[ES] La presente tesis doctoral titulada "Reconocimiento de neurotransmisores basado en nanopartículas de oro y de sílice mesoporosa para aplicaciones de detección y liberación controlada" es una tesis realizada por compendio de artículos la cual se centra en el diseño, preparación, caracterización y evaluación de distintos nanodispositivos para la detección colorimétrica de neurotransmisores y sistemas de liberación controlada que responden a neurotransmisores basados en nanopartículas de oro y nanopartículas de sílice mesoporosa, equipadas con ligandos orgánicos, efectores enzimáticos, puertas moleculares y especies cromofluorogénicas o medicamentos. En el primer capítulo se introduce una visión general de lo que son los neurotransmisores, sus principales características y el importante papel que éstos desempeñan en el funcionamiento de nuestro organismo. Además, se presenta una descripción general de las propiedades y potenciales aplicaciones de las nanopartículas de oro funcionalizadas con ligandos orgánicos como sistemas de detección y las nanopartículas mesoporosas de sílice funcionalizadas con puertas moleculares como sistemas de liberación controlada. A continuación, en el segundo capítulo se presentan los objetivos generales que son abordados en los siguientes capítulos experimentales. En el tercer capítulo, se presentan tres sistemas de detección colorimétrica de neurotransmisores basados en la agregación de nanopartículas de oro doblemente funcionalizadas con ligandos orgánicos. El primer sistema es un sensor capaz de detectar de forma selectiva el neurotransmisor serotonina, utilizando nanopartículas de oro funcionalizadas con ditio-bis(propionato de succinimidilo) y N-Acetil-L-Cisteína. El segundo sistema consiste en un sensor para la detección selectiva del neurotransmisor norepinefrina diseñado a partir de nanopartículas de oro funcionalizadas con 4-(liponiloxi)benzaldehído y ácido 4-mercato fenilborónico. El tercer sistema está compuesto por nanopartículas de oro funcionalizadas con 4-(liponiloxi)benzaldehído y N-Acetil-L-Cisteína, para la detección de normetanefrina, un importante biomarcador del tumor feocromocitoma. Todos estos sistemas se evalúan en medios competitivos como suero sanguíneo u orina. En el cuarto capítulo se muestran dos sistemas de liberación controlados enzimáticamente basados en la apertura de puertas moleculares. El primer sistema de liberación controlada responde a la presencia del neurotransmisor acetilcolina. En concreto, se utilizan nanopartículas de sílice mesoporosa funcionalizadas en su superficie con grupos de ácido fenilborónico y tapadas con la enzima acetilcolinesterasa mediante la formación de ésteres cíclicos de ácido fenilborónico entre las cadenas de oligosacáridos de la enzima y los grupos fenilborónicos de la superficie de las nanopartículas. En este caso la reacción enzimática produce ácido acético que da lugar a la hidrolisis de los ésteres borónicos, destapando los poros y liberando la carga contenida en el interior. Además, se evalúa la capacidad del dispositivo diseñado para liberar el citotóxico doxorubicina en células cancerosas en presencia de acetiltiocolina. El segundo sistema consiste en un nanodispositivo para la liberación controlada en respuesta al neurotransmisor L-glutamato. Para esto se utilizan nanopartículas tipo Janus de oro-sílice mesoporosa funcionalizadas con la enzima L-glutamato oxidasa en la parte del oro y con una puerta molecular autoinmolante de arilboronato en la superficie de la sílice. La liberación controlada se basa en el reconocimiento del L-glutamato por la enzima L-glutamato oxidasa y la posterior formación de peróxido de hidrogeno, que es la especie que induce la escisión de la puerta autoinmolante y la subsecuente apertura de los poros. Finalment es mostra que el sistema dissenyat és capaç d'alliberar un fàrmac citotòxic en cèl·lules de càncer de cervell després de detectar la presència de L-glutamat. / [CA] La present tesi doctoral titulada "Reconeixement de neurotransmissors basat en nanopartícules d'or i de sílice mesoporosa per a aplicacions de detecció i alliberació controlada" és una tesi realitzada per compendi d'articles la qual se centra en el disseny, preparació, caracterització i avaluació de diferents nanodispositius per a la detecció colorimètrica de neurotransmissors i sistemes d'alliberació controlada que responen a neurotransmissors basats en nanopartícules d'or i nanopartícules de sílice mesoporosa equipades amb lligands orgànics, efectors enzimàtics, portes moleculars i espècies cromofluorogénicos o medicaments. En el primer capítol s'introdueix una visió general del que són els neurotransmissors, les seves principals característiques i l'important paper que aquests tenen en el funcionament del nostre organisme. A més es presenta una descripció general de les propietats i potencials aplicacions de les nanopartícules d'or funcionalitzades amb lligands orgànics com a sistemes de detecció, i de les nanopartícules mesoporoses de sílice funcionalitzades amb portes moleculars com a sistemes d'alliberament controlat. A continuació, en el segon capítol es presenten els objectius generals que són abordats en els següents capítols experimentals. En el tercer capítol, es presenten tres sistemes de detecció colorimètrica de neurotransmissors basats en l'agregació de nanopartícules d'or doblement funcionalitzades amb lligands orgànics. El primer sistema és un sensor capaç de detectar de forma selectiva el neurotransmissor serotonina, utilitzant nanopartícules d'or funcionalitzades amb ditiobis (propionat de succinimidilo) i N acetil-L-cisteïna. El segon sistema consisteix en un sensor per a la detecció selectiva de neurotransmissor norepinefrina dissenyat a partir de nanopartícules d'or funcionalitzades amb 4- (liponiloxi) benzaldehid i Àcid 4-mercatofenilborònic. El tercer sistema està compost per nanopartícules d'or funcionalitzades amb 4- (liponiloxi) benzaldehid i N acetil-L-cisteïna, per a la detecció de normatanefrina un important biomarcador del tumor feocromocitoma. Tots aquests sistemes s'avaluen en mitjans competitius com sèrum sanguini u orina. En el quart capítol es mostren dos sistemes d'alliberament controlats enzimàticament basats en l'obertura de portes moleculars. El primer sistema d'alliberament controlat respon a la presència del neurotransmissor acetilcolina. En concret, s'utilitzen nanopartícules de sílice mesoporosa funcionalitzades en la seva superfície amb grups d'àcid fenilborònic i tapades amb l'enzim acetilcolina esterasa mitjançant la formació d'èsters cíclics d'àcid fenilborònic entre les cadenes d'oligosacàrids de l'enzim i els grups fenilborónicos de la superfície de les nanopartícules. En aquest cas, la reacció enzimàtica produeix àcid acètic que dóna lloc a la hidròlisi dels èsters borònics, destapant els porus i alliberant la càrrega continguda a l'interior. A més, s'avalua la capacitat del dispositiu dissenyat per alliberar el citotòxic doxorubicina en cèl·lules canceroses en presència d'acetiltiocolina. El segon sistema consisteix en un nanodispositiu per alliberació controlada en resposta al neurotransmissor L-glutamat, per al que s'utilitzen nanopartícules tipus Janus d'or-sílice mesoporosa funcionalitzades amb l'enzim L-glutamat oxidasa en la part de l'or i amb una porta molecular autoimmolant d'arilboronat a la superfície de la sílice. La alliberació controlada es basa en el reconeixement de L-glutamat per l'enzim L-glutamat oxidasa i la posterior formació de peròxid d'hidrogen, que és l'espècie que indueix l'escissió de la porta autoimmolant i la subseqüent obertura dels porus. Finalment es mostra que el sistema dissenyat és capaç d'alliberar un fàrmac citotòxic en cèl·lules de càncer de cervell després de detectar la presència de L-glutamat. / [EN] This doctoral thesis entitled "Neurotransmitters recognition based on gold and mesoporous silica nanoparticles for sensing and controlled release applications" it is a thesis carried out by compendium of articles, which is focused on the design, preparation, characterization and evaluation of nanodevices for the colorimetric sensing of neurotransmitters and controlled delivery systems responsive to neurotransmitters, based on gold nanoparticles and mesoporous silica nanoparticles equipped with organic ligands, enzymatic effectors, molecular gates and chromo-fluorogenic species or drugs. The first chapter introduces an overview about what neurotransmitters are, their main characteristics and the important role they play in the functioning of our body. In addition, a general description of the properties and potential applications of gold nanoparticles functionalized with organic ligands as detection systems and mesoporous silica nanoparticles functionalized with molecular gates as controlled delivery systems is presented. In the second chapter, the general objectives that are addressed in the following experimental chapters are presented. In the third chapter, three colorimetric detection systems of neurotransmitters based on the aggregation of gold nanoparticles doubly functionalized with organic ligands are presented. The first system is a sensor capable of selectively detecting the neurotransmitter serotonin, using gold nanoparticles functionalized with dithio-bis(succinimidyl propionate) and N acetyl-L-cysteine. The second system consists of a sensor for the selective detection of the neurotransmitter norepinephrine designed from gold nanoparticles functionalized with 4- (liponyloxy)benzaldehyde and 4-mercaptophenylboronic acid. The third system is composed of gold nanoparticles functionalized with 4-(liponyloxy)benzaldehyde and N-Acetyl-L-Cysteine, for the detection of normetanephrine, an important biomarker of the pheochromocytoma tumor. All these systems are evaluated in competitive media such as blood serum or urine. In the fourth chapter, two enzymatic controlled delivery systems based on the opening of molecular gates are developed. The first controlled delivery system responds to the presence of the neurotransmitter acetylcholine. Specifically, it consists of mesoporous silica nanoparticles functionalized on their surface with phenylboronic acid groups and capped with the enzyme acetylcholinesterase, via the formation of cyclic phenylboronic acid esters between the oligosaccharide chains of the enzyme and the phenylboronic groups on the nanoparticles surface. In this case, the enzymatic reaction produces acetic acid that induces the hydrolysis of the boronic esters, uncapping the pores and releasing the entrapped payload. In addition, the ability of the nanodevice to release the cytotoxic doxorubicin in cancer cells in the presence of acetylthiocholine is evaluated. The second delivery system consists of a nanodevice responsive to the neurotransmitter L-glutamate. It is based on Janus gold-silica mesoporous nanoparticles functionalized with the enzyme L-glutamate oxidase in the gold part and with a self-immolative arylboronate molecular gate on the surface of the silica. Controlled delivery is based on the recognition of L-glutamate by the enzyme L-glutamate oxidase and the subsequent formation of hydrogen peroxide, which results in the cleavage of the self-immolative gate and the uncapping of the pores. Finally, it is shown that the designed system is capable of releasing a cytotoxic drug in brain cancer cells after detecting the presence of L-glutamate. / The authors acknowledge financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R, MAT2015-64139-C4-4-R (MINECO/FEDER) and Project AGL2015-70235-C2-2-R) and the Generalitat Valenciana (Projects PROMETEOII/2014/047 and PROMETEO/2018/024). T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisolía fellowship. A. García-Fernández is grateful to the Spanish Government for her FPU fellowship. A. Llopis-Lorente thanks “La Caixa” Foundation for his PhD grant. SCSIE (Universitat de València) is gratefully acknowledged for all the equipment employed. / Godoy Reyes, TM. (2020). Neurotransmitters recognition based on gold nanoparticles and mesoporous silica nanoparticles for sensing and controlled release applications [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/158420

[ES] La presente tesis doctoral se desarrolla en el ámbito de la catálisis, la cual está enmarcada dentro del concepto de Química Sostenible. En concreto, la investigación se ha centrado en el desarrollo y aplicación de nuevos catalizadores basados en nanopartículas metálicas coloidales y soportadas para llevar a cabo reacciones de interés. Todas las MNPs sintetizadas en esta tesis doctoral se llevaron a cabo a partir de la aproximación organometálica, donde generalmente se descompone un precursor organometálico bajo condiciones suaves de reacción y en presencia de un agente estabilizador (molécula orgánica o soporte). En el Capítulo 4 de la tesis, se ha descrito el primer ejemplo de estabilización de Ru NPs con una nueva familia de ligandos policíclicos aromáticos no planos, denominados nanografenos (hept-HBC). Específicamente, se han utilizado dos tipos distintos de nanografeno distorsionado: i) uno funcionalizado con un grupo carbonilo, y ii) otro funcionalizado con una grupo metileno en la misma posición (Ru@1 y Ru@2, respectivamente). Gracias a la similitud con los sistemas basados en MNPs soportadas en grafeno o derivados, este material puede utilizarse como referencia para estudiar los modos de coordinación y las dinámicas de estos con la superficie de la nanopartícula. A partir de un estudio combinado teórico/experimental se ha demostrado que la curvatura de los nanografenos hept-HBC es crucial para la estabilización de las Ru NPs. Por último, se ha evaluado la actividad catalítica de estas Ru NPs en la hidrogenación de multitud de sustratos aromáticos, observándose diferencias significativas en función del ligando estabilizador utilizado. En el Capítulo 5 se ha investigado la formación de MNPs a través de la aproximación organometálica utilizando el óxido de grafeno reducido dopado con átomos de nitrógeno (NH2-rGO) como soporte. En la primera parte del capítulo, sintetizamos Ru NPs soportadas sobre NH2-rGO (Ru@NH2-rGO) y rGO (Ru@rGO), con la intención de investigar el rol de los átomos de N en la estabilización de las MNPs, así como en su actividad catalítica. Para ello, se estudió la hidrogenación del ácido palmítico a 1-hexadecanol, siendo el Ru@NH2-rGO el catalizador heterogéneo monometálico de Ru más activo y selectivo reportado hasta la fecha (99% conversión y 93 % selectivo). En la segunda parte del capítulo, generamos PtRu NPs con distintas composiciones atómicas (5:1, 1:1 y 1:5) sobre NH2-rGO, siguiendo la aproximación organometálica. La misma velocidad de descomposición de los precursores Pt(NBE)3 y Ru(COD)(COT) nos permitió generar las NPs de tipo aleación. Estos sistemas bimetálicos (PtxRuy@NH2-rGO) se estudiaron en la hidrogenación de multitud de compuestos con grupos polares (C=O), observándose diferencias significativas en función del soporte utilizado y la composición atómica de las MNPs. Por último, en el Capítulo 6 se investigó el uso de nanopartículas magnéticas (MagNPs) para emitir calor por pérdidas de histéresis en presencia de un campo magnético oscilante de alta frecuencia. En primer lugar, se generaron nuevos agentes calefactores basados en MagNPs bimetálicas de tipo "core-shell" de CoNi encapsuladas en carbono (Co@Ni@C), con el objetivo de hidrogenar selectivamente el CO2 a CO (RWGS) obteniéndose excelentes resultados catalíticos. Por último, también presentamos la síntesis de una nueva MagNP de tipo "core-shell" (FeCo@Ni) para su aplicación en catálisis inducida magnéticamente en disolución, siendo capaz de modular su selectividad al producto de la hidrogenación o de la hidrodesoxigenación del HMF en función del campo magnético aplicado. Además, después de su encapsulación en carbono (FeCo@Ni@C) han demostrado ser activas, selectivas y estables en la reducción de multitud de sustratos oxigenados derivados de la biomasa en medio acuoso, siendo el primer ejemplo reportado hasta la fecha de catálisis magnética realizada en agua. / [CAT] La present Tesi Doctoral es desenvolupa en l'àmbit de la catàlisi, la qual està emmarcada dins del concepte de Química Sostenible. Concretament, la investigació s'ha centrat en el desenvolupament i aplicació de nous catalitzadors basats en nanopartícules metàl·liques col·loïdals i suportades per dur a terme reaccions d'interès. Totes les MNPs sintetitzades en aquesta tesi doctoral es van dur a terme a partir de l'aproximació organometàl·lica, on generalment es descompon un precursor organometàl·lic sota condicions suaus de reacció i en presència d'un agent estabilitzador (molècula orgànica o suport). En el Capítol 4 de la Tesi, s'ha descrit el primer exemple d'estabilització de Ru NPs amb una nova família de lligands policíclics aromàtics no plans, denominats nanografens (hept-HBC). Específicament, s'han utilitzat dos tipus diferents de nanografen distorsionat: i) un funcionalitzat amb un grup carbonil, i un altre ii) funcionalitzat amb un grup metilè en la mateixa posició (Ru@1 i Ru@2, respectivament). Gràcies a la similitud amb els sistemes basats en MNPs suportades en grafè o derivats, aquest material pot utilitzar-se com a referència per a estudiar els modes de coordinació i dinàmiques d'aquests amb la superfície de la nanopartícula. A partir d'un estudi combinat teòric/experimental s'ha demostrat que la curvatura dels nanografens hept-HBC és crucial per a l'estabilització de les Ru NPs. Finalment, s'ha avaluat l'activitat catalítica d'aquestes Ru NPs en la hidrogenació de multitud de substrats aromàtics, observant diferències significatives en funció del lligand estabilitzador utilitzat. En el Capítol 5 s'ha investigat la formació de MNPs a través de l'aproximació organometàl·lica utilitzant l'òxid de grafè reduït dopat amb àtoms de nitrogen (NH2-rGO) com a suport. En la primera part del capítol, vam sintetitzar Ru NPs suportades sobre NH2-rGO (Ru@NH2-rGO) i rGO (Ru@rGO), amb l'intenció d'investigar el paper dels àtoms de N en l'estabilització de les MNPs, així com en la seua activitat catalítica. Per a això, es va estudiar la hidrogenació de l'àcid palmític a 1-hexadecanol, sent el Ru@NH2-rGO el catalitzador heterogeni monometàl·lic de Ru més actiu i selectiu reportat fins a la data (99% conversió i 93 % selectiu). En la segona part del capítol, es van generar PtRu NPs amb diferents composicions atòmiques (5:1, 1:1 i 1:5) sobre NH2-rGO, seguint l'aproximació organometàl·lica. La mateixa velocitat de descomposició dels precursores Pt(NBE)3 i Ru(COD)(COT) ens va permetre generar les NPs de tipus aliatge. Aquests sistemes bimetàl·lics (PtxRuy@NH2-rGO) es van estudiar en la hidrogenació de multitud de compostos amb grups polars (C=O), observant-se diferències significatives en funció del suport utilitzat i la composició atòmica de les MNPs. Finalment, en el Capítol 6 es va investigar l'ús de nanopartícules magnètiques (MagNPs) per emetre calor per pèrdues d'histèresi en presència d'un camp magnètic oscil·lant d'alta freqüència. En primer lloc, es van generar nous agents calefactores basats en generar MagNPs bimetàl·liques de tipus "core-shell" de CoNi encapsulades en carbó (Co@Ni@C), amb l'objectiu d'hidrogenar selectivament el CO2 a CO (RWGS) obtenint excel·lents resultats catalítics. Finalment, també presentem la síntesi d'una nova MagNP de tipus "core-shell" (FeCo@Ni) per a la seva aplicació en catàlisi induïda magnèticament en solució, demostrant ser capaç de modular la seva selectivitat al producte de l'hidrogenació o de l'hidrodesoxigenació del HMF en funció del camp magnètic aplicat. A més, després de la seva encapsulació en carbó (FeCo@Ni@C) han demostrat ser actives, selectives i estables en la reducció de multitud de substrats oxigenats derivats de la biomassa en medi aquós, sent el primer exemple reportat fins a la data de catàlisi magnètica realitzada en aigua. / [EN] This Doctoral Thesis is developed in the field of catalysis, which is framed within the concept of Sustainable Chemistry. Specifically, the research has focused on the development and application of new catalysts based on colloidal and supported metallic nanoparticles to carry out relevant catalytic reactions. All the MNPs synthesized in this doctoral thesis were carried out from the organometallic approach, where an organometallic precursor is generally decomposed under mild conditions, room temperature and 3 bar H2, in the presence of a stabilizing agent (organic molecule, polymer, or support). The catalytic properties of MNPs are greatly influenced by the stabilizing agents used, which are capable of modifying their electronic and steric properties. Therefore, the search for new ligands capable of modulating these properties is of great scientific interest. In Chapter 4 of the Thesis, we describe the first example of Ru NPs stabilized with a new family of non-planar polycyclic aromatic ligands, called nanographenes (hept-HBC). Specifically, two different types of distorted nanographene have been used: i) one functionalized with a carbonyl group, and another ii) functionalized with a methylene group in the same position (Ru@1 and Ru@2, respectively). Thanks to the resemblance with systems based on supported-MNPs on graphene or derivatives, this material can be used as a reference to study the coordination modes and dynamics of these with the surface of the nanoparticle. A combined theoretical/experimental study revealed that the curvature of hept-HBC nanographenes is crucial for the stabilization of Ru NPs. Finally, the catalytic activity of these Ru NPs has been evaluated in the hydrogenation of multitude of arenes, observing significant differences depending on the stabilizing ligand used. In Chapter 5, the formation of MNPs through the organometallic approach was investigated using reduced graphene oxide N-doped (NH2-rGO) as support. In the first part of the chapter, Ru NPs supported on NH2-rGO (Ru@NH2-rGO) and rGO (Ru@rGO) were synthesized, with the aim of investigating the role of N atoms in the stabilization of the MNPs, as well as their catalytic activity. For this purpose, the hydrogenation of palmitic acid to 1-hexadecanol was studied, and Ru@NH2-rGO was found to be the most active and selective monometallic Ru-based heterogeneous catalyst reported to date (99% conversion and 93% selectivity). In the second part of the chapter, PtRu NPs with different atomic compositions (5:1, 1:1, and 1:5) were generated on NH2-rGO using the organometallic approach. The same decomposition rate of Pt(NBE)3 and Ru(COD)(COT) precursors allowed us to generate alloy-type NPs. These bimetallic systems (PtxRuy@NH2-rGO) were studied in the hydrogenation of a variety of compounds with polar groups (C=O), and significant differences were observed depending on the support used and the atomic composition of the MNPs. Finally, in Chapter 6 the use of magnetic nanoparticles (MagNPs) for heat generation through hysteresis losses in the presence of a high-frequency oscillating magnetic field was investigated. Firstly, new heat-generating agents based on bimetallic core-shell type CoNi MagNPs encapsulated in carbon (Co@Ni@C) were synthesized with the aim of selectively hydrogenate CO2 to CO (RWGS), obtaining excellent catalytic results. Finally, a new core-shell type MagNP (FeCo@Ni@C), the MagNPs proved to be active, selective, and stable in the reduction of several oxygenated substrates derived from biomass in aqueous media, being the first reported example of magnetic catalysis performed in water to date. In Chapter 6, the crucial role of MagNP encapsulation was demonstrated, where carbon not only limits the total oxidation of MagNPs but also prevents their sintering at high temperatures (~ 700 °C) in gas phase and avoids their aggregation in liquid phase. / Cerezo Navarrete, C. (2023). Aplicación catalítica de nuevos nanosistemas obtenidos a partir de la aproximación organometálica [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/196366

A fully oxidized state of graphene behaves as a pure insulating while a pristine graphene behaves as a pure conducting. The in-between oxide state in graphene which is the controlled state of oxide behaves as a semiconducting. This is the key condition for tuning optical band gap for the better light emitting property. The controlling method of oxide in graphene structure is known as reduction which is the mixed state of sp2 and sp3 hybrid state in graphene structure. sp2 hybridized domains correspond to pure carbon-carbon bond i.e. pristine graphene while sp3 hybridized domains correspond to the oxide bond with carbon i.e. defect in graphene structure. This is the uniqueness of the graphene-base material. Graphene is a gapless material i.e. having no bandgap energy and this property prevents it from switching device applications and also from the optoelectronic devices applications. The main challenge for this material is to tune as a semiconducting which can open the optical characteristics and emit light of desired color. There may be several possibilities for the modification of graphene-base material that can tune a band gap. One way is to find semiconducting property by doping the defects into pristine graphene structure. Other way is oxides functional groups in graphene structure behaves as defects. The physical properties of graphene depend on the amount of oxides present in graphene structure. So if there are more oxides in graphene structure then this material behaves as a insulating. By any means if it can be reduced then oxides amount to achieve specific proportion of sp2 and sp3 that can emit light of desired color. Further, after achieving light emission from graphene base material, there is more possibility for the study of non-linear optical property. In this work, plasmonic effect in graphene oxide has been focused. Mainly there are two kinds of plasmon effects have been studied, one is long range (surface) and short range (localized) plasmon. For long range plasmon gold thin film was deposited on partially reduced graphene oxide and for short range plasmon silver nanoparticles have used. Results show that there are 10-fold enhancement in light emission from partial graphene oxide coated with gold thin film while 4-fold enhancement from reduced graphene oxide solution with silver nanoparticles. Chemical method and photocatalytic method have been employed for the reduction of graphene oxide for the study of surface plasmon and localized plasmon. For the characterization UV-Vis spectrometer for absorption, spectrofluorophotometer for fluorescent emission, Raman spectrometer for material characterization, photoluminescence and time resolved photoluminescence have been utilized. Silver and gold nanoparticles are spherical of average size of 80 nm and 40 nm have been used as plasmons.

Doctor of Philosophy / Department of Chemistry / Kenneth J. Klabunde / In recent years both metal and semiconductor nanoparticles have gained the attention of many research groups because of their unique properties. Synthesizing metal and semiconductor nanoparticles with narrow size distribution, uniform shape, and good crystalline nature represents a significant challenge. Our research group has taken the synthesis procedure a step forward when we discovered that “when a polydispersed colloidal solution upon heating at or near the boiling point of the solvent in presence of excess surface active ligands, the particles evolve into a thermodynamic equilibrium size regime and this phenomenon was named “Digestive Ripening”. The ability to tune the nanoparticles size with a narrow size distribution after post - preparation in a reproducible fashion is remarkable. The current dissertation research encompasses the field of metal and semiconductor nanoparticles and the major part of the work is devoted to understand the digestive ripening of gold-dodecanethiol system, and the effect of the nature of the ligand and solvent temperature on a low melting point indium metal – digestive ripening. A noteworthy achievement of the current work is the ability to extent the digestive ripening to the semiconductor materials cadmium selenide and cadmium telluride by employing different ligands and by the use of different solvents. A diverse set of instrumental techniques is used for the characterization of both metal and semiconductor nanoparticles.

A firm knowledge about the interaction between the metal surface and adsorbed molecules is imperative for formulating procedures to synthesize nanoparticles (NPs) with predetermined shape and size. The ligand‐metal interaction during NP formation can be mimicked on an electrode surface by electrosorbing ligand molecules on a charged metal surface. Electrochemical methods can provide an ideal platform to study the adsorption behaviour of molecules at the solid‐liquid interface. In addition to classical electrochemical techniques, the combination of spectroscopy with electrochemical methods amplifies mechanistic insights about the surface adsorption processes. The adsorption behaviour of pyridine and one of its derivatives, 4‐dimethylamino pyridine (DMAP) have been well studied due to their potential application in nanoparticle synthesis. However, prior to this work, there has been very limited and conflicting literature available about the adsorption of of pyridine derivatives analogous to DMAP. Among the pyridine derivatives that were studied, some reports indicate that, other than DMAP, only 4‐methoxy pyridine (MOP) can stabilize gold nanoparticles. However, very little is known about the possible differences in the adsorption energy and general behaviour of MOP compared to DMAP. Resolving this knowledge gap is imperative to resolving the conflicting information about pyridine‐based stabilizers for metal nanoparticle applications. The adsorption behaviour of MOP on different crystallographic Au surfaces as a function of pH and surface potential has been investigated in this project. These studied were carried out using classical electrochemical methods including chronocoulometry and differential capacity, as well as modern spectroscopic techniques like Surface Enhanced Infrared Absorption Spectroscopy (SEIRAS). The thermodynamic parameters obtained from electrochemical data shows that adsorption features of MOP is similar to that of DMAP. However, there is a significant difference in the adsorption strength of MOP and DMAP at positive potentials. The SEIRAS data provides much more detailed information about the potential depended orientation of MOP on polycrystalline Au. Cumulative analysis of electrochemical and spectroscopic data provides strong evidence that MOP can stabilize Au(111) facets over wide pH ranges. Moreover, this work provides convincing evidence that the basic nature of substituted pyridine alters the metal to ligand adsorption strength.

Today, it is possible to restore hearing in congenitally deaf children and severely hearing-impaired adults through cochlear implants (CIs). A CI consists of an external sound processor that provides acoustically induced signals to an internal receiver. The receiver feeds information to an electrode array inserted into the fluid-filled cochlea, where it provides direct electrical stimulation to the auditory nerve. Despite its great success, there is still room for improvement, so as to provide the patient with better frequency resolution, pitch information for music and speech perception and overall improved quality of sound.  A better stimulation mode for the auditory nerves by increasing the number of stimulation points is believed to be a part of the solution. Current technology depends on strong electrical pulses to overcome the anatomical gap between neurons and the CI. The spreading of currents limits the number of stimulation points due to signal overlap and crosstalk. Closing the anatomical gap between spiral ganglion neurons and the CI could lower the stimulation thresholds, reduce current spread, and generate a more discrete stimulation of individual neurons. This strategy may depend on the regenerative capacity of auditory neurons, and the ability to attract and guide them to the electrode and bridge the gap. Here, we investigated the potential of cultured human and murine neurons from primary inner ear tissue and human neural progenitor cells to traverse this gap through an extracellular matrix gel. Furthermore, nanoparticles were used as reservoirs for neural attractants and applied to CI electrode surfaces. The nanoparticles retained growth factors, and inner ear neurons showed affinity for the reservoirs in vitro. The potential to obtain a more ordered neural growth on a patterned, electrically conducting nanocrystalline diamond surface was also examined. Successful growth of auditory neurons that attached and grew on the patterned substrate was observed. By combining the patterned diamond surfaces with nanoparticle-based reservoirs and nerve-stimulating gels, a novel, high resolution CI may be created. This strategy could potentially enable the use of hundreds of stimulation points compared to the 12 – 22 used today. This could greatly improve the hearing sensation for many CI recipients.

Submitted in complete fulfillment for the Degree of Master of Technology: Biotechnology, Durban University of Technology, 2013. / The biosynthesis of NPs has many advantages over the tedious, expensive and toxic physical and chemical methods of synthesis. Plants are stocked with valuable metabolites that are capable of reducing metal salts to form NPs. In this study, aqueous leaf extracts of A. dubius, G. perpensa, C. roseus and C. triloba were reacted with AgNO3 and HAuCl4 to determine the plants reducing abilities and hence synthesis of Ag and Au NPs capabilities. The synthesis reactions were carried out at different temperatures and extract concentrations for optimization. The goal was to form NPs within the specific wavelength range. Polar solvents: methanol and ethyl acetate extractions were carried out at the optimized conditions to evaluate the best solvent for the extraction of phytochemicals from the plants. The plant leaf extracts that were successful (A. dubius, G. perpensa and C. triloba) in synthesizing NPs were then micropropagated to form callus cultures. The reducing abilities of these callus cultures extracts were determined by varying temperature and concentration parameters. Characterization of the NPs formed by the different extracts was performed using UV-vis, TEM and FTIR. UV-vis spectrophotometry was used as a confirmatory as well as characterizing tool. TEM analysis was able to provide a description on the size and shape of the NPs whereas FTIR provided information on the biomolecules responsible for synthesis and capping of NPs. The stability of the NPs was determined by UV-vis scans over a period of 30 days which allowed observation of the alteration in peak shape and absorbance and hence condition of particles. Phytochemical tests were performed on the leaf extracts of the four plants to elucidate possible phytochemicals responsible for the reduction of metal salts. Antibacterial activity of the NPs was evaluated by using the disk diffusion assay and MICs were determined by the broth dilution method against pathogenic bacteria. A. dubius, G. perpensa and C. triloba were capable of synthesizing Ag NPs and Au NPs which were indicated by yellowish orange and reddish purple colour changes respectively. G. perpensa was able to spontaneously form Ag and Au NPs without any addition of heat whereas A. dubius and C. triloba required heat to form Au NPs. As the temperature of the reactions increased, the absorbance and possibly the number of NPs produced, increased. When the concentration of the extract was doubled, the absorbance was seen to decrease. C. roseus did not produce any Ag or Au NPs with any of the leaf extracts. Only A. dubius and C. triloba callus extracts were investigated for NP synthesis and it was found that A. dubius callus extracts were unsuccessful in synthesizing NPs and C. triloba callus extracts were able to form unstable Ag and Au NPs. The spherical Ag NPs that were formed from aqueous extracts of A. dubius were slightly larger than the methanolic Ag NPs. The Ag NPs produced by G. perpensa were in the same size range for aqueous and methanolic extracts. C. triloba Ag NPs formed from the methanolic extract were closer in size to A. dubius aqueous Ag NPs but the C. triloba aqueous extract produced much larger Ag NPs than the other extracts. The Ag NPs produced from A. dubius aqueous and methanolic extracts as well as C. triloba methanolic extracts exhibited the longest stability of 30 days. Ag NPs from G. perpensa aqueous extracts had the least stability. G. perpensa did not form any hexagonal Au NPs and the spherical and triangular Au NPs were smaller unlike in A. dubius and C. triloba Au NPs. The Au NPs formed by the aqueous extracts of A. dubius and C. triloba were larger in comparison to their methanolic counterparts. The Au NPs produced from G. perpensa aqueous and methanolic extracts as well as A. dubius and C. triloba methanolic extracts exhibited the longest stability of 30 days. Au NPs were stable for longer in comparison to Ag NPs. FTIR provided evidence that Ag and Au NPs have a chemical bond with the amide group in amino acids. However the intensities of biomolecules for Au NPs are more pronounced compared to the Ag NPs. It was also found that the Ag NPs synthesized by methanolic leaf extracts have slightly higher intensities than Ag NPs synthesized from aqueous leaf extracts. Phytochemical screening showed the absence of tannins in the C. roseus leaf, A. dubius and C. triloba callus extracts and presence in the other three plants. C. triloba methanolic extract Ag NPs showed the highest activity against Gram-positive S. aureus. Aqueous and methanolic Ag NPs from G. perpensa and C. triloba as well as A. dubius methanolic Ag NPs had activity against all fourteen bacteria. A. dubius aqueous Ag NPs had no activity against Enterobacter spp. and a strain of Klebsiella pneumoniae. G. perpensa Ag NPs had better antibacterial activity and lower MICs against Gram-positive and Gram-negative pathogenic bacteria compared to A. dubius and C. triloba. There was no antibacterial activity seen with Au NPs. The size and shape of NPs are the keys to their biomedical properties. Green synthesis of NPs is a feasible way for the future. This study showed that NPs can be synthesized very easily and economically. A key finding of this study is that different plants produce varying sizes and aggregation of NPs. / National Research Foundation

Nanoparticles are thought to present a unique hazard to human health. Furthermore, the increasing use of nanomaterials in consumer products has not been accompanied by relevant risk assessments. It is conceivable that skin flexion may assist the translocation of nanoparticles across the stratum corneum. However, current in vitro methodology to study dermal absorption involves the exclusive use of immobile skin within diffusion cells. Therefore, a novel skin-flexing diffusion cell system (“CutaFlex™”) was developed to incorporate reproducible skin flexing (2 flexes min-1; 6 mm maximum amplitude). The initial aims of this Thesis were to characterise the CutaFlex™ system to eliminate the possibility of flexion-induced (experimental) skin damage, demonstrate equivalence with historical permeability data to model compounds and assess the effect of skin flexing on barrier disruption. Subsequent work aimed to investigate the hypothesis that nanoparticles require dermal flexion to penetrate intact skin. In supporting these aims, this Thesis also performed work to assess the correlation between direct measurements of skin barrier function (using tritiated water) and transepidermal water loss (TEWL), the effect of flexing on the performance of topical skin protectants (barrier creams) and to further validate in vitro diffusion cell measurements against in vivo data acquired under identical conditions. The results demonstrated that skin flexing did not alter skin barrier function and that the CutaFlex™ system was in general agreement with historical measurements of skin permeability. Furthermore, controlled chemical or physical damage to the stratum corneum was not exacerbated by skin flexing. Skin flexion did not facilitate the dermal absorption of a range of nanoparticles (quantum dots). However, differences in the partitioning of nanoparticles into the stratum corneum were observed (independent of the degree of flexing), with greater amounts of negatively charged nanoparticles found in the superficial layers of the stratum corneum in comparison with positive or neutral nanoparticles. Flexing had a modest effect on the performance of a skin barrier cream which was limited to low dose applications; an effect tentatively ascribed to flexion-induced movement of cream to previously untreated areas. A poor correlation was found between 3H2O water permeability and TEWL flux. Most importantly, there was excellent agreement between in vitro skin permeability studies and in vivo studies (which used a surrogate measure of skin permeability). To summarise, the data in this Thesis has led to the development and characterisation of a novel diffusion cell (CutaFlex™), capable of simultaneously flexing skin whilst performing dermal absorption measurements comparable with the OECD-compliant models.

Nanoparticles (NP) offer great merits over controlling thermal, chemical and physical properties when compared to their micro-sized counterparts. The effectiveness of the dispersion of the NP is the key aspect of the applications in nanotechnology. The project studies the characterization and modification of functional NPs aided by the means of large scale molecular thermal dynamic computerized dispersing simulations, in the level of Nanoclusters (NC). Carrying out NP functionality characterisation in fluids can be enhanced, and analysed through computational simulation based on their interactions with fluidic media; in terms of thermo-mechanical, dynamic, physical, chemical and rheological properties. From the engineering perspective, effective characterizations of the nanofluids have also been carried out based on the particles sizes and particle-fluids Brownian motion (BM) theory. The study covered firstly, investigation of the pure CuO NP diffusion in water and hydrocarbon fluids, secondly, examination of the modified CuO NP diffusion in water. In both cases the studies were put under experiments and simulations for data collection and comparison. For simulation the COMPASS forcefield, smoothed particle hydrodynamic potential (SPH) and discrete particle dynamics potential (DPD) were implemented through the system. Excellent prediction of BM, Van der Waals interaction, electrostatic interaction and a number of force-fields in the system were exploited. The experimental results trend demonstrated high coherence with the simulation results. At first the diffusion coefficient was found to be 1.7e-8m2/s in the study of CuO NC in water based fluidic system. Secondly highly concurrent simulation results (i.e. data for viscosity and thermal conductivity) have been computed to experimental coherence. The viscosity trend of MD simulation and experimental results show a high level of convergence for temperatures between 303-323K. The simulated thermal conductivity of the water-CuO nanofluid was between 0.6—0.75W•m−1•K−1, showing a slight increase following a rise in temperature from 303 to 323 K. Moreover, the alkane-CuO nanofluid experimental and simulated work was also carried out, for analysing the thermo-physical quantities. The alkane-CuO nanofluid viscosity was found 0.9—2.7mpas and thermal conductivity is between 0.1—0.4W•m−1•K−1. Finally, the successful modification of the NPs on experimental and simulation platform has been analysed using different characterization variables. Experimental modification data has been quantified by using Fourier Transformation Infrared (FTIR) peak response, from particular ranges of interest i.e. 1667-1609cm-1 and 1668-1557cm-1. These FTIR peaks deduced Carboxylate attachment on the surface of NPs. Later, MD simulation was approached to mimic experimental setup of modification chemistry and similar agglomerations were observed as during experimental conditions. However, this approach has not been presented before; therefore this study has a significant impact on describing the agglomeration of modified NPs on simulation and experimental basis. Henceforth, the methodology established for metal oxide nanoparticle dispersion simulation is a novelty of this work.

The extensive use of nanoparticles (NPs) has started receiving increased attention because of the knowledge gaps regarding their fate in the environment and the possible impact on the environment and human health. The production of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (TiO2-NPs) is increasing and it is expected that, due to their great number of applications, their concentration in waste streams will increase in the future. The presence of NPs in waste streams may affect the treatment process (e.g., composting) and, if they are not successfully removed from the waste streams, their presence in the treated waste (e.g., compost) may present an environmental risk. Composting of the biodegradable fractions of municipal solid waste (MSW) is a widely used waste management practice, mainly because it is a cost-effective treatment technology and the final product (i.e., compost) presents several benefits to the environment, particularly as a soil conditioner. The overall aim of this thesis is to assess the effect of Ag-TiO2NPs and AgNPs that may be present in the biodegradable fractions of municipal solid waste on composting and subsequent soil application of compost. For that purpose in-vessel composting of artificial municipal solid waste contaminated with commercial nanoparticles was investigated at laboratory scale, simulating a range of relevant concentration levels. Subsequently, the fate of NPs present in mature compost use as a top-layer soil conditioner was investigated using a column approach at laboratory scale. The toxicity effect of NPs present mature compost on plant growth was further investigated. The impact of NPs during composting was assessed by monitoring the temporal dynamics of organic matter (OM) using Excitation Emission Matrix (EEM) fluorescence spectroscopy. The fate of NPs following application of contaminated mature compost as a top-soil conditioner and potential release to groundwater was investigated using a column leaching experiment while the phytotoxicity of mature compost contaminated with NPs was assessed using a seed germination bioassay. Finally, to investigate further possible environmental impacts due to the application of mature compost contaminated with NPs to soils, a Life Cycle Assessment (LCA) was conducted. The impact of commercial Ag-TiO2 NPs and AgNPs on the in-vessel composting of biodegradable municipal solid waste was investigated over 21 days, using initial concentrations of 0, 5, 10, 20 and 50 mg Ag / kg of OM. Microbial activity was inhibited in the biodegradable waste reactors using 2% NaN3 to evaluate abiotic losses. Physicochemical parameters such as pH, ash content, weight loss, and the formation of humic substances (HS) were determined after 0, 4, 7, 14 and 21 days of composting and after a maturation phase. The results indicated that the presence of 2% NaN3 in biodegradable MSW inhibited effectively the microbial activity during the first week of composting. The microbial population was activated during the second week of composting but the decomposition rate was so low that did not result in the formation of humic substances (HS) following 21 days of composting when 2% NaN3 was used. Both treatments, using Ag-TiO2-NPs and AgNPs, did not show any inhibition of the decomposition process for all the tested concentrations and EEM peaks shifted towards the HS region during in-vessel composting. Higher inorganic carbon removal resulted from NP-contaminated compost with higher NP concentrations. This may indicate that the formation of humins was higher for non-contaminated compost and decreased as the NP concentration in waste increased. The shift of the peaks towards the HS region during composting for all the treatments suggested that NPs did not have an effect on humification and therefore on compost stability. The leaching properties of the NP-contaminated compost were investigated using a column leaching test. Five samples of leachate, of 50 mL each, were collected. The highest concentrations of HS were observed in the first two leaching samples. The leaching results suggested that only a low percentage of the total NPs (in weight) in compost, up to ca. 5% for Ag and up to ca. 15% for Ti, leached out from the columns, which was assumed the amount that potentially could leach to the environment. These results suggested that NPs will mainly accumulate in soils’ top layers following application of compost contaminated with NP. The phytotoxicity of NP-contaminated compost was assessed using a seed germination bioassay and the germination index was then calculated. The results indicated that the NP-contaminated compost did not present any toxic effects to cress germination. The possible environmental impacts due to the NP-contaminated compost application to soils were investigated by conducting a comparative LCA study. The LCA study indicated that the effects of NP-contaminated compost to human health and ecosystems endpoint categories increased due to the presence of NPs. The risks are associated with terrestrial ecotoxicity and human toxicity midpoint categories and are mainly attributed to the accumulation of Ag to soils.