Rozprawy doktorskie na temat „Hydrogelator”

Systems formed by the supramolecular assemblages of organic molecules known as organogelators and hydrogelators are currently, and only recently, a subject of great attention and promise. In this context, low molecular weight gelators (LMWGs) are of particular interest because they provide a bottom-up approach to the formation of supramolecular architectures through self-assembly. Gelator molecules do so via the initial formation of a one-dimensional array of individual molecules bound non-covalently through forces such as: hydrogen bonds, electrostatic forces, Van der Waals interactions, and other weak forces such as π-π interactions. These interactions then lead to secondary structure formation through a similar assembly mechanism. Understanding the gelation process through characterization techniques is critical to the development of a design rationale for gelator molecules. Past and current research performed by the Wang group indicates that analogues of various 4,6-benzylidene acetals form stable gels in organic, aqueous, and organic/aqueous solvents at varying concentrations. The basis of varying the 4,6-protecting groups on glucose and glucosamine derivatives is to discern the relative structure activity relationships of these systems, and as well to fabricate functional systems which respond to external stimulus. Stimuli responsive or trigger release gel systems formed by sugar based low molecular weight gelators (LMWGs) have applications as smart biocompatible materials, and such responsiveness in various media was explored and developed to determine the feasibility of such applications using monosaccharide derivatives.

This thesis will cover aspects of functionalised dipeptide hydrogels and their application in energy transfer and as vehicles for drug delivery. In the first section, a large number of dipeptides conjugated to different aromatic groups were synthesised. We synthesised 35 dipeptides conjugated to different aromatic groups (naphthalene, anthracene, phenanthrol, anthraquinone, carbazole and pyrene). We synthesised a large number of dipeptides with different hydrophobicity and different aromatic groups in order to study their ability to form gels and study the mechanical properties of the gels. The second part of this thesis will investigate the formation of hydrogels based on dipeptides with different aromatic groups. The focus in this section was on the gelation as well as the effect of changing the solvent and changing the amino acids used. This section then explores the properties of the resulting hydrogels. A number of different dipeptides containing different amino acids were tested, some of which formed gels and others. The dipeptides also had different pKa values. This factor was shown to be important in driving the preferential selection of a certain amino acids. The thesis then describes energy transfer which can occur between two dipeptides (pyrene and anthracene dipeptides), or between a dipeptide and a dansyl derivative (phenanthrol and dansyl, or carbazole and dansyl). These results showed that energy transfers can occur in these specific hydrogels. In all other cases, no evidence for energy transfer was found. This may imply that the packing of the fibres is important for energy transfer and this should be the focus of future work. The final section of this thesis describes the controlled release of model dyes from these gels. We studied controlled release from FmocFF hydrogels and from one other functionalised dipeptide hydrogel at different gelator concentrations and at different pH. The release of the dye from the hydrogel can be controlled by different factors, including the pH, peptide concentration, the microstructure and the mesh size. Furthermore, choosing the right method to prepare hydrogel allows us to control the microstructure for hydrogel to be injectable. Therefore, by controlling these entire factors we can use these kinds of hydrogels for drug delivery applications.

The overall objective of this thesis was to elucidate molecular design rules for the preparation of self-assembled aromatic peptide amphiphile based hydrogels. Aromatic peptide amphiphiles can be considered as having three distinct parts: the N-terminal aromatic group, peptide sequence, and the linker between the two. A systematic variation of these three molecular components has in the first instance revealed that contrary to popular belief, the antiparallel or parallel H-bonding supramolecular conformations associated with aromatic peptide amphiphiles cannot be distinguished by FTIR experiments alone. Instead, the 1685 cm-1 peak commonly assigned to an antiparallel arrangement, relates to the methoxycarbonyl linker if present in these systems. The choice of linker is also seen to have implications for assembly in both the aromatic and peptidic domains - as seen by fluorescence emission and FTIR respectively. In addition, the linker influences the supramolecular chirality of the f ibrous nanostructures by CD. The optimal linker for effective self-assembly and gelation is observed to depend primarily on the corresponding aromatic moiety, with fluorenyl and pyrenyl systems exhibiting differential preferences for relatively rigid and relatively flexible linkers, respectively. Besides covalent alterations, aromatic peptide amphiphile materials can also be modified through co-assembly. Here, the co-assembly structure is found to vary depending upon the aromatic and peptide segments associated with co-assembly constituents. Orthogonal co-assembly is observed in systems with different aromatic and peptide parts, as inferred by a preservation of characteristic spectroscopy and material properties associated with the assembly of individual constituents. In contrast, nanoscale phase separation is found to be disfavoured in systems that share either a common aromatic or peptide segment between co-assembly constituents. Consequently, for cooperative and disruptive systems, spectroscopy reveals substantial interactions between constituents, whilst material properties are also found to be affected through co-assembly. Finally, preliminary work demonstrates the functionalisation of bulk electrodes and MEA devices with electrochemically deposited hydrogel coatings possessing an electronic core furnished with a biocompatible coating as derived from the aforementioned co-assembly design rules. Coated electrodes are found to exhibit similar impedances to those of uncoated nodes, but prove inferior to platinised equivalents. Future work will focus on optimising said electrode impedances for potential neuron-device interface applications.

This thesis reports a number of studies that examines low molecular weight hydrogelators forming through in situ chemical reactions and gel the water in which this reaction occurs. This in situ gelation process has allowed a number of chemical and physical reactions and assembly processes to be investigated. Pathway complexity, an exciting concept within chemical systems has been explored with a multi-reactive hydrazone based gelation system that allows different gels to be formed from a single starting point through navigation of the systems' energy landscape. This work inspired the development of a large family of imine based gelators that would undergo an effectively irreversible tautomerisation. This allowed exploration and characterisation of the systems' ability to self-sort and co-assemble, at both the molecular and macroscopic level. One particular imine inspired gelator featured a much slower in situ reaction. This allowed characterisation of its reaction kinetics and demonstrated its autocatalytic behaviour. This thesis highlights the link between the chemical reactions that form the individual gelator molecules and the supramolecular assembly process. By using one to control the other, an in-depth understanding of the presented systems has been developed, allowing for the accurate targeting of desired physical properties.

La bioimpression 3D est une branche de l’ingénierie tissulaire actuellement en plein essor, cherchant à reproduire avec fidélité la microarchitecture complexe de tissus et organes. Malgré un large éventail de biomatériaux utilisés dans la formulation de bioencres, il s’avère essentiel de trouver une alternative aux biomatériaux naturels et synthétiques classiquement utilisés, permettant de mimer la matrice extracellulaire et de présenter des capacités d’impression de façon conjointe.Le présent travail met en avant, pour la première fois, les capacités de la molécule bioinspirée de type nucléolipide diC16dT à permettre la formulation d’une encre de bioimpression par extrusion. L’encre, formulée dans du milieu de culture cellulaire présentait des propriétés rhéologiques lui permettant d’être imprimée de façon continue. Il a également été possible d’y incorporer des fibroblastes gingivaux tout en maintenant leur viabilité cellulaire au sein des bioconstructions. Cette encre offre également plusieurs possibilités d’adaptation, notamment en terme de concentration en diC16dT et de milieux de culture en vue de répondre aux exigences d’autres types cellulaires. Enfin, des travaux préliminaires ont permis l’incorporation de liposomes dans la formulation de l’encre sans affecter ses capacités d’impression. Ceci permettra d’envisager la délivrance de substances actives ou d’éléments nutritifs au sein des bioimpressions, fonctionnalité des liposomes qui, à notre connaissance n’avait jamais été mise en valeur auparavant
3D bioprinting is an emerging field of tissue engineering, that aims at faithfully reproducing the complex microarchitecture of tissues and organs. Despite a wide range of biomaterials used in bioink formulation, it is essential to find an alternative to the natural and synthetic biomaterials conventionally used, mimicking extracellular matrix and presenting printing capabilities jointly.The present work demonstrated for the first time, the ability of the bioinspired nucleolipid molecule diC16dT to formulate an extrusion bioprinting ink. The ink formulated in cell culture medium showed rheological properties allowing its continuous printability. It was also possible to incorporate gingival fibroblasts while maintaining the cell viability within bioconstructions. This ink also offered several adaptation possibilities, especially in terms of diC16dT concentration and cell culture medium to meet other cellular types requirements. Finally, the preliminary work showed the feasibility of the incorporation of liposomes into the ink formulation without affecting its printing capabilities. Thus, it would possible to further consider the delivery of active substances or nutrients within the bioconstructions. This application has to the best of our knowledge not been developed yet for liposomes

碩士
中原大學
化學研究所
103
Two low molecular weight hydrogelators have been developed by us. These two hydrogelators are the glycolipids that consist of glucosamine, tethering the (2S,3S)-2,3-dihydroxydecanoyl acid and (2R,3R)-2,3- dihydroxy tetradecanoyl acid, respectively.(S10 and R14). Among these two compounds, S10 a reversible gelator exhibits the stimulus-responsive ability at pH 3.0-5.0. The asymmetric synthese of these two dihydroxyalkanoyl acids have been accomplished by using chiral-pool method strategy. Herein, D-ribose is used as the starting material to synthesize these two optically active dihydroxyalkanoyl acids that configurations are mirro image each other at the same time.

Dissertação de mestrado em Medicinal Chemistry
Self-assembly of nanometric structures from molecular building blocks is an effective way to make new functional materials for biological and technological applications. In this work we synthesized new N-modified dehydrodipeptides based on phenylalanine and dehydroamino acid units attached to aromatic modifiers, namely trimesoyl, terephtaloyl, diphenylacetyl and 2,2´-(1,3-phenylene)diacetyl in a pattern that afforded mono or polysubstitued organic molecules. The potential use of these new compounds as hydrogelators was evaluated. The results showed that most of the prepared compounds behave as efficient molecular hydrogelators forming hydrogels at minimum gelation concentrations of 0.3-0.8 wt%. Two new compounds failed to form hydrogels probably due to unfavorable thermodynamic contribution of intermolecular interactions. The self-aggregation pattern of the hydrogelators was investigated by STEM microscopy technique, revealing different shapes depending on the N-aromatic moiety. A circular dichroism analysis was also performed in order to evaluate if the peptides aggregate into any characteristic secondary structure, usually found in protein folding. We found that the 5 hydrogelators had characteristic signals, demonstrating the presence of organized structures even below the minimum gelation concentration. At elevated pH or for the non-hydrogelating compounds, it was not observed signals indicative of the presence of such structures.
A automontagem de estruturas manométricas, a partir de entes de dimensão molecular, consiste em uma alternativa eficiente para a síntese de novos materiais funcionais para aplicações biotecnológicas. Neste trabalho, foram sintetizados novos desidrodipéptidos modificados em sua porção N-terminal. Os dipéptidos continham fenilalanina e desidroaminoácidos e os grupos modificadores foram grupos aromáticos (trimesoil, tereftaloil, difenilacetil e o 2,2´-(1,3- phenileno)diacetil) os quais foram conjugados de forma a gerar compostos mono ou polissubstituídos. A capacidade de gelificar em meio aquoso, destes novos compostos, foi avaliada e os resultados mostraram que a maioria deles conseguiram gelificar em meio aquoso em concentrações mínimas na faixa 0.3-0.8 m%. Dois destes compostos não conseguiram originar hidrogéis, provavelmente devido a um balanço termodinamicamente desfavorável das interacções intermoleculares entre os constituintes do sistema. O padrão morfológico resultante da auto-agregação dos compostos que geraram os hidrogéis foi investigado pela técnica de microscopia electrónica de transmissão por scaneamento (STEM). Esta análise revelou que houve a ocorrência de diferentes tipos de estruturas nos hidrogéis, dependendo de qual modificador aromático foi utilizado. Também realizou-se uma análise de Dicroísmo Circular para avaliar se os péptidos agregavam-se em algum padrão de estrutura secundária característica de enovelamento proteico. Detectou-se que nos 5 agentes gelificates haviam sinais característicos da presença de estruturas organizadas mesmo abaixo da concentração de gelificação mínima. Em pH elevado e nas moléculas não gelificantes, não se observam sinais indicativos da presença deste tipo de estruturas.
Fundação para a Ciência e a Tecnologia (FCT)

Chapter 1. Supramolecular Gels and their Applications Supramolecular gels are viscoelastic materials composed of a solid like three dimensional fibrillary network that is embedded in a liquid. Supramolecular gels are derived from low molecular weight compounds (typically MW < 3000). In the 1990s, the investigations on gels were mainly focused on designing new gelator molecules. However, during the last decade, research focus shifted towards designing functional gels and their applications. As a result of extensive work in this area, gels have been found to have varied applications in the templated synthesis of inorganic nanomaterials, hybrid materials, light harvesting systems, as responsive system and sensors, and also in drug delivery, tissue engineering etc. This chapter gives an introduction to supramolecular hydrogels/organogels and relevant bile acid chemistry touching upon the gelation properties of the bile acid derivatives. Diverse applications of the supramolecular gels are also illustrated with several examples. Scheme 1. Various applications of functional supramolecular gels Chapter 2. Bile Acid derived novel Hydrogelators Part 1. Hydrogelation of Bile acid protected Amino acids and Hybrid Materials Hydrogels from low molecular weight molecules have significant importance in biomedical applications. In this chapter, we report injectable hydrogel formation from bile acid conjugates of various amino acids. Hydrogel formation was found to be dependent on multiple factors such as bile acid backbone structure, linkage between the bile acid and the amino acid, pH etc. Single crystal structures of lithocholyl phenylalanine, lithocholyl-glycine, lithocholyl-L valine and lithocholyl-L alanine were also determined. Finally, the hydrogel frameworks were utilized to produce hybrid materials with Gold and ZnO nanoparticles. Scheme 2. (a) Crystal structure of LC-LF-OH gelator molecule, (b) photograph of gel, (c) SEM and (d) AFM image of LC-LF-OH xerogel Part 2. Hydrogelation of bile acid-dipeptide conjugates and in situ synthesis of silver and gold nanoparticles in the hydrogel matrix Fabricating supramolecular hydrogels with embedded metal nanostructures are important for the design of novel hybrid nanocomposite materials for diverse applications such as bio sensing and chemo sensing platforms, catalytic and antibacterial functional materials etc. Supramolecular self-assembly of bile acid-dipeptide conjugates have led to the formation of new supramolecular hydrogels. Gelation of these molecules depends strongly on the hydrophobic character of the bile acids. Ag+ and Au3+ salts were incorporated in the hydrogels, and photo reduction and chemical reduction led to the in situ generation of Ag and Au NPs in these supramolecular hydrogels without the addition of any external stabilizing agent. The color, size and shape of silver nanoparticles formed by photo reduction depended on the amino acid residue on the side chain. Furthermore, the hydrogel-Ag nanocomposite was tested for its antimicrobial activity. Scheme 3. Bile acid based dipeptide hydrogelators and soft hybrid materials Chapter 3. Sonogels of bile salts of In(III): use in the formation of self-templated indium sulfide nanostructures In this chapter, facile hydrogel formation by Indium(III) cholate and deoxy cholate are reported. When In(III) solution was added to aqueous solutions of sodium cholate and sodium deoxy cholate and sonicated, the mixtures formed gels. The gels thus obtained were translucent/turbid and thermos irreversible. Rheological measurements showed that all of them could be classified as viscoelastic soft solids. Scanning electron microscopy and atomic force microscopy showed typical entangled three dimensional fibrous networks. The In-Ch hydrogel were further used to prepare nanostructured In2S3 in which the cholate units possibly acted as a surfactant to confine the growth of the Nano flakes. Scheme 4. In-Ch hydrogel (Photograph and SEM image of In-Ch gel) Chapter 4. Palladium-Hydrogel Nanocomposite for C-C Coupling Reactions Supported metallic nanoparticles are important composite materials owing to their enormous potential for applications in various fields. This chapter describes the in situ formation of palladium nanoparticles in a calcium-cholate (Ca-Ch) hydrogel by reduction with sodium cyan borohydride. The hydrogel matrix appeared to assist the controlled growth as well as stabilization of palladium nanoparticles. The palladium nanoparticle/Ca-Ch hydrogel hybrid was characterized by scanning and transmission electron microscopy, atomic force microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. Furthermore, PdNP/Ca-Ch hybrid xerogel was shown to act as an active catalyst for Suzuki reaction under aqueous aerobic conditions, up to 4 cycles. This PdNP/Ca-Ch xerogel retained its catalytic activities on storage for several months. Scheme 5. Palladium-hydrogel nanocomposite for C-C coupling reactions in water Chapter 5. Sensitization of Terbium/Europium in self-assembled cholate hydrogel: An approach towards the detection of amine vapours "Luminescent" lanthanides have intrinsic low molar absorptivity, although this problem can be addressed by complexing the lanthanide ion with suitable chelating ligands which improve the luminescence properties drastically. However the design of such systems often involves careful planning and laborious synthetic steps. It is therefore desirable to have a simpler way to sensitize lanthanides with high efficiency. It was observed in our group that trivalent lanthanides formed hydrogels on the addition of sodium cholate. This chapter describes the discovery of the several biphenyl derivatives (such as 4-biphenylcarbaxaldehyde, 4-acetylbiphenyl) for sensitization of Tb(III) and Eu(III) in lanthanide hydrogels. Sensitization of Tb(III) and Eu(III) were observed by doping was characterized by scanning and transmission electron microscopy, atomic force microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. Furthermore, PdNP/Ca-Ch hybrid xerogel was shown to act as an active catalyst for Suzuki reaction under aqueous aerobic conditions, up to 4 cycles. This PdNP/Ca-Ch xerogel retained its catalytic activities on storage for several months. Scheme 6. Schematic representation of the sensitization process (the arrangement of themolecules in the gel fiber is arbitrary)(For figures pl refer the abstract pdf file)

Chapter 1. Supramolecular Gels and their Applications Supramolecular gels are viscoelastic materials composed of a solid like three dimensional fibrillary network that is embedded in a liquid. Supramolecular gels are derived from low molecular weight compounds (typically MW < 3000). In the 1990s, the investigations on gels were mainly focused on designing new gelator molecules. However, during the last decade, research focus shifted towards designing functional gels and their applications. As a result of extensive work in this area, gels have been found to have varied applications in the templated synthesis of inorganic nanomaterials, hybrid materials, light harvesting systems, as responsive system and sensors, and also in drug delivery, tissue engineering etc. This chapter gives an introduction to supramolecular hydrogels/organogels and relevant bile acid chemistry touching upon the gelation properties of the bile acid derivatives. Diverse applications of the supramolecular gels are also illustrated with several examples. Scheme 1. Various applications of functional supramolecular gels Chapter 2. Bile Acid derived novel Hydrogelators Part 1. Hydrogelation of Bile acid protected Amino acids and Hybrid Materials Hydrogels from low molecular weight molecules have significant importance in biomedical applications. In this chapter, we report injectable hydrogel formation from bile acid conjugates of various amino acids. Hydrogel formation was found to be dependent on multiple factors such as bile acid backbone structure, linkage between the bile acid and the amino acid, pH etc. Single crystal structures of lithocholyl phenylalanine, lithocholyl-glycine, lithocholyl-L valine and lithocholyl-L alanine were also determined. Finally, the hydrogel frameworks were utilized to produce hybrid materials with Gold and ZnO nanoparticles. Scheme 2. (a) Crystal structure of LC-LF-OH gelator molecule, (b) photograph of gel, (c) SEM and (d) AFM image of LC-LF-OH xerogel Part 2. Hydrogelation of bile acid-dipeptide conjugates and in situ synthesis of silver and gold nanoparticles in the hydrogel matrix Fabricating supramolecular hydrogels with embedded metal nanostructures are important for the design of novel hybrid nanocomposite materials for diverse applications such as bio sensing and chemo sensing platforms, catalytic and antibacterial functional materials etc. Supramolecular self-assembly of bile acid-dipeptide conjugates have led to the formation of new supramolecular hydrogels. Gelation of these molecules depends strongly on the hydrophobic character of the bile acids. Ag+ and Au3+ salts were incorporated in the hydrogels, and photo reduction and chemical reduction led to the in situ generation of Ag and Au NPs in these supramolecular hydrogels without the addition of any external stabilizing agent. The color, size and shape of silver nanoparticles formed by photo reduction depended on the amino acid residue on the side chain. Furthermore, the hydrogel-Ag nanocomposite was tested for its antimicrobial activity. Scheme 3. Bile acid based dipeptide hydrogelators and soft hybrid materials Chapter 3. Sonogels of bile salts of In(III): use in the formation of self-templated indium sulfide nanostructures In this chapter, facile hydrogel formation by Indium(III) cholate and deoxy cholate are reported. When In(III) solution was added to aqueous solutions of sodium cholate and sodium deoxy cholate and sonicated, the mixtures formed gels. The gels thus obtained were translucent/turbid and thermos irreversible. Rheological measurements showed that all of them could be classified as viscoelastic soft solids. Scanning electron microscopy and atomic force microscopy showed typical entangled three dimensional fibrous networks. The In-Ch hydrogel were further used to prepare nanostructured In2S3 in which the cholate units possibly acted as a surfactant to confine the growth of the Nano flakes. Scheme 4. In-Ch hydrogel (Photograph and SEM image of In-Ch gel) Chapter 4. Palladium-Hydrogel Nanocomposite for C-C Coupling Reactions Supported metallic nanoparticles are important composite materials owing to their enormous potential for applications in various fields. This chapter describes the in situ formation of palladium nanoparticles in a calcium-cholate (Ca-Ch) hydrogel by reduction with sodium cyan borohydride. The hydrogel matrix appeared to assist the controlled growth as well as stabilization of palladium nanoparticles. The palladium nanoparticle/Ca-Ch hydrogel hybrid was characterized by scanning and transmission electron microscopy, atomic force microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. Furthermore, PdNP/Ca-Ch hybrid xerogel was shown to act as an active catalyst for Suzuki reaction under aqueous aerobic conditions, up to 4 cycles. This PdNP/Ca-Ch xerogel retained its catalytic activities on storage for several months. Scheme 5. Palladium-hydrogel nanocomposite for C-C coupling reactions in water Chapter 5. Sensitization of Terbium/Europium in self-assembled cholate hydrogel: An approach towards the detection of amine vapours "Luminescent" lanthanides have intrinsic low molar absorptivity, although this problem can be addressed by complexing the lanthanide ion with suitable chelating ligands which improve the luminescence properties drastically. However the design of such systems often involves careful planning and laborious synthetic steps. It is therefore desirable to have a simpler way to sensitize lanthanides with high efficiency. It was observed in our group that trivalent lanthanides formed hydrogels on the addition of sodium cholate. This chapter describes the discovery of the several biphenyl derivatives (such as 4-biphenylcarbaxaldehyde, 4-acetylbiphenyl) for sensitization of Tb(III) and Eu(III) in lanthanide hydrogels. Sensitization of Tb(III) and Eu(III) were observed by doping was characterized by scanning and transmission electron microscopy, atomic force microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. Furthermore, PdNP/Ca-Ch hybrid xerogel was shown to act as an active catalyst for Suzuki reaction under aqueous aerobic conditions, up to 4 cycles. This PdNP/Ca-Ch xerogel retained its catalytic activities on storage for several months. Scheme 6. Schematic representation of the sensitization process (the arrangement of themolecules in the gel fiber is arbitrary)(For figures pl refer the abstract pdf file)

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.

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.

碩士
中原大學
化學研究所
101
The primary concern of this study is to explore the research on a series of glycolipids with homochiral α,β-dihydroxyfatty acid moiety of low-molecular-mass gelators (GR-1~GR-4) and apply to drug delivery system. In gelation test, the gelators GR-1 was developed a stable gel form in purified water, in which the minimal concentration of gelation was 4 mg/mL and the temperature (Tgel) of gel-solution transition was at 64 oC. The self-assembly of intermolecular hydrogen bonding gelator GR-1 was confirmed by 1H NMR spectra. The bilayer-packed lamellar structure within ribbon-like fibers was resulted in the self-assembly of GR-1 by entanglement to produce 3-D network structures. In the pH-stimuli responsive test, the hydrogel generated from gelators GR-1 was proving responsive to the change of pH value, and gel was formed only at pH 7.0, 8.0, 9.0. It was identified that the respondence between the gelator and the pH-stimuli was provided with the reversible feature. In the investigation of drug delivery in vitro, the hydrogel was generated from gelators GR-1 regarded as the carrier. A model drug 5-fluorouracil (5-FU) was entrapped in supramolecular hydrogels.. The influence of the concentration of hydrogelator, concentration of 5-FU and pH values of phosphate buffer saline was investigated by high performance liquid chromatography (HPLC) on the releasing behavior of 5-FU. The study of the releasing kinetics was indicated that the releasing behavior of 5-FU was in accord with the Non- Fickian model by the Peppas equation .

The present thesis titled “Molecular Modulation of Material Properties: Stud- ies on Nanoparticles, Nanoassemblies and Low Molecular Mass Gelator” deals with the preparation, characterization, and investigations into the properties of gold nanoparticles coated with novel thiols. The coverage of nanoparticle surfaces with these thiols renders them with special characteristics that will be of interest in biological and sensor applications. Also, a novel low molecular mass tetrameric sugar-based hydrogelator was synthesized and its gelation properties were studied in detail. Chapter 1 gives a general introduction and an overview about Nanomaterials, with emphasis towards nanoparticles of gold, which form the basis of this work. It delves with the history of research in noble metal nanoparticles, their interesting electronic and optical properties, the present methods of synthesis of high quality nanoparticles of noble metals, numerous potential applications of these novel materials, as well as the challenges in their real-life applications, and ends with the future outlook of this field of research. Chapter 2 describes the synthesis and characterization of three cationic lipid-like disulfides whose molecular structures are shown in Fig. 2.1. Gold nanoparticles capped with these molecules were then synthesized in small size dispersion by a simple one-phase protocol. These particles exhibited remarkably different solubility properties that were dictated by the molecular structure of the capping agent. The nanoparticles were characterized by a variety of techniques like UV-visible spec- troscopy, Transmission Electron Microscopy (TEM), proton Nuclear Magnetic Resonance (1H NMR), Fourier Transform Infra-red (FTIR) spectroscopy, and Zeta Potential measurements. These nanoparticles were then examined for their interactions (structural formula) Figure 1: Chemical Structures of the cationic lipid-like thiols used for nanoparticle preparation with dipalmitoyl phosphatidyl choline (DPPC) vesicles as model biological membranes. TEM, UV-vis, and Differential Scanning Calorimetry (DSC) were employed to probe the interactions. It was found that the capping agent of the nanoparticle had a strong bearing upon the interactions of the nanoparticles with DPPC vesicles. Chapter 3 describes the assembly of hydrophilic cationic nanoparticles upon elec- trostatic interaction with a variety of anionic surfactants. The chemical structures of some of the anions employed in the study, as well as a schematic of cationic nanopar- ticle are shown in Fig. 2. Upon ion pairing with long-chain anionic surfactants, the hydrophilic cationic nanoparticles were completely hydrophobized. They could then be phase-transferred to organic layer. TEM showed that nanoparticles assemble in to a variety of mesostructures upon ion-pairing with anions. The aggregate formation was found to depend critically upon length of the hydrophobic alkyl chain as well as the head-group of the anion. Isothermal Titration Calorimetry (ITC) was employed to probe the interactions of these nanoparticles with anions. It was found that the anions that resulted in nanoparticle precipitation displayed exothermic interactions with the nanoparticle. Chapter 4 deals with the synthesis of -thiolated metal chelator derivatives whose structures are shown in Fig. 3. The molecules are based on well-known chelators viz. iminodiacetic acid and bis-(2-pyridylmethyl)amine. While the first one is carboxylic acid-based chelator, the second one is pyridine-based. Nanoparticles coated with these chelators were synthesized in a size-controlled manner. These nanoparticles exhibited pH-controlled reversible assembly. However, while S-IDA based nanoparticles aggregated at low pH values, the S-BPA based nanoparticles aggregated in high pH regimes. Mixed monolayer protected gold nanoparticles were synthesized by employing S-BPA and C12H25SH as capping agents. It resulted in the formation of nanoparticles in low size-dispersion. These nanoparticles were characterized by 1H NMR spectroscopy to infer the ratio of the two capping agents on the nanoparticle surface. These nanoparticles demonstrated metal-ion induced aggregation. It was found that the nanoparticles could differentiate Cu2+ ions from other ions, and immediately formed aggregates in presence of Cu2+ ions. Chapter 5 describes the synthesis of novel mono-thiolated “Gemini” surfactants for nanoparticle synthesis. Gemini surfactants with different spacers were prepared. These surfactants had a 12-n-12 kind of molecular structure as shown in the Fig. 4. Upon preparation of nanoparticles with these thiols, the resulting material was soluble in water in the case of rigid thiols like D2S and DBPS Chapter 6 deals with the synthesis and hydrogelation properties of a low molecular mass hydrogelator based on an azobenzene based tetrameric sugar derivative (Fig. 5). The pKa of carboxylic acids in the molecule were determined using 13C NMR. The trans-to-cis isomerization of the compound was probed by time-dependent UV-vis studies. The sugar derivative exhibited pronounced hydrogelation capacity, gelling water at micromolar concentration. The gel formed was characterized extensively (structural formula) Figure 2: Schematic of cationic nanoparticles and molecular structures of the anions employed for nanoparticle assembly (structural formula) Figure 3: Chemical structures of metal-chelator containing thiols employed for the pH-controlled and metal-ion mediated nanoparticle assembly (structural formula) Figure 4: Schematic of cationic nanoparticles and molecular structures of the anions employed for nanoparticle assembly (structural formula) Figure 5: Chemical Structure of azobenzene-based tetrameric sugar derivative exhibit- ing pronounced hydrogelation using melting temperature analysis, UV-vis, FT-IR, circular dichroism spectroscopy and scanning electron microscopy. The resultant gel exhibited impressive tolerance to the pH variation of the aqueous phase and gelated water in the pH range of 4 to 10. While UV-vis and CD spectroscopy indicated that pronounced aggregation of the azobenzene chromophores in the gelator was responsible for gelation, FT-IR studies showed that hydrogen bonding is also a contributing factor in the gelation process. The melting of gel was found to depend upon the pH of the aqueous medium in which gel was formed. The gel showed considerable photostability to UV irradiation indicating tight intermolecular packing inside gelated state that render azobenzene groups in the resultant aggregate refractory to photoisomerization. The electron micrographs of the aqueous gels thus formed showed the existence of spongy globular aggregates in such gelated materials. Addition of salts to the aqueous medium led to a delay in the gelation process and also caused remarkable morphological changes in the microstructure of the gel. Appendix A describes the employment of ligand-free palladium nanoparticles towards efficient catalysis of Heck and Suzuki reactions in aqueous medium. Hexadecyl trimethylammonium bromide was employed as the surfactant to achieve solubilization of organic compounds in aqueous medium. UV-vis and TEM investigations into the formation of nanoparticles in the reaction media were undertaken. These studies indicate that the nanoparticles were formed by reduction of potassium tetrachloropalladinate by methyl acrylate used as one of the reactants. TEM investigation indicated the formation of nanoparticle assemblies upon solvent drying. Efficient and catalytic synthesis of a number of organic compounds could be achieved in high yield.

The present thesis titled “Molecular Modulation of Material Properties: Stud- ies on Nanoparticles, Nanoassemblies and Low Molecular Mass Gelator” deals with the preparation, characterization, and investigations into the properties of gold nanoparticles coated with novel thiols. The coverage of nanoparticle surfaces with these thiols renders them with special characteristics that will be of interest in biological and sensor applications. Also, a novel low molecular mass tetrameric sugar-based hydrogelator was synthesized and its gelation properties were studied in detail. Chapter 1 gives a general introduction and an overview about Nanomaterials, with emphasis towards nanoparticles of gold, which form the basis of this work. It delves with the history of research in noble metal nanoparticles, their interesting electronic and optical properties, the present methods of synthesis of high quality nanoparticles of noble metals, numerous potential applications of these novel materials, as well as the challenges in their real-life applications, and ends with the future outlook of this field of research. Chapter 2 describes the synthesis and characterization of three cationic lipid-like disulfides whose molecular structures are shown in Fig. 2.1. Gold nanoparticles capped with these molecules were then synthesized in small size dispersion by a simple one-phase protocol. These particles exhibited remarkably different solubility properties that were dictated by the molecular structure of the capping agent. The nanoparticles were characterized by a variety of techniques like UV-visible spec- troscopy, Transmission Electron Microscopy (TEM), proton Nuclear Magnetic Resonance (1H NMR), Fourier Transform Infra-red (FTIR) spectroscopy, and Zeta Potential measurements. These nanoparticles were then examined for their interactions (structural formula) Figure 1: Chemical Structures of the cationic lipid-like thiols used for nanoparticle preparation with dipalmitoyl phosphatidyl choline (DPPC) vesicles as model biological membranes. TEM, UV-vis, and Differential Scanning Calorimetry (DSC) were employed to probe the interactions. It was found that the capping agent of the nanoparticle had a strong bearing upon the interactions of the nanoparticles with DPPC vesicles. Chapter 3 describes the assembly of hydrophilic cationic nanoparticles upon elec- trostatic interaction with a variety of anionic surfactants. The chemical structures of some of the anions employed in the study, as well as a schematic of cationic nanopar- ticle are shown in Fig. 2. Upon ion pairing with long-chain anionic surfactants, the hydrophilic cationic nanoparticles were completely hydrophobized. They could then be phase-transferred to organic layer. TEM showed that nanoparticles assemble in to a variety of mesostructures upon ion-pairing with anions. The aggregate formation was found to depend critically upon length of the hydrophobic alkyl chain as well as the head-group of the anion. Isothermal Titration Calorimetry (ITC) was employed to probe the interactions of these nanoparticles with anions. It was found that the anions that resulted in nanoparticle precipitation displayed exothermic interactions with the nanoparticle. Chapter 4 deals with the synthesis of -thiolated metal chelator derivatives whose structures are shown in Fig. 3. The molecules are based on well-known chelators viz. iminodiacetic acid and bis-(2-pyridylmethyl)amine. While the first one is carboxylic acid-based chelator, the second one is pyridine-based. Nanoparticles coated with these chelators were synthesized in a size-controlled manner. These nanoparticles exhibited pH-controlled reversible assembly. However, while S-IDA based nanoparticles aggregated at low pH values, the S-BPA based nanoparticles aggregated in high pH regimes. Mixed monolayer protected gold nanoparticles were synthesized by employing S-BPA and C12H25SH as capping agents. It resulted in the formation of nanoparticles in low size-dispersion. These nanoparticles were characterized by 1H NMR spectroscopy to infer the ratio of the two capping agents on the nanoparticle surface. These nanoparticles demonstrated metal-ion induced aggregation. It was found that the nanoparticles could differentiate Cu2+ ions from other ions, and immediately formed aggregates in presence of Cu2+ ions. Chapter 5 describes the synthesis of novel mono-thiolated “Gemini” surfactants for nanoparticle synthesis. Gemini surfactants with different spacers were prepared. These surfactants had a 12-n-12 kind of molecular structure as shown in the Fig. 4. Upon preparation of nanoparticles with these thiols, the resulting material was soluble in water in the case of rigid thiols like D2S and DBPS Chapter 6 deals with the synthesis and hydrogelation properties of a low molecular mass hydrogelator based on an azobenzene based tetrameric sugar derivative (Fig. 5). The pKa of carboxylic acids in the molecule were determined using 13C NMR. The trans-to-cis isomerization of the compound was probed by time-dependent UV-vis studies. The sugar derivative exhibited pronounced hydrogelation capacity, gelling water at micromolar concentration. The gel formed was characterized extensively (structural formula) Figure 2: Schematic of cationic nanoparticles and molecular structures of the anions employed for nanoparticle assembly (structural formula) Figure 3: Chemical structures of metal-chelator containing thiols employed for the pH-controlled and metal-ion mediated nanoparticle assembly (structural formula) Figure 4: Schematic of cationic nanoparticles and molecular structures of the anions employed for nanoparticle assembly (structural formula) Figure 5: Chemical Structure of azobenzene-based tetrameric sugar derivative exhibit- ing pronounced hydrogelation using melting temperature analysis, UV-vis, FT-IR, circular dichroism spectroscopy and scanning electron microscopy. The resultant gel exhibited impressive tolerance to the pH variation of the aqueous phase and gelated water in the pH range of 4 to 10. While UV-vis and CD spectroscopy indicated that pronounced aggregation of the azobenzene chromophores in the gelator was responsible for gelation, FT-IR studies showed that hydrogen bonding is also a contributing factor in the gelation process. The melting of gel was found to depend upon the pH of the aqueous medium in which gel was formed. The gel showed considerable photostability to UV irradiation indicating tight intermolecular packing inside gelated state that render azobenzene groups in the resultant aggregate refractory to photoisomerization. The electron micrographs of the aqueous gels thus formed showed the existence of spongy globular aggregates in such gelated materials. Addition of salts to the aqueous medium led to a delay in the gelation process and also caused remarkable morphological changes in the microstructure of the gel. Appendix A describes the employment of ligand-free palladium nanoparticles towards efficient catalysis of Heck and Suzuki reactions in aqueous medium. Hexadecyl trimethylammonium bromide was employed as the surfactant to achieve solubilization of organic compounds in aqueous medium. UV-vis and TEM investigations into the formation of nanoparticles in the reaction media were undertaken. These studies indicate that the nanoparticles were formed by reduction of potassium tetrachloropalladinate by methyl acrylate used as one of the reactants. TEM investigation indicated the formation of nanoparticle assemblies upon solvent drying. Efficient and catalytic synthesis of a number of organic compounds could be achieved in high yield.

The thesis entitled ‘‘Development of Stimuli-Responsive Self-Assembled Materials for Biomolecular Applications’’ deals with the design, synthesis, and characterisation of low molecular weight hydrogel systems as well as small molecular probes and their responses towards various stimuli. Depending upon the nature of their association, the present work has been divided into two main subsections. Chapter 1 presents an overview of the general area of the low molecular weight hydrogel and stimuli-responsive hydrogel, different types of gelator molecules, their self-assembly patterns, along with applications of the LMOGs hydrogels. Chapter 2A deals with the synthesis of pyrene-based monosaccharides namely D-gluconic acid and glucose and their gelation propensity. Selective gelation of pyrene linked gluconic acid-based amphiphilic compound, both in aqueous medium and EtOH. Further, the gelator was utilized to differentiate between alcoholic and non-alcoholic beverages and the sensing of insulin. Chapter 2B describes the synthesis and self-assembly properties of two different pyrene-disaccharide compounds (with maltose and lactose) in an aqueous medium. Lactose based Hydrogel is successfully utilized for studying the sustainable release of anticancer drugs, such as Doxorubicin (DOX) and mitoxantrone (MT). In addition, lactose-based amphiphile also showed specific interaction with Cholera Toxin B (CTB). Chapter 3A. describes the self-assembly studies as well as hydrogelation of a tyrosine-functionalized low molecular weight pyrenyl probe (L-PyTyrOH) in a buffered medium (pH 7.4). Then lanthanide ion (Eu3+) is doped into the hydrogel network and the resultant metallogel is used for the detection of pathogenic biomarkers such as dipicolinic (DPA) acid and phytic acid at physiological pH. Chapter 3B describes the formation of a two-component ‘charge transfer’ (CT) hydrogel system, comprising of a pyrene-amino acid conjugate and a 4-Chloro-7-nitrobenzofurazan (NBD) derivative in 1:1 molar ratio. CT gel was used for the ‘Turn-on’ sensing (cyan emission) of the biogenic amino acids, namely cysteine and homocysteine Chapter 4A. describes the design and self-assembly studies of the pyrene-based amphiphilic compounds having different amino acids residues at the terminal position, such as histidine and tryptophan. Moreover, the present system was also used for detecting the α-chymotrypsin in a human blood serum sample Chapter 4B. describes the synthesis and self-assembly studies of the of gallate attached pyrenyl derivatives connected via aromatic amino acid namely phenylalanine and tyrosine. The hydrogels were then involved in designing sensor array for Cu2+, Hg2+, and Fe3+ and selective sensing of hypochlorite Chapter 4C. deals with the studies of different hydrogel-nanocomposite hybrid materials where graphene oxide has been involved as carbon nanomaterial. The hybrid hydrogels are utilized for the removal of organic dye namely methylene Blue (MB) and rhodamine B (RhB) from the aqueous solution and spermine estimation. Chapter 5A presents the design and synthesis of a ruthenium complex-based charge transfer probe and its application in selective detection of Spodoptera Litura Nuclear Polyhedrosis Virus (SLNPV). Chapter 5B describes the ratiometric sensing of the Spilosoma Obliqua Nuclear Polyhedrosis Virus (SONPV) by acetyl ester derivative of pyranine dye.

Chapter 1. Introduction This chapter is an overview on the literature of self-association of small organic molecules. The chapter is presented in four parts. First, an introduction to aggregation of small molecules is given with the emphasis on micelles and gels(Parts 1 and 2) In part 3, a short overview is given on bile acid based aggregates and their applications. Lastly, the content of the thesis is outlined. Chapter 2. Solution properties of novel cationic bil salts: A structure-aggregation property study Scheme 1: Structures of Cationic bile salts(Refer PDF File) Bile Salts are biosurfactants and they are known to form micelles in aqueous medium. We studied the micellar properties of cationic bile salts(Scheme 1) and compared with their natural (anionic) counterparts. A serendipitous discovery of the gelation of a cationic bile salt(4) led us to investigate the aggregation properties of this new class of cationic hydrogelators. This chapter highlights the recent efforts on the study of side chain structure-aggregation property relationship of cationic bile salts. Bile acid analogues with a quaternary ammonium group(Scheme 1, compounds 2, 3, 4, 6, 8 and 12) on the side chain were found to efficiently gel aqueous salt solutions. Some of the cationic bile salts gelled water alone and many of them gelled aqueous salt solutions even in the presence of organic co-solvents(≤ 20%) such as ethanol, methanol, DMSO and DMF. A strong counter ion dependent gelation was observed. These gels showed interconnected fibrous networks. Unlike natural anionic bile salt gels(reported for NaDC, NaLC), the cationicgels reported here are pH independent. Cationic gels derived from DCA showed more solid-like rheological response compared to natural NaDC gels studied earlier by Tato et al. A strong structure(side-chain) andcounter-ion dependent flow of the cationic bile salt gels was seen. Chapter 3. Applications of cationic bile salts and their aggregates Cationic bile salts are useful in many ways. We have studied some of the applications of cationic bile salts(discussed in chapter 2) and their aggregates in this chapter. The chapter is presented in three parts. Part 1. Interaction of Cationic bile salts and DNA The bile acid amphiphilicity is believed to help the DNA binding process of polyamines. This has prompted us to study the DNA-bile salt binding interaction of bile salts. The binding of cationic bile salts has been expressed in terms of C50 values, which were determined from the plot of fluorescence of ethidium bromide bound DNA vs. bile salt concentration(Fig 1) The C50 values for cationic bile salts were estimated to be about 1.2 mM. Fig1: A plot of fluorescene of ethidium bromide bound DNA against bile salt concentration (Refer PDF File) Part 2. Cholesterol solubilization and crystallization studies in aqueous bile salt solutions. Dihydroxy bile salt micelles are well known for cholesterol dissolution(e.g. UDCA and CDCA). We studied the dissolution of cholesterol in the cationic bile salt micelles(of 21-25) and the results are discussed in this part. Scheme 2: Cationic bile salt chlorides studied for cholesterol dissolution (Refer PDF File) A powder dissolution method was used to study the solubility of anhydrous cholesterol in cationic bile salt solution. These cationic bile salt micelles can dissolve cholesterol to the same extent as the taurine conjugates of bile acids, but lesser than the natural anionic bile salts(Fig.2) Addition of PC(Phosphatidylcholine) to cationic bile salt micelles enhanced the micellar cholesterol solubilization. Fig 2:Cholesterol dissolution in cationic bile salt solutions(Refer PDF File) The crystal nucleation time of cholesterol did not change significantly by adding 5-30 mM of the cationic bile salts. The bile salt analogues did, however, attenuate cholesterol crystallization to a similar extent at all concentrations studied. All these effects wer comparable to those fo cholic acid. Part 3. Hydrogels as a reaction vessel for photodimerization Bile salt micelles have been shown to control the product selectivity in photochemical reactions. The dynamic nature of the bile salt micelles results in differential effects on reaction selectivity. The photodimerization of acenaphthylene(sheme 3) was studied in micellar and hydrogel medium(e.g. NaDC, 22, 28, etc.) The ratio of anti- to synphotodimer was found to be greater in gel bound state than in solution. Substitution on the CAN ring did not show larger variation on the product distribution from solution gel. Scheme 3: Photodimerization of acenaphthylene(Refer PDF File) Chapter 4. Bile acid derived sulfur analogues in designing novel materials. Part 1. A simple approach towards nanoparticle-gel hybrid material. Scheme 4: Scheme for the synthesis of thiols derived from bile acids (Refer PDF File) Our interest in bile acid based gelator molecules led us to explore the synthesis and properties of bile analogues with the side chain carboxylic acid replaced by a thiol(Scheme 4) to stabilize metal NPs. We reasoned that the specific self-aggregation modes of facially amphiphilic bile units would enable a metal NP capped by such a thiol to “lock” onto a gel fiber derived from a structurally related gelator molecule. AuNPs stabilized by 38-40 were obtained by the NaBH4 reduction of homogeneous methanolic solutions of the thiol and gold salt. These steroid capped nanoparticles were found to stay dispersed in a gel of 28, thus providing a simple approach to obtain gel-nanoparticle hybrid. A photograph of the hybrid material and their morphology are shown in Fig 3.(Refer PDF File) Chart 1: Structure of the gelator used for designing a hybrid material(Refer PDF File) Part 2. Gelation of aromatic solvents using sulfur analogues of bile acid A few of the sulfur derivatives were serendipitously fouond to gel organic solvents (Fig 4). Thiol 38 formed stable gels at room temperatures while the disulphide 36 formed stable gels below 5º C. The aggregation properties, morphology, and the melting profiles of gels of disulfides and thiols derived from bile acids have been highlighted in this part. Fig 4: A photograph of the gels derived from 38(Refer PDF File) (For Figures and Molecular Formula Pl refer the Original Thesis)

Chapter 1. Introduction This chapter is an overview on the literature of self-association of small organic molecules. The chapter is presented in four parts. First, an introduction to aggregation of small molecules is given with the emphasis on micelles and gels(Parts 1 and 2) In part 3, a short overview is given on bile acid based aggregates and their applications. Lastly, the content of the thesis is outlined. Chapter 2. Solution properties of novel cationic bil salts: A structure-aggregation property study Scheme 1: Structures of Cationic bile salts(Refer PDF File) Bile Salts are biosurfactants and they are known to form micelles in aqueous medium. We studied the micellar properties of cationic bile salts(Scheme 1) and compared with their natural (anionic) counterparts. A serendipitous discovery of the gelation of a cationic bile salt(4) led us to investigate the aggregation properties of this new class of cationic hydrogelators. This chapter highlights the recent efforts on the study of side chain structure-aggregation property relationship of cationic bile salts. Bile acid analogues with a quaternary ammonium group(Scheme 1, compounds 2, 3, 4, 6, 8 and 12) on the side chain were found to efficiently gel aqueous salt solutions. Some of the cationic bile salts gelled water alone and many of them gelled aqueous salt solutions even in the presence of organic co-solvents(≤ 20%) such as ethanol, methanol, DMSO and DMF. A strong counter ion dependent gelation was observed. These gels showed interconnected fibrous networks. Unlike natural anionic bile salt gels(reported for NaDC, NaLC), the cationicgels reported here are pH independent. Cationic gels derived from DCA showed more solid-like rheological response compared to natural NaDC gels studied earlier by Tato et al. A strong structure(side-chain) andcounter-ion dependent flow of the cationic bile salt gels was seen. Chapter 3. Applications of cationic bile salts and their aggregates Cationic bile salts are useful in many ways. We have studied some of the applications of cationic bile salts(discussed in chapter 2) and their aggregates in this chapter. The chapter is presented in three parts. Part 1. Interaction of Cationic bile salts and DNA The bile acid amphiphilicity is believed to help the DNA binding process of polyamines. This has prompted us to study the DNA-bile salt binding interaction of bile salts. The binding of cationic bile salts has been expressed in terms of C50 values, which were determined from the plot of fluorescence of ethidium bromide bound DNA vs. bile salt concentration(Fig 1) The C50 values for cationic bile salts were estimated to be about 1.2 mM. Fig1: A plot of fluorescene of ethidium bromide bound DNA against bile salt concentration (Refer PDF File) Part 2. Cholesterol solubilization and crystallization studies in aqueous bile salt solutions. Dihydroxy bile salt micelles are well known for cholesterol dissolution(e.g. UDCA and CDCA). We studied the dissolution of cholesterol in the cationic bile salt micelles(of 21-25) and the results are discussed in this part. Scheme 2: Cationic bile salt chlorides studied for cholesterol dissolution (Refer PDF File) A powder dissolution method was used to study the solubility of anhydrous cholesterol in cationic bile salt solution. These cationic bile salt micelles can dissolve cholesterol to the same extent as the taurine conjugates of bile acids, but lesser than the natural anionic bile salts(Fig.2) Addition of PC(Phosphatidylcholine) to cationic bile salt micelles enhanced the micellar cholesterol solubilization. Fig 2:Cholesterol dissolution in cationic bile salt solutions(Refer PDF File) The crystal nucleation time of cholesterol did not change significantly by adding 5-30 mM of the cationic bile salts. The bile salt analogues did, however, attenuate cholesterol crystallization to a similar extent at all concentrations studied. All these effects wer comparable to those fo cholic acid. Part 3. Hydrogels as a reaction vessel for photodimerization Bile salt micelles have been shown to control the product selectivity in photochemical reactions. The dynamic nature of the bile salt micelles results in differential effects on reaction selectivity. The photodimerization of acenaphthylene(sheme 3) was studied in micellar and hydrogel medium(e.g. NaDC, 22, 28, etc.) The ratio of anti- to synphotodimer was found to be greater in gel bound state than in solution. Substitution on the CAN ring did not show larger variation on the product distribution from solution gel. Scheme 3: Photodimerization of acenaphthylene(Refer PDF File) Chapter 4. Bile acid derived sulfur analogues in designing novel materials. Part 1. A simple approach towards nanoparticle-gel hybrid material. Scheme 4: Scheme for the synthesis of thiols derived from bile acids (Refer PDF File) Our interest in bile acid based gelator molecules led us to explore the synthesis and properties of bile analogues with the side chain carboxylic acid replaced by a thiol(Scheme 4) to stabilize metal NPs. We reasoned that the specific self-aggregation modes of facially amphiphilic bile units would enable a metal NP capped by such a thiol to “lock” onto a gel fiber derived from a structurally related gelator molecule. AuNPs stabilized by 38-40 were obtained by the NaBH4 reduction of homogeneous methanolic solutions of the thiol and gold salt. These steroid capped nanoparticles were found to stay dispersed in a gel of 28, thus providing a simple approach to obtain gel-nanoparticle hybrid. A photograph of the hybrid material and their morphology are shown in Fig 3.(Refer PDF File) Chart 1: Structure of the gelator used for designing a hybrid material(Refer PDF File) Part 2. Gelation of aromatic solvents using sulfur analogues of bile acid A few of the sulfur derivatives were serendipitously fouond to gel organic solvents (Fig 4). Thiol 38 formed stable gels at room temperatures while the disulphide 36 formed stable gels below 5º C. The aggregation properties, morphology, and the melting profiles of gels of disulfides and thiols derived from bile acids have been highlighted in this part. Fig 4: A photograph of the gels derived from 38(Refer PDF File) (For Figures and Molecular Formula Pl refer the Original Thesis)