Síntese e caracterização de complexos de lantanídeos pesados e ítrio(III) como o fármaco ibuprofeno no estado sólido

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Síntese, caracterização e estudo termoanalítico dos nicotinatos de lantanídeos (III) e de ítrio (III), no estado sólido

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Metalosupramoléculas discretas e Metal Organic Frameworks (MOFs) baseados em íons lantanídeos: design, síntese, caracterização e propriedades

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Síntese, caracterização e estudo do comportamento térmico dos glicolatos de lantanídeos e ítrio no estado sólido

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estrutura e algumas propriedades ópticas de difenilfosfinatos de terras-raras

Coordination compounds of trivalent lanthanides cations with diphenylphosphinate are originated from direct reaction between a lanthanide salt and diphenylphosphinic acid. These complexes have peculiar and intriguing features, as (i) quickly obtainment through wet process precipitation, (ii) appreciable thermal stability, similar to inorganic phosphates, (iii) polymeric structure, and consequently, (iv) low solubility in both polar and non-polar solvents. Nowadays, coordination polymers are classified as coordination networks or, in case of porous materials, as metal-organic frameworks (MOFs). By this study, we aim to determine some optical properties of rare-earth diphenylphosphinate (RE = La3+, Eu3+, Gd3+, Lu3+) and conduct an updated classification of these compounds, bringing more details of its structure and the possible proposal of new materials with applications in lighting, detection of ionizing radiation and magnetism. The complexes of trivalent rare-earth cation with diphenylphosphinate were prepared by direct mixture of diphenylphosphinic acid with rare-earth metal chloride, both in ethanolic solution. The solution of diphenylphosphinic acid was kept in a beaker under constant stirring with pH measurements of the solution and gadolinium chloride solution was then dripped slowly with the aid of a burette until its complete addition; the following metal:ligand molar ratios were tested: 1:1, 1:2, 1:3, 2:1 e 3:1. The compounds were characterized by spectroscopic and structural techniques. By Fourier Transform Infrared Spectroscopy (FT-IR), it was possible to check the total ionization of diphenylphosphinic acid in synthesized complexes, confirmed by the absence of the band type A, B, C related to ѵ(O-H) of the acid (2663 cm-1, 2168 cm-1, 1684 cm-1), as well as the disappearance of ѵ(P-OH)=961 cm-1. Furthermore, the occurrence of bands shifts of ѵ(POO-) [symmetrical and asymmetrical] of...

Estrutura e algumas propriedades ópticas de difenilfosfinatos de terras-raras

Coordination compounds of trivalent lanthanides cations with diphenylphosphinate are originated from direct reaction between a lanthanide salt and diphenylphosphinic acid. These complexes have peculiar and intriguing features, as (i) quickly obtainment through wet process precipitation, (ii) appreciable thermal stability, similar to inorganic phosphates, (iii) polymeric structure, and consequently, (iv) low solubility in both polar and non-polar solvents. Nowadays, coordination polymers are classified as coordination networks or, in case of porous materials, as metal-organic frameworks (MOFs). By this study, we aim to determine some optical properties of rare-earth diphenylphosphinate (RE = La3+, Eu3+, Gd3+, Lu3+) and conduct an updated classification of these compounds, bringing more details of its structure and the possible proposal of new materials with applications in lighting, detection of ionizing radiation and magnetism. The complexes of trivalent rare-earth cation with diphenylphosphinate were prepared by direct mixture of diphenylphosphinic acid with rare-earth metal chloride, both in ethanolic solution. The solution of diphenylphosphinic acid was kept in a beaker under constant stirring with pH measurements of the solution and gadolinium chloride solution was then dripped slowly with the aid of a burette until its complete addition; the following metal:ligand molar ratios were tested: 1:1, 1:2, 1:3, 2:1 e 3:1. The compounds were characterized by spectroscopic and structural techniques. By Fourier Transform Infrared Spectroscopy (FT-IR), it was possible to check the total ionization of diphenylphosphinic acid in synthesized complexes, confirmed by the absence of the band type A, B, C related to ѵ(O-H) of the acid (2663 cm-1, 2168 cm-1, 1684 cm-1), as well as the disappearance of ѵ(P-OH)=961 cm-1. Furthermore, the occurrence of bands shifts of ѵ(POO-) [symmetrical and asymmetrical] of...

The Chameleon-Like Nature of Zwitterionic Micelles: Effect of Cation Binding

Addition of salts, especially perchlorates, to zwitterionic micelles of SB3-14, C(14)H(29)NMe(2)(+)(CH(2))(3)SO(3)(-), induces anionic character and uptake of H(3)O(+) by SB3-14 micelles. Thus, the addition of alkali metal perchlorates accelerates the acid hydrolysis of 2-(p-heptoxypheny1)-1,3-dioxolane, HPD, in the presence of SB3-14 micelles, which depends on the local proton concentration at the micelle surface. The addition of metal chlorides to solutions of such perchlorate-modified SB3-14 micelles decreases both the negative zeta potential of the micelles and the observed rate constant for acid hydrolysis of HPD. The effect of the monovalent cations Li(+), Na(+), and K(+) is smaller than that of the divalent cations Be(2+), Mg(2+), and Ca(2+), and much smaller than that of the trivalent cations Al(3+), La(3+), and Er(3+). The major factor responsible for this cation valence dependence of these effects is shown to be electrostatic in nature, reflecting the strong dependence of the micellar surface potential on the cation valence. The fact that the salt effects are not identical after correction for the electrostatic effects indicates that additional secondary nonelectrostatic effects may contribute as well.

Synthesis and Characterization of the Europium(III) Pentakis(picrate) Complexes with Imidazolium Countercations: Structural and Photoluminescence Study

Six new lanthanide complexes of stoichiometric formula (C)(2)[Ln(Pic)(5)]-where (C) is a imidazolium cation coming from the ionic liquids 1-butyl-3-methylimidazolium picrate (BMIm-Pic), 1-butyl-3-ethylimidazolium picrate (BEIm-Pic), and 1,3-dibutylimidazolium picrate (BBIm-Pic), and Ln is Eu(III) or Gd(III) ions-have been prepared and characterized. To the best of our knowledge, these are the first cases of Ln(III) pentakis(picrate) complexes. The crystal structures of (BEIm)(2)[Eu(Pic)(5)] and (BBIm)(2)[Eu(Pic)(5)] compounds were determined by single-crystal X-ray diffraction. The [Eu(Pic)(5)](2-) polyhedra have nine oxygen atoms coordinated to the Eu(III) ion, four oxygen atoms from bidentate picrate, and one oxygen atom from monodentate picrate. The structures of the Eu complexes were also calculated using the sparkle model for lanthanide complexes, allowing an analysis of intramolecular energy transfer processes in the coordination compounds. The photoluminescence properties of the Eu(III) complexes were then studied experimentally and theoretically, leading to a rationalization of their emission quantum yields.

Natural Membranes for Application in Biomedical Devices

Polymers from natural sources are particularly useful as biomaterials for medical devices applications. In this study, the results of characterization of a gelatin network electrolyte doped with europium triflate (Eu(CF3SO3)(3)) are described. The unusual electronic properties of the trivalent lanthanide ions make them well suited as luminescent reporter groups, with many applications in biotechnology. Samples of solvent-free electrolytes were prepared with a range of guest salt concentration. Materials based on Eu(CF3SO3)(3) were obtained as mechanically robust, flexible, transparent, and completely amorphous films. Samples were characterized by thermal analysis (thermo-gravimetry analysis (TGA) and differential scanning calorimetry (DSC), electrochemical stability, scanning electronmicroscopy (SEM), and photoluminescence spectroscopy.

Discovery of the Persistent Luminescence Mechanism of CdSiO3:Tb3+

The persistent luminescence of CdSiO3:Tb3+ was investigated with photoluminescence, thermoluminescence (TL), synchrotron radiation X-ray absorption (XANES and EXAFS) and UV-VUV spectroscopies. Only the typical intraconfigurational 4f(8)-4f(8) transitions of the Tb3+ ion were observed with no traces of band emission in either the conventional UV excited or persistent luminescence spectra. The trap structure from TL with three traps from 0.65 to 0.85 eV is ideal for room-temperature persistent luminescence similar to, e.g., Sr2MgSi2O7:Eu2+,R3+. Despite the rather low band gap energy, 5.28 eV, the persistent luminescence from Tb3+ is produced only under UV irradiation due to the inauspicious position of the F-7(6) ground level deep in the band gap of CdSiO3. This confirms the role of electrons as the charge carriers in the mechanism of Tb3+ persistent luminescence. The XANES spectra indicated the presence of only the trivalent Tb3+ species, thus excluding the direct Tb3+ -> Tb-IV oxidation during the charging process of persistent luminescence. Eventually, a unique persistent luminescence mechanism for Tb3+ in CdSiO3 was constructed based on the comprehensive experimental data.

Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients

Background Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. Methods Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. Results During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. Conclusion ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.

Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.

Development of newly conceived biomimetic nano-structured biomaterials as scaffolds for bone and osteochondral regeneration

The present research thesis was focused on the development of new biomaterials and devices for application in regenerative medicine, particularly in the repair/regeneration of bone and osteochondral regions affected by degenerative diseases such as Osteoarthritis and Osteoporosis or serious traumas. More specifically, the work was focused on the synthesis and physico-chemical-morphological characterization of: i) a new superparamagnetic apatite phase; ii) new biomimetic superparamagnetic bone and osteochondral scaffolds; iii) new bioactive bone cements for regenerative vertebroplasty. The new bio-devices were designed to exhibit high biomimicry with hard human tissues and with functionality promoting faster tissue repair and improved texturing. In particular, recent trends in tissue regeneration indicate magnetism as a new tool to stimulate cells towards tissue formation and organization; in this perspective a new superparamagnetic apatite was synthesized by doping apatite lattice with di-and trivalent iron ions during synthesis. This finding was the pin to synthesize newly conceived superparamagnetic bone and osteochondral scaffolds by reproducing in laboratory the biological processes yielding the formation of new bone, i.e. the self-assembly/organization of collagen fibrils and heterogeneous nucleation of nanosized, ionically substituted apatite mimicking the mineral part of bone. The new scaffolds can be magnetically switched on/off and function as workstations guiding fast tissue regeneration by minimally invasive and more efficient approaches. Moreover, in the view of specific treatments for patients affected by osteoporosis or traumas involving vertebrae weakening or fracture, the present work was also dedicated to the development of new self-setting injectable pastes based on strontium-substituted calcium phosphates, able to harden in vivo and transform into strontium-substituted hydroxyapatite. The addition of strontium may provide an anti-osteoporotic effect, aiding to restore the physiologic bone turnover. The ceramic-based paste was also added with bio-polymers, able to be progressively resorbed thus creating additional porosity in the cement body that favour cell colonization and osseointegration.

Massenspektrometrische Untersuchungen des Komplexierungsverhaltens von Actinid-Ionen in Lösung

Da die Langzeit-Radiotoxizität von abgebrannten Kernbrennstoffen von Plutonium und den minoren Actiniden dominiert wird, sind diese Elemente im Fokus der Untersuchungen bezüglich der Entsorgung der radioaktiven Abfälle.rnUm ein besseres Verständnis der Selektivität der Partitioning-Liganden BTP und BTBP bezüglich der Extraktion von trivalenten Actiniden zu erlangen, wurden die Komplexe, die diese mit Lanthaniden in octanolischer Lösung bilden charakterisiert. Das unterschiedliche Extraktionsverhalten der Lanthaniden untereinander konnte dabei auf unterschiedliche Präferenz zur Bildung von Ln(BTP)3-Komplexen abhängig vom Ionenradius der Lanthaniden zurückgeführt werden. Darüber hinaus konnte gezeigt werden, dass abhängig vom sterischen Anspruch der BTBP-Liganden in Eu(BTBP)2-Komplexen Nitratliganden in der ersten Koordinationssphäre gebunden werden. rnDa das Verhalten von Plutonium unter geochemischen Bedingungen von besonderem Interesse für die Risikoabschätzung von nuklearen Endlagern ist, widmet sich der zweite Teil der Arbeit dem Hydrolyse- und Kolloidbildungsverhalten von wässrigen Plutoniumlösungen in den Oxidationsstufen IV bis VI. Daher wurden die Lösungsspezies von sowohl Zirconium(IV) als Analogon für Plutonium(IV), als auch die von Uran(VI) und Plutonium(VI) direkt mittels massenspektrometrischer Methoden charakterisiert und quantifiziert. Darüber hinaus wurde die kinetische Hemmung der Reduktion von Pu(V) zu Pu(IV) und nachfolgender Kolloidbildung untersucht, welche sich durch oberflächeninduzierte Reduktion an kolloidalen Kristallisationskeimen deutlich beschleunigen lässt.rn

Radiomarkierung von HPMA-basierten, funktionalisierten Polymeren mit metallischen Radionukliden für die medizinische Anwendung als Theranostika

Für eine erfolgreiche Behandlung bösartiger Tumore ist eine frühzeitige Diagnose, aber auch eine effektive und effiziente Therapie essentiell. In diesem Zusammenhang sind Nanomaterialien in den Fokus der Arzneimittelentwicklung gerückt, welche für Diagnostik und Therapie genutzt werden könnten.rnSystematische Studien zur Radiometallmarkierung von Nanopartikeln und deren Stabilität in vitro im Zusammenhang mit der Struktur des Linkers und dem Anteil an Chelator wurden anhand verschiedener HPMA-DOTA-Konjugate durchgeführt. Es konnte gezeigt werden, dass die Linkerstruktur und der Belegungsgrad sowohl die Markierung als auch die in vitro -Stabilität von radiometallmarkierten HPMA-rnDOTA-Konjugaten beeinflussen.rnFür die Markierung selbst stehen mehrere Generator-produzierte metallische Positronenemitter zur Verfügung. Infolge der gesetzlichen Bestimmungen muss das Eluat der Generatoren bestimmte Spezifikationen (Elutionsausbeute, Durchbruch des Mutternuklids, Gehalt an Fremdionen, pH-Wert etc.) erfüllen, um für die Darstellung von Radiopharmaka verwendet werden zu können.rnFür das bereits etablierte PET-Nuklid 68Ga konnte eine Ethanol-basierte Aufreinigung entwickelt werden, welche hohe Elutions- und Markierungsausbeuten sowie Radionuklidreinheit garantiert und damit einen wichtigen Schritt für die Entwicklung von Kit-Formulierungen repräsentiert. Ausserdem konnten zwei Methoden zur Qualitätskontrolle entwickelt werden, welche es ermöglichen die Radionuklidreinheit des initialen 68Ga-Eluats, aber auch des finalen 68Ga-Radiopharmakons innerhalb einer Stunde ohne γ–Spektroskopie zu bestimmen.rnWährend mit 68Ga die Pharmakokinetik markierter Derivate für einen Zeitraum von bis 3 Stunden zugänglich ist, deckt das Generator-produzierte 44Sc eine Periode von bis zu einem Tag ab. Damit lässt sich die Pharmakokinetik markierter polymerer Drug Carrier-Systeme – von der frühen Ausscheidungsphase bis hin zu organspezifischen Akkumulationen durch passives und aktives Targeting – gut beschreiben.rnFür 44Sc konnte anhand der Modellverbindung DOTATOC gezeigt werden, dass das aufgereinigte Generatoreluat für die Markierung mit hohen radiochemischen Ausbeuten geeignet ist und etablierte Markierungsmethoden übertragbar sind. In weiterführenden Studien zur molekularen Bildgebung könnte das Potential dieses PET-Nuklids für die Langzeitbildgebung gezeigt werden.