a terminal aliphatic dimethylamino group at the imide site, are reported. The absorption and fluorescence properties of the ligand were investigated in DMSO and in aqueous solution at variable pH and in the presence of increasing concentration of Fe 3þ ,C u 2þ and Zn 2þ . Analysis of the UVeVis spectra at variable pH allowed the determination of three pKa values (pKa1 ¼ 3.19, pKa2 ¼ 8.38, pKa3 ¼ 9.95) and establishment of the corresponding speciation diagram. Fluorescence spectra obtained in the same conditions show that the fluorescence intensity of the probe decreases with increasing pH and are off above pH 9 as a result of photo-induced electron transfer arising from the aliphatic dimethylamino group. Under physiological pH conditions, the probe shows an absorption band centred at 439 nm and emits in the green at l ¼ 536 nm. Analysis of UVeVis and EPR spectra of the ligand in the presence of Fe 3þ and Cu 2þ is consistent with the formation of the corresponding metal ion complexes. The fluorescence intensity of the ligand is quenched in the presence of variable concentrations of Fe 3þ ,C u 2þ and Zn 2þ and under physiological pH conditions the fluorescence of the probe is ca 92%, 88% and 91% quenched in the presence of Fe 3þ ,C u 2þ and Zn 2þ respectively.

A series of rosamine fluorophores was obtained by reaction of the appropriate benzaldehyde and 3-(diethylamino)phenol followed by an oxidation step. Both conventional heating and microwave irradiation methods were utilized, and higher yields in a remarkably shorter period of time (10 min) were achieved by using the microwave irradiation protocol under closed vessel conditions (80 °C). The nitro-substituted rosamine was further converted into the corresponding amino derivative through Pd/C-catalysed hydrogenation. The synthetic protocol used for rosamines was also successfully employed to synthesise naphthyl analogues by using 1- and 2-naphthaldehyde. In the latter case, a novel hydroxy analogue was also obtained as a minor product. The photophysical behaviour of all the rosamines was studied in different solvents to rationalize the influence of the substituent groups on the electronic distribution, the effect of steric hindrance caused by the naphthyl ring, and the effect of the solvent. The results demonstrate that the introduction of different substituents in the periphery of the rosamine framework (in particular NO2 and NH2 groups) alters the fluorescence properties of the molecule such as emission wavelength and fluorescence quantum yield. All the rosamines are shown to be more fluorescent in dichloromethane than in more polar solvents such as ethanol. The spectroscopic properties of the 4′-carboxy-substituted rosamine, which is particularly attractive for labelling purposes, was also studied at physiological pH.

In the present work we report the synthesis and characterization of a novel fluorescein-based dye containing a catechol chelating unit designed to act as a chemosensor for iron(III). The compound was prepared using conventional and microwave-assisted amide coupling of a catechol derivative with a 5(6)-carboxyfluorescein scaffold. One of the most interesting features of this conjugate structure is a high affinity binding site on the catechol ring close to the fluorophore. As a consequence, the behaviour of the new compound in the presence of metal ions of biological importance was monitored by optical spectroscopy (at physiological pH). The results show that the conjugate is particularly sensitive to iron(III), thus suggesting that it may be used as fluorescent chemosensor for the detection of iron(III) in cellular systems.

The two new fluorescent ligands RosCat1 and RosCat2 contain catechol receptors connected to rosamine platforms through an amide linkage and were synthesized by using microwave-assisted coupling reactions of carboxyl- or amine-substituted rosamines with the corresponding catechol units and subsequent deprotection. RosCat1 possesses a reverse amide, whereas RosCat2 has the usual oriented amide bond (HNCO vs. CONH, respectively). The ligands were characterized by means of NMR spectroscopy, mass-spectrometry, and DFT calculations and X-ray crystallography studies for RosCat1. The influence of the amide linkage on the photophysical properties of the fluorescent ligands was assessed in different solvents and showed a higher fluorescence quantum yield for RosCat1. The coordination chemistry of these ligands with a Fe(III) center has been rationalized by mass-spectrometric analysis and semiempirical calculations. Octahedral Fe(III) complexes were obtained by the chelation of three RosCat1 or RosCat2 ligands. Interestingly, the unconventional amide connectivity in RosCat1 imposes the formation of an eight-membered ring on the chelate complex through a "salicylate-type" mode of coordination.

We have recently demonstrated that tripodal hexadentate chelators, based on 3-hydroxy-4-pyridinone units, can limit the access of iron to bacteria and have a significant inhibitory effect in the intramacrophagic growth of Mycobacterium avium. The results showed that the chelation of iron is a determinant although not sufficient property for antimicrobial activity. The rhodamine B isothiocyanate labelled chelator (MRH7) exhibited the strongest inhibitory activity and was identified as a lead compound since a dose response effect was observed. Significant inhibition of M. avium growth was achieved at a concentration as low as 1 μM. To identify key molecular features essential for the biological activity we designed parent hexadentate and bidentate chelators, in which different structural groups are introduced in the molecular framework. Herein, we report the work concerning three novel fluorescent chelators: a hexadentate ligand labelled with 5(6)-carboxytetramethylrhodamine (MRH8) and two 3-hydroxy-4-pyridinone fluorescent bidentate ligands labelled with rhodamine B isothiocyanate (MRB7) and 5(6)-carboxytetramethylrhodamine (MRB8). The results show that all fluorescent chelators are capable of restricting the intramacrophagic growth of M. avium and that the inhibitory effect is dependent on the fluorophore. In fact, for compounds bearing the same fluorophore the results obtained with the hexadentate or bidentate chelator (MRH7/MRB7 or MRH8/MRB8) are identical as long as the appropriate stoichiometric amount of chelator is used. The inhibitory effect of the rhodamine B isothiocyanate labelled compounds (MRH7 and MRB7) is significantly greater than that observed for the other two chelators, thus pointing out the significance of the rhodamine B isothiocyanate molecular fragment.

The current world economy and energy situation demands the search for alternative energies to conventional fuels, the optimization of current energy technologies, and the search for new and clean working fluids. In the field of heat transfer, all current liquid coolants used at low and moderate temperatures exhibit very poor thermal conductivity and heat storage capacities, as the classical equipments for heat transfer use working fluids that were developed, tested and applied in a world of positive economical growth. In contrast, the uses of chemical technologies today are considered unsustainable. Although increased heat transfer can be achieved creating turbulence, increasing surface area and so on, ultimately the transfer will still be limited by the low thermal conductivity of the conventional fluids. Therefore, there is a need for new and efficient heat transfer liquids that can meet the cooling challenges for advanced devices as well as energy conversion for domestic and industrial applications. Ionic liquids (IL) have proven to be safe and sustainable alternatives for many applications in industry and chemical manufacturing. Their success arises mainly from their thermophysical and phase-equilibria properties, and the versatility of their synthesis, manageable to be tailored for a given application. Their solvent properties as well as their heat transfer or heat storage and surface properties make this class of fluids possible to use in a high plethora of applications (Earle & Seddon, 2007; Nieto de Castro & Santos, 2007). Other advantages of ionic liquids include high ionic conductivity, high chemical and thermal stabilities, negligible vapor pressure and an ability to dissolve a wide range of inorganic and organic compounds. Due to all of these fascinating characteristics they have been investigated extensively as alternatives to molecular solvents for liquid phase reactions (Wasserscheid & Welton,2007; Pârvulescu & Hardacre, 2007). Ionic liquids are of great interest to scientists as well as chemical companies, not only because of their interesting properties, but also for their actual and potential applications in the chemical process industries. In the past, the values of their thermophysical properties found to have significant effect on the design of physico-chemical processing and reaction units, influencing directly the design parameters and performance of equipments like heat exchangers, distillation columns and reactors (Franca et al., 2009). Their thermophysical properties justify the replacement of several of the chemical processes now under exploitation, and some of the solvents used, because they can, in certain conditions, be