GOLD NANO- AND SUPRA-PARTICLES TOWARDS LUMINESCENT AGGREGATION PEPTIDE DETECTION AND HOST-GUEST CHEMISTRY

Abstract

The thesis entitled, “Gold nano peptide detection and host Chapter 1 presents a general introduction and supraparticles along with their the variation of its color and its size. of the AuNP solution. AuNP has been successfully utilized biomolecule by modulation in its size and nanoparticles have been observed by comparative studies in the r stabilizing ligands, specially Gold nanoparticles’ role in biomedical field is known for its carrier. Different organic s target analytes have been discussed them an attractive candidate for in the Alzheimer’s disease and diverse detection and plaque forms of the peptides The scope of the thesis part of the introduction section by the self-assembly of AuNP molecules (Scheme 1). luminescent AuNPs has been targeted to AuNPs with small organic fluorophores has been used for the instantaneous detection of A peptide. The combination of organic macrocycles with AuNP has been targeted for the formation of different gold Scheme 1. i ABSTRACT nano- and supra-particles towards luminescent aggregation host-guest chemistry” has been divided into four chapters. for the gold nanoparticles (AuNP) synthetic methods and their properties. Surface plasmon resonance (SPR) in the colorimetric capping reagents. Luminescence properties in gold role of phosphine, alkane-thiol, sulphides and tetraoctyl ammonium ion application as supramolecular architecture and their nonhave discussed. Interaction of AuNP with organic host-guest chemistry. The role of a methodologies for monomer, oligomer, fibril have been compared in this section. work based on literature studies has been discussed in section. Different gold nano-and supra-architectures or gold nanorod in presence of acid mixture or organic . A facile method for the synthesis of organic develop for bioimaging. Surface functionalization of supra structures, which might be suitable for Gold-based nano- and supra different potential applications. aggregation, AuNP), gold nanorods AuNP is known for urface is the origin of the color detection for ion, ole solvents and different ion. drug delivery -covalent interactions with supramolecules makes amyloid beta (A) peptides . the last has been targeted fluorogen free NIR ight host-guest chemistry Chapter 2 describes the free aggregation-induced emission and monomeric nanomolar Amyloid β peptide detection. This chapter has been divided into two luminescence from gold nanoparticles due to the addition of diluted aqua regia. nanoparticles with variable shape and sizes and characterized by absorbance and TEM images. The addition of diluted aqua regia to gold nanoparticles led to the development of a second absorbance peak at 670 nm due to aggregation. Citrate stabilized gold nanoparticles do not show luminescence proper to gold nanoparticles result aggregation of nanoparticles induced emission of gold nanoparticles was further confirmed by DLS and FE for a variety of reducing agents used in gold nanoparticle syntheses and independent of the synthetic methods of fluorescein emission in the visible region, which nanoparticle solution. More importantly, cell viability experiments show that the nanoparticles were nontoxic and imaging studies show were localized in cell nuclei of human liver carcinoma HepG2 cells. Section B describes the surface modification of citrate stabilized AuNP with small molecular fluorophore SEA-SC1. Fluorescence of SEASC1 was quenched in the presence of AuNP at ii surface modification of gold nanoparticles for fluorogen sections. Section A were synthesized via the citrate reduction method property. The controlled addition resulted in the development of luminescence peak at 916 nm due to the (Scheme 2). This is the first report of fluorogen free at NIR region. The aggregation of gold nanoparticles FE-SEM images. This aggregation process methods. This aggregation technique was applied had initially been showed that the aggregated gold nanoparticles Scheme 2. NIR luminescence from AuNP due to aggregation after the addition of diluted aqua regia. Scheme 3. Methodology for the detection of nanomolar amyloid beta monomer in presence of gold nanoparticle and a small molecule fluorophore SEA anoparticles describes the NIR Gold ty. of diluted aqua regia aggregation was compared found to be particle for the recovery quenched in the gold aggregated SEA-SC1.the physiological condition. showed enhancement in enhancement was observed after 60 nM was observed in the presence of between amyloid beta peptide monomers and 1.5 equivalent of Cu(II) ion selectivity of this methodology confirmed by using competitive proteins or peptide sequences amyloid polypeptide and glutathione in excess quantities cerebrospinal fluid. This strategy concentration of amyloid beta peptide monomer in human serum albumin and artificial cerebrospinal fluid. Chapter 3 describes the and supraparticle for anticancer drugs uptake and release into two sections. Section A addition of acidic solution of cucurbit[8]uril (CB[8]) to an aqueous solution of citrate stabilized gold nanoparticles (AuNP) confirmed by FE-SEM different acids such as HCl, formation of suprapyramids but the size of the synthesized suprapyramids was controlled by the anionic part of these acids (bromide, nitrate, sulfate and chloride) were used as a host for available for non-Hodgkin’s lymphoma supraparticle. Different physiological pH buffers with glutathione or human serum albumin showed the selective release of these drugs The release of doxorubicin was further confirmed by fluorescence microscopic imaging studies Scheme 4. iii Addition of 10-60 nM Aβ monomer to this fluorescence intensity (Scheme 3). The saturation in the fluorescence Aβ monomers. The second step fluorogenic response stoichiometric Cu(II) ion due to the instantaneous interaction for Aβ monomers and their initial Cu(II) such as α bovine serum albumin, all amino acids and biomolecules such as utathione compared to their natural abundance in blood plasma and was further applied in the detection anion dependent cucurbit[8]uril stabilized gold supra release. This chapter has been divided describes the development of supraaddition (Scheme 4). The stepwise formation of these and TEM images. The addition of CB[8], HBr, HNO3, and H2SO4, to gold nanoparticles also resulted in the chloride). These anion dependent supra anticancer drugs such as doxorubicin, etoposide and prednisolone and showed uptake of these drugs . from the supra-pyramid under different conditions cin Synthetic route of CB[8] stabilized supra addition of an acidic solution of CB[8] to AuNP an host-guest chemistry. quenched solution . (Scheme 3). The adduct was further α-synuclein, islet , process of nanomolar supra-pyramid -pyramid structures by the supra-pyramids was separately dissolved in supra-pyramids shaped particles in the cavity of the conditions.with human prostrate cancer DU experiment with 1-adamantanamine confirmed the role of supra known CB[8] host. Section B describes that the addition of trimethylammonium bromide pyramid structures (Scheme 5). The formation of these suprapyramids was confirmed by FESEM images. Addition of CB[8], dissolved in HBr, HNO formation of a layered structure, distorted cube (Scheme 5). The addition of methyl viologen to the GNR solution treated with CB[8] in the presence of these acids resulted in the disruption of these supraparticles due to its reported interaction with CB[8]. doxorubicin, etoposide and prednisolone Chapter 4 describes the regioisomeric cryptands and calix[n]arene (n = chapter has been divided into two sections. regioisomeric cryptands ( of second absorbance peak addition of 25 μM and 500 μM of cryptand and gold suprasphere (AuSS μM cryptand 2 resulted (AuEDL, Scheme 6) respectively. The addition of 1 or 2 to the nonluminescent 0.8 Scheme 6. Scheme 5. iv DU-145 cell line. The poor release of drugs during the controlled supra-pyramid as host instead of well CB[8] in hydrochloric acid to stabilized gold nanorod (GNR) led to the HNO3 and H2SO4 separately to gold cube-like structure, and supraspheres These different shape supraparticle hosts showed uptake prednisolone. tunable morphologies of gold supraparticles in presence of 6 & 8) for host Section A deals with the 1 and 2) to the citrate stabilized AuNP, which due to the aggregation of AuNP. FE-SEM study show 1 to AuNP led to the formation of small aggregates AuSSL, Scheme 6) respectively. However, treatment of ted in the formation of aggregated AuNP and elongated dodecahedron Synthetic route of cryptand stabilized Synthesis of anion dependendent supra by the addition of acidic solution of CB[8] to gold nanorod and their host-guest chemistry. cetyl formation of suprato nanorod resulted in the respectively and release of ) host-guest chemistry. This separate treatment of , led to the development showed that the . 25 μM and 500 AuSSL and AuEDLnM AuNP showed NIR emission (λ AuSSL and AuEDL were isolated from the reaction mixture and stored for days at room temperature for further use. The formation of supraspheres depends upon the nature of the cryptand. The reversible host small molecule fluorophores, fluorescein and was achieved in the aqueous medium. Recovery of small molecule fluorophores, fluorescein, and SEA-SC2 from the host organic solvent respectively due to less stability of the host Section B Addition of calix[6]arene and calix[8]arene to an aqueous solution of citrate stabilized AuNP resulted in the broadening of SPR peak. FE of gold rhomboid and hexagon calix[8]arene respectively used as a host which showed the uptake of three previously used anticancer drugs doxorubicin, etoposide and prednisolone. Different physiological pH buffers of these drugs from the host The thesis ends with an overall conclusion and provides scopes for further research in this area. Scheme 7. v λem = 916 nm) due to the aggregation of AuNP. The settled host-guest chemistry of AuSSL and AuED ecule SEA-SC2. The maximum uptake of host-guest complex was achieved by the addition of acetic acid and anic host-guest complex in these solvents. FE-SEM study showed the formation hexagonal supra-particles after the addition of calix[6]arene and alix[(Scheme 7). These gold supra-rhombus and al and human serum albumin were used to monitor the host. Synthetic route of calixarene stabilized supra-hexagon by the addition of calixarene solution to AuNP. AuEDL were studied with two SEA-SC2 supra-hexagon were release