The development of new reagents to efficiently cleave peptides and proteins has become increasingly important for protein structural studies and other applications. However, this has proved to be a very challenging task due to the extreme stability of the peptide amide bond. Transition metal complexes cleave proteins and peptides through either oxidative or hydrolytic pathways. However, hydrolytic cleavage is preferred over oxidative cleavage, because the latter process produces irreversibly modified peptide fragments. Metal-assisted peptide hydrolysis is introduced in Chapter I. The metals Ce(IV), Co(II), Co(III), Cu(II), Fe(III), Mo(IV), Ni(II), Pd(II), Pt(II), Zn(II), and Zr(IV) are described as promising non-enzymatic hydrolysis reagents. In Chapter II, Zr(IV)-assisted hydrolysis of the dipeptide Gly-Gly and of its N- and C- blocked analogs is described. The highest levels of cleavage were observed at pH values ranging from 4.4 to 4.7. When the pH was raised to ~ 7.0, hydrolysis yields were decreased and amounts of zirconium precipitation were increased proportionately. Zirconium(IV)-assisted peptide hydrolysis in the presence of 4,13-diaza-18-crown-6 is reported in Chapter III. The goal of this work was to use an azacrown ether to reduce Zr(IV) precipitation and enhance levels of hydrolysis at neutral pH. An experiment in which 16 glycine containing dipeptides were hydrolyzed by Zr(IV) and by Zr(IV)/4,13-diaza-18-crown-6 indicated that 4,13-diaza-18-crown-6 markedly enhanced the reactivity of Zr(IV) under near physiological conditions. Because Zr(IV) precipitation was not reduced in these reactions, we proposed that hydrolysis of peptides by Zr(IV)/4,13-diaza-18-crown-6 might be heterogeneous in nature. In Chapter IV, seventeen macrocyclic and open-chain Zr(IV) ligands were compared in order to gain mechanistic insights that would enable hydrolysis yields at neutral pH to be further improved. While the macrocyclic ligands 4,13-diaza-18-crown-6 and 4,10-trioxa-7,13-diazacyclopentadecane tended to produce higher levels of Zr(IV)-assisted dipeptide cleavage, it was not necessary to have a ring structure to enhance Zr(IV) reactivity. With respect to the open-chain ligands, the potential ability to form multiple chelate rings appeared to coincide with reduced levels of Zr(IV) precipitation as well as with reduced levels of dipeptide hydrolysis. In Chapter V, a summary of our results and conclusions is presented.

The crown ether derivative application have been widely reported,but is very difficult to see by the liquid crystal primarily report. We have used dibezn-18-crown-6 as the starting material to synthesis and study their properties of liquid crystal.

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>Magister Scientiae - MSc / Amperometric sensors for Tenofovir, a model nucleotide/ nucleoside reverse transcriptase inhibitor ARV drug, were studied based on the principle of ion-transfer electrochemistry at the membrane-stabilized oil/ water interface (O||W) in a four-electrode cell set-up. Solutions of the hydrophobic salts tetradodecylammonium tetrakis(4-chlorophenyl) borate (ETH500), ethyl violet tetraphenylborate (EthVTPB), tetrabutylammonium tetraphenylborate (TBATPB), tetraphenylphosphnium tetraphenylborate (TPphTPB) and three ionic liquids (Methyltrioctylammonium bis(trifluoromethyl sulfonyl)imide (IL1), 1-butyl-3- methylimdazolium bis(trifluoromethyl sulfonyl)imide (IL3) and 1-propyl-3- methylimdazolium bis(trifluoromethylsulfonyl)imide (IL4)) in nitrobenzene (NB), 1,2- dichloroethane (DCE), and 2-nitrophenyloctyl ether (NPOE) were each tested as O-phases. The cyclic voltammograms of the resulting O||W interfaces in aq. Li2SO4 or aq. MgSO4 were compared with respect to noise, potential window, and other parameters. The three ILs were also tested as self-sufficient salts without a solvent medium. In the end, the ETH500/ DCE salt/ solvent pair was found to yield the best behaved polarizable O||W interface in aq. MgSO4. The analytical characteristics of the resulting sensors to tenofovir without (Ag|ETH500/DCE||) and with the dibenzo-18-crown-6 (Ag|ETH5000/DB18C6/DCE|| in the O-phase were studied with respect to the two pairs of peaks in the CV, namely the WO ion transfer peak and the reverse OW peak. Both sensors exhibited operational stability of 90 min. After consideration of reasonable S/N ratio and sample throughput rates, the scan rate of 25 mV/ s was used in subsequent signal interrogation with CV. The final potential windows were 0.95 V wide for Ag|ETH500 (10 mM)/ DCE|| in aq. MgSO4 (50 mM) and 0.70 V wide for Ag|ETH500 (10 mM)/ DB18C6 (50 mM)/ DCE|| in aq. MgSO4 (50 mM). From plots of peak currents versus square of scan rate, tenofovir diffusion coefficients of about 2.48 × 10-11 cm2/ s were estimated, which indicated diffusion through the supporting membrane as the rate limiting process. Based on WO ion transfer peaks, the first one exhibited a detection limit of about 5 M, a linear range of 15 – 100 M, and sensitivity of 7.09 nA M-1 towards tenofovir, whereas for the second one these were respectively 3 M, 6.32 nA M-1, and 9 – 100 M. In this way, a four-electrode amperometric detection of ion transfer process at liquid | liquid interface, both under simple and ionophore-facilitated mode, has been demonstrated as promising for analysis of tenofovir as a representative of the nucleotide/ nucleoside reverse transcriptase inhibitor ARV drugs