Studies of catalyzed phosphodiester hydrolysis and of isomerization in azobenzene-chain liposomes

Hydrolytic cleavages of DNA and RNA have many potential applications in molecular biology. Many DNA and RNA models have been prepared and cleaved by various metal ions. The first chapter of this dissertation reports the synthesis of a novel micellizable RNA model compound, 2-hydroxy-n -hexadecyl p-nitrophenyl phosphate (HHNP) and the cleavage of this model by various lanthanides. Among the lanthanides tested, Tm3+ is the most effective catalyst, able to cleave HHNP with kobs = 0.0368 s-1 at pH 7.0 and 37°C. This corresponds to a rate enhancement of >105 over basic hydrolysis. Micellar substrates can be hydrolyzed 4--5 times faster than their nonmicellar analogues. The enhanced binding of the lanthanides to the micellar interface is the major contributor to the interfacial activation.; Photoisomerization of azobenzene AB and its derivatives has received considerable attention over past few years because of potential applications in areas such as high-density optical memory elements and molecular switching devices. The second chapter describes the synthesis of single and double AB-chain cationic lipids (AB-1 and AB-2) and their isomerization behavior under various conditions. AB-1 and AB-2 undergo efficient photoisomerizations and thermal cis to trans isomerizations both in acetonitrile solution and in 1:9 coliposomes with the cationic bisether host lipid 2C18 at room temperature. This is also true of the hololiposomes of a single chain AB lipid and its 1:1 coliposome with 2C18. The trans AB unit in hololiposomes of a double chain AB lipid and its 1:1 coliposome with 2C18 can also efficiently photoisomerize to the cis isomer at 60°C, but the isomerization is severely impacted at lower temperature. The extent of the temperature effect on the trans to cis photoisomerization of the liposomes is as follows: Holo-AB-2 > 1:1 AB-2/2C18 > 1:9 AB-2/2C18 ∼ holo-AB-1/2C18 > 1:1 AB1/2C18 > 1:9 AB-1/2C18. The order is consistent with the strength of interaction between neighboring AB units; the stronger the interaction, the more severely isomerization is hindered. The thermal cis to trans isomerization of a cis AB in 1:9 coliposomes of AB-2 and 2C18 is faster than the isomerization of AB-2 in acetonitrile solution, probably because of the less unfavorable entropy of activation for isomerization in the coliposomes. Comparable first order rate constants were found for cis to trans isomerizations of AB-1 in liposomes and in solution, and for AB-2 in solution.