University of Illinois Urbana-Champaign

Topologically constrained DNA intercalators: Synthesis and DNA binding studies

Lamberson, Carol R.

This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.

Permalink

https://hdl.handle.net/2142/19162

Description

Title
Topologically constrained DNA intercalators: Synthesis and DNA binding studies
Author(s)
Lamberson, Carol R.
Issue Date
1991
Doctoral Committee Chair(s)
Zimmerman, Steven C.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Language
eng
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.
Type of Resource
text
Permalink
http://hdl.handle.net/2142/19162
Copyright and License Information
Copyright 1991 Lamberson, Carol R.

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Chemistry