Browsing by Author "Macia, Nicolas"

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    Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives
    (Springer Nature, 2020-06-24) Capper, Miles S.; Enriquez Garcia, Alejandra; Macia, Nicolas; Lai, Barry; Lin, Jian-Bin; Nomura, Masaharu; Alihosseinzadeh, Amir; Ponnurangam, Sathish; Heyne, Belinda; Shemanko, Carrie S.; Jalilehvand, Farideh
    The potential chemotherapeutic properties coupled to photochemical transitions make the family of fac-[Re(CO)3(N,N)X]0/+ (N,N = a bidentate diimine such as 2,2'-bipyridine (bpy); X = halide, H2O, pyridine derivatives, PR3, etc.) complexes of special interest. We have investigated reactions of the aqua complex fac-[Re(CO)3(bpy)(H2O)](CF3SO3) (1) with potential anticancer activity with the amino acid l-cysteine (H2Cys), and its derivative N-acetyl-l-cysteine (H2NAC), as well as the tripeptide glutathione (H3A), under physiological conditions (pH 7.4, 37 °C), to model the interaction of 1 with thiol-containing proteins and enzymes, and the impact of such coordination on its photophysical properties and cytotoxicity. We report the syntheses and characterization of fac-[Re(CO)3(bpy)(HCys)]·0.5H2O (2), Na(fac-[Re(CO)3(bpy)(NAC)]) (3), and Na(fac-[Re(CO)3(bpy)(HA)])·H2O (4) using extended X-ray absorption spectroscopy, IR and NMR spectroscopy, electrospray ionization spectrometry, as well as the crystal structure of {fac-[Re(CO)3(bpy)(HCys)]}4·9H2O (2 + 1.75 H2O). The emission spectrum of 1 displays a variance in Stokes shift upon coordination of l-cysteine and N-acetyl-l-cysteine. Laser excitation at λ = 355 nm of methanol solutions of 1–3 was followed by measuring their ability to produce singlet oxygen (1O2) using direct detection methods. The cytotoxicity of 1 and its cysteine-bound complex 2 was assessed using the MDA-MB-231 breast cancer cell line, showing that the replacement of the aqua ligand on 1 with l-cysteine significantly reduced the cytotoxicity of the Re(I) tricarbonyl complex. Probing the cellular localization of 1 and 2 using X-ray fluorescence microscopy revealed an accumulation of 1 in the nuclear and/or perinuclear region, whereas the accumulation of 2 was considerably reduced, potentially explaining its reduced cytotoxicity.
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    Exploring the Factors Influencing the Plasmon-Enhanced Production of Singlet Oxygen by Developing Model Hybrid Photosensitizer-Metal Nanoparticles
    (2020-01-20) Macia, Nicolas; Heyne, Belinda; Trudel, Simon; Anikovskiy, Max; Turner, Raymond Joseph; Boudreau, Denis
    Singlet oxygen is arguably one of the most important and well-studied electronically excited species in the molecular realm. The photochemistry and photophysics of the lowest and most stable excited-state of molecular oxygen are remarkable from many perspectives, from its high reactivity against organic substrates to its emission signature in the near-infrared. Singlet oxygen is a ubiquitous, yet highly dichotomic reactive species, as it is both beneficial and harmful to life. To advance our comprehension of singlet oxygen’s complex biological roles and to expand and improve upon its applications, efficient production and detection of this reactive species are important prerequisites. However, the successful achievement of these goals is hindered by the forbidden character of the photophysical events leading to its production and emission. Plasmonics, the science of controlling light at subwavelength dimensions by excitation of surface plasmons in nanostructures, has emerged over the past few decades as a unique tool to boost the efficiency of a plethora of intrinsically weak phenomena, including the production of singlet oxygen. The overreaching goal of the work presented within this thesis is to advance our understanding of how plasmonic nanostructures enhance the production of singlet oxygen. To investigate the puzzling mechanisms governing this phenomenon, a model hybrid photosensitizer-metal nanoparticle which can efficiently enhance the production of singlet oxygen via plasmonic effects was developed. The design of this model system consists of a spherical metal core@silica shell nanoparticle, decorated with an efficient singlet oxygen photosensitizer, Rose Bengal. The robust and highly tunable architecture of this model system has allowed the synthesis of a library of hybrid nanoparticles made of different silica shell thicknesses, core shapes and core compositions. Through the numerous iterations of the hybrid nanoparticle’s design, a set of structure-property relationships was established. For instance, the dependence on the separation distance between the photosensitizer and the metal nanoparticle on the plasmon-enhanced singlet oxygen production was unveiled, revealing that an optimal effect is reached when the photosensitizer is located at approximately 10 nm from the nanoparticle. Furthermore, the greater amplification effect of plasmonic hot-spots on the production of singlet was demonstrated by changing the nanoparticle’s core shape from a symmetric spherical-based morphology to an anisotropic cubic-based one. Also, modifying the core composition by using Ag, Au and their AuAg alloy spherical nanoparticles made the model system an efficient tool to investigate for the first time the plasmon-enhancement of singlet oxygen production in terms of its intrinsic plasmonic near- and far-field properties. Finally, by performing a meta-analysis on the data obtained for a library of hybrid photosensitizer-metal nanoparticles, a quantification of the plasmonic effect on the singlet oxygen production was achieved. Altogether, these studies lead to an unprecedent interpretation of the plasmon-enhancement of singlet oxygen production in terms of the morphological parameters (shell and core size; core shape and composition) and the plasmonic properties (hot-spots, near- and far-fields) of a model system. Ultimately, this new applied and fundamental knowledge establish a first set of rules for a more rational design of hybrid photosensitizer-metal nanoparticles, which can extend to other photosensitizer’s nanoplatforms to boost singlet oxygen production.