Exploring Coumarin-Based Boron Emissive Complexes as Temperature Thermometers in Polymer-Supported Materials.

Three coumarin-based boron complexes (L1, L2 and L3) were designed and successfully incorporated into polymeric matrixes for evaluation as temperature probes. The photophysical properties of the complexes were carried out in different solvents and in the solid state. In solution, compound L1 exhibited the highest fluorescence quantum yield, 33%, with a positive solvatochromism also being observed on the absorption and emission when the polarity of the solvent increased. Additionally in the presence of anions, L1 showed a colour change from yellow to pink, followed by a quenching in the emission intensity, which is due to deprotonation with the formation of a quinone base. Absorption and fluorescence spectra of L1 were calculated at different temperatures by the DFT/B3LYP method. The decrease in fluorescence of compound L1 with an increase in temperature seems to be due to the presence of pronounced torsional vibrations of the donor and acceptor fragments relative to the single bond with C(carbonyl)-C (styrene fragment). L1, L2 and L3, through their incorporation into the polymeric matrixes, became highly emissive by aggregation. These dye@doped polymers were evaluated as temperature sensors, showing an excellent fluorescent response and reversibility after 15 cycles of heating and cooling.

Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer.

The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles' surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit® enteric coating and studied under extreme conditions.

Ofloxacin@Doxorubicin-Epirubicin functionalized MCM-41 mesoporous silica-based nanocarriers as synergistic drug delivery tools for cancer related bacterial infections.

Mesoporous silica nanoparticles (MNs) emerged as new promising drug-delivery platforms capable to overcome resistance in bacteria. Dual loading of drugs on these nanocarriers, exploiting synergistic interactions between the nanoparticles and the drugs, could be considered as a way to increase the efficacy against resistant bacteria with a positive effect even at very low concentrations. Considering that patients with cancer are highly susceptible to almost any type of bacterial infections, in this work, nanocarriers mesoporous silica-based, MNs and MNs@EPI were synthetized and submitted to single and/or dual loading of antibiotics (ofloxacin - OFLO) and anticancer drugs (Doxorubicin - DOX; Epirubicin - EPI), and investigated regarding their antibacterial activity against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis and Pseudomonas aeruginosa. Formulations containing ofloxacin such as MNs-OFLO, MNs-EPI + OFLO, MNs-DOX + OFLO and MNs@EPI + OFLO, present antibacterial activity in all bacterial strains tested. All these are more effective in E.coli with MIC and MBC values for MNs-OFLO, MNs-EPI + OFLO and MNs-DOX + OFLO of around 1 and 2 µgnanomaterial/mL, corresponding to ofloxacin concentrations of 0.03, 0.02 and 0.04 µg/mL, respectively. In the cocktail formulations the conjugation of epirubicin with ofloxacin presents a more effective antibacterial activity with more than 3-fold reduction of ofloxacin concentration when comparing to the single ofloxacin system. By far, the most effective synergistic effect was obtained for the system where epirubicin was functionalized at nanoparticles surface (MNs@EPI), where a 40-fold and 33-fold reductions of ofloxacin concentration were obtained, in P. aeruginosa in comparison to the MNs-OFLO and MNs-EPI + OFLO systems, respectively. These effects are shown in all bacterial strains tested, even in strains that have acquired resistance mechanisms, such as MRSA.

Neonatal Thrombocytopenia Due to Dual Alloimmune and Autoimmune Mechanisms.

Alloantibody-mediated and autoantibody-mediated immune destruction are common causes of early neonatal thrombocytopenia. The authors report a case of severe, early-onset thrombocytopenia with mucocutaneous bleeding in an otherwise well-appearing full-term neonate. Recurrence of thrombocytopenia following initial treatment and its persistence after 2 weeks of life suggested a dual immune mechanism. This is a rare case of immune thrombocytopenia caused by human platelet antigen-5b alloimmunization and passive transfer of maternal antiplatelet antibodies. Appropriate, timely treatment and absence of severe bleeding complications, namely intracranial hemorrhage, conferred a good overall prognosis.

Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer.

Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin-ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.

Untangling interactions of a zinc(II) complex containing a coumarin-porphyrin unit with alkaloids in water solutions: a photophysical study.

A metal complex 1 derivative from a coumarin bearing a porphyrin unit was spectroscopically characterized and its sensing ability towards the alkaloids caffeine 2, nicotine 3 and cotinine 4 was evaluated in these studies. This probe shows to be sensitive to the alkaloids studied, where a detectable amount of 2.5 ± 0.3 µM of cotinine was determined in dam water from the Vigia Dam located in the Montoito village region, Alentejo district, Portugal. The interaction of 1 with cotinine was also verified by MALDI-TOF-MS, where it was found with peaks at 877.2 and 1053.3 m/z corresponding to the species [1H](+) and [1CotinineH](+), respectively.

Proteomics analysis of the peritoneal dialysate effluent reveals the presence of calcium-regulation proteins and acute inflammatory response.

BACKGROUND: Peritoneal dialysis (PD) is a form of renal replacement used for advanced chronic kidney disease. PD effluent holds a great potential for biomarker discovery for diagnosis and prognosis. In this study a novel approach to unravelling the proteome of PD effluent based-on dithiothreitol depletion followed by 2D-SDS-PAGE and protein identification using tandem mass spectrometry is proposed. RESULTS: A total of 49 spots were analysed revealing 25 proteins differentially expressed, among them many proteins involved in calcium regulation. CONCLUSIONS: Remarkably, a group of proteins dealing with calcium metabolism and calcium regulation has been found to be lost through peritoneal dialysate effluent, giving thus a potential explanation to the calcification of soft tissues in patients subjected to peritoneal dialysis and kidney injury. Comparison of literature dealing with PD is difficult due to differences in sample treatment and analytical methodologies.

Synthesis and solvatochromism studies of novel bis(indolyl)methanes bearing functionalized arylthiophene groups as new colored materials.

The demand for dyes with solvatochromic properties has increased in the last few years, mainly due to their wide range of applications in the analytical and industrial fields, such as in the textile industry. The phenomenon of solvatochromism is associated with the differential solvation of the ground and excited states of the solvatochromic compounds, leading to an important tool for the study of the nature of solute-solvent interactions. In this paper we report the synthesis of new bis(indolyl)methane derivatives bearing arylthiophene spacers (2a-d) functionalized with electron-donating and electron-withdrawing groups, and the photophysical studies in different solvents, such as ethanol, acetonitrile, dichloromethane, trichloromethane, dimethylsulfoxide, diethylether and 1,4-dioxane. Aiming to explore their solvatochromic behaviour in the ground and excited states, all solvents employed have different hydrogen-bond donor abilities. The largest colour modifications were visualized for compound 2b, the solution colours of which are orange in DMSO, blue in trichloromethane, green in dichloromethane and purple in 1,4-dioxane. A negative solvatochromism was observed in 2b and a positive one in 2a, 2c and 2d.

Tailoring Mesoporous Silica-Coated Silver Nanoparticles and Polyurethane-Doped Films for Enhanced Antimicrobial Applications.

The global increase in multidrug-resistant bacteria poses a challenge to public health and requires the development of new antibacterial materials. In this study, we examined the bactericidal properties of mesoporous silica-coated silver nanoparticles, varying the core sizes (ca. 28 nm and 51 nm). We also investigated gold nanoparticles (ca. 26 nm) coated with mesoporous silica as possible inert metal cores. To investigate the modification of antimicrobial activity after the surface charge change, we used silver nanoparticles with a silver core of 28 nm coated with a mesoporous shell (ca. 16 nm) and functionalized with a terminal amine group. Furthermore, we developed a facile method to create mesoporous silica-coated silver nanoparticles (Ag@mSiO2) doped films using polyurethane (IROGRAN®) as a polymer matrix via solution casting. The antibacterial effects of silver nanoparticles with different core sizes were analyzed against Gram-negative and Gram-positive bacteria relevant to the healthcare and food industry. The results demonstrated that gold nanoparticles were inert, while silver nanoparticles exhibited antibacterial effects against Gram-negative (Escherichia coli and Salmonella enterica subsp. enterica serovar Choleraesuis) and Gram-positive (Bacillus cereus) strains. In particular, the larger Ag@mSiO2 nanoparticles showed a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 18 µg/mL in the Salmonella strain. Furthermore, upon terminal amine functionalization, reversing the surface charge to positive values, there was a significant increase in the antibacterial activity of the NPs compared to their negative counterparts. Finally, the antimicrobial properties of the nanoparticle-doped polyurethane films revealed a substantial improvement in antibacterial efficacy. This study provides valuable information on the potential of mesoporous silica-coated silver nanoparticles and their applications in fighting multidrug-resistant bacteria, especially in the healthcare and food industries.

Turn-on selective vitamin B6 derivative fluorescent probe for histidine detection in biological samples.

A new compound L soluble in water derived from vitamin B6 was successfully synthesized and characterized. The complex LAl(3+) is a turn-on selective fluorescent probe for histidine in HEPES buffer, with detection and quantification limits of 0.3 µM and 0.6 µM, respectively. The application of the complex LAl(3+) in real urine samples is reported.

Corrole and corrole functionalized silica nanoparticles as new metal ion chemosensors: a case of silver satellite nanoparticles formation.

Corrole macrocycles are very appealing dyes for incorporation into light harvesting devices. This work shows the sensorial ability of 5,10,15-tris(pentafluorophenyl)corrole 1 and its monoanionic species toward Na(+), Ca(2+), Cu(2+), Cd(2+), Pb(2+), Hg(2+), Ag(+), and Al(3+) metal ions in toluene and acetonitrile. The photophysical studies toward metal ions were carried out by absorption and emission spectroscopy. From all metal ions studied, corrole 1 shows to be colorimetric for Hg(2+) allowing a naked-eye detection of Hg(2+) through a change of color from purple to blue in acetonitrile and from green to yellow in toluene. In addition a new ß-imine corrole 4 was successful synthesized and further functionalized with 3-isocyanatopropyl-trimethoxysilane resulting in an alkoxysilane derivative 5. The grafting of alkoxysilane derivative 5 with optically transparent silica nanoparticles (SiNPs) was achieved succesfully. The new-coated silica nanoparticles with corrole 5 were studied in the presence of Cu(2+), Hg(2+), and Ag(+) as metal ion probes. Interestingly, upon addition of Ag(+), groups of satellite AgNPs were formed around the SiNPs and were checked by transmission electron microscopy (TEM). At same time, a change of color from green to yellow was observed.

The use of nanoparticles for targeted drug delivery in non-small cell lung cancer.

Lung cancer is a global health problem affecting millions of people each year. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with various conventional treatment available in the clinic. Application of these treatments alone often results in high rates of cancer reoccurrence and metastasis. In addition, they can cause damage to healthy tissues, resulting in many adverse effects. Nanotechnology has emerged as a modality for the treatment of cancer. When used in combination with nanoparticles, it is possible to improve the pharmacokinetic and pharmacodynamic profiles of pre-existing drugs used in cancer treatment. Nanoparticles have physiochemical properties such as small size which allowing passage through challenging areas of the body, and large surface area allows for higher doses of drugs to be brought to the tumor site. Nanoparticles can be functionalized which involves modifying the surface chemistry of the particles and allows for the conjugation of ligands (small molecules, antibodies, and peptides). Ligands can be chosen for their ability to target components that are specific to or are upregulated in cancer cells, such as targeting receptors on the tumor surface that are highly expressed in the cancer. This ability to precisely target the tumor can improve the efficacy of drugs and decrease toxic side effects. This review will discuss approaches used for targeting drugs to tumors using nanoparticles, provide examples of how this has been applied in the clinic and highlight future prospects for this technology.

Novel emissive bio-inspired non-proteinogenic coumarin-alanine amino acid: fluorescent probe for polyfunctional systems.

Two new bio-inspired non-proteinogenic compounds L1 and L2, containing coumarin and/or acridine chromophores and bearing as spacer an alanine amino acid were successfully synthesized and fully characterized by elemental analysis, (1)H and (13)C NMR, infrared spectroscopy (KBr discs), melting point, ESI-TOF (electrospray ionization-time of flight-mass), UV-vis absorption and emission spectroscopy, fluorescence quantum yields and lifetime measurements. A relative fluorescence quantum yield of 0.02 was determined for both compounds. In L2 the presence of an intramolecular energy transfer from the coumarin to the acridine unit was observed. L1 and L2 are quite sensitive to the basicity of the environment. At alkaline values both compounds show a strong quenching in the fluorescence emission, attributed to the photoinduced electron transfer (PET). However, both deprotonated forms recover the emission with the addition of Zn(2+), Cd(2+) and Al(3+) metal ions. As multifunctional emissive probes, the titration of L1 and L2 with lanthanides (III), Eu(3+) and Tb(3+) was also explored as new visible bio-probes in the absence and in the presence of liposomes. In a liposomal environment a lower energy transfer was observed.

Validation of a Standard Luminescence Method for the Fast Determination of the Antimicrobial Activity of Nanoparticles in Escherichia coli.

The use of nanoparticles in multiple industries has raised concerned voices about the assessment of their toxicity/antimicrobial activity and the development of standardized handling protocols. Issues emerge during the antimicrobial assaying of multiple cargo, colorimetric, colloidal nanoformulations, as standard protocols often rely on visual evaluations, or optical density (OD) measurements, leading to high variance inhibitory concentrations (MIC). Thus, a fast, luminescence-based assay for the effective assessment of the antimicrobial activity of nanoparticles is herein reported, using the bioluminescence of an in-house E. coli ATCC® 8739TM construct with the pMV306G13 + Lux plasmid (E. coli Lux). The new strain's sensitivity to ofloxacin as a standard antibiotic was confirmed, and the methodology robustness verified against multiple nanoparticles and colorimetric drugs. The reduction of incubation from 24 to only 8 h, and the sole use of luminescence (LUX490) to accurately determine and distinguish MIC50 and MIC90, are two main advantages of the method. By discarding OD measurements, one can avoid turbidity and color interferences when calculating bacterial growth. This approach is an important tool that contributes to the standardization of methods, reducing samples' background interference and focusing on luminescence as a direct probe for bacterial metabolic activity, growth and, most importantly, the correct assessment of nanomaterials' antimicrobial activity.

Functional Cyanine-Based PVA:PVP Polymers as Antimicrobial Tools toward Food and Health-Care Bacterial Infections.

The rising of multidrug-resistant bacteria and their associated proliferation as harmful microorganisms boosts the creation of new antibacterial surfaces and biomaterials with applications ranging from health to food packing. Herein, low-cost antibacterial PVA:PVP copolymers containing cyanine derivatives (1, 2, and 3) and their respective Cu2+ complexes are successfully obtained and tested against Gram-negative and Gram-positive bacteria. The possible application in food packing is addressed by covering the surface of typical paper mockups with the doped polymers. All dye-doped polymers present a broad-spectrum antibacterial effect against Gram-positive bacteria, especially for Bacillus cereus (B. cereus), Staphylococcus aureus (S. aureus), and methicillin-resistant S. aureus (MRSA) strains, with PVA:PVP@3 and PVA:PVP@3-Cu being the most effective. Moreover, polymers containing cyanine derivatives present interesting inhibition effects against Pseudomonas aeruginosa (P. aeruginosa), where the production of its characteristic blue/green virulent pigment is not observed. Of the coated paper mockups, PVA:PVP:paper@2 and PVA:PVP:paper@2-Cu are most effective against B. cereus and S. aureus, while PVA:PVP:paper@3 and PVA:PVP:paper@3-Cu are most effective against the MRSA strain. In these formulations, direct contact inhibition mechanisms appear to be more significant than diffusional mechanisms, due to cyanine release hindrance, making them very interesting and versatile platforms for medical and food applications.

Novel small stable gold nanoparticles bearing fluorescent cysteine-coumarin probes as new metal-modulated chemosensors.

Emissive molecular probes based on amino acid moieties are very appealing because of their application as new building blocks in peptide synthesis. Two new bioinspired coumarin probes (L1 and L2) were synthesized and fully characterized by elemental analysis, infrared, (1)H NMR, (13)C NMR, UV-vis absorption and emission spectroscopy, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), lifetime measurements, and X-ray crystal diffraction. Their sensing ability toward alkaline earth, transition, and post-transition metal ions (Ca(2+), Zn(2+), Cd(2+), Cu(2+), Ni(2+), Hg(2+), Ag(+), and Al(3+)) and their acid-base behavior (H(+), OH(-)) were explored in absolute ethanol by absorption and fluorescence spectroscopy. Compound L1 shows a strong complexation constant with the soft metal ions Zn(2+), Cd(2+), and Ag(+). Compound L2 shows a high fluorescence quantum yield, and it could be used as a non-pH-dependent fluorescent biological probe. Very small gold nanoparticles (AuNPs) using compounds L1 and L2 as stabilizers were obtained by using a reductive method and were characterized by UV-vis, light scattering, and transmission electron microscopy (TEM). Dynamic light scattering and TEM studies show that the formation of small nanoparticles is around 4.27 ± 0.64 nm for L1 and around 2.69 ± 0.96 nm for L2. The new stable Cou@AuNPs behaved as supramolecular chemosensors, which have been selective for the heavy element Hg(2+), with a concomitant change of color from pink to dark red/brown and an increase of size up to 100-fold.

Bioinspired systems for metal-ion sensing: new emissive peptide probes based on benzo[d]oxazole derivatives and their gold and silica nanoparticles.

Seven new bioinspired chemosensors (2-4 and 7-10) based on fluorescent peptides were synthesized and characterized by elemental analysis, (1)H and (13)C NMR, melting point, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and IR and UV-vis absorption and emission spectroscopy. The interaction with transition- and post-transition-metal ions (Cu(2+), Ni(2+), Ag(+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Fe(3+)) has been explored by absorption and fluorescence emission spectroscopy and MALDI-TOF-MS. The reported fluorescent peptide systems, introducing biological molecules in the skeleton of the probes, enhance their sensitivity and confer them strong potential for applications in biological fields. Gold and silica nanoparticles functionalized with these peptides were also obtained. All nanoparticles were characterized by dynamic light scattering, transmission electron microscopy, and UV-vis absorption and fluorescence spectroscopy. Stable gold nanoparticles (diameter 2-10 nm) bearing ligands 1 and 4 were obtained by common reductive synthesis. Commercial silica nanoparticles were decorated at their surface using compounds 8-10, linked through a silane spacer. The same chemosensors were also taken into aqueous solutions through their dispersion in the outer layer of silica core/poly(ethylene glycol) shell nanoparticles. In both cases, these complex nanoarchitectures behaved as new sensitive materials for Ag(+) and Hg(2+) in water. The possibility of using these species in this solvent is particularly valuable because the impact on human health of heavy- and transition-metal-ion pollution is very severe, and all analytical and diagnostics investigations involve a water environment.

Light and colour as analytical detection tools: a journey into the periodic table using polyamines to bio-inspired systems as chemosensors.

This critical review describes some developments on the chemistry of fluorescent and colorimetric molecular probes or chemosensors, based on polyamines and associated compounds having oxygen and/or sulfur as donor atoms. The reported systems are essentially based on some selected published work in this field in the last five years, and in the work developed by the authors from 2000 onwards. Some interesting properties beyond sensing molecules, ions or/and cations by fluorescence, colorimetry as well as by MALDI-TOF MS spectrometry can arise from these systems. A short brief on different examples activated by PET (photoinduced electron transfer), ICT (internal charge transfer) and EET (electronic energy transfer) phenomena will be provided. Finally the introduction of bio-inspired compounds derived from emissive amino acid or short peptide systems and nanoparticle devices to detect metal ions will be reviewed (202 references).

Impacts of environmental issues on health and well-being: a global pollution challenge.

Every 2 years, the environmental, chemical, and health research communities meet in Costa de Caparica, Portugal to showcase the latest technologies, methodologies and research advances in pollution detection, contamination control, remediation, and related health issues. Since its inception in 2015, the International Caparica Conference on Pollution Metal Ions and Molecules (PTIM) has become a biennial global forum to hear from those who protect the land, the water, and the air at all environmental scales. During past PTIM editions, we have learned about numerous efforts to develop new recovery and clean-up processes to restore the natural equilibria of our planet. Soil, land, water, and air are the key focus of efforts that will require deeper understanding and better control.

Exploring the emissive properties of new azacrown compounds bearing aryl, furyl, or thienyl moieties: a special case of chelation enhancement of fluorescence upon interaction with Ca(2+), Cu(2+), or Ni(2+).

Three new compounds bearing furyl, aryl, or thienyl moieties linked to an imidazo-crown ether system (1, 2, and 3) were synthesized and fully characterized by elemental analysis, infrared, UV-vis absorption, and emission spectroscopy, X-ray crystal diffraction, and MALDI-TOF-MS spectrometry. The interaction toward metal ions (Ca(2+), Cu(2+), Ni(2+), and Hg(2+)) and F(-) has been explored in solution by absorption and fluorescence spectroscopy. Mononuclear and binuclear metal complexes using Cu(2+) or Hg(2+) as metal centers have been synthesized and characterized. Compounds 2 and 3 show a noticeable enhancement of the fluorescence intensity in the presence of Ca(2+) and Cu(2+) ions. Moreover compound 3 presents a dual sensory detection way by modification of the fluorimetric and colorimetric properties in the presence of Cu(2+) or Hg(2+). EPR studies in frozen solution and in microcrystalline state of the dinuclear Cu(II)3 complex revealed the presence of an unique Cu(2+) type.