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Hidróxidos Duplos Lamelares (HDL) são materiais lamelares constituídos de camadas positivamente carregadas de um hidróxido misto de dois metais (um di e um trivalente), com ânions hidratados no domínio interlamelar. Apesar de serem potenciais adsorventes, o estudo da adsorção de colato de sódio sobre estes sólidos foi pouco explorado até hoje. Este estudo é importante, pois abre caminho para uma potencial aplicação farmacêutica de HDL na remoção de colato produzido em excesso pelo corpo humano, e diminuindo o risco de doenças conseqüentes desse excesso. Este trabalho teve por objetivo estudar a adsorção e a sorção de colato de sódio a partir de soluções aquosas, em hidróxido duplo lamelar de magnésio e alumínio intercalado com carbonato, Mg-Al-CO3-HDL, verificando o efeito de variáveis como temperatura, pH e força iônica do meio. O adsorvente foi preparado pelo método de coprecipitação a pH variável e caracterizado quanto à composição, organização estrutural, textura e morfologia, sendo utilizado na forma original ou após calcinação. A adsorção de colato de sódio no HDL não calcinado indicou que não ocorre a substituição do ânion interlamelar (CO32-), mas sim a adsorção por interação do ânion orgânico com as cargas residuais na superfície do HDL. O processo mostrou uma grande dependência das variáveis estudadas. A análise multivariacional confirmou e quantificou a importância de cada variável. Em todos os casos, o aumento da temperatura resultou em uma diminuição na quantidade máxima adsorvida. O aumento da força iônica do meio, por meio da adição de um sal neutro, resulta em uma melhoria na capacidade de remoção de ânions. Na faixa avaliada, quanto maior o valor do pH das soluções de colato, menor a quantidade máxima adsorvida. Os resultados obtidos para a sorção no HDL calcinado mostraram que inicialmente o HDL é reconstituído com a intercalação de ânions OH-. Em casos onde a concentração do composto orgânico era alta, o colato foi intercalado formando uma nova fase. Neste caso, a sorção de colato apresentou curvas com perfil semelhante às da adsorção: as isotermas atingem um patamar onde a sorção torna-se constante e o aumento da temperatura diminui a quantidade sorvida. Pelos resultados obtidos, foi proposto um modelo de intercalação de colato em bicamada. Os resultados indicam também que a remoção do colato pelo HDL calcinado se mostra mais eficiente do que aquela obtida com o HDL não calcinado. / Layered Double Hydroxides (LDH), are lamellar materials constituted of positively charged layers of two mixed cations hydroxide (a bi and a trivalent one), with hydrated anions in the interlayer domain. In spite of being potential adsorbents, the study of the sodium cholate adsorption on these solids has not been well explored yet. This study is important, because it opens the perspective for the application of LDH in the pharmaceutical field in the removal of cholate produced in excess by the human organism and decreasing the risk of consequent diseases from this excess. The aim of this work was to study the adsorption and the sorption of sodium cholate from aqueous solutions, in Mg-Al-CO3-LDH, verifying the effect of the variables: temperature, pH and ionic strength of the media. The adsorbent was prepared by the coprecipitation at variable pH method and characterized with respect to their composition, structural organization, texture and morphology, being utilized in the pristine form or after calcination. The adsorption of sodium cholate in pristine LDH indicated that the exchange of the interlayer anion (CO32-) doesn\'t occur, but the adsorption process occurs by the interaction of the anion with the residual charges on the LDH surface. The process showed great dependence on the parameters studied. The multivariational analysis confirmed and quantified the influence of each variable. In all the experiments, increasing the temperature resulted in a decrease in the maximum adsorbed quantity. Increasing the ionic strength of the media, by the addition of a neutral salt, results in a better anions removal capacity. In the evaluated interval, the bigger the initial pH value of the cholate solutions, the lower the maximum adsorbed quantity. The results obtained for the sorption in calcined LDH showed that initially the LDH are reconstituted with the OH- anions intercalated. In the experiments at high concentration, the cholate is intercalated forming a new phase. The profile of cholate sorption are similar to that of the adsorption: the isotherms reach a plateau where the sorption becomes constant and the raise in the temperature decreases the sorbed quantity. By the obtained results, it was proposed a cholate intercalation model forming a bilayered structure. The results indicate that the cholate removal by the calcined LDH is more efficient than that presented by the uncalcined one.

Hidróxidos Duplos Lamelares (HDL) são materiais lamelares constituídos de camadas positivamente carregadas de um hidróxido misto de dois metais (um di e um trivalente), com ânions hidratados no domínio interlamelar. Apesar de serem potenciais adsorventes, o estudo da adsorção de colato de sódio sobre estes sólidos foi pouco explorado até hoje. Este estudo é importante, pois abre caminho para uma potencial aplicação farmacêutica de HDL na remoção de colato produzido em excesso pelo corpo humano, e diminuindo o risco de doenças conseqüentes desse excesso. Este trabalho teve por objetivo estudar a adsorção e a sorção de colato de sódio a partir de soluções aquosas, em hidróxido duplo lamelar de magnésio e alumínio intercalado com carbonato, Mg-Al-CO3-HDL, verificando o efeito de variáveis como temperatura, pH e força iônica do meio. O adsorvente foi preparado pelo método de coprecipitação a pH variável e caracterizado quanto à composição, organização estrutural, textura e morfologia, sendo utilizado na forma original ou após calcinação. A adsorção de colato de sódio no HDL não calcinado indicou que não ocorre a substituição do ânion interlamelar (CO32-), mas sim a adsorção por interação do ânion orgânico com as cargas residuais na superfície do HDL. O processo mostrou uma grande dependência das variáveis estudadas. A análise multivariacional confirmou e quantificou a importância de cada variável. Em todos os casos, o aumento da temperatura resultou em uma diminuição na quantidade máxima adsorvida. O aumento da força iônica do meio, por meio da adição de um sal neutro, resulta em uma melhoria na capacidade de remoção de ânions. Na faixa avaliada, quanto maior o valor do pH das soluções de colato, menor a quantidade máxima adsorvida. Os resultados obtidos para a sorção no HDL calcinado mostraram que inicialmente o HDL é reconstituído com a intercalação de ânions OH-. Em casos onde a concentração do composto orgânico era alta, o colato foi intercalado formando uma nova fase. Neste caso, a sorção de colato apresentou curvas com perfil semelhante às da adsorção: as isotermas atingem um patamar onde a sorção torna-se constante e o aumento da temperatura diminui a quantidade sorvida. Pelos resultados obtidos, foi proposto um modelo de intercalação de colato em bicamada. Os resultados indicam também que a remoção do colato pelo HDL calcinado se mostra mais eficiente do que aquela obtida com o HDL não calcinado. / Layered Double Hydroxides (LDH), are lamellar materials constituted of positively charged layers of two mixed cations hydroxide (a bi and a trivalent one), with hydrated anions in the interlayer domain. In spite of being potential adsorbents, the study of the sodium cholate adsorption on these solids has not been well explored yet. This study is important, because it opens the perspective for the application of LDH in the pharmaceutical field in the removal of cholate produced in excess by the human organism and decreasing the risk of consequent diseases from this excess. The aim of this work was to study the adsorption and the sorption of sodium cholate from aqueous solutions, in Mg-Al-CO3-LDH, verifying the effect of the variables: temperature, pH and ionic strength of the media. The adsorbent was prepared by the coprecipitation at variable pH method and characterized with respect to their composition, structural organization, texture and morphology, being utilized in the pristine form or after calcination. The adsorption of sodium cholate in pristine LDH indicated that the exchange of the interlayer anion (CO32-) doesn\'t occur, but the adsorption process occurs by the interaction of the anion with the residual charges on the LDH surface. The process showed great dependence on the parameters studied. The multivariational analysis confirmed and quantified the influence of each variable. In all the experiments, increasing the temperature resulted in a decrease in the maximum adsorbed quantity. Increasing the ionic strength of the media, by the addition of a neutral salt, results in a better anions removal capacity. In the evaluated interval, the bigger the initial pH value of the cholate solutions, the lower the maximum adsorbed quantity. The results obtained for the sorption in calcined LDH showed that initially the LDH are reconstituted with the OH- anions intercalated. In the experiments at high concentration, the cholate is intercalated forming a new phase. The profile of cholate sorption are similar to that of the adsorption: the isotherms reach a plateau where the sorption becomes constant and the raise in the temperature decreases the sorbed quantity. By the obtained results, it was proposed a cholate intercalation model forming a bilayered structure. The results indicate that the cholate removal by the calcined LDH is more efficient than that presented by the uncalcined one.

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder linked to obesity that is rapidly increasing in incidence worldwide. It is a disorder that ranges in severity; from a benign condition of hepatic steatosis to a potentially deadly one resulting in cirrhosis and hepatocellular carcinoma. It is currently known that NAFLD is strongly associated with various aspects of metabolic syndrome: insulin resistance, elevated triglyceride levels, obesity, and type two diabetes mellitus. The multifactorial pathogenesis of NAFLD is still uncertain and closer attention is needed on the effect of one’s diet on NAFLD. In this study, we directly compare a westernized diet containing high levels of fat and fructose to a diet high in fat and containing cholate using mouse models in order to determine the role of each dietary factor in the incidence and severity of the different stages of NAFLD. We will evaluate the severity of hepatic steatosis and hepatocellular damage via hematoxylin and eosin (H&E) stained liver tissue and the severity of hepatic fibrosis via trichrome-stained liver tissue. Our hypothesis is that mice on the fructose-based diet are expected to have higher levels of hepatic steatosis and hepatocellular damage relative to mice on the cholate-based diet while mice on the cholate-based diet are expected to have higher levels of hepatic fibrosis relative to the fructose-based diet. The results of this study will aid in elucidating and strengthening the connection between one’s diet and the prevalence and severity of NAFLD.

Στην παρούσα διατριβή, μελετήθηκε η χρήση ελαστικών λιποσωμάτων στη διαδερμική χορήγηση υδατοδιαλυτών ουσιών και πραγματοποιήθηκαν επίσης μελέτες προ-μορφοποίησης αντιϋπερτασικών βιοδραστικών ενώσεων για διαδερμική χορήγηση. Αρχικά, πραγματοποιήθηκαν μελέτες της φυσιολογίας του δέρματος με τεχνικές μικροσκοπίας και μέτρησης της απώλειας ύδατος μέσω της επιδερμίδας (TEWL) με σκοπό να διαπιστωθεί η λειτουργία του φραγμού της κεράτινης στοιβάδας, καθώς και η ορθότητα χρήσης των σχετικών τεχνικών προετοιμασίας των δειγμάτων δέρματος που χρησιμοποιήθηκαν. Η οπτική μικροσκοπία ειδικά μας έδωσε πληροφορίες ως προς τη δομή της επιδερμίδας και ως προς τον πιθανό μηχανισμό μεταφοράς ουσιών μέσω της χρήσης λιποσωμάτων. Στη συνέχεια πραγματοποιήθηκε μελέτη και σύγκριση των διαφόρων φυσικοχημικών χαρακτηριστικών ελαστικών λιποσωμάτων που μπορεί να χρησιμοποιηθούν ως πρώτοι δείκτες για πρόγνωση της διαδερμικής απορρόφησης (in vivo) των υδρόφιλων βιοδραστικών ενώσεων. Ως μοντέλα υδρόφιλων βιοδραστικών ενώσεων χρησιμοποιήθηκαν οι φθορίζουσες χρωστικές καλσεΐνη και καρβοξυφλουορεσκεΐνη. Όλες οι λιποσωμικές διασπορές (τόσο τα συμβατικά λιποσώματα-CLs, όσο και τα ελαστικά λιποσώματα τύπου transfersome-TRs και τύπου invasomes-INVs) χαρακτηρίστηκαν ως προς τα εξής φυσικοχημικά χαρακτηριστικά: Την κατανομή μεγέθους, το ζ-δυναμικό, το σφαιρικό σχήμα και τη μορφολογία τους, την ικανότητα εγκλωβισμού υδρόφιλων ουσιών, τη σταθερότητά τους (ως προς τα μορφολογικά χαρακτηριστικά, τη διασπορά μεγέθους και το φορτίο επιφανείας, και τη συγκράτηση της εγκλωβισμένης σε αυτά ουσίας) σε σχέση με το χρόνο, την ελαστικότητα και τέλος ως προς τη δυνατότητα διαπέρασης εγκλωβισμένων σε αυτές υδρόφιλων ουσιών μέσω ανθρώπινου δέρματος in vitro. Το μέγεθος των λιποσωμάτων ήταν παρόμοιο και αρκετά ομοιογενές, ενώ η προσθήκη διαφορετικών τύπων ενισχυτικών διαπέρασης στα ελαστικά λιποσώματα, στα συνήθη εύρη συγκεντρώσεων που χρησιμοποιούνται, δεν επηρεάζει καθόλου το επιφανειακό φορτίο των παραχθέντων λιποσωμάτων. Αύξηση του μεγέθους και αστάθεια ως προς τη συγκράτηση της εγκλωβισμένης ουσίας παρατηρήθηκε στην περίπτωση προσθήκης μεγαλύτερης ποσότητας ενισχυτικού διαπέρασης, η οποία αλλάζει και τα φυσικοχημικά χαρακτηριστικά των λιποσωμάτων. Τα TRs που περιείχαν χολικό νάτριο ήταν πιο ελαστικά από τα αντίστοιχα με Tween 80, τα οποία είχαν συγκριτικά χαμηλές τιμές ελαστικότητας (<40mg/s∙cm2). Οι υψηλότερες τιμές ελαστικότητας από όλους τους τύπους ελαστικών λιποσωμάτων που παρασκευάστηκαν στα πλαίσια αυτής της διατριβής, παρατηρήθηκε στην περίπτωση των INVs με 1% w/w PE και 1% w/w LIM. Επιπλέον, τα περισσότερα λιποσώματα τύπου INVs είχαν υψηλότερες τιμές ελαστικότητας σε σχέση με τα αντίστοιχα χωρίς τερπένια (INVs αναφοράς), εκτός από την περίπτωση των INVs με citral και cineol, όπου η ελαστικότητα σημείωσε μείωση σε σχέση με τα INVs χωρίς τερπένια. Οι διάφοροι τύποι λιποσωμάτων φαίνεται να μεταβάλλουν τη διαπέραση της χρωστικής με την εξής σειρά: Διάλυμα<CLs<TRs<<INVs. H διαπερατότητα (permeability), η ροή (flux) και ο λόγος προσαύξησης (ER) δείχνουν ότι τα συμβατικά λιποσώματα αύξησαν ελάχιστα τη ροή της καλσεΐνης, ενώ τα TRs και INVs κατά 1.8 και 7.2 φορές, αντίστοιχα. Τα αποτελέσματα αυτά επιβεβαιώνουν το γεγονός ότι τα συμβατικά λιποσώματα είναι ανεπαρκή συστήματα μεταφοράς υδρόφιλων μορίων μέσω του δέρματος, ενώ παράλληλα δείχνουν ότι τα ελαστικά λιποσώματα με τη μεγαλύτερη τιμή ελαστικότητας είναι πιο αποτελεσματικά στη μεταφορά της ουσίας μέσω του δέρματος. Σε επόμενα πειράματα μελετήθηκε η δυνατότητα διείσδυσης τόσο υδρόφιλων όσο και λιπόφιλων μορίων στις στοιβάδες του δέρματος, σε μια προσπάθεια να διερευνηθεί ο μηχανισμός αύξησης της διαδερμικής διαπέρασης των υδρόφιλων χρωστικών από τους διάφορους τύπους ελαστικών λιποσωμάτων. Ως μοντέλο υδρόφιλης ουσίας χρησιμοποιήθηκε η φθορίζουσα χρωστική καλσεΐνη, ενώ η λιπιδική ροδαμίνη χρησιμοποιήθηκε ως μοντέλο λιπόφιλης ουσίας (που δεν φεύγει από τα λιποσώματα και ουσιαστικά μας δείχνει το βάθος εις το οποίο εισχωρούν μέσα στο δέρμα τα αντίστοιχα είδη λιποσωμάτων). Τα λιποσώματα τύπου TR φαίνεται ότι επάγουν τη διαπέραση με το να βοηθούν τη χρωστική να προχωρά (υπό μορφή λιποσωμάτων που την εγκλωβίζουν) σε βαθύτερα στρώματα της κεράτινης στιβάδας σε σχέση με τα συμβατικά λιποσώματα όπου σε μεγάλο ποσοστό διαρρηγνύονται και απελευθερώνουν την υδρόφιλη ουσία η οποία στη συνέχεια διέρχεται μόνη της, ως ελεύθερο μόριο, στις στιβάδες του χορίου. Αντίθετα, τα λιποσώματα τύπου INV αποδείχτηκε ότι εισδύουν σε βαθύτερες στιβάδες της επιδερμίδας, φθάνοντας σε αρκετά υψηλά ποσοστά σε στιβάδες του χορίου, παρασύροντας μαζί τους και τα μόρια του εγκλωβισμένου σε αυτά υδρόφιλου φαρμάκου. Τέλος, μελετήθηκε η δυνατότητα μορφοποίησης ενός πειραματικού φαρμάκου με ανάλογη δομή γνωστού φαρμάκου προκειμένου για διαδερμική αντιϋπερτασική θεραπεία. Αρχικά, μελετήσαμε το πειραματικό φάρμακο ως προς τις φυσικοχημικές του ιδιότητες (διαλυτότητα σε διάφορα μέσα, σύνδεση με πρωτεΐνες) και στη συνέχεια μελετήσαμε τη δυνατότητα χορήγησης μιας φαρμακοτεχνικής μορφής μέσω του δέρματος σε κατάλληλο σύστημα διαλυτών. Αφού βρέθηκαν οι κατάλληλες συνθήκες, χρησιμοποιήθηκαν ενισχυτικά διαπέρασης στη φαρμακοτεχνική μορφή για να επιταχυνθεί η διαδερμική απορρόφηση του φαρμάκου, όσο είναι δυνατόν, και να ευρεθεί η βέλτιστη φαρμακοτεχνική μορφή. Τέλος, πραγματοποιήθηκαν πειράματα σύγκρισης μεταξύ του πειραματικού φαρμάκου και γνωστού αντιϋπερτασικού (Los) ως προς τις φυσικοχημικές ιδιότητες και την ικανότητα μεταφοράς τους διαδερμικά. Τα αποτελέσματα έδειξαν ότι το ΠΦ παρουσίασε μεγαλύτερη διαπέραση υπό μορφή ουδέτερου μορίου (σε σχέση με την αντίστοιχη του άλατος με TFA (όπως φάνηκε από τα αρχικά πειράματα αυτής της σειράς) ή του μετά Καλίου άλατος (όπως προκύπτει μετά από σύγκριση των σχετικών τιμών Ροής και Συντελεστή Διαπερατότητας (P). Συγκρίνοντας λοιπόν τις τιμές διαπερατότητα και ροής διαμέσου ανθρώπινης επιδερμίδας με τις αντίστοιχες τιμές του φαρμάκου Los θα πρέπει να λάβουμε υπ’ όψη και τις τιμές για το ουδέτερο μόριο. Η διαπέραση του ουδέτερου μορίου του ΠΦ είναι σημαντικά χαμηλότερη από την αντίστοιχη του μετά καλίου άλατος της los. / In this study, we investigated the use of elastic liposomes in transdermal delivery of hydrophilic substances and we studied the possibility of formulating a new antihypertensive drug for transdermal delivery. Primarily, morphological studies of human skin were conducted by the use of optical microscopy and transepidermal water loss measurements (TEWL), in order to assess the barrier function of stratum corneum (SC), and the integrity of the techniques used in this study. By optical microscopy, in particular, data concerning the skin structure and the possible mechanism by which substances can be delivered through / into the skin, were obtained. Secondly, we studied and compared various physicochemical characteristics of two different types of elastic liposomes, which could help us predict the transdermal absorption (in vivo) of hydrophilic molecules. Fluorescent markers calcein and carboxyfluorescein were used as hydrophilic model drugs. All liposomal dispersions (conventional liposomes CLs, and elastic liposomes i.e. transfersomes TRs and invasomes INVs) were evaluated in means the following physicochemical properties: size distribution, z-potential, stability upon storage, morphology by cryo-electron microscopy and membrane elasticity. Moreover, their ability to encapsulate and also to retain aqueous soluble markers, was investigated. Finally, the permeation of calcein through human skin was tested and compared by use of elastic and conventional rigid liposomes. The mean diameter was found relatively homogenous, similar for most liposomal dispersions, while the addition of different penetration enhancers during the preparation did not influence z-potential. Increase of size average and instability – as far as the retention of the encapsulated substance is concerned – was observed at higher concentrations of penetration enhancers used. Sodium cholate containing TRs were found more elastic compared to Tween 80 containing TRs, which showed relatively low elasticity values (<40mg/s∙cm2). The highest elasticity values among all types of elastic liposomes prepared, were found in the case of INVs with 1%w/w PE and 1% w/w LIM. Furthermore, most INVs showed higher elasticity values compared to the ones without terpenes (control INVs), except from citral and cineol INVs, where elasticity decreased compared to the control ones. It appears that different types of liposomes can alter fluorescent permeation in the following order: Solution<CLs<TRs<<INVs. Permeability, flux and enhancement ratio (ER) show that conventional liposomes increased slightly calcein flux, while TRs and INVs 1.8 and 7.2 times respectively. These findings confirm the fact that CLs are inefficient drug delivery systems for water soluble molecules through human skin, and show that elastic liposomes having the highest elasticity value are more efficient in delivering CF transdermally. In further experiments, the penetration of both hydrophilic and lipophilic molecules in human skin was studied, in order to investigate the mechanism of action by which liposomes could enhance the drug delivery in skin. Fluorescent marker calcein was used as a hydrophilic drug model, while lipid rhodamine-PE was used as a lipophilic model (it shows us how deeply the liposomes penetrate into the skin). Liposomes TRs seem to enhance skin permeation by helping the marker to penetrate (through liposomes) in deeper stratum corneum layers while conventional liposomes the hydrophilic substance which penetrates the skin layers as a free molecule. In contrast, INV liposomes were proved to be able to penetrate in deeper skin layers, and deliver relatively high amounts of the encapsulated substance. In the end, experiments with a new molecule with similar structure to losartan were conducted. This study aimed at discovering a new formulation for this experimental drug in order to be used as a transdermal antihypertensive. First, we studied the physicochemical properties (solubility in PBS, BSA etc, and protein binding). Secondly, we investigated the possibility of preparing a formulation to be used transdermally. After establishing the techniques and drug properties we used penetration enhancers in order to increase the transdermal absorption as possible and help find the right skin formulation. Last, we compared the experimental drug and losartan in terms of physicochemical properties and their ability to be transported through human skin. The results showed that the experimental drug had better permeation rate as a neutral molecule compared to TFA salt, (as shown in preliminary experiments) or K+ (as shown after comparing P and flux values). Therefore, the values given for the neutral molecule should be taken into consideration when comparing the two drugs. (losartan and experimental drug). The permeation of the neutral molecule nevertheless is significantly lower than the one for losartan.

Chapter 1: Functional and Responsive Supramolecular Gels In this chapter ‘supramolecular gels’ derived from small organic molecules with molecular mass of typically less than 2000 daltons are discussed. Representative examples of various low molecular weight gelators based on their natural availability and also divergent functionalities are mentioned (Scheme 1). Scheme 1 Advances in the recent years have been very rapid in the field of supramolecular chemistry of gels giving rise to ‘Tunable responsive gels’. Control of the gel property in a reversible fashion has been the highlight of responsive gels. A few of the gels which are responsive towards various stimuli such as pH, photoirradiation, cations, anions, neutral species have been discussed. Advances and scope of supramolecular gels in various applications have also been mentioned in detail with respective examples. Utilities of supramolecular gels in synthesis of nanostructures, in biology and medicine, enzyme recognition, catalysis etc are discussed. (Scheme 2). Chapter 2: Charge transfer triggered organogels of bis(bile acid)anthracene conjugates and 2,4.7-trinitrofluorenone. In this chapter the study involves the synthesis of a special class of anthracene based steroidal derivatives. The appending of two amphiphilic bile acid units imparts a unique hydrophobic/ hydrophilic balance on the chromophore. The 2,3-didecyloxyanthracene (DDOA) was reported to be a gelator of various organic solvents but none of the three bile acid derivatives of anthracene synthesized was a gelator on its own. It was also observed that dialkoxy (propyl, heptyl, decyl) derivatives of anthracene formed strong charge-transfer gels in the presence of 2,4,7-trinitrofluorenone (TNF). The addition of electron deficient TNF to the steroidal derivatives of anthracene resulted in the gelation of some specific organic solvents. The driving force behind the gel formation resulted from the charge-transfer (CT) interaction between the electron rich anthracene and electron deficient fluorenone. Figure 1. Chemical structures of 2,3-bis(bile acid)anthracenes and TNF (centre), a scanning electronic microscopy image of xerogels prepared from bis(deoxycholyl)anthracene and TNF (left) and a photograph of the gel of bis(deoxycholyl)anthracene and TNF in n-octanol. Thermochromic property (during sol to gel phase transition), absorption and variable temperature fluorescence measurements supported CT interaction. Thermal stability studies and dynamic rheology experiments confirmed that CT gels were thermally most stable and mechanically stronger with equi-molar amounts of the two components. Stiffness values obtained from rheological experiments also suggested that the gels were viscoelastic solids. Chapter 3(A): Tb(III) sensitization in an organogel matrix: Selective luminescence quenching by an aromatic nitro derivative In this chapter the discovery of metallo organogel formation by mixing methanolic solutions of Tb(OAc)3 and sodium deoxycholate (NaDCh) has been explored. Sensitization of Tb3+ was observed by doping micromolar quantities of 2,3-dihydroxynaphthalene (DHN). Mechanical properties of Tb3+-DCh gels were investigated by rheology at three different ratios of Tb3+ and DCh. It was observed that increasing in the Tb3+ to DCh ratio increased the mechanical property of the gels. Time delayed emission spectra were recorded with increasing concentration of DHN and luminescence increase was noticed in a linear fashion. Importance of gel matrix was demonstrated by measuring the Tb3+ luminescence at fixed concentration (5 mM) with/without DHN in the solution and gel media. Figure 2:: Schematic representation of Tb3+ sensitization by DHN. Photograph (right)) of the Tb3++-DCh (5/15 mM) gels with (a) 50 µM DHHN (b) No DHHN under UVV (365 nm). Sensitization by an electron rich chromophore created interest in us to dope relatively electron deficient compounds into the gel matrix for possible quenching off Tb3+-luminescence. Among the electron deficient analytes screened included 1,5-difluro-2,4-diinitrobenzenne (DFDNB)), 2,4 dinitrophenol (DNPPh), p-nitrobenzaldehydde (p-NB), 2,4,6-trinitrootoluene (TTNT) and 22,4,7¬trinitrofluuorenone (TTNF). Microscopy studies such as AFM, TEMM and SEMM revealed highly entangled fibrous network in the morphology of Tb3+--DCh xerogel. Solid state luminescence experiments suggested that sensiitization was observed in the xerogels and extent of sensitization was comparable to that of the gel state. Xerogel soaking studies inferred the strong adherence of the DHNN to the gel fibres. Chapter 3(B): Anion dependent structural, morphological and mechanical features of Ln(III)-Cholate gels In this chapter the counter anion influence on various aspects of hydrogels has been discussed. It has been reported from our laboratory that mixing of aqueous solutions of sodium cholate (15 mM) and various lanthanide acetates (5 mM) followed by sonication resulted in either transparent or transluscent gels. Unsurprisingly we found that aqueous solutions of lanthanide nitrates and lanthanide chlorides also formed hydrogels upon mixing with sodium cholate (Figure 33). Dried films of Tb3++-cholate and Eu3+-cholate gels prepared from their respective nitrate salts displayed birefringent structures under polarizing optical microscopy (POM). But no significant textures of any type were observed in the case of gels prepared from either chloride or acetate salts. Figure 3:: Photographs of the hydrogels prepared by mixing of aqueous solutions of various salts Tb33+ and Eu3+ with sodium cholate solutions. Scanning electron microscopic images exhibited fibrous structures for all the xerogels in the morphology. Atomic force microscopy and transmission electron microscopy measurements revealed helical morphology for xerogels prepared from nitrate salts where as flat tape-like cross linkage was observed for chloride or acetate based xerogels. Anion effect on mechanical properties was significant in the sense that gels prepared from acetate salts displayed highest mechanical strength followed by nitrate based gels which were stronger than that of chloride based gels. Titration of sodium cholate solution with various lanthanide salt solutions gave the direct evidence of thee pH variation as a function of the anions. Figure 4: TEM images of xerogels prepared from gels of nitrate salts of Tb3+ (left) and Eu3+ (right) Chapter 4: Design, synthesis a nd study of bile acid ‘click’ conjugates of perylene bisimides (PBIs) and naphthalene bisimides (NBIs) In this chapter the synthesis of novel bile acid derivatives of perylene and naphthalene bisimides is discussed. The ‘click’ chemistry procedure was used to link bile acid groups on to the chromophores. Azide derivatives of PBIs and NBIs were prepared inn 3 step methods which were coupled to propargyl esters of bile acids by following standard ‘click chemistry’ protocols to achieve the target molecules (Scheme 3). Scheme 3 The studies conducted mainly focused on Cholic acid (CA) conjugates of PBIs and NBIs. Steady state absorption and emission studies of CA conjugates were performed in 10% MeOH/DCM system. POM and fluorescence images showed red emissive aggregates in case of PBI films. TEM measurements revealed uniform aggregate sizes for both the films of PBI(CA)2 and NBI(CA)2. SEM and AFM (Fig 5) studies exhibited spherical aggregates of diameter around 100-200 nm for PBI(CA)2 films where as aggregates of diameter around 500-700 nm were observed for NBI(CA)2 films. Figure 5: AFM images and their corresponding height profiles of PBI films (left) and NBI films (right)

Optically transparent carbon based nanomaterials including graphene and carbon nanotubes(CNTs) are promising candidates as transparent conductive electrodes due to their high electrical conductivity coupled with high optical transparency, can be flexed several times with minimal deterioration in their electronic properties, and do not require costly high vacuum processing conditions. CNTs are easily solution processed through the use of surfactants sodium dodecyl sulfate(SDS) and sodium cholate(SC). Allowing CNTs to be deposited onto transparent substrates through vacuum filtration, ultrasonic spray coating, dip coating, spin coating, and inkjet printing. However, surfactants are electrically insulating, limit chemical doping, and increase optical absorption thereby decreasing overall performance of electrodes. Surfactants can be removed through nitric acid treatment and annealing in an inert environment (e.g. argon). In this thesis, the impact of surfactant removal on electrode performance was investigated. Nitric acid treatment has been shown to p-dope CNTs and remove the surfactant SDS. However, nitric acid p-doping is naturally dedoped with exposure to air, does not completely remove the surfactant SC, and has been shown to damage CNTs by creating defect sites. Annealing at temperatures up to 1000°C is advantageous in that it removes insulating surfactants. However, annealing may also remove surface functional groups that dope CNTs. Therefore, there are competing effects when annealing CNT electrodes. The impacts on electrode performance were investigated through the use of conductive-tip atomic force microscopy, sheet resistance, and transmittance measurements. In this thesis, the potential of graphene CNT composite electrodes as high performing transparent electrodes was investigated. As-made and annealed graphene oxide CNT composites electrodes were studied. Finally, a chemical vapor deposition grown graphene CNT composite electrode was also studied.

Chapter 1: Introduction to the luminescent properties of lanthanides Luminescence properties of trivalent lanthanides have been explored extensively over the past few decades owing to their unique properties. Lanthanides emission is known to be due to intra-configurational f-f transitions. Because the partially filled 4f shell is well shielded from its 26 environment by the closed 5sand 5pshells, the ligands in the first and second coordination sphere perturb the electronic configurations of the trivalent lanthanide ions only to a very limited extent. This leads to interesting properties such as long lifetimes, sharp line-like emissions etc. which in turn make lanthanides very attractive choice for commercial optical applications. Despite this, the scope of applications remained limited because of the low molar extinction coefficient values of the forbidden lanthanide f-f transitions. However, this problem has been successfully addressed by complexing the lanthanide ion with suitable ligands which can sensitize it resulting in a significant increase in the emission intensity (so called “antenna effect”). The strategy worked very well and resulted in widespread applications of lanthanides form biology to optoelectronics. This chapter discusses elementary ideas regarding the mechanism of sensitization and relevant examples that traces various applications of such lanthanide complexes from the current literature. Chapter 2: A self-assembled Europium Cholate hydrogel: a novel approach towards lanthanide sensitization Luminescent lanthanides can be of great value in a number of possible applications but their scope is limited by their intrinsic low molar absorptivities. Though this problem can be circumvented by complexing the lanthanide ion with suitable chelating ligands to improve the luminescence properties drastically, the design of such systems often involves meticulous planning and laborious synthetic steps to obtain a ligand suitable for the job. It is therefore desirable to have a simpler version of a sensitizing system that does not require the complexities of a chelating ligand but can sensitize trivalent lanthanides with comparable efficiency. It was observed in our group that divalent metal ions (Ni2+, Zn2+, Cu2+, Coetc.) form hydrogels on addition of sodium cholate. We extended to obtain hydrogels of trivalent lanthanides. Furthermore, when the gel was doped with pyrene, a ten-fold increase in the intensity of Eu(III) emission was observed (Fig 2). Thus we established a unique way to sensitize lanthanides in a hydrogel media by non-coordinating chromophores. The approach was completely modular in nature and avoids any laborious synthesis. We also tried other derivatives of pyrene as sensitizers and found that 1-pyreneboronic acid also caused similar sensitization of Eu(III). Fig 2. (a) Schematic representation of the sensitization process (the arrangement of molecules in the gel fiber is arbitrary). Eu-cholate (5 mM/15 mM) gel (a) normal light and (b) 354 nm UV excitation in the presence of 6 μM pyrene Further studies revealed, that 2,3-dihydroxynapthalene (DHN) can sensitize Tb(III) in a similar hydrogel. We also demonstrated Tb(III) to Eu(III) energy transfer process occurring in the gel when doped with DHN. This allowed us to achieve a hydrogel system with tunable luminescence properties (by varying relative ratios of Tb(III) and Eu(III) ). When the effect of divalent metal ions on such energy transfer processes were explored, it was observed that the luminescence from the composite gel of Tb(III)/ Eu(III) is tunable by Zn(II) and through proper manipulation of concentrations one can obtain white light emitting gel (Fig 3). Fig 3. Effect of Zn(II) (from left to right 0 mM, 2.8 mM, 11.3 mM) on Tb3+ (4.5 mM)/Eu3+ (0.11mM)/ sodium cholate (13.6 mM) gels. b) Tb/Eu/Zn-cholate gel (Tb3+ (4.4 mM), Eu3+ (0.11 mM), Zn2+ (7.4 mM), NaC (13.6 mM, DHN 0.2 mM) under 365 nm UV lamp (c) CIE 1931 diagram depicting the luminescence as white (black spot). Chapter 3. A “Pro-Sensitizer” based Sensing of Enzymes using Tb(III) Luminescence in a Hydrogel matrix This chapter descirbes design and realisation of a sensor system based on Tb(III) luminescnece for the detection of enzymes. The idea involved synthesizing a covalently modified DHN molecule by attaching appropriate enzyme cleavable units. We coined the term “pro-sensitizer”to describe the modified molecule which would not sensitize Tb(III) in the gel matrix but when proper enzymes are applied the free form of DHN would be released triggering a luminescence response from Tb(III). This would enable us to monitor the acitivities of the particular enzyme by examining the luminescence intensity enhancement with time (Fig 4) Fig 4. A “pro-sensitizer” based approach to detect different types of enzymes in a hydrogel matrix through Tb(III) luminescence. We applied the idea to develop a novel luminogenic gel probe for inexpensive and rapid detection of three different hydrolases, lipase, β–glucosidase and α-chymotrypsin. The corresponding “pro-sensitizer”for each enzyme were synthesized (Fig 5).The sensing technique depends on the gel matrix to provide the nessesary platform for lanthanide sensitization. Thereofore, it enjoys an edge over the contemporary techniques that typically involve specially designed and synthesized multidentate chelating ligands for this purpose. We also determined important kinetic parameters of all the enzymes, thus enabling us to have a better insight into the activity of the enzymes in the hydrogel matrix. Fig 4. Pro-sensitizers molecules for (1) lipase, (2) β-glucosidase and (3)α-chymotrypsin Chapter 4. A novel approach towards templated synthesis of lanthanide trifluoride nanoparticles Nanomaterials with excellent optical properties have been of special interest. Lanthanide derived nanoparticles, owing to their unique physical properties, provide an excellent choice for applications such as biolabels, lasers, optical amplifiers, and optical-display phosphors. Several types of lanthanide nanoparticles or nanocrystals are reported in the literature such as Nd2O3, Eu2O3, Gd2O3, Tb2O3, and Y2O3. Among them lanthanide fluoride nanoparticles have emerged as the best choice because of their low phonon energy, and thus minimum quenching of emissive Lnions thereby allowing maximum efficiency for several optical applications. In previous literature precedence, LnF3 nanoparticles were typically synthesized following conventional approaches which necessitate use of high temperatures, high pressures (hydrothermal techniques) and capping ligands. In this chapter, we demonstrated a simpler synthesis of LnF3 nanoparticles at ambient temperatures without the requirement of added capping agents. The room temperature synthesis of LnF3 was unprecedented and was achieved simply by diffusing NaF solution through the hydrogels of corresponding Ln-cholate gels. The nanoparticles were characterized by transmission electron microscopy (TEM) and by powder XRD analysis which established the presence of very small (3-4 nm) nanoparticles mono-dispersed uniformly over the the gel matrix (Fig 6). The LnF3 containing xerogels of Tb(III) and Eu(III) cholate gels were also shown to be highly emissive. Fig 6. HRTEM images of a) TbF3, b) GdF3, c) NdF3 and d) DyF3 in their corresponding gel media.

Chapter 1. General Introduction This chapter gives an introduction to supramolecular organo/hydrogels and the related bile acid chemistry touching upon the gelation properties of the bile acid derivatives. Diverse applications of the supramolecular gels are illustrated with several examples. In the concluding section of this chapter, a brief introduction on the semiconductor nanocrystals is provided. Finally, the content of the thesis is outlined. Chapter 2. Bile Acid Derived Novel Organo/hydrogelators Part 1. Bile Acid Derived Organo/hydrogelators With a Basic Side Chain Cationic analogues of bile acids which showed remarkable gelation properties in water were reported from our laboratory. This led us to investigate the aggregation behaviour of some of the lithocholic and deoxycholic acid derivatives having a basic side-chain. Figure 1. Bile acid based organo/hydrogelators containing a basic side-chain. In this part, an organogelator 1 and a hydrogelator 2 derived from parent bile acids have been described with respect to their gelation properties, morphology, thermal and mechanical stability of the gels. The organo/hydrogels were shown to be responsive to acid-base stimuli as the organogel formed only in the protonated state and the hydrogel formed in the neutral form of the tertiary amines. The xerogel fibres obtained from the organogel were found to be solid-like and stable up to 200 oC as confirmed by variable temperature polarizing optical microscopy. The non-fluorescent organogel was doped with a fluorescent dye (coumarin 153) to design a novel dye-organogel composite material which was investigated with laser scanning confocal fluorescence microscopy showing the dye molecules were uniformly deposited on the organogel fibres. Part 2. Serendipitous Organogelation by Dimeric Bile Acid Esters This section highlights our work on the organogelators based on a number of dimeric esters consisting of different bile acid units. Figure 2. The three different dimeric bile acid esters as organogelators. In this part, three bile acid derived dimeric esters (1, 2 and 3) were shown to possess organogelation properties in aromatic and halogenated aromatic solvents. We studied the morphological features and rheological properties of these organogels. Next, the organogel matrix was exploited to generate and stabilize gold nanoparticles and prepare AuNP/gel hybrid material. Chapter 3. Cholate Hydrogels and Soft Gel-nanoparticle Hybrid Materials Sodium cholate does not form gel in water under any condition as compared to other sodium salts of other bile acids such as sodium deoxycholate and lithocholate which show pH-dependent gelation behaviour. Figure 3. Metal cholate hydrogels derived from sodium cholate and a variety of metal ions. In this chapter, super hydrogelation of sodium cholate induced by a variety of metal ions (Ca2+, Cu2+, Co2+, Zn2+, Cd2+, Hg2+ and Ag+) is highlighted with respect to their morphology and mechanical strength/stability. The calcium cholate supramolecular system showed the presence of helically twisted nanofibres which were utilised in the synthesis of soft hybrid materials containing metal (Au and Ag) and metal sulphide (CdS, ZnS, HgS, etc.) nanoparticles. Chapter 4. Cadmium Deoxycholate and Highly Luminescent CdSe Nanocrystals Bile acid derivatives have very high chemical and thermal stability owing to the presence of a rigid steroidal nucleus. We explored the possibility of utilizing the bile salt derived from Cd as a metal complexes as precursor to high quality nanocrystals (NCs) which can only be accessed at high temperatures (>200 oC). Figure 4. Synthesis of high quality CdSe NCs from cadmium deoxycholate. In this chapter, the synthesis of high quality CdSe nanocrystals is discussed using a novel bile acid based precursor: cadmium salt of 7-deoxycholic acid, which has high thermal stability and can be conveniently used at very high temperatures (>300 oC) required for the synthesis of high quality nanocrystals. Syntheses were done both by ‘injection’ and ‘non-injection’ modes. The as-prepared nanocrystals have high photoluminescence quantum yield, multiple excitons, narrow size-distributions and zinc blende/wurtzite crystalline cores. Appendix. Steroidal Thiols in Design of Novel Quantum dot (QD)/Gel Hybrid Materials Bile acid derived steroidal thiols were reported to be efficient capping agents for silver and gold nanoparticles from our laboratory. So, we wanted to check whether they could stabilize the semiconductor nanocrystals as well. Figure 5. Steroidal thiols as stabilizers of semiconductor quantum dots. In this short report, we describe the efficient capping by bile acid derived thiols of group II-VI semiconductor nanocrystals/quantum dots (QDs) (CdS, CdSe). After synthesizing the thiol capped QDs, we tried to disperse the capped nanoparticles into the gel fibres. The hybrid gels showed the presence of nanoparticles inside the fibres as observed by transmission electron microscopy, although the photoluminescence of the QDs was very low in the gel matrix, which might be due to the inefficient surface passivation of the nanoparticles in the gel.