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Title:Topologically constrained DNA intercalators: Synthesis and DNA binding studies
Author(s):Lamberson, Carol R.
Doctoral Committee Chair(s):Zimmerman, Steven C.
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Chemistry, Organic
Abstract:The synthesis and DNA binding properties of three macrocyclic diacridines (31, 32 and 33) is discussed. The two acridines are connected by linker chains at the 4- and 9-positions. Macrocycles 31 and 32 are linked via spermine at the 9-position and have been shown to bind to DNA by bisintercalation using absorption spectroscopy titrations, thermal denaturation studies, and viscometric titrations of both calf thymus DNA and closed circular supercoiled DNA. Macrocycle 31 dissociates 10 to 40 times slower from poly(d(A-T)) $\sb2$ and poly(d(G-C)) $\sb2$ than its analogous mono-linked analogue, spermine diacridine (7). $\sp1$H NMR studies of 31 complexed to d(CGCG)$\sb2$ indicate that the macrocycle binds to DNA by formation of a catenated complex in which one linking chain is located in opposite grooves of the DNA. The NMR studies and absorption spectral titrations suggest that 31 binds by insertion of the acridines on each side of one base pair in violation of the neighbor exclusion principle.
Macrocycle 33 has a diamide linker chain at the 9-position of the acridine rings. This molecule binds to DNA by intercalation as evident from its ability to remove and reverse the supercoils in closed circular DNA. However, the results are inconclusive as to whether it binds by mono- or bisintercalation. The mono-linked diacridine 34 has been shown to bind to DNA by bisintercalation.
The preliminary synthetic results for a novel trisintercalator are discussed. Trimer 35 consists of a naphthalene diimide as the central chromophore and two 9-aminoacridines as the terminal chromophores. Trimer 35 was synthesized from 1,4,5,8-naphthalene dianhydride which was reacted with the mono-Boc protected diamine to give the N,N$\sp\prime$-disubstituted naphthalene diimide. After deprotection, the diimide was reacted with two moles of 9-phenoxyacridine to produce 35. The dimer 36 containing a naphthalene diimide and one 9-aminoacridine was synthesized in a similar manner.
Issue Date:1991
Type:Text
Language:English
URI:http://hdl.handle.net/2142/19162
Rights Information:Copyright 1991 Lamberson, Carol R.
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9136644
OCLC Identifier:(UMI)AAI9136644


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