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1.
Oncotarget ; 9(85): 35541-35552, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30473749

RESUMO

Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a). Specific lipid classes and species, such as phospholipids (e.g., phosphatidylethanolamine 18:1/16:0 and 18:1/18:1) and cholesteryl esters, detected by LC-ESI-MS/MS, allowed statistical separation of all four prostate cell lines. Lipid mapping by FTIR revealed that variations in these lipid classes could also be detected at a single cell level, however further investigation into this approach would be needed to generate large enough data sets for quantitation. Visualisation by fluorescence microscopy showed striking variations that could be observed in lipid staining patterns between cell lines allowing visual separation of cell lines. In particular, polar lipid staining by a fluorescent marker was observed to increase significantly in prostate cancer lines cells, when compared to PNT1a cells, which was consistent with lipid quantitation by LC-ESI-MS/MS and FTIR spectroscopy. Thus, multiple technologies can be employed to either quantify or visualise changes in lipid composition, and moreover specific lipid profiles could be used to detect and phenotype prostate cancer cells.

2.
Chemistry ; 23(62): 15666-15679, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-28782852

RESUMO

A family of five neutral cyclometalated iridium(III) tetrazolato complexes and their methylated cationic analogues have been synthesised and characterised. The complexes are distinguished by variations of the substituents or degree of π conjugation on either the phenylpyridine or tetrazolato ligands. The photophysical properties of these species have been evaluated in organic and aqueous media, revealing predominantly a solvatochromic emission originating from mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity. These emissions are characterised by typically long excited-state lifetimes (∼hundreds of ns), and quantum yields around 5-10 % in aqueous media. Methylation of the complexes caused a systematic red-shift of the emission profiles. The behaviour and the effects of the different complexes were then examined in cells. The neutral species localised mostly in the endoplasmic reticulum and lipid droplets, whereas the majority of the cationic complexes localised in the mitochondria. The amount of complexes found within cells does not depend on lipophilicity, which potentially suggests diverse uptake mechanisms. Methylated analogues were found to be more cytotoxic compared to the neutral species, a behaviour that might to be linked to a combination of uptake and intracellular localisation.


Assuntos
Complexos de Coordenação/química , Irídio/química , Tetrazóis/química , Animais , Cátions/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , Retículo Endoplasmático/química , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Ligantes , Luz , Microscopia de Fluorescência , Conformação Molecular , Fotólise/efeitos da radiação , Piridinas/química , Ratos
3.
PLoS One ; 11(8): e0161557, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27551717

RESUMO

Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular compartments.


Assuntos
Fenômenos Fisiológicos Celulares , Metabolismo dos Lipídeos , Lipídeos , Sondas Moleculares , Adipócitos , Tecido Adiposo/metabolismo , Aminoácidos/metabolismo , Animais , Autofagia , Transporte Biológico , Metabolismo dos Carboidratos , Drosophila , Gotículas Lipídicas/metabolismo , Lipídeos/química , Metamorfose Biológica , Camundongos , Análise Espectral Raman , Coloração e Rotulagem
4.
FEBS Lett ; 590(18): 3051-60, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27543777

RESUMO

Live cell imaging can provide important information on cellular dynamics; however, the full utilisation of this technology has been hampered by the limitations of imaging reagents. Metal-based complexes have the potential to overcome many of the issues common to many current imaging agents. The rhenium (I)-based complex fac-[Re(CO)3 (1,10-phenanthroline)(4-pyridyltetrazolate)], herein referred to as ReZolve-ER(™) , shows promise as a live cell imaging agent with rapid cell uptake, low cytotoxicity, resistance to photobleaching and compatibility with multicolour imaging. ReZolve-ER(™) localised to the nuclear membrane/endoplasmic reticulum (ER) and allowed the detection of exocytotic events at the plasma membrane. Thus, we present a new imaging agent for monitoring live cell events in real time, which is ideal for imaging either short- or long-time courses.


Assuntos
Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Retículo Endoplasmático/metabolismo , Imagem Molecular/métodos , Transporte Ativo do Núcleo Celular , Animais , Linhagem Celular , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Exocitose , Corantes Fluorescentes , Humanos , Compostos Organometálicos , Fenantrolinas , Rênio
5.
Dalton Trans ; 44(47): 20636-47, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26563409

RESUMO

Three new complexes of formulation fac-[Re(CO)3(diim)L], where diim is either 1,10-phenanthroline or 1,10-phenanthroline functionalised at position 5 by a thioalkyl chain, and L is either a chloro or aryltetrazolato ancillary ligand, were synthesised and photophysically characterised. The complexes exhibit phosphorescent emission with maxima around 600 nm, originating from triplet metal-to-ligand charge transfer states with partially mixed ligand-to-ligand charge transfer character. The emission is relatively long-lived, within the 200-400 ns range, and with quantum yields of 2-4%. The complexes were trialed as cellular markers in live HeLa cells, along with two previously reported rhenium tetrazolato complexes bound to unsubstituted 1,10-phenanthroline. All five complexes exhibit good cellular uptake and non-specific perinuclear localisation. Upon excitation at 405 nm, the emission from the rhenium complexes could be clearly distinguished from autofluorescence, as demonstrated by spectral detection within the live cells. Four of the complexes did not appear to be toxic, however prolonged excitation could result in membrane blebbing. No major sign of photobleaching was detected upon multiple imaging on the same cell sample.


Assuntos
Complexos de Coordenação/química , Fenantrolinas/química , Rênio/química , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Células HeLa , Humanos , Ligantes , Fenantrolinas/farmacologia , Rênio/farmacologia
6.
Inorg Chem ; 53(7): 3629-41, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24665819

RESUMO

A family of tricarbonyl Re(I) complexes of the formulation fac-[Re(CO)3(NHC)L] has been synthesized and characterized, both spectroscopically and structurally. The NHC ligand represents a bidentate N-heterocyclic carbene species where the central imidazole ring is substituted at the N3 atom by a butyl, a phenyl, or a mesityl group and substituted at the N1 atom by a pyridyl, a pyrimidyl, or a quinoxyl group. On the other hand, the ancillary L ligand alternates between chloro and bromo. For the majority of the complexes, the photophysical properties suggest emission from the lowest triplet metal-to-ligand charge transfer states, which are found partially mixed with triplet ligand-to-ligand charge transfer character. The nature and relative energy of the emitting states appear to be mainly influenced by the identity of the substituent on the N3 atom of the imidazole ring; thus, the pyridyl complexes have blue-shifted emission in comparison to the more electron deficient pyrimidyl complexes. The quinoxyl complexes show an unexpected blue-shifted emission, possibly occurring from ligand-centered excited states. No significant variations were found upon changing the substituent on the imidazole N3 atom and/or the ancillary ligand. The photochemical properties of the complexes have also been investigated, with only the complexes bound to the pyridyl-substituted NHC ligands showing photoinduced CO dissociation upon excitation at 370 nm, as demonstrated by the change in the IR and NMR spectra as well as a red shift in the emission profile after photolysis. Temperature-dependent photochemical experiments show that CO dissociation occurs at temperatures as low as 233 K, suggesting that the Re-C bond cleaves from excited states of metal-to-ligand charge transfer nature rather than thermally activated ligand field excited states. A photochemical mechanism that takes into account the reactivity of the complexes bound to the pyridyl-NHC ligand as well as the stability of those bound to the pyrimidyl- and quinoxyl-NHC ligands is proposed.

7.
Inorg Chem ; 53(1): 229-43, 2014 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-24354312

RESUMO

One of the distinct features of metal-tetrazolate complexes is the possibility of performing electrophilic additions onto the imine-type nitrogens of the coordinated five-membered ring. These reactions, in particular, provide a useful tool for varying the main structural and electronic properties of the starting tetrazolate complexes. In this paper, we demonstrate how the use of a simple protonation-deprotonation protocol enables us to reversibly change, to a significant extent, the light-emission output and performance of a series of Re(I)-tetrazolate-based phosphors of the general formulation fac-[Re(N(∧)N)(CO)3L], where N(∧)N denotes diimine-type ligands such as 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) and L represents a series of different 5-aryl tetrazolates. Indeed, upon addition of triflic acid to these neutral Re(I) complexes, a consistent blue shift (Δλmax ca. 50 nm) of the emission maximum is observed and the protonated species also display increased quantum yield values (4-13 times greater than the starting compounds) and longer decay lifetimes. This alteration can be reversed to the initial condition by further treating the protonated Re(I) complex with a base such as triethylamine. Interestingly, the reversible modulation of luminescent features by the same protonation-deprotonation mechanism appears as a quite general characteristic of photoactive metal tetrazolate complexes, even for compounds in which the 2-pyridyl tetrazolate ligands coordinate the metal center with a bidentate mode, such as the corresponding Ir(III) cyclometalates [Ir(C(∧)N)2L] and the Ru(II) polypyridyl derivatives [Ru(bpy)2L](+). In these cases, the protonation of the starting materials leads to red-shifted and more intense emissions for the Ir(III) complexes, while almost complete quenching is observed in the case of the Ru(II) analogues.

8.
Dalton Trans ; 42(39): 14100-14, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-23939232

RESUMO

The photophysical and photochemical properties of the new tricarbonyl rhenium(I) complexes bound to N-heterocyclic carbene ligands (NHC), fac-[Re(CO)3(N^C)X] (N^C = 1-phenyl-3-(2-pyridyl)imidazole or 1-quinolinyl-3-(2-pyridyl)imidazole; X = Cl or Br), are reported. The photophysics of these complexes highlight phosphorescent emission from triplet metal-to-ligand ((3)MLCT) excited states, typical of tricarbonyl rhenium(I) complexes, with the pyridyl-bound species displaying a ten-fold shorter excited state lifetime. On the other hand, these pyridyl-bound species display solvent-dependent photochemical CO dissociation following what appear to be two different mechanisms, with a key step being the formation of cationic tricarbonyl solvato-complexes, being themselves photochemically active. The photochemical mechanisms are illustrated with a combination of NMR, IR, UV-Vis, emission and X-ray structural characterization techniques, clearly demonstrating that the presence of the NHC ligand is responsible for the previously unobserved photochemical behavior in other photoactive tricarbonyl rhenium(I) species. The complexes bound to the quinolinyl-NHC ligand (which possess a lower-energy (3)MLCT) are photostable, suggesting that the photoreactive excited state is not any longer thermally accessible. The photochemistry of the pyridyl complexes was investigated in acetonitrile solutions and also in the presence of triethylphosphite, showing a competing and bifurcated photoreactivity promoted by the trans effect of both the NHC and phosphite ligands.

9.
Dalton Trans ; 42(23): 8188-91, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23661108

RESUMO

The reaction of 2-pyridyltetrazolate with [Re(CO)5X] (X = Cl, Br) yielded the formation of an unexpected cyclic metallacalix[3]arene, as revealed by X-ray structural studies, characterised by aqua emission and reversible three-electron oxidation.

10.
Dalton Trans ; 42(12): 4233-6, 2013 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-23400310

RESUMO

The coordination of 2-pyridyltetrazolate and ortho-xylene-linked bis(NHC)cyclophane to Pt(II) yielded a novel complex characterised by enhanced pure deep-blue emission, whose intensity can be modulated via methylation of the tetrazole ring.


Assuntos
Complexos de Coordenação/química , Platina/química , Xilenos/química , Cloreto de Metileno/química , Piridinas/química , Teoria Quântica , Espectrofotometria
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