Luminescent and electrochemical probes based on Au(I), Ir(III) and Fe(II) coordination complexes for bioimaging, diagnostics and therapeutics

This thesis describes the development and synthesis of a range of novel fluorophores based on 1,8-naphthalimide, N-heterocyclic carbene (NHC) and phosphine derivatives, as well as coordination chemistry with Au(I), Ir(III) and Fe(II). Detailed discussions on the characterisation and the photophysical properties are described, with reference to applications including bioimaging, diagnostics and therapeutics. Chapter 2 describes the synthetic development and spectroscopic analysis of a series of NHC-functionalised 1,8-naphthalimide fluorophores, generating ten new ligands that were successfully utilised for Au(I) coordination chemistry. The optical properties of the compounds were dictated by ligand-centred transitions. Cytotoxicity assessments revealed that compounds were the most toxic to LOVO and MCF-7 cell lines. In addition, lysosomal localisation was observed in cell imaging studies with MCF-7 cells, as seen with structurally related anticancer compounds. Chapter 3 describes the synthetic development and spectroscopic analysis of a series of aminophosphine and phosphinite fluorophores, generating six new ligands, with some successfully utilised for Au(I) coordination chemistry. The photophysical properties were explored in detail due to the presence of different fluorescent groups, including naphthalene, anthracene, pyrene and anthraquinone. In this chapter, 31P NMR was particularly important in confirming the success of the synthetic routes. Chapter 4 describes the comparative syntheses of six new phenyl-1H-pyrazoles and their corresponding cyclometalated iridium(III) complexes using both batch and, successfully applied, flow-microwave methodologies. Isolation of spectroscopically pure species in less than 1 hour of reaction time from IrCl3 was observed, along with ligand-dependent, tuneable green-yellow luminescence. Chapter 5 outlines determination of a successful synthetic route to a series of fluorescent electrochemical biosensors that incorporate both a redox active ferrocene unit and a naphthalimide moiety, with the intention to be applied as an electrochemical detection method for Clostridium Difficile (CDF). Detailed photophysical and electrochemical investigations were used to determine suitability for the desired application

Ming Shan Digital Experience

The Ming Shan Digital Experience is an immersive installation designed to support meditation in the context of a new Taoist center. Its creation confronted current academic literature on digital technology for meditation with the practical and cultural requirements of Taoist practice. Quantitative and qualitative learnings show the effectiveness of multimodal biofeedback on individual and collective meditative experience. Now instated in the Taoist center, the installation opens new perspectives for combining digital technology with ancient practice

Luminescent 1,8-Naphthalimide-Derived ReI Complexes: syntheses, spectroscopy, X-ray structure and preliminary bioimaging in fission yeast cells

A series of picolyl-functionalised, fluorescent 1,8-naphthalimide ligands (L) have been synthesised and coordi-nated to ReI to form luminescent cationic complexes of the general form fac-[Re(phen)(CO)3(L)]BF4. The complexes were characterised by using a range of spectroscopic and analytical techniques. One example of a complex was also characterised in the solid-state by using single-crystal X-ray diffraction, reveal-ing a distorted octahedral coordination sphere at ReI and Re– C/Re–N bond lengths within the expected ranges. All ligands were shown to be fluorescent, with the 4-amino derivatives showing intramolecular charge transfer in the visible region (511–534 nm). The complexes generally showed a mixture of ligand-centred and/or 3MLCT emission depending upon the na-ture of the coordinated 1,8-naphthalimide ligand. For selected complexes, confocal fluorescence microscopy was undertaken by using fission yeast cells (Schizosaccharomyces pombe) and showed that the structure of the 1,8-naphthalimide ligand influ-ences the uptake and localisation of the rhenium complex

Simulation of habituation to simple and multiple stimuli

Within the psychological literature there are a number of models that reproduce the defining properties of habituation to a single stimulus. However, most of them do not reproduce the phenomenon of dishabituation shown in empirical studies, consisting in the recovery of a stimulus previously habituated upon the appearance of a novel stimulus. The present work offers a model of habituation which, in addition to reproducing the basic properties of habituation to a stimulus, also does so when more than one stimulus is presented, and thus includes the dishabituation phenomenon. This model consists of two functions, one called “activation” and the other “availability”, and is tested by means of simulation of the responses in the context of different stimulus patterns. The results of the simulation show a good qualitative fit to the empirical results on the phenomena of habituation, including dishabituation. In addition, the model is suitable for inclusion in associative models that reproduce classical conditioning, which will make it possible in the future to incorporate into these the influence that the habituation of each stimulus may have on its association with other stimuli

Synthesis and characterisation of fluorescent aminophosphines and their coordination to gold(i)

Three novel fluorescent aminophosphine ligands have been synthesised that incorporate napthyl (L1), pyrenyl (L2) and anthraquinone (L3) chromophores into their structures. The ligands react with [AuCl(tht)] (tht = tetrahydrothiophene) to give neutral complexes of the form [AuCl(L1–3)]. Solid state, X-ray crystallographic data was obtained for the anthraquinone derivative, [AuCl(L3)], and showed a distorted linear coordination geometry at Au(I). The packing structure also revealed a number of intermolecular π–π interactions that involve the anthraquinone and phenyl units of the aminophosphine ligand. 31P NMR spectroscopic data revealed δP values of +42.2 (L1), +42.1 (L2) and +26.1 (L3) ppm, which shifted downfield upon coordination to Au(I) to +64.6, +64.7, and +55.8 ppm, respectively. Supporting TD-DFT studies were able to reproduce the structure and 31P NMR chemical shifts of [AuCl(L3)] as well as rationalise the HOMO–LUMO compositions. Photophysical studies showed that the appended fluorophore dominates the absorption and emission properties for the ligands and complexes, with the anthraquinone derivatives showing visible emission at ca. 570 nm which was attributed to the intramolecular charge transfer character of the phosphinoaminoanthraquinone fragment

Scaling relations of metallicity, stellar mass, and star formation rate in metal-poor starbursts: II. Theoretical models

Scaling relations of metallicity (O/H), star formation rate (SFR), and stellar mass give important insight on galaxy evolution. They are obeyed by most galaxies in the Local Universe and also at high redshift. In a companion paper, we compiled a sample of ~1100 galaxies from redshift 0 to ~3, spanning almost two orders of magnitude in metal abundance, a factor of $\sim10^6$ in SFR, and of ~10^5 in stellar mass. We have characterized empirically the star-formation "main sequence" (SFMS) and the mass-metallicity relation (MZR) for this sample, and also identified a class of low-metallicity starbursts, rare locally but more common in the distant universe. These galaxies deviate significantly from the main scaling relations, with high SFR and low metal content for a given M*. In this paper, we model the scaling relations and explain these deviations from them with a set of multi-phase chemical evolution models based on the idea that, independently of redshift, initial physical conditions in a galaxy's evolutionary history can dictate its location in the scaling relations. Our models are able to successfully reproduce the O/H, M*, and SFR scaling relations up to z~3, and also successfully predict the molecular cloud fraction as a function of stellar mass. These results suggest that the scaling relations are defined by different modes of star formation: an "active" starburst mode, more common at high redshift, and a quiescent "passive" mode that is predominant locally and governs the main trends.Comment: 17 pages, 7 figures, accepted for publication by MNRA

How well do the existing and proposed reserve networks represent vertebrate species in Chile?

Increasingly, biogeographical knowledge and analysis are playing a fundamental role in assessing the representativeness of biodiversity in protected areas, and in identifying critical areas for conservation. With almost 20% of the country assigned to protected areas, Chile is well above the conservation target (i.e. 10-12%) proposed by many international conservation organizations. Moreover, the Chilean government has recently proposed new conservation priority sites to improve the current protected area network. Here, we used all 653 terrestrial vertebrate species present in continental Chile to assess the performance of the existing and proposed reserve networks. Using geographical information systems, we overlaid maps of species distribution, current protected areas, and proposed conservation priority sites to assess how well each species is represented within these networks. Additionally, we performed a systematic reserve selection procedure to identify alternative conservation areas for expanding the current reserve system. Our results show that over 13% of the species are not covered by any existing protected area, and that 73% of Chilean vertebrate species can be considered partial gaps, with only a small fraction of their geographical ranges currently under protection. The coverage is also deficient for endemic (species confined to Chile) and threatened species. While the proposed priority sites do increase coverage, we found that there are still several gaps and these are not the most efficient choices. Both the gap analysis and the reserve selection analysis identified important areas to be added to the existing reserve system, mostly in northern and central Chile. This study underscores the need for a systematic conservation planning approach to redefine the conservation priority sites in order to maximize the representation of species, particularly endemic and threatened species.Fil: Tognelli, Marcelo Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina. Pontificia Universidad Católica de Chile; ChileFil: De Arellano, Pablo I. Ramirez. Pontificia Universidad Católica de Chile; Chile. State University of New York; Estados UnidosFil: Marquet, Pablo A.. Instituto de Ecologia y Biodiversidad, Santiago; Chile. Pontificia Universidad Católica de Chile; Chile. National Center For Ecological Analysis And Synthesis; Estados Unido

Fluorescent functionalised naphthalimides and their Au(i)–NHC complexes for potential use in cellular bioimaging

A series of cationic, dihydroimidazolinium-functionalized 1,8-naphthalimide fluorophores have been isolated as their hexafluorophosphate salts, [HL]PF6. These pro-ligands react with [AuCl(tht)] in the presence of base to form N-heterocyclic carbene (NHC) complexes, [AuCl(L)]. Two X-ray structures represent a pro-ligand and complex pairing: the latter reveals the two-coordinate linear geometry of the NHC–Au(I) species, as well as intermolecular interactions supported by both ligand π–π stacking and a weak aurophilic interaction of 3.3205(6) Å. The luminescence properties of the pro-ligands and complexes are dominated by the ICT character of the substituted fluorophore at ca. 500 nm, which is further modulated via functionalization at the 4-position of the naphthalimide. Cytotoxicity assessments were performed for all [HL]PF6 and [AuCl(L)] species against LOVO, MCF-7, A549 and PC3 cell lines; added lipophilicity seems to correlate with increased cytotoxicity. Confocal fluorescence microscopy was undertaken on a selected [HL]PF6 and [AuCl(L)] species and showed that the intracellular distribution is dependent upon the specific ligand structure. More detailed co-localisation studies show that selected examples present a predominant lysosomal staining pattern. FLIM studies exemplified the applicability of these probes, and secondly suggest that fluorescence lifetime could be used to provide information on the integrity of the complex and thus liberation of gold in a biological environment

Over-pressurized bioreactors : application to microbial cell cultures

In industrial biotechnology, microbial cultures are exposed to different local pressures inside bioreactors. Depending on the microbial species and strains, the increased pressure may have detrimental or beneficial effects on cellular growth and product formation. In this review, the effects of increased air pressure on various microbial cultures growing in bioreactors under moderate total pressure conditions (maximum, 15 bar) will be discussed. Recent data illustrating the diversity of increased air pressure effects at different levels in microbial cells cultivation will be presented, with particular attention to the effects of oxygen and carbon dioxide partial pressures on cellular growth and product formation, and the concomitant effect of oxygen pressure on antioxidant cellular defense mechanisms.The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-000028," cofunded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. A special aknowledgement is given to FCT for the support to the improvement of infrastructures awarded by the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462)

Over-pressurized bioreactors : application to microbial cell cultures

In industrial biotechnology, microbial cultures are exposed to different local pressures inside bioreactors. Depending on the microbial species and strains, the increased pressure may have detrimental or beneficial effects on cellular growth and product formation. In this review, the effects of increased air pressure on various microbial cultures growing in bioreactors under moderate total pressure conditions (maximum, 15 bar) will be discussed. Recent data illustrating the diversity of increased air pressure effects at different levels in microbial cells cultivation will be presented, with particular attention to the effects of oxygen and carbon dioxide partial pressures on cellular growth and product formation, and the concomitant effect of oxygen pressure on antioxidant cellular defense mechanisms.The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-000028," cofunded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. A special aknowledgement is given to FCT for the support to the improvement of infrastructures awarded by the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462)