Les récepteurs couplés aux protéines G constituent la plus grande famille de protéines membranaires et interviennent dans de nombreux processus physiologiques. La compréhension de l’interaction ligand-récepteur d’un point de vue mécanistique mais également thérapeutique est cruciale. Appartenant à la famille des récepteurs couplés aux protéines G, les récepteurs de la vasopressine et de l’ocytocine ont été choisis comme modèle d’étude. Ces hormones jouent un rôle important dans la modulation de l’attachement et de l’affect chez les mammifères. Afin d’accélérer la découverte de ligands ocytocinergiques et d’explorer les mécanismes fondamentaux de leurs interactions, nous avons conçu les premiers ligands fluorescents non peptidiques des récepteurs de la vasopressine V1a et de l’ocytocine. Ces ligands ont été utilisés pour développer des tests de liaisons par TR-FRET et démontrer la dimérisation des récepteurs de la vasopressine V1a et V2 sur cellules. Des études autour de petites plates-formes dérivées d’aza-dicétopipérazine ont permis d’accéder à un nouvel antagoniste non peptidique du récepteur de l’ocytocine. L’optimisation de dérivés benzodiazépines ocytocinergiques par des études de relations structure-activité a permis d’identifier les meilleurs agonistes non peptidiques du récepteur de l’ocytocine à ce jour. Une étude in vivo chez la souris et chez le singe est amorcée pour apporter dans un futur, une solution thérapeutique aux problèmes d’interaction sociale en général et d’autisme en particulier. / G protein coupled receptors are the largest membrane protein family and play an important role in a large number ofphysiological processes. The comprehension of the ligand-receptor interaction from a mechanistic point of view but alsofor therapeutic use is crucial. Belonging to the G protein coupled receptors, the oxytocin and vasopressin receptors havebeen used as a model system. These two hormones play an important role in the modulation of attachment and affectin mammals. To accelerate the discovery of new ligands for oxytocin and vasopressin receptors and to explore thefundamental role of their interactions, we designed the first non-peptide fluorescent ligands for oxytocin and vasopressin V1a receptors. These ligands have been used to develop new binding tests based on TR-FRET technology and to prove the V1a and V2 receptor dimerisation. In parallel, we developed a new non-peptide oxytocin antagonist around an aza-diketopiperazine platform. . Optimization of benzodiazepine derivatives enables us to identify the best non peptideoxytocin agonists to date. In vivo studies in mice and monkeys are initiated to bring in the future a therapeuticsolution to social interaction problems in general and autism in particular

La protéine farnésyltransférase (FTase) est une métalloenzyme à zinc catalysant le transfert d’une chaîne farnésyle provenant du pyrophosphate de farnésyle (FPP) sur le résidu cystéine de certaines protéines possédant un motif CaaX C-terminal où C est la cystéine farnésylée, a est un acide aminé aliphatique et X est Ser, Ala, Gln ou Met. Une fois additionné, le groupement farnésyle fait office de point d’ancrage rendant possible la fixation des protéines à la membrane cellulaire et de guide moléculaire facilitant la liaison de ces protéines prénylées à d’autres protéines. D’abord étudiée en oncologie, la FTase constitue aujourd’hui une cible potentielle pour la thérapie antiparasitaire qui manque cruellement de médicaments suite à l’apparition de phénomènes de résistance. La nécessité d’améliorer les thérapies existantes ouvre la voie de recherches innovantes pour trouver de nouvelles molécules bioactives.Lors de ces travaux de thèse, les deux stratégies de recherche pratiquées en chimie médicinale ont été utilisées.La première approche a consisté à synthétiser des analogues bisubstrats 1,2,3-triazoles pouvant se lier à la fois sur le site de liaison de la protéine et sur celui du FPP. Cette approche rationnelle a aussi permis d’ébaucher une synthèse monotope de triazoles 1,5-disubstitués à partir d’amines primaires. L’approche par criblage constitue la deuxième méthode de recherche de nouveaux inhibiteurs. Dans ce contexte, la chimiothèque de l’ICSN a été criblée et deux composés de type 3-arylthiophène ont révélé de bonnes activités et une structure originale dans l’inhibition de la FTase. Ainsi, des travaux de relations structure-activité ont été réalisés pour moduler les différentes positions du thiophène et la nature de l’hétérocycle central.Ce travail nous a permis d’élaborer une librairie de plus d’une centaine de composés. L’évaluation biologique de ces analogues sur FTases isolées humaine et de T. brucei et sur parasites T. brucei et P. falciparum a révélé des molécules particulièrement intéressantes et prometteuses. / Protein farnesyltransferase (FTase) is a zinc metalloenzyme which catalyzes the transfer of a farnesyl chain from farnesyl pyrophosphate (FPP) to the cysteine residue of some proteins possessing a C-terminal CaaX moiety where C is the farnesylated cysteine, a is an aliphatic amino-acid and X is Ser, Ala, Gln or Met. Once attached, the farnesyl group serves as anchors for fixing proteins to cell membrane and as molecular handles for facilitating binding of these prenylated proteins to other proteins.First studied in oncology, FTase constitutes nowadays a potential target for antiparasitic therapies, where drugs are missing due to the appearance of resistance phenomena. The necessity to improve the existing therapies paves the way of innovating researches to find new bioactive molecules.During this Ph.D work, two strategies of research used in medicinal chemistry were performed.The first approach consisted in the synthesis of bisubstrate analogues with a 1,2,3-triazole core deviced to tie up both to the protein and the FPP binding sites. This rational approach also allowed to draft a one-pot synthesis of 1,5-disubstituted triazoles from primary amines.The screening approach was the second strategy to search for new inhibitors. For this purpose, ICSN chemical library was screened and two 3-arylthiophene compounds disclosed good activities and an original scaffold for FTase inhibition. Therefore, a structure-activity relationship study was carried out to modulate the different positions of the thiophene and the nature of the central heterocycle.This work allowed us to create a above-hundred-molecule library. The biological evaluation of these analogues on human and T. brucei isolated FTase and on T. brucei and P. falciparum parasites revealed particularly interesting and promising molecules.

Le 26RFa est un neuropeptide de la famille des RFamide initialement isolé à partir d’un extrait de cerveaux de grenouille par notre laboratoire grâce à des anticorps dirigés contre le motif Arg-Phe-NH2 du NPFF de boeuf. Simultanément, deux laboratoires pharmaceutiques ont identifié le GPR103, un récepteur couplé aux protéines G jusque là orphelin, comme étant le récepteur de ce neuropeptide. Depuis, le GPR103 a été renommé QRFPR pour Pyroglutamylated RFamide peptide receptor. L’ADNc du pro-26RFa a été cloné chez différentes espèces, de l’amphioxus Branchiostoma floridae jusqu’à l’homme, ce qui a permis d’identifier dans le précurseur plusieurs sites de clivage potentiels par les prohormone convertases susceptibles de générer, outre le 26RFa, une forme allongée en N-terminal, le 43RFa aussi dénommé QRFP, et un peptide situé à l’extrémité C-terminale des 26RFa et 43RFa, le 26RFa(20-26), dont la séquence (GGFSFRF-NH2) est hautement conservée des amphibiens aux mammifères. Des expériences menées in vivo ou ex vivo chez le rongeur ont montré que le 26RFa et/ou le QRFP augmentent de façon dose-dépendante la consommation de nourriture, stimulent la sécrétion de gonadotropines et d’aldostérone et modulent la libération d’insuline induite par le glucose. Par ailleurs, l’invalidation du gène codant le QRFPR chez la souris provoque une ostéoporose sévère. L’ensemble de ces données indique que le 26RFa pourrait exercer diverses activités biologiques chez les vertébrés telles que le contrôle de la prise alimentaire, de l’insulinémie, de la reproduction, de l’homéostasie hydrominérale et de l’ostéogenèse. Enfin, il avait été montré précédemment que le 26RFa(20-26) mime les effets orexigèniques, insulinostatiques et hypophysiotropes du peptide de référence. Dans le cadre de cette thèse, nous nous sommes fixés comme objectifs de répondre aux questions suivantes (1) quel est l’impact de la variation de la longueur de la chaîne et de l’alkylation de la fonction guanidinium de l’Arg25 du 26RFa(20-26) sur l’activation du QRFPR ? (2) quel est l’effet d’analogues remarquables du 26RFa humain sur la prise alimentaire et l’homéostasie glucidique chez la souris ? et (3) la boucle extracellulaire reliant les domaines transmembranaires 4 et 5 (ECL2) du QRFPR présente-t-elle réellement une hélice-α dans le récepteur in cellulo et est-elle capable d’interagir avec l’hélice-α du 26RFa ? / 26RFa is a neuropeptide of the RFamide family, originally isolated from a frog brain extract by using antibodies raised against the Arg-Phe-NH2 motif. Concomitantly, two pharmaceutical companies have shown that 26RFa is the endogenous ligand of the former orphan G protein-coupled receptor GPR103 now renamed QRFPR. Analysis of the human 26RFa precursor indicates that pre-pro26RFa may generate several additional peptides including an N-terminally extended form (43RFa) and a truncated peptide 26RFa(20-26) (GGFSFRF-NH2) which is strictly conserved in mammals. In rodents, 26RFa and 43RFa induce a dose dependent increase in food intake, stimulate secretion of gonadotropins and aldosterone, as well as modulating glucose-induced insulin release. Furthermore, QRFPR-knockout mice suffer from osteopenia and exhibit the characteristic kyphotic hump of osteoporotic patients. Altogether these data indicate that 26RFa may exert diverse biological activities in vertebrates such as food intake control, reproduction and osteogenesis. It is important to note that the Cterminal heptapeptide, 26RFa(20-26), mimics the orexigenic and gonadotropic effects of 26RFa. The purpose of the present study was (1) to determine the impact of Arg25-modified 26RFa(20-26) analogues on the activation of the QRFPR (2) to evaluate the effect of remarkable analogues of hQRFPR, in vivo in a food intake and glucose homeostasis paradigm (3) to evaluate if the second extracellular loop (ECL2) of the QRFPR really presents a short α-helix and is able to interact with 26RFa α-helix?

Indiana University-Purdue University Indianapolis (IUPUI) / Recent work has shown that specific ALDH isoenzymes can contribute to the underlying pathology of different diseases. Many ALDH isozymes are important in oxidizing reactive aldehydes resulting from lipid peroxidation, and, thus, help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes are found in many human cancers and are often associated with poor prognosis. Therefore, the development of inhibitors of the different ALDH enzymes is of interest as means to treat some of these disease states. Here I describe the results of assays designed to characterize the site of interaction and the mode of inhibition for the unique compounds that function as inhibitors of aldehyde dehydrogenase 2 and determine their respective IC50 values with intent to develop structure-activity relationships for future development.

Indiana University-Purdue University Indianapolis (IUPUI) / Intrinsically disordered proteins (IDPs) are flexible proteins without defined 3D structures. Studies show that IDPs are abundant in nature and actively involved in numerous biological processes. Two crucial subjects in the study of IDPs lie in analyzing IDPs’ functions and identifying them. We thus carried out three projects to better understand IDPs. In the 1st project, we propose a method that separates IDPs into different function groups. We used the approach of CH-CDF plot, which is based the combined use of two predictors and subclassifies proteins into 4 groups: structured, mixed, disordered, and rare. Studies show different structural biases for each group. The mixed class has more order-promoting residues and more ordered regions than the disordered class. In addition, the disordered class is highly active in mitosis-related processes among others. Meanwhile, the mixed class is highly associated with signaling pathways, where having both ordered and disordered regions could possibly be important. The 2nd project is about identifying if an unknown protein is entirely disordered. One of the earliest predictors for this purpose, the charge-hydropathy plot (C-H plot), exploited the charge and hydropathy features of the protein. Not only is this algorithm simple yet powerful, its input parameters, charge and hydropathy, are informative and readily interpretable. We found that using different hydropathy scales significantly affects the prediction accuracy. Therefore, we sought to identify a new hydropathy scale that optimizes the prediction. This new scale achieves an accuracy of 91%, a significant improvement over the original 79%. In our 3rd project, we developed a per-residue C-H IDP predictor, in which three hydropathy scales are optimized individually. This is to account for the amino acid composition differences in three regions of a protein sequence (N, C terminus and internal). We then combined them into a single per-residue predictor that achieves an accuracy of 74% for per-residue predictions for proteins containing long IDP regions.

Indiana University-Purdue University Indianapolis (IUPUI) / Murine double minute (Mdm2) is a highly modified and multi-faceted protein that is overexpressed in numerous human malignancies. It engages in many cellular activities and is essential for development since deletion of mdm2 is lethal in early stages of embryonic development. The most studied function of Mdm2 is as a negative regulator of the tumor suppressor protein p53. Mdm2 achieves this regulation by binding to p53 and inhibiting p53 transcriptional activity. Mdm2 also functions as an E3 ubiquitin ligase that signals p53 for destruction by the proteasome. Interestingly recent evidence has shown that Mdm2 can also function as an E3 neddylating enzyme that can conjugate the ubiquitin-like molecule, nedd8, to p53. This modification results in inhibition of p53 activity, while maintaining p53 protein levels. While the signaling events that regulate Mdm2 E3 ubiquitin ligase activity have been extensively studied, what activates the neddylating activity of Mdm2 has remained elusive. My investigations have centered on understanding whether tyrosine kinase signaling could activate the neddylating activity of Mdm2. I have shown that c-Src, a non-receptor protein tyrosine kinase that is involved in a variety of cellular processes, phosphorylates Mdm2 on tyrosines 281 and 302. This phosphorylation event increases the half-life and neddylating activity of Mdm2 resulting in a neddylation dependent reduction of p53 transcriptional activity. Mdm2 also has many p53-independent cellular functions that are beginning to be linked to its role as an oncogene. There is an emerging role for Mdm2 in tumor metastasis. Metastasis is a process involving tumor cells migrating from a primary site to a distal site and is a major cause of morbidity and mortality in cancer patients. To date, the involvement of Mdm2 in breast cancer metastasis has only been correlative, with no in vivo model to definitively define a role for Mdm2. Here I have shown in vivo that Mdm2 enhances breast to lung metastasis through the up regulation of multiple angiogenic factors, including HIF-1 alpha and VEGF. Taken together my data provide novel insights into important p53-dependent and independent functions of Mdm2 that represent potential new avenues for therapeutic intervention.

<p>G-protein coupled receptors (GPCRs) are membrane proteins that constitute ~30% of the FDA-approved drug targets. Opioid receptors are a subtype of GPCRs with four different receptor types: delta, kappa, mu, and nociception opioid receptors. Opioids such as morphine have been used for thousands of years and are deemed the most effective method for treating pain. However, opioids can have detrimental effects if used illicitly or over an extended period of time. Intriguingly, most of the clinically used opioids act on the mu opioid receptor (µOR). Hence, efforts in recent decades have focused on other opioid receptors to treat pain and other disorders. The delta opioid receptor (δOR) is one of four opioid receptors expressed in the central and peripheral nervous system. The δOR has attracted much attention as a potential target for a multitude of diseases and disorders including substance and alcohol use disorders, ischemia, migraine, and neurodegenerative diseases. However, to date, no δOR agonists, or drugs that act directly at the δOR, have been successful as clinical candidates. Nonetheless, the therapeutic potential of the δOR necessitates the targeting its pharmacologically. In this dissertation, I highlight peptide-based modulation as well as the identification of novel agonists at the δOR. I report research findings in the context of biased agonism at δOR, which is a hypothesized cellular signaling mechanism with potential therapeutic benefits. The focus on this work is the molecular determinants of biased agonism, which were investigated using a combination of cellular and computational approaches.  </p>

<p dir="ltr">Chemical science can be imagined as a universe of information in which individual galaxies, solar systems, stars, and planets are compounds, reactions, biomolecules, etc. which need to be discovered, researched, and documented. The problem with this is that the universe of chemical science is potentially vaster than the one in which we live, and we are exploring it in a relatively inefficient manner. There is a scene in one of my favorite television shows, Futurama, which paints a picture of traditional chemical exploration. Taking place in the 30^th century, the main character Fry loses his robot friend Bender in outer space and resorts to using a giant telescope in the Himalayan mountains to randomly search through points in space to try to find him. After days of searching nonstop, he gives up noting that it is an impossible task because space is so vast in size, and he is searching so inefficiently. While human exploration of chemistry may not be as inefficient, there are a lot of steps which are driven by trial and error and educated guesswork which ultimately introduce major inefficiencies into scientific discovery. While we don’t live in the 30^th century yet, we do have access to 21^stcentury technology which can assist in exploring chemistry in a more directed manner. This mainly involves using machine learning, search algorithms, and generative powered exploratory AI to serve as a force multiplier which can serve to assist human chemists in chemical exploration. To shamelessly compare this with another space-based sci-fi reference, this would be akin to deploying hundreds or thousands of automated space probes to search unexplored planets, akin to how the empire found the rebellion on Hoth in the Empire Strikes Back.</p><p dir="ltr">The journey to integrate AI with chemical exploration starts with the important concept of standardization and how to apply it to chemically relevant data. To easily organize, store, and access relevant aspects of small molecules, macromolecules, chemical reactions, biological assays, etc. it is imperative that data be represented in a standard format which accurately portrays necessary chemical information. This becomes especially relevant as humans aggregate more and more chemical data. In this thesis, we tackle a subset of standardization in Chapter 2 involving benchmarking sets for comparative evaluation of docking software. One major reason why standardization is so important is that standardization promotes ease of access to relevant data, regardless of if this access is attempted by human or computational means. While improving data access for humans is beneficial, computationally it is a game changer when datamining training data for machine learning (ML) applications. Having standardized data readily available for computational access allows for software to rapidly access and preprocess relevant data boosts efficiency in ML model training. In Chapter 4 of this thesis, the central database of the CIPHER close-loop system is standardized and integrated with a REST API, allowing for rapid data acquisition via a structured URL call. Having database standardization and a mechanism for easy data mining makes a database “ML ready” and promotes the database for ML applications.</p><p dir="ltr">Build upon data standardization and training ML models for chemical applications, the next step of this journey revolves around a concept known as a “chemical space” and how chemists can approximate and sample chemical spaces in a directed manner. In the context of this thesis, a chemical space can be visualized in the following manner. Start by envisioning any chemical relationship between some inputs and outputs as an unknown mathematical function. For example, if one is measuring the assay response of a specific drug at a certain concentration, the input would be the concentration, and the output would be the assay response. Then the bounds of this space are set by determining the range of input values and this forms a chemical space which corresponds to the chemical problem. Chemists sample these spaces every day when they go into the lab, run experiments, and analyze their data. While the example described above is relatively simple in scope, even if the relationship is very complex techniques such as ML can be used to approximate the relationship. An example of this approximation is shown in Chapter 3 of this thesis, where normalizing flow architecture is used to bias a vector space representation of molecules with chemical properties, creating a space which correlates compound and property and can be sampled to provided compounds with specific values of trained chemical properties. Training individual models is important, but to truly emulate certain chemical processes multiple models may need to be combined with physical instrumentation to efficiently sample and validate a chemical space. Chapter 4 of this thesis expands upon this concept by integrating a variety of ML modules with high-throughput (HT) bioassay instrumentation to create a “close loop” system designed around discovering, synthesizing, and validating non-addictive analgesics.</p><p dir="ltr">The final step of this journey is to integrate these systems which sample chemical spaces with AI, allowing for automated exploration of these spaces in a directed manner. There are several AI frameworks which can be used separately or combined to accomplish this task, but the framework that is the focus of this thesis is AI agents. AI agents are entities which use some form of AI to serve as a logical processing center which drives their exploration through a problem space. This can be a simple algorithm, some type of heuristic model, or an advance form of generative AI such as an LLM. Additionally, these agents generally have access to certain tools which serve as a medium for interaction with physical or computational environments, such as controlling a robotic arm or searching a database. Finally, these agents generally have a notion of past actions and observations, commonly referred to as memory, which allows agents to recall important information as they explore. Chapter 5 of this thesis details a custom agentic framework which is tailored towards complex scientific applications. This framework builds agents from source documentation around a specific user defined scope, provides them with access to literature and documentation in the form of embeddings, has custom memory for highly targeted retention, and allows form agents to communicate with one another to promote collaborative problem solving. Chapter 6 of this thesis showcase an application of a simpler agentic framework to an automated lipidomic workflow which performs comparative analysis on 5xFAD vs. WT mice brain tissue. The group of AI agents involved in this system generate mass spectrometry worklists, filter data into categories for analysis, perform comparative analysis, and allow for the user to dynamically create plots which can be used to answer specific statistical questions. In addition to performing all these operational and statistical analysis functions, the system includes an agent which uses document embeddings trained on curated technical manuals and protocols to answer user questions via a chatbot style interface. Overall, the system showcases how AI can effectivity be applied to relevant chemical problems to enhance speed, bolster accuracy, and improve usability.</p>

Indiana University-Purdue University Indianapolis (IUPUI) / ALDH isoenzymes are known to impact the sensitivity of certain neoplastic cells toward cyclophosphamides and its analogs. Despite its bone marrow toxicity, cyclophos-phamide is still used to treat various recalcitrant forms of cancer. When activated, cyclo-phosphamide forms aldophosphamide that can spontaneously form the toxic phospho-ramide mustard, an alkylating agent unless detoxified by ALDH isozymes to the carbox-yphosphamide metabolite. Prior work has demonstrated that the ALDH1A1 and ALDH3A1 isoenzymes can convert aldophosphamide to carboxyphosphamide. This has also been verified by over expression and siRNA knockdown studies. Selective small molecule inhibitors for these ALDH isoenzymes are not currently available. We hypothe-sized that novel and selective small molecule inhibitors of ALDH3A1 would enhance cancer cells’ sensitivity toward cyclophosphamide. If successful, this approach can widen the therapeutic treatment window for cyclophosphamides; permitting lower effective dos-ing regimens with reduced toxicity. An esterase based absorbance assay was optimized in a high throughput setting and 101, 000 compounds were screened and two new selective inhibitors for ALDH3A1, which have IC50 values of 0.2 µM (CB7) and 16 µM (CB29) were discovered. These two compounds compete for aldehyde binding, which was vali-dated both by kinetic and crystallographic studies. Structure activity relationship dataset has helped us determine the basis of potency and selectivity of these compounds towards ALDH3A1 activity. Our data is further supported by mafosfamide (an analog of cyclo-phosphamide) chemosensitivity data, performed on lung adenocarcinoma (A549) and gli-oblastoma (SF767) cell lines. Overall, I have identified two compounds, which inhibit ALDH3A1’s dehydrogenase activity selectively and increases sensitization of ALDH3A1 positive cells to aldophosphamide and its analogs. This may have the potential in improving chemotherapeutic efficacy of cyclophosphamide as well as to help us understand better the role of ALDH3A1 in cells. Future work will focus on testing these compounds on other cancer cell lines that involve ALDH3A1 expression as a mode of chemoresistance.

La intensificación de procesos consiste en el desarrollo de equipos y técnicas innovadoras que ofrecen mejoras sustanciales en el proceso, principalmente mediante la disminución del volumen del equipo, consumo de energía o generación de residuos, dando lugar a tecnologías más baratas, seguras y sostenibles. Esta tesis enfatiza la intensificación de procesos como estrategia en la recuperación de dióxido de azufre mediante el empleo de la tecnología de membranas y de líquidos iónicos como absorbente con objeto de eliminar las pérdidas de disolvente.La intensificación del proceso se lleva a cabo en dos etapas:i) Sustitución del equipo convencional (e.g. scrubbers) por un sistema de membranas para eliminar el arrastre de gotas y,ii) Sustitución del disolvente de absorción (N,N-dimetilanilina) por líquidos iónicos para eliminar pérdidas de disolvente por su volatilización en la corriente de gas debido a su presión de vapor despreciable. La selección de un líquido iónico adecuado se basa en su afinidad hacia dióxido de azufre, baja viscosidad, bajo coste y baja ecotoxicidad.En resumen, esta tesis es el primer trabajo que combina el empleo de un contactor de membranas de fibra hueca con líquidos iónicos, contribuyendo al desarrollo de procedimientos innovadores para intensificar el proceso de absorción de dióxido de azufre. / Process intensification consists of the development of innovative devices and techniques that offer significant improvements in chemical manufacturing and processing, decreasing substantially equipment volume, energy consumption, or wastes, and ultimately leading to cheaper, safer and sustainable technologies. This thesis emphasizes the process intensification as the strategy to the recovery of sulfur dioxide, according to the material efficiency and environmental protection, by means of technology based on membranes and ionic liquids as absorption solvents in order to avoid solvent losses.Process intensification is performed in two steps:i) Substitution of conventional equipment (e.g. scrubbers) for a membrane device to avoid drops dragging and,ii) Substitution of the absorption solvent (N,N-dimethylaniline) for ionic liquids to avoid solvent losses due to volatilization of solvent into the gas stream because of their negligible vapor pressure. Selection of a suitable ionic liquid is based on its affinity towards sulfur dioxide, low viscosity, low cost and low ecotoxicity.Thus, this thesis is the first work that combines a hollow fibre membrane contactor and ionic liquids, contributing to the development of innovative procedures to intensify the sulfur dioxide absorption process.