RESUMO
In order to obtain new functional soft systems for use as templating agents for the construction of functional mesostructured materials, the dynamic ordered soft systems formed by a hydrophilic ionic iridium(III) complex (IrPa) embedded into two different concentration F127-water mixtures have been investigated. To this aim, combined spectral and time-resolved photophysical techniques and rheological methods have been employed. The position of the chromophore inside the micellar, cubic and hexagonal phases of the F127 polymeric neutral surfactant in water was effectively determined. The hydrophilic character of the iridium(III) complex chosen allowed preferential functionalization of the F127 corona in the micellar and cubic phases.
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Monoclonal B-cell lymphocytosis (MBL) is classified as chronic lymphocytic leukemia (CLL)-like, atypical CLL, and CD5(-) MBL. The number of B cells per microliter divides CLL-like MBL into MBL associated with lymphocytosis (usually detected in a clinical setting) and low-count MBL detected in the general population (usually identified during population screening). After a median follow-up of 34 months we reevaluated 76 low-count MBLs with 5-color flow cytometry: 90% of CLL-like MBL but only 44.4% atypical CLL and 66.7% CD5(-) MBL persisted over time. Population-screening CLL-like MBL had no relevant cell count change, and none developed an overt leukemia. In 50% of the cases FISH showed CLL-related chromosomal abnormalities, including monoallelic or biallelic 13q deletions (43.8%), trisomy 12 (1 case), and 17p deletions (2 cases). The analysis of the T-cell receptor ß (TRBV) chains repertoire showed the presence of monoclonal T-cell clones, especially among CD4(high)CD8(low), CD8(high)CD4(low) T cells. TRBV2 and TRBV8 were the most frequently expressed genes. This study indicates that (1) the risk of progression into CLL for low-count population-screening CLL-like MBL is exceedingly rare and definitely lower than that of clinical MBL and (2) chromosomal abnormalities occur early in the natural history and are possibly associated with the appearance of the typical phenotype.
Assuntos
Linfócitos B/metabolismo , Aberrações Cromossômicas , Leucemia Linfocítica Crônica de Células B/genética , Linfocitose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 17/genética , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/metabolismo , Contagem de Linfócitos , Linfocitose/diagnóstico , Linfocitose/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia , Recombinação V(D)J/genéticaRESUMO
The ability to identify the broadest range of targetable gene fusions is crucial to facilitate personalized therapy selection for advanced lung adenocarcinoma (LuADs) patients harboring targetable receptor tyrosine kinase (RTK) genomic alterations. In order to evaluate the most effective testing approach for LuAD targetable gene fusion detection, we analyzed 210 NSCLC selected clinical samples, comparing in situ (Fluorescence In Situ Hybridization, FISH, and ImmunoHistoChemistry, IHC) and molecular (targeted RNA Next-Generation Sequencing, NGS, and RealTime-PCR, RT-PCR) approaches. The overall concordance among these methods was high (>90%), and targeted RNA NGS was confirmed to be the most efficient technique for gene fusion identification in clinical practice, allowing the simultaneous analysis of a large set of genomic rearrangements at the RNA level. However, we observed that FISH was useful to detect targetable fusions in those samples with inadequate tissue material for molecular testing as well as in those few cases whose fusions were not identified by the RNA NGS panel. We conclude that the targeted RNA NGS analysis of LuADs allows accurate RTK fusion detection; nevertheless, standard methods such as FISH should not be dismissed, as they can crucially contribute to the completion of the molecular characterization of LuADs and, most importantly, the identification of patients as candidates for targeted therapies.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Quinase do Linfoma Anaplásico/genética , Hibridização in Situ Fluorescente/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores Proteína Tirosina Quinases/genética , RNA/uso terapêutico , Fusão Gênica/genéticaRESUMO
OBJECTIVES: Alterations in mucin (MUC) glycosylation and expression have been described in cancer. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can provide material for molecular biology analysis. This study assessed the feasibility of evaluating MUC expression from material obtained by EUS-FNA and studied the profile of MUC expression in benign and malignant pancreatic lesions. METHODS: A total of 90 patients with solid or cystic pancreatic lesions underwent FNA. The aspirated material was used for cytological analysis and RNA extraction to assess the expression pattern of MUCs by reverse transcription-PCR with primers specific for the MUC1, MUC2, MUC3, MUC4, MUC5A, MUC5B, MUC6, and MUC7 genes. RESULTS: RNA extraction was successful in 81% of the biopsies. The prevalences of MUC1, MUC2, MUC4, and MUC7 in ductal adenocarcinoma were 57.7, 51.4, 18.9, and 73.0%, respectively. Fifty percent of benign lesions and neuroendocrine tumors (NETs), and 63% of intraductal papillary mucinous neoplasms (IPMNs) were positive for MUC1. Twenty-five percent of benign lesions, 86% of NETs, and 47% of IPMNs were positive for MUC2. Of NETs, 50% were positive for MUC1, and 14% were positive for MUC7. None of the benign lesions or NETs expressed MUC4. MUC7 expression was highly significant for adenocarcinoma (P=0.007) and borderline for IPMN (P=0.05). MUC7 was expressed in 37.5% of chronic pancreatitis cases. CONCLUSIONS: RNA can be extracted from samples obtained under EUS-FNA. MUC7 could serve as a potential biological marker to identify malignant lesions, especially pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Mucinas/metabolismo , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Pseudocisto Pancreático/metabolismo , Pancreatite Crônica/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Biópsia por Agulha Fina/métodos , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/genética , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/genética , Pseudocisto Pancreático/genética , Pseudocisto Pancreático/patologia , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , RNA/genética , RNA/metabolismo , Ultrassonografia de IntervençãoRESUMO
In the field of molecular spintronics, the use of magnetic molecules for information technology is a main target and the observation of magnetic hysteresis on individual molecules organized on surfaces is a necessary step to develop molecular memory arrays. Although simple paramagnetic molecules can show surface-induced magnetic ordering and hysteresis when deposited on ferromagnetic surfaces, information storage at the molecular level requires molecules exhibiting an intrinsic remnant magnetization, like the so-called single-molecule magnets (SMMs). These have been intensively investigated for their rich quantum behaviour but no magnetic hysteresis has been so far reported for monolayers of SMMs on various non-magnetic substrates, most probably owing to the chemical instability of clusters on surfaces. Using X-ray absorption spectroscopy and X-ray magnetic circular dichroism synchrotron-based techniques, pushed to the limits in sensitivity and operated at sub-kelvin temperatures, we have now found that robust, tailor-made Fe(4) complexes retain magnetic hysteresis at gold surfaces. Our results demonstrate that isolated SMMs can be used for storing information. The road is now open to address individual molecules wired to a conducting surface in their blocked magnetization state, thereby enabling investigation of the elementary interactions between electron transport and magnetism degrees of freedom at the molecular scale.
RESUMO
Mitochondria physically associate with the endoplasmic reticulum to coordinate interorganelle calcium transfer and regulate fundamental cellular processes, including inflammation. Deregulated endoplasmic reticulum-mitochondria cross-talk can occur in cystic fibrosis, contributing to hyperinflammation and disease progression. We demonstrate that Pseudomonas aeruginosa infection increases endoplasmic reticulum-mitochondria associations in cystic fibrosis bronchial cells by stabilizing VAPB-PTPIP51 (vesicle-associated membrane protein-associated protein B-protein tyrosine phosphatase interacting protein 51) tethers, affecting autophagy. Impaired autophagy induced mitochondrial unfolding protein response and NLRP3 inflammasome activation, contributing to hyperinflammation. The mechanism by which VAPB-PTPIP51 tethers regulate autophagy in cystic fibrosis involves calcium transfer via mitochondrial calcium uniporter. Mitochondrial calcium uniporter inhibition rectified autophagy and alleviated the inflammatory response in vitro and in vivo, resulting in a valid therapeutic strategy for cystic fibrosis pulmonary disease.
Assuntos
Fibrose Cística , Pneumonia , Cálcio/metabolismo , Canais de Cálcio , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Humanos , Proteínas Mitocondriais/metabolismo , Pneumonia/tratamento farmacológico , Pneumonia/etiologiaRESUMO
CDC25A phosphatase, an essential component of the cell cycle machinery, is also a key player in integrating the specific signals of checkpoint control in response to DNA damage. There are several lines of evidence that indicate a role for CDC25A in cancer development, consistent with the fact that its overexpression is detected in human cancers. In particular we previously reported that CDC25A is overexpressed also in early breast carcinoma. Recent data suggest that oncogene activation during early stages of tumor development causes DNA replication stress resulting in the induction of DNA damage response (DDR) and that the selection of cells defecting in their DDR could lead to malignant progression. To address how CDC25A overexpression contributes to breast cancer development we established a cell model in which CDC25A was constitutively overexpressed in hTERT-immortalized primary human mammary epithelial cells. At the earliest passages following CDC25A transduction we observed DDR signs associated with unscheduled DNA replication origins. In the latest passages DDR was significantly impaired and, even after ionizing radiation exposition, cells failed to induce G1 and G2 checkpoints; moreover DNA replication stress conditions, such as aphidicolin treatment, highlighted increased fragile site breakages and destabilized chromosomes just in these latest passages cells. Our data suggest that CDC25A overexpression, pushing the cell through the cell cycle transitions, induces DDR alterations that might enhance genomic instability.
Assuntos
Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Reparo do DNA , Células Epiteliais/metabolismo , Glândulas Mamárias Humanas/metabolismo , Fosfatases cdc25/biossíntese , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/fisiologia , Transformação Celular Neoplásica/metabolismo , Células Cultivadas , Dano ao DNA , Células Epiteliais/patologia , Feminino , Imunofluorescência , Humanos , Hibridização in Situ Fluorescente , Glândulas Mamárias Humanas/patologia , Regulação para CimaRESUMO
BACKGROUND: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. METHODS: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including "fentanyl", "fentanyl analogs", "death", "overdose", "intoxication", "synthetic opioids", "Novel Psychoactive Substances", "MT-45", "AH-7921", and "U-47700" were used for the inquiry. RESULTS: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. CONCLUSIONS: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.
RESUMO
Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well-established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the psychotropic effects of its "parent" compounds. Recent animal studies show that MXE is able to stimulate the mesolimbic dopaminergic transmission and to induce KET-like discriminative and rewarding effects. In light of the renewed interest in KET and PCP analogs, we decided to deepen the investigation of MXE-induced effects by a battery of behavioral tests widely used in studies of "safety-pharmacology" for the preclinical characterization of new molecules. To this purpose, the acute effects of MXE on neurological and sensorimotor functions in mice, including visual, acoustic and tactile responses, thermal and mechanical pain, motor activity and acoustic startle reactivity were evaluated in comparisons with KET and PCP to better appreciate its specificity of action. Cardiorespiratory parameters and blood pressure were also monitored in awake and freely moving animals. Acute systemic administrations of MXE, KET and PCP (0.01-30â¯mg/kg i.p.) differentially alter neurological and sensorimotor functions in mice depending in a dose-dependent manner specific for each parameter examined. MXE and KET (1 and 30â¯mg/kg i.p.) and PCP (1 and 10â¯mg/kg i.p.) also affect significantly cardiorespiratory parameters, systolic and diastolic blood pressure in mice.
Assuntos
Cicloexanonas/efeitos adversos , Cicloexilaminas/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Ketamina/efeitos adversos , Fenciclidina/efeitos adversos , Animais , Comportamento Animal/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Oxigênio/sangue , Medição da Dor/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Respiração/efeitos dos fármacosRESUMO
Recent cardiology research studies have reported the role, function, and structure of the mitochondrial permeability transition pore (mPTP) and have shown that its opening plays a key role in the progression of myocardial cell death secondary to reperfusion. In this manuscript, we validated a new pharmacological approach as an adjunct to reperfusion in myocardial infarction (MI) treatment and describe the discovery, optimization, and structure-activity relationship (SAR) studies of the first small-molecule mPTP opening inhibitors based on a 1,3,8-triazaspiro[4.5]decane scaffold that targets the c subunit of the F1/FO-ATP synthase complex. We identified three potential compounds with good mPTP inhibitory activity and beneficial effects in a model of MI, including a decreased apoptotic rate in the whole heart and overall improvement of cardiac function upon administration during reperfusion. The selected compounds did not show off-target effects at the cellular and mitochondrial levels. Moreover, the compounds preserved the mitochondrial ATP content despite interacting with the ATP synthase complex.
Assuntos
Cardiotônicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Alcanos/química , Animais , Cardiotônicos/química , Modelos Animais de Doenças , Camundongos , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Terapia de Alvo Molecular , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Subunidades Proteicas/antagonistas & inibidores , Ratos Wistar , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-AtividadeRESUMO
Mirtazapine is a noradrenergic and specific serotoninergic antidepressant agent that stimulates norepinephrine and serotonin release while also blocking serotonin receptors (5-HT2 and 5-HT3). Although the drug is used extensively, at present we do not know of any fatal cases due to mirtazapine alone. On the contrary, the published literature describes several fatal poisoning cases related to the intake of mirtazapine together with other drugs. Here we describe a fatal case of mirtazapine self-poisoning, since the other drug detected (lorazepam), was within the therapeutic range. Analyses were performed by LC-MS/MS on body fluids and a hair sample and mirtazapine concentration measured in blood was very high: 9.3mg/L. N-Desmethylmirtazapine was also quantitated. We then compared our results with those of previously published cases. In conclusion, even though mirtazapine can be considered a relatively safe drug, taking a large amount alone or in combination with other drugs, could lead to death.
Assuntos
Antidepressivos Tricíclicos/intoxicação , Mianserina/análogos & derivados , Suicídio , Antidepressivos Tricíclicos/sangue , Cromatografia Líquida , Humanos , Masculino , Espectrometria de Massas , Mianserina/sangue , Mianserina/intoxicação , Pessoa de Meia-Idade , MirtazapinaRESUMO
OBJECTIVES: Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. METHODS: 133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups. RESULTS: In the whole OAT group both warfarin and 3'-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3'-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3'-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3'-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3'-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles. CONCLUSION: Our results overall suggest that 3'-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators.
Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Coeficiente Internacional Normatizado , Farmacogenética , Varfarina/análogos & derivados , Varfarina/metabolismo , Varfarina/uso terapêutico , Administração Oral , Idoso , Calibragem , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase , Fatores de Tempo , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/sangueRESUMO
Two anionic iridium complexes [(R-ppy)2Ir(O^N)]TBA with R-ppy = 2-phenylpyridine or 4,5'-dimethyl-2-phenylpyridine, O^N = dianionic form of orotic acid and TBA = tetrabutylammonium have been synthesised and fully characterised by UV-Vis, emission, IR, NMR and cyclic voltammetric studies. These cyclometallated luminescent complexes containing a dianionic bidentate ancillary ligand show bright emission (60-70% PLQY) with maxima in the green region of the visible spectrum. Coupled with the ionic iridium complexes [(ppy)2Ir(N^N)]X, where N^N = 2-picolylamine or 2,2'-bipyridyl, and X = Cl(-) or CH3CO2(-), a series of new soft salts of general formula [(ppy)2Ir(N^N)][(R-ppy)2Ir (O^N)] have been obtained and fully characterized, with enhanced luminescent properties up to ca. 80% of phosphorescence quantum yields.
RESUMO
The CDC25A-CDK2 pathway has been proposed as critical for the oncogenic action of human epidermal growth factor receptor 2 (HER2) in mammary epithelial cells. In particular, transgenic expression of CDC25A cooperates with HER2 in promoting mammary tumors, whereas CDC25A hemizygous loss attenuates the HER2-induced tumorigenesis penetrance. On the basis of this evidence of a synergism between HER2 and the cell cycle regulator CDC25A in a mouse model of mammary tumorigenesis, we investigated the role of CDC25A in human HER2-positive breast cancer and its possible implications in therapeutic response. HER2 status and CDC25A expression were assessed in 313 breast cancer patients and we found statistically significant correlation between HER2 and CDC25A (P = .007). Moreover, an HER2-positive breast cancer subgroup with high levels of CDC25A and very aggressive phenotype was identified (P = .005). Importantly, our in vitro studies on breast cancer cell lines showed that the HER2 inhibitor efficacy on cell growth and viability relied also on CDC25A expression and that such inhibition induces CDC25A down-regulation through phosphatidylinositol 3-kinase/protein kinase B pathway and DNA damage response activation. In line with this observation, we found a statistical significant association between CDC25A overexpression and trastuzumab-combined therapy response rate in two different HER2-positive cohorts of trastuzumab-treated patients in either metastatic or neoadjuvant setting (P = .018 for the metastatic cohort and P = .021 for the neoadjuvant cohort). Our findings highlight a link between HER2 and CDC25A that positively modulates HER2-targeted therapy response, suggesting that, in HER2-positive breast cancer patients, CDC25A overexpression affects trastuzumab sensitivity.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Fosfatases cdc25/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Valor Preditivo dos Testes , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Transdução de Sinais , TrastuzumabRESUMO
The synthesis, crystal structure and luminescence properties of three cyclometalated Ir(III) complexes of general formula [(ppy)(2)Ir(pam)]X, where X = Cl(-) (1), PF(6)(-) (2), ClO(4)(-)(3), and pam = 2-picolylamine, are described. While 2 and 3 crystallize in a unique form, two pseudo-polymorphs, a solvated (1a) and a non-solvated (1b) species, have been observed for compound 1. 1a crystallizes in the monoclinic centrosymmetric space group P2(1)/c. On the contrary, 1b, 2 and 3 crystallize in the non-centrosymmetric space group P2(1)2(1)2(1) (1b) and Pca2(1) (2 and 3), respectively. All the crystalline supramolecular materials have been fully photophysically characterized. While 1 shows a bright blue-green emission in both solution and solvated crystalline state 1a, crystals of 1b, 2 and 3 show a significantly red shifted emission with respect to solution. Unexpectedly, and differently from 1a, mechanical stimuli-responsive colour and luminescence changes have been observed for 1b, 2 and 3. Upon mechanical grinding the colour of the crystalline solids changes from orange to yellow while the emission energy is partially (2 and 3) or completely (1b) converted from orange to green. The grinding-triggered colour and luminescence changes have been attributed to a crystal-to-amorphous phase conversion for all crystalline solids.
Assuntos
Complexos de Coordenação/química , Irídio/química , Aminas/química , Cátions/química , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Conformação Molecular , Espectrometria de FluorescênciaRESUMO
Synthesis, crystal structural determination and photophysical properties of a series of heteroleptic cationic cyclometalated iridium(III) derivatives of general formula [(ppy)(2)Ir(en)]X (X = ClO(4)(-) (1), PF(6)(-) (2), Cl(-) (3), BPh(4)(-) (4)), are described. The assembly of the common molecular building block allows to get highly luminescent crystalline materials or to assemble poorly luminescent supramolecular channelled architectures, for which the additional contribution of oxygen quenching effects has been observed. Moreover, the high reproducibility of the preparations of the crystalline materials in their specific crystalline phases, makes the control of the supramolecular organization of photo-active iridium(III) complexes within the crystalline structures a useful synthetic procedure for the construction of highly luminescent materials.
Assuntos
Complexos de Coordenação/química , Etilenodiaminas/química , Irídio/química , Cristalização , Ligação de Hidrogênio , Luminescência , Espectroscopia de Ressonância Magnética , Oxigênio/química , Espectrofotometria InfravermelhoRESUMO
The solvent induced polymorphism observed in a cyclometalated iridium(iii) ethylenediamine ionic complex is a new tool to modulate and enhance emission in the solid crystalline state.
Assuntos
Irídio/química , Luminescência , Compostos Organometálicos/química , Cristalografia por Raios X , Modelos Moleculares , Fotoquímica , Solventes/químicaRESUMO
OBJECTIVE: The prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral second-generation alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas. DESIGN: This was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150-200 mg/m(2) per day for 5 days every 4 weeks for a maximum of 12 cycles. METHODS: Response assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels. RESULTS: Four patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O(6)-methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response. CONCLUSIONS: Temozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.
Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Terapia de Salvação , Adenoma/enzimologia , Carcinoma/tratamento farmacológico , Carcinoma/enzimologia , Dacarbazina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Neoplasias Hipofisárias/enzimologia , Estudos Prospectivos , TemozolomidaRESUMO
Synthetic nanographenes have been self-assembled from solution on the surface of nanometric channels of an alumina membrane template. By controlling the interplay between intermolecular and interfacial interactions, the molecules have been adsorbed either 'face-on' or 'edge-on' on the pore's surfaces, leading to the formation of columnar stacks in the latter case. Upon thermal treatment at high temperature, the molecular cross-linking of the columns has been triggered, transforming the delicate supramolecular arrangement into robust carbon nanotubes, with the graphitic planes at predetermined orientations with respect to the tube axis. Scanning force microscopy characterization of single nanotubes deposited from suspensions on mica showed that the nanotubes can self-assemble on flat surfaces adopting preferential alignments which reflect the threefold symmetry of the mica substrate. Kelvin probe force microscopy studies revealed that the nanotubes possess a surface potential much smaller than the work function of both graphite and conventional vacuum-processed nanotubes, providing evidence for their more confined electronic structure.
RESUMO
The processability of giant (macro)molecules into ultrapure and highly ordered structures at surfaces is of fundamental importance for studying chemical, physical and biological phenomena, as well as their exploitation as active units in the fabrication of hybrid devices. The possibility of handling larger and larger molecules provides access to increasingly complex functions. Unfortunately, larger molecules commonly imply lower processability due to either their low solubility in liquid media or the occurrence of thermal cracking during vacuum sublimation. The search for novel strategies to process and characterize giant building blocks is therefore a crucial goal in materials science. Here we describe a new general route to process, at surfaces, extraordinarily large molecules, that is, synthetic nanographenes, into ultrapure crystalline architectures. Our method relies on the soft-landing of ions generated by solvent-free matrix-assisted laser desorption/ionization (MALDI). The nanographenes are transferred to the gas phase, purified and adsorbed at surfaces. Scanning tunnelling microscopy reveals the formation of ordered nanoscale semiconducting supramolecular architectures. The unique flexibility of this approach allows the growth of ultrapure crystalline films of various systems, including organic, inorganic and biological molecules, and therefore it can be of interest for technological applications in the fields of electronics, (bio)catalysis and nanomedicine.